Graduate Diploma in Family Medicine Trainees' Notes: Module 6: Tutorial

Graduate Diploma In Family Medicine
TRAINEES’ NOTES
Module 6: Tutorial
(2021 version – for use by the 2019 & 2020 intakes)
Tutorial reading notes

M6 GDFM Tutorial 6
Note to candidates and tutors on the OSCE Exercises
• In the OSCE Examination, the candidate will only have the “Instruction to candidates”
information containing sections A, B, and C on one page but can be longer if there are more
clinical details given (as is in this case scenario)
• The examiners will have the Instructions to the candidate plus “Instructions to examiners” to
brief them on how to conduct, assess, and grade the candidate’s performance.
• The OSCE Case-Rating Checklist gives the standard to be achieved for this OSCE. These will be
the take home points for the trainees to note at the end of this OSCE exercise
• Executing the role-play. The Tutor will be the role-playing examiner. One of the trainees will
be the candidate. The rest of the trainees will be “examiners” to grade the colleagues’
performance. They will be asked to comment at the end of the role play on: (1) overall
assessment – a show of hands whether the colleague passes, (2) grounds on which the
“Candidate” passed or otherwise, and then the tutor will give the answers based on the OSCE
Case Rating Checklist.
• Please DO NOT give this set of Instructions to Examiners or the OSCE Case Rating Checklist to
the trainees. Doing so will diminish the value of this exercise for subsequent years’ tutorial
where this exercise is repeated.
2021 GDFM Tutorial 6 -- TRAINEES

Page 2 of 46
M6 GDFM Tutorial 6
M6T WORK RELATED HEALTH, ENDOCRINE DISORDERS, MEN’S HEALTH, RENAL PROBLEMS
Unit 1
OSCE Exercise: Hairdresser with hand dermatitis
Unit 2
OSCE Exercise: Patient with borderline thyroid function tests
Unit 3
OSCE Exercise: Patient with problem of erectile dysfunction
Unit 4
OSCE Exercise: Patient coming to receive his urinalysis results
Reading Notes
Table of contents
1-Hollins LC, Flamm A. Occupational Contact Dermatitis: Evaluation and 9
Management Considerations. Dermatol Clin. 2020 Jul;38(3):329-338. doi:
10.1016/j.det.2020.02.001. Epub 2020 May 4. PMID: 32475511.
2- Worth A, Arshad SH, Sheikh A. Occupational dermatitis in a hairdresser. BMJ. 19
2007 Aug 25;335(7616):399. doi: 10.1136/bmj.39252.524317.94. PMID: 17717371;
PMCID: PMC1952494.
3-Biondi B. "Is there any reason to treat subclinical hypo and 20
hyperthyroidism?". Ann Endocrinol (Paris). 2021 Jun;82(3-4):161-162. doi:
10.1016/j.ando.2020.03.003. Epub 2020 Mar 4. PMID: 32204892.
4-Hughes K, Eastman C. Thyroid disease: Long-term management of hyperthyroidism 22
and hypothyroidism. Aust J Gen Pract. 2021 Jan-Feb;50(1-2):36-42. doi:
10.31128/AJGP-09-20-5653. PMID: 33543160.
5-Rew KT, Heidelbaugh JJ. Erectile Dysfunction. Am Fam Physician. 2016 Nov 29
15;94(10):820-827. PMID: 27929275.
6: Barocas DA, Boorjian SA, Alvarez RD, Downs TM, Gross CP, Hamilton BD, Kobashi 38
KC, Lipman RR, Lotan Y, Ng CK, Nielsen ME, Peterson AC, Raman JD, Smith-Bindman
R, Souter LH. Microhematuria: AUA/SUFU Guideline. J Urol. 2020
Oct;204(4):778-786. doi: 10.1097/JU.0000000000001297. Epub 2020 Jul 23. PMID:
32698717.

Page 3 of 46
M6 GDFM Tutorial 6
M6T: Unit 1
OSCE Exercise: Hairdresser with hand dermatitis
INSTRUCTIONS TO THE CANDIDATE
A Instructions To the Candidate
• This is an 8-minute OSCE station.
• Read the scenario carefully.
• This is an examination and diagnosis station
• You are expected to assess the patient clinically and manage her
appropriately.
• Take additional history as required
B Scenario
Ms. Lim, aged 25, a hairdresser, complains of a rash on her hands for the past 3
months.
C Details of the Case
Ms. Lim, aged 25, a hairdresser, complains of a rash on her hands for the past 3
months. She thinks she might be allergic to the solutions she uses at work. She
has started work as a hairdresser 6 months ago.
Physical examination:
Rash on both hands palmar and fingers. No rash on elsewhere of body
* End of instructions *

Page 4 of 46
M6 GDFM Tutorial 6
M6T: Unit 2
OSCE Exercise: Patient with Borderline Thyroid Function Tests
 This is an 8-minute History-taking and Examination station.
 Read the scenario carefully.
 Take a relevant history.
 The physical examination will be performed by indicating to the examiner what
examination you will be performing and what you would expect to find. The
examiner will then inform you of the findings.
 Provide two differential diagnosis.
B Scenario
Mr. Tan, aged 50, comes to see you with a set of his multiphasic health screening
results.
Mr Tan comes by himself. He is able to give his own history. He has never seen you
before. His multiphasic health screening results are normal except for the following:
Free T4 34pmol/L (10.3- 31.0)

TSH 0.1mU/L (0.5-5.0mU/L

Page 5 of 46
M6 GDFM Tutorial 6
M6T: Unit 3
OSCE Exercise: A Patient With Problems of Erectile Dysfunction
 This is an 8-minute Management station.
 Formulate a management plan for the patient.
B Scenario
Mr Tan a 51 year old mechanic comes to see you requesting Viagra.
This is his first visit to your clinic. He has a history of declining sexual activity for
the past five years, loss of libido and lately has not been able to sustain an
erection. When asked about his past medical history, he mentions that he has not
had any health checks for the last 3 years. He is not on any medications.
He smokes about 10 cigarettes a day for 20 years; does not drink alcohol. He is
not on any Western or traditional medication nor supplements. He is married to
his wife for 30 years and denies any marital problems. He mentions that his
mother has diabetes mellitus and hyperlipidaemia.
Physical examination reveals:-

 Blood pressure of 120/70mmHg, pulse 72 beats/min regular
 Height of 165cm
 Weight of 82kg
 BMI of 30.1 kg/m2
 Cardiovascular, abdominal, neurological examination unremarkable
 Genitalia normal
 Prostate 4 finger breaths wide, smooth median sulcus, no masses felt

Page 6 of 46
M6 GDFM Tutorial 6
M6T: Unit 4
OSCE Exercise: Patient Coming to Receive His Urinalysis Results
 This is an 8-minute Management station.
 Explain the results to the patient.
 Advise the patient the next appropriate steps to take.
B Scenario
Mr R is seeing you to receive the urinalysis results that were ordered the day before.
He has had “red” urine intermittently over the past 3 weeks.
Mr R comes by himself. He is able to give his own history. He is 55 years old. He has
no flank pain, abdominal pain, or pain refereed to the groin or testes. He has noticed
however of a narrowed stream, increasing hesitancy, frequency of urination, and
nocturia two or three times nightly for the last 6 months. As for the “red” urine, he
initially did not pay attention to it and hoped that it will resolve spontaneously. His
friend had a similar problem and a renal biopsy was done.
He has no past medical history of note. He does not exercise. He smokes 20

cigarettes a day for the last 30 years. He does. Not drink alcohol.
He was seen the day earlier by your partner. Examination of the abdomen showed no
abnormal findings. A rectal examination showed a 3+ enlarged smooth, firm non-
tender prostate. A urinalysis was ordered.
The urinalysis results:

Specific gravity 1.024, pH6. Glucose absent. Protein trace. Microscopic examination:
RBC>200 cells per high power field. One white blood cell per high power field. No
bacteria, crystals or abnormal casts.
*End of instructions *

Page 7 of 46
M6 GDFM Tutorial 6
Reading Notes
Table of contents
1-Hollins LC, Flamm A. Occupational Contact Dermatitis: Evaluation and 9
Management Considerations. Dermatol Clin. 2020 Jul;38(3):329-338. doi:
10.1016/j.det.2020.02.001. Epub 2020 May 4. PMID: 32475511.
2- Worth A, Arshad SH, Sheikh A. Occupational dermatitis in a hairdresser. BMJ. 19
2007 Aug 25;335(7616):399. doi: 10.1136/bmj.39252.524317.94. PMID: 17717371;
PMCID: PMC1952494.
3-Biondi B. "Is there any reason to treat subclinical hypo and 20
hyperthyroidism?". Ann Endocrinol (Paris). 2021 Jun;82(3-4):161-162. doi:
10.1016/j.ando.2020.03.003. Epub 2020 Mar 4. PMID: 32204892.
4-Hughes K, Eastman C. Thyroid disease: Long-term management of hyperthyroidism 22
and hypothyroidism. Aust J Gen Pract. 2021 Jan-Feb;50(1-2):36-42. doi:
10.31128/AJGP-09-20-5653. PMID: 33543160.
5-Rew KT, Heidelbaugh JJ. Erectile Dysfunction. Am Fam Physician. 2016 Nov 29
15;94(10):820-827. PMID: 27929275.
6: Barocas DA, Boorjian SA, Alvarez RD, Downs TM, Gross CP, Hamilton BD, Kobashi 38
KC, Lipman RR, Lotan Y, Ng CK, Nielsen ME, Peterson AC, Raman JD, Smith-Bindman
R, Souter LH. Microhematuria: AUA/SUFU Guideline. J Urol. 2020
Oct;204(4):778-786. doi: 10.1097/JU.0000000000001297. Epub 2020 Jul 23. PMID:
32698717.

Page 8 of 46
M6 Reading 1
Dermatol Clin 2020
O c c u p a t i o n a l Co n t a c t PMID: 32475511
Dermatitis
Evaluation and Management Considerations
Lauren Claire Hollins, MD, Alexandra Flamm, MD*
KEYWORDS
Contact dermatitis Allergic contact dermatitis Irritant contact dermatitis
Occupational contact dermatitis Management Evaluation Patch testing
Workers compensation
KEY POINTS
Occupational contact dermatitis is commonly encountered among workers, particularly those in
wet work.
Eighty percent of occupational contact dermatitis is due to irritant contact dermatitis and the re-
maining 20% is categorized as allergic contact dermatitis.
An accurate diagnosis by the dermatologist relies on meticulous physical examination and inquis-
itive history taking.
Comprehensive patch testing is the gold standard for diagnosing allergic contact dermatitis.
Although occupational contact dermatitis management represents a challenge to the dermatolo-
gist, it can be achieved with attention to detail and appropriate patient follow-up.
INTRODUCTION history, perform a thorough physical examination,

and carefully interpret data obtained about the
Contact dermatitis in the workplace is responsible workplace. At times, a work site visit is helpful to
for most skin disease in the industrialized world, further gather crucial data and corroborate the
accounting for up to 90% of occupational skin dis- diagnosis. This article provides an overview of
orders.1 It is also likely underreported, especially in how to evaluate a patient, perform a workplace
mild cases, and a recent survey of more than visit, and properly manage this potentially frus-
27,000 adults determined that the overall preva- trating diagnosis, both for the worker and the
lence of dermatitis was 9.8%, representing more dermatologist.
than 15 million affected US workers.2 Occupa-
tional contact dermatitis (OCD) can be divided EVALUATION CONSIDERATIONS
broadly into irritant contact dermatitis (ICD) and
allergic contact dermatitis (ACD). ICD makes up OCD is responsible for almost all cutaneous reac-
the vast majority, approximately 80% of OCD, tions that happen in the workplace, and has the
whereas ACD encompasses the remaining per- potential to significantly impact the quality of life
centage. However in many cases, ACD and ICD in those affected.3 It encompasses a wide range
are present concomitantly, especially on exposed of clinical manifestations from various potential ex-
parts of the body, such as the hands.1 To make an posures, typically depending on the patient’s cate-
accurate diagnosis, the dermatologist must work gory of work. The most important parts of
deliberately and slowly to acquire a detailed determining the cause of a worker’s rash are in
derm.theclinics.com
Department of Dermatology, Penn State Health, Milton S. Hershey Medical Center, 500 University Drive, Her-
shey, PA 17033, USA
* Corresponding author.
E-mail address: aflamm@pennstatehealth.psu.edu
Dermatol Clin 38 (2020) 329–338

https://doi.org/10.1016/j.det.2020.02.001
0733-8635/20/Ó 2020 Elsevier Inc. All rights reserved.
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9
14, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.
330 Hollins & Flamm
the evaluation of the patient, the collecting of data, allergens when exposed to chemicals.7 It should
which may or may not include a patch test, and be noted that the questions mentioned elsewhere
potentially conducting a site visit. in this article will not rule in or out whether the pre-
sent rash is ACD or an atopic flare. That must be
The Office Visit done by the physical examination and, if needed,
a patch test.
Many patients present to a health care provider as
Perhaps the most important part of history taking
a first step in the evaluation of their rash. The
is the occupational history. Sometimes, the rash
referral to a dermatology clinic may come from
has resolved when the patient presents in clinic
the patient themselves, their employer, a primary
(eg, difficulty scheduling or time spent away from
care physician, an occupational medicine physi-
work). Therefore, the physician must work as a de-
cian, or an insurer. The time allotted for this initial
tective to elicit proper information. The exact time-
visit is crucial to gathering information, and an
line of a typical day at work from arrival to departure
extended appointment will likely be required to
should be elicited, as well as dates the rash began.
gather the proper history, discuss possible expo-
This information is helpful not only to determine the
sures and perform the physical examination.
causative allergen, but it is important legally for the
employer. If the patient has the rash at all times,
The History
whether on extended vacations or working, then
A detailed elicitation of the patient history begins the symptoms are less likely to be due to work ex-
the diagnostic quest, including the timing, location posures. Details about the work site, the daily tasks
of the rash, and change in the rash in relation to the job entails, products used in restrooms if
work (ie, improvement away from work with wors- known, personal protective equipment and if other
ening upon return heightens suspicion that the coworkers are affected should be elicited. Distribu-
dermatitis is work related). A detailed discussion tion of the rash is also paramount. Simplified,
of the description of the work is also important. repeated questions may be needed, because it is
The dermatologist will want to know what potential likely that many patients will not think to discuss
contactants are used, what the patient believes the daily and routine actions performed at work,
they are exposed to, and whether or not they such as exposure to contaminated water from leak-
have access to information about the composition ing pipes or the regular protective gear used in the
of these materials. Encourage patients to bring work area. Finally, inquire about treatments used,
these data with them to the appointment if avail- including prescriptions, over-the-counter medica-
able. One Canadian survey of dermatologists tions, and home remedies.
revealed that only 5% of dermatologists inquired The steps to acquiring this history may take
about exposures and only 3% asked patients to time, so it is appropriate to schedule 1 appoint-
bring Material Safety Data Sheets (MSDSs; now ment solely for obtaining a detailed history. It is
referred to as Safety Data Sheets [SDSs]) from also appropriate to schedule a longer appoint-
the workplace to the clinic visit.4 Also inquire about ment, to obtain the history, perform the physical
physical symptoms. If the patient describes examination, and potentially place patches. It is
burning, erythema, or stinging, these findings likely that the patient may have to drive far dis-
may be suggestive of irritant dermatitis, potentially tances for this appointment, so minimizing travel
negating the need for a patch test. However, if the time with 1, longer visit is ideal.
patient notes intense, intractable pruritus, this may Even with a detailed history, the diagnosis for
be indicative of ACD. Another important question OCD is often difficult because no one clinical or
to ask is whether or not the patient is currently tak- dermatopathologic finding is characteristic.
ing oral corticosteroids, or any other immunosup- Criteria have been proposed to help guide the
pressive medications, which may dampen the practitioner to the correct diagnosis if OCD is sus-
results of patch testing, if a patch test is required.5 pected, named the Mathias criteria (Table 1).8 The
Patients can take oral antihistamines as needed 7 criteria proposed by Mathias assess the proba-
for symptoms because they should not alter patch bility for workplace causality. Responding yes to
test results.6 at least 4 items suggests that there is greater
You will also want to know about the patient’s than 50% probability of occupational causation,
past medical history. Do they have a history of implying a reasonable degree of medical certainty
atopy, hay fever, or self-described sensitive skin? that the dermatitis is workplace induced. The
These questions can point to a history of atopic criteria has been validated, which is helpful as it
dermatitis (AD). AD results in an impairment of can be used to help build a case for workers’
the skin barrier, for involved as well as uninvolved compensation, which is discussed elsewhere in
skin, and it can result in increased absorption of this article.9
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Occupational Contact Dermatitis 331
Table 1
patient is in a gown with all affected skin easily
Summary of the Mathias criteria for assessing accessible. During a full skin examination, look
occupational causation and/or aggravation of for corroborating evidence to the patient’s history,
contact dermatitis and also make note of the distribution of the
dermatitis. In classical airborne contact dermatitis,
Criterion 1 Is the clinical appearance look for areas of involvement that can help to
consistent with contact differentiate between photo-related dermatitis
dermatitis? such as underneath the chin, the eyelids, and
Criterion 2 Are there workplace exposures to any other exposed skin of concern.10 It is also
potential cutaneous irritants or important to assess the morphology of the lesions.
allergens? Lichenified plaques can denote chronicity,
Criterion 3 Is the anatomic distribution of whereas weeping, bullous plaques can lead one
dermatitis consistent with to think of a more acute process (Table 2).
cutaneous exposure in relation After assessing the exposed skin for dermatitis,
to the job task?
confirm that the patient’s skin is clear enough for
Criterion 4 Is the temporal relationship patch placement. This step is important to ensure
between exposure and onset accurate interpretation of the results. Do not hesi-
consistent with contact
tate to perform a potassium hydroxide preparation
dermatitis?
to evaluate for dermatophytosis or skin biopsy as
Criterion 5 Are nonoccupational exposures
needed to avoid unnecessary treatments.
excluded as probable causes?
Patch testing, the cornerstone of diagnosing
Criterion 6 Does dermatitis improve away ACD, is a cost-effective test with a sensitivity and
from work exposure to the
specificity of 70% to 80%.11 Be mindful that it is
suspected irritant or allergen?
only helpful if there is a strong suspicion for ACD
Criterion 7 Do patch or provocation tests
and if the allergens that are tested will be relevant
identify a probable causal
to potential occupational exposures.12 If a patch
agent?
test is warranted owing to suspicion of ACD,
Data from Clark SC, Zirwas MJ. Management of Occupa- discuss with the patient about what to expect
tional Dermatitis. Dermatol Clin. 2009;27(3):365-383.
https://doi.org/10.1016/j.det.2009.05.002.
with the results and set expectations. After
patches have been placed, the appropriate inter-
val for reading must be adhered to. Patches
The Physical Examination
should be left in place for at least 48 to 72 hours
Once the history is elicited, the physical examina- from the date of initial application, ensuring proper
tion and, if needed, patch placement, can be per- contact time for the allergens to react. It is impor-
formed. First, the provider should ensure that the tant to provide patients with written instructions for
Table 2
Distinguishing features of ICD and ACD
Feature ICD ACD

Pathogenesis Direct cytotoxicity, skin barrier Activation of allergen-specific
disruption. Does not require T cells; delayed
sensitization to allergen. hypersensitivity. Requires
sensitization to allergen.
Concentration of contactant High. Low.
Affected Anyone and everyone. A minority of patients.
Clinical features Subacute to chronic eczema Acute to subacute eczema,
with fissuring, scaling, occasionally with weeping,
erythema. bullae, or vesicles.
Patient complaint Pain or burning. Pruritus.
Onset Immediately. Slowly; after initial
sensitization, 12–48 h to
elicitation of dermatitis.
Diagnosis History and physical History and physical
examination. examination, patch testing.
332 Hollins & Flamm
when they go home, stressing that they should necessary involved persons. At the start of a visit,
refrain from showering, because doing so can it is common to meet with a human resources
make the patch test results difficult to interpret. representative, who may provide a presentation
At 48 hours, the patches can be removed and or overview of events surrounding the dermatitis,
interpreted for a first reading. The second reading which can be quite helpful to corroborate patient
can take place 24 hours after the first reading, to narratives.
allow slower allergens to develop. Some allergens Meeting with officials is also helpful to obtain the
do require more time to develop beyond the names of the chemicals and potential allergens in
typical time frame that a clinician would read re- question, if not previously provided by the worker.
sults. A recent study noted additional readings af- They will likely provide SDSs, which are docu-
ter day 7 were useful for identifying reactions to ments providing information regarding hazardous
many metals, including gold and cobalt; some pre- materials or mixtures present on site. More details
servatives such as propolis; and the topical anti- about SDSs are discussed elsewhere in this
biotic neomycin.13 Therefore, patients should be article. At this time, one can meet with other
adequately counseled on delayed reactions and workers who may have also had dermatitis but
alert the dermatologist if they become symptom- could not come to clinic. Keep in mind that no
atic. Alternatively, it may be helpful to schedule a question is too simple; ask basic questions that
follow-up visit in the appropriate time interval for provide information on how machines work, how
a manual check. they are maintained, start and end times for shifts,
Sometimes the patient may bring their own and whether or not workers on different shifts have
allergen sample for testing, but be cautious similar rashes, for example.
because the substance may be caustic, and it After initial meetings and oftentimes after don-
may need to be diluted to avoid potentially severe ning appropriate protective gear, a walkthrough
reactions like ulceration and infection if applied of the facility will be performed. This step is as
directly to the skin. Published guidelines are avail- crucial to the site visit as a physical examination
able to help mix potential allergens to appropriate is to a clinic visit. This is the time for the physician
levels and should be consulted in these to look closely at the work environment, make as-
situations.14 sessments, ask real-time questions, and take
notes. Many observations can be made: What do
the employees wear to protect their skin? How
Performing a Site Visit
many workers are in an area? If time allows, it is
At times, an actual site visit may be required. This ideal to act as a “fly on the wall” for at least a
can be the case when multiple persons are portion of the visit to get as close to unbiased
affected, if the patient history is unclear, or if doing data as possible. The cleanliness of the area and
a site visit is requested by the employer. A site visit potential exposures, such as materials from leaks,
is helpful because the dermatologist can perform a spills, and contaminated surfaces, should be
thorough walkthrough, including breakrooms, documented. Make time to evaluate common
bathrooms, and other indirect locations. A site visit areas like bathrooms and breakrooms. Take note
is also helpful because it allows the physician to of the ingredients in hand cleansers, the use of dis-
become familiar with work conditions and to un- infecting wipes used by staff, and other potential
derstand the work environment of a site. discoveries.
Perhaps the best way to arrange a visit is to call After the walkthrough is completed, have a
the site manager or occupational medicine wrap-up session with the involved parties. This is
specialist associated with the company. In this a time to meet with everyone again and debrief.
way, you can establish relationships and navigate A summary should be provided at the end of the
through proper protocols for a visit. Sometimes, visit, and at that time it can be decided if a formal
special shoes or garments are required, and write-up is needed. A timeline should be provided
proper sizing will need to be obtained before to the site to set expectations. Finally, obtain con-
beginning the visit. Any discussion of compensa- tact information for all relevant parties in case new
tion should be discussed with appropriate persons evidence becomes available.
before scheduling the visit, although it should be
noted that the dermatologist can perform these
MANAGEMENT CONSIDERATIONS:
visits free of charge; one should be mindful of
PREVENTION AND THERAPY
potential lost revenue if running a practice.
Prevention
Once a date for the visit has been established,
plan for at least a half day. This amount of time Prevention is the foundation of managing occupa-
will be enough to do a proper visit and meet with tional dermatitis. After the cause of the dermatitis
is determined, education for affected workers is the Occupational Safety and Health Administration
paramount. Education involves patient recognition implemented The Hazard Communication Stan-
of hazardous materials and the various names un- dard to align with the Globally Harmonized System
der which allergens can be listed as ingredients. of Classification and Labeling of Chemicals. This
Because some allergens that are found in work en- updated system standardized chemical safety in-
vironments may also be found in home products, it formation, and improved on the MSDSs, thus
is important to relay this information clearly to improving workplace safety. Although the MSDS
workers. Providing patients with a list of products could include various levels of detail about chem-
that are devoid of allergens is helpful. The icals, the SDS format is more in-depth and meets
American Contact Dermatitis Society maintains international standards. More information can be
the Contact Allergen Management Program for located from the United States Department of La-
members, an online service that will list all prod- bor website (osha.gov).
ucts that do not contain the allergens in question.
Free videos that describe some allergens are
The employer and employee
available at www.contactdermatitisinstitute.com;
The employer should be sure that the facility meets
other databases listing products are also available
safety codes, and that all employees are aware of
for a fee.
SDSs, accident protocols, and how to report them
Information must be provided for the patient to
correctly. Ventilation of the work environment
make changes in products used and for the work-
should be proper and regulated by correct govern-
site to make updates to its safety protocols and
ing bodies to avoid airborne OCD. Access to
products used (eg, changing the cleanser in the
detailed accounts of maintenance reports should
restrooms). When discussing with the patient, in-
be available and up to date. Wash stations for
formation must also be presented in a way that is
splashes, drips, and spills should be visible, clean,
easily understood and concise, keeping in mind
and in working order.
the various levels of education and health literacy
Proper clothing, eye protection, and other
in patients. The use of pictures on handouts is
necessary safety needs should be in place. It is
encouraged, as well as in-office demonstrations
important to ensure that these recommendations
of label reading.15 There are standardized patient
and protocols are done at the companywide level
education materials available from reputable re-
to help decrease the rate at which other workers
sources such as the American Contact Dermatitis
may be affected. For the individual workers,
Society that can be accessed online. Caution must
following all protocols in place and consideration
be used to avoid information overload, and it may
of appointing a safety liaison is helpful.
be pertinent to bring the patient back for multiple
appointments or provide access to a nurse or
physician line for additional questions that may Gloves
arise after leaving the clinic. Alternatively, it is It is known that hand dermatitis is seen in most
reasonable to schedule a follow-up phone call if cases of OCD and poses a large burden on
returns to clinic are not feasible. workers owing to increased sick leave, job loss,
and even early retirement.16 Thus, appropriate
glove use is critical for hand protection. The type
Hazard Control
of glove used depends heavily on the type of
Safety data sheets chemicals the gloves are meant to protect workers
Ensuring that all hazardous materials are from, as well as their allergenic potential, and the
accounted for and controlled is imperative. skin exposure time, because many gloves that
SDSs, previously known as MSDSs, are docu- are billed as impermeable may eventually allow
ments and communications providing information small amounts of chemical or irritant to leak
concerning hazardous materials or mixtures pre- through. Hand sweating can further contribute to
sent at a given worksite. Employers are required existing dermatitis, so gloves should be changed
to have these data available, and all workers frequently.11 In addition, patients should be careful
should be aware of the location and contents of to avoid allergens becoming trapped in gloves
the SDSs, or be able to request information. accidently, exacerbating OCD. It should be
Before the 2012 switch, MSDSs frequently had lit- remembered that actual glove materials have the
tle helpful information to the dermatologist. Ingre- potential to cause ACD or ICD. Permeation and
dients were frequently not listed correctly, terms degradation are types of chemical resistance
were often too general, and potential allergens properties that should be considered when select-
were not listed at all if deemed unnecessary by ing gloves, and some general glove characteristics
the manufacturer. Because of these shortcomings, are listed in Table 3.
334
Hollins & Flamm
Table 3
Summary of general characteristics of glove materials
Chemical Protection
Puncture and Tear
Material Good Poor Biologic Protection Resistance Dexterity Price Allergy
Latex Water Most chemicals Excellent Good Excellent Low Type I, type IV
Nitrite Water, most organic Ketones, aromatics, Good Good Good Low Type IV
solvents, most chlorinated
hydrocarbons, oils, hydrocarbons, esters,
greases, selected acids some acids
and bases
Vinyl Acids, bases, oils, Organic or petroleum Poor Poor Poor Low Rare
greases, peroxides, based solvents,
amines aldehydes
Neoprene Alcohols, phenols, Halogenated and Good Good Good Medium Type IV
peroxides, acids, aromatic
hydrocarbons, bases hydrocarbons
Multilayer All classes Isolated small molecule N/A Medium Very poor High Rare
laminates solvents
Chemical Protection Biologic Protection Dexterity Durability Price Allergy
Latex Poor Best Best Good Low Type I, type IV
Nitrite Good Good Good Good Low Type IV
Vinyl Fair Poor Poor Poor Low None
Neoprene Good Good Good Good High Uncommon
Data from Clark SC, Zirwas MJ. Management of Occupational Dermatitis. Dermatol Clin. 2009;27(3):365-383. https://doi.org/10.1016/j.det.2009.05.002.
14
Ointments and barrier creams diagnosis is made, identification of the hazard so

Ointments are the standard bearers of OCD pre- that it can be avoided. Worker education is also vi-
vention. They act as a protective layer, shielding tal. The worker should be well-versed in their
the skin from potential irritants and allergens. Oil- allergen and should know what to do if subse-
based products provide the most protection; quently exposed. Providing safe lists as found
they repel paints, solvents, and other chemicals through the Contact Allergen Management Pro-
workers encounter. They have also been shown gram database can also be helpful because
to be efficacious against water-based products some allergens are found both in the workplace
like acids, alkalis, and metalworking fluids.17 His- and at home. Patients must also understand the
torically, it has been difficult to prove the benefits proper use and side effect profile of prescribed
of ointment skin protectants in OCD treat- medications and general skin care tips. Printed
ment.18–20 Nevertheless, ointments are the au- handouts are helpful to relay information.
thors’ preferred vehicle for therapy. Barrier
creams represent another option for prevention,
Therapies
albeit a controversial one, because some studies
failed to find benefit.21,22 A systematic review re- Topical corticosteroids remain the cornerstone
ported mixed evidence for the effectiveness of treatment for most cases of acute contact derma-
prework barrier creams,23 but did conclude that titis, particularly ACD. Studies have documented
barrier creams containing products such as the efficacy of topical steroids in ACD,27,28 and
dimethicone could help in preventing ICD. their efficacy using even class II or III corticoste-
Winker and colleagues22 found a benefit to bar- roids is undisputed.29
rier creams when used with mild cleansers and ICD has a somewhat less clear benefit from
after work treatments. It is important to note weaker preparations of topical steroid29; however,
that barrier creams themselves may cause as associated inflammation is reduced, they are
allergic reactions, and should not be used on still recommended for acute relief. There have
affected skin. Additionally, they must be applied been reports of systemic absorption of corticoste-
frequently enough in adequate amounts to be roids from misused topical formulations30; there-
effective. fore, steroids should be given in the correct
Many patients prefer the relative cosmetic strength and for the proper duration for the body
elegance of creams to ointment-based products. site affected to avoid potential side effects.31
However, use of barrier creams should not be Finally, some studies32,33 have documented pa-
oversold as preventative treatment because they tient allergy to certain classes of topical steroids,
may confer a sense of security that is not war- so keep this in mind when treating patients who
ranted and could lead to a laxity in stringent pre- are not improving or worsening on appropriate
ventive measures.24 topical therapy.
Systemic steroids can be used for brief periods,
Harsh soaps and degreasers ideally less than 4 weeks, for extensive dermatitis,
Patients should be educated on the potential irrita- and sedative antihistamines can be used to help
tion caused by harsh soaps and degreasers. If patients sleep through the night and potentially
these products must be used, proper gloves help with pruritus, and both treatments remain
must be worn, as discussed elsewhere in this helpful adjuncts for OCD.
article. If the skin is dry or even slightly irritated, Topical calcineurin inhibitors (TCIs) have
a thick moisturizer should be used after hand become important treatment options to help miti-
washing.25 gate the side effects of chronic topical steroid
The workers should use the mildest cleansers use. After an initial topical and/or oral steroid burst
available, as intermittently as possible, to avoid to quell patient symptoms, TCIs can be used for
complications. Mild synthetic detergents called maintenance as needed. A prospective study on
“syndets” are commonly used replacements for hand dermatitis found comparable outcomes
true soaps. Closer to physiologic skin pH, syndets with use of tacrolimus 0.1% ointment compared
contain less than 10% soap and work to minimize with mometasone furoate for hand ACD.34 Com-
cutaneous alkalinization.26 Recognizable syndets mon side effects of topical TCIs include burning
include Dove (Unilever, London, UK) and Cetaphil or a warm sensation, and both symptoms should
(Galderma Laboratories, Fort Worth, TX). resolve with consistent use. TCIs are a good op-
tion for OCD in sensitive locations such as the
The physician face and neck.
The role of the physician lies most importantly in Crisaborole, a topical phosphodiesterase-4 in-
providing the correct diagnosis and, after the hibitor, is a newer therapy option; however, it is
336 Hollins & Flamm
currently only approved by the US Food and Drug DISABILITY

Administration for mild to moderate AD. However,
because ACD represents a potential comorbidity Disability insurance is different from workers’
and exacerbates AD,35 the use of crisaborole compensation. Disability insurance functions simi-
can be considered in patients with a known diag- larly to health insurance. It can be purchased by in-
nosis of AD and concomitant suspected or dividual workers for themselves, provided through
confirmed ACD. Social Security Disability Insurance, or purchased
Recommending a sensitive skin care routine to from the worker’s employer. Contrasting workers’
patients is essential. Patients should be directed compensation, disability is not reliant on work-
to use gentle, nonsoap cleansers such as Ceta- place injury or illness, only on how severely the
phil (Galderma Laboratories), CereVe (Coria functional abilities of the worker are affected, no
Laboratories, Dallas, TX), or Vanicream (Pharma- matter where the injury took place. The range is
ceutical Specialties, Inc., Rochester, MD), which from totally disabled to partially or not disabled.
are void of many common allergens, but certainly In the case of Social Security Disability Insurance,
direct patients to read the ingredient labels. Thick a judge makes the decision. If the worker uses
creams or ointments should be used after their insurance, the insurance company will deter-
washing hands. Regular washing of contami- mine disability, which depends on the details of
nated clothing should be performed in unscented the policy.
laundry detergent. It has been reported numerous In summary, workers’ compensation answers
times in the literature that alcohol-based, water- the question of whether or not a worker is injured
less hand sanitizers cause less irritation than as a direct result of their job, and that determina-
traditional soap and water, and this should be dis- tion is based on occupational causality, which
cussed with workers and management teams as must be established. Disability describes whether
needed. or not an injury or illness is severe enough to limit
the person’s ability for gainful employment,
without regard to how or where it occurred.
WORKERS’ COMPENSATION
The Physician’s Role
Workers’ compensation laws were an instru-
mental development beginning in the early parts Often times, physicians must fill out a work abilities
of the Industrial Revolution, as society moved form, which reports on worker limitations, and
from being mostly agricultural to predominantly these forms are used in part to determine workers’
industrial. First enacted in parts of Europe in the compensation or disability. This paperwork is
late 1800s, they became part of United States important to fill out as accurately as possible, not
law in 1911. Before these laws, the employee or only for good medical care and diagnosis, but
their representative sued the employer for dam- also for the large impact it will have on the worker’s
ages, resulting in lengthy and expensive pro- economic and emotional well-being. Before filling
cesses, and ultimately, put the worker at a out any forms, establishing a causal relationship
major disadvantage. The principal idea behind between work and the skin condition is most
workers’ compensation laws ensure that em- important for the worker, albeit difficult to prove.
ployees have medical treatment and compensa- The basis of the physician’s findings are crucial
tion without regard to fault, and that costs are here, because the place of employment may
assumed by the employer. Modern-day workers’ dispute the claim. Patch test results will oftentimes
compensation is an insurance that almost all em- be critical and should be used if ACD is suspected.
ployers must carry, and varies widely between Positive patch test results that have workplace
states. According to the Insurance Journal, in a relevance are the most significant for establishing
majority of states, a small business with even 1 a causal relationship for workers’ compensation.
employee must carry workers’ compensation in- The timing of the rash in relation to work can also
surance, and if employers skip coverage, they help to determine a relationship and aid in any diffi-
are liable to hefty penalties. The percentage of a cult cases.
worker’s compensated salary and/or the amount Physicians may have a potentially difficult role
of work lost before benefits start also vary in workers’ compensation claims. It should be
depending on the worker’s state of residence. noted that the more restrictions physicians place
For these reasons, it is advisable for workers to on the worker, the less likely the worker will be
consider retaining an attorney. In most cases, able to return to work. However, not placing
there are no upfront costs, and attorneys get enough restrictions can lead to the worker sus-
fees from awarded workers’ compensation taining continuing injury.24 Overall, the history
benefits. and physical examination should lead the
physician on any decision making with regards to factors may be of major importance influencing
the work abilities form. occupational dermatitis. Olesen and colleagues16
reported that tobacco smoking and high stress
Preparing a Letter and/or Report levels had an inverse relationship to healing occu-
A medical report will need to be drafted and should pational hand dermatitis, whereas high levels of
follow the same format as any letter to a referring exercise was significantly related to healing, as
physician. However, it is important to take into well as change of profession, predictably. Age,
consideration that this letter needs to be under- sex, AD history, and education were also found
stood and interpreted by workers, employers, in previous studies to have an impact on OCD.24
and disability and workers’ compensation Generally, factors leading to improved prog-
personnel, and should be written in nonphysician nosis involve removal and avoidance of the caus-
terms. The letter should include the history and ative agent, worker education, and proper
physical examination, patch test results, site visit treatment. For the dermatologist, being readily
findings, results of follow-up clinic visits, and available and establishing worker relationships
physician recommendations. As described by are also central.
Clark and Zirwas,24 the report may also include
the following if desired: (1) an overview of the DISCLOSURE
Mathias criteria to demonstrate occupational
causation/aggravation, (2) a description of which The authors have nothing to disclose.
Mathias criteria were met and physician justifica-
tion, (3) acknowledgment that because at least 4 REFERENCES
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symptoms before diagnosis is correlated with a soc 2016;8(3):209–11.
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situations; in a recent study by Skudlik and col- dermatitis model. clinical evaluation of patch tests
leagues36 involving 1164 workers in high-risk pro- is not hampered by antihistamines. Acta Derm Vene-
fessions, the efficacy of a 6-week, intensive reol 1998;78(3):194–7.
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workers were able to successfully remain in their matoses. J Am Acad Dermatol 1988;19. https://doi.
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it may be difficult to complete the intensive 9. Ingber A, Merims S. The validity of the Mathias
regimen, it is worth making employers and em- criteria for establishing occupational causation and
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is severe and recalcitrant. Additionally, lifestyle titis 2004;51(1):9–12.
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31. Veien NK, Larsen PØ, Thestrup-Pedersen K, et al.
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an afterwork emollient cream against cutting fluid 2007;56(1):56–7.
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18
PRACTICE
BMJ: first published as 10.1136/bmj.39252.524317.94 on 23 August 2007. Downloaded from http://www.bmj.com/ on 14 December 2021 at National University of Singapore. Protected by
Reading M6 R2
10-minute consultation BMJ 2007
Occupational dermatitis in a hairdresser PMID: 1771371
Allison Worth,1 S Hasan Arshad,2 Aziz Sheikh1
1
Allergy and Respiratory Research A 25 year old hairdresser complains of a rash on her her skin, especially the forearms and face. Consider
Group, Division of Community hands. She thinks she might be allergic to the solutions other possible skin disorders, such as urticaria and
Health Sciences: GP Section, she uses at work. psoriasis. Typically, contact urticaria presents as acute,
University of Edinburgh, Edinburgh
EH8 9DX raised, erythematous, and itchy wheals after contact
2
Infection, Inflammation and What issues you should cover with the allergen or chemical. Psoriasis is a diverse
Repair Research Division, School Defining the problem—Up to 50% of hairdressers develop skin disease, but in its commonest form (plaque pso-
of Medicine, University of
Southampton, Southampton
dermatitis of the hand within three years of starting riasis) the lesions are characterised by raised, inflamed
Correspondence to: A Sheikh work, usually either irritant contact dermatitis result- red lesions covered by a silvery white scale.
Aziz.Sheikh@ed.ac.uk ing from chemical damage or allergic contact dermati-
tis from a delayed (type IV) hypersensitivity reaction. Referral for a patch test
Distinguishing between these is difficult but important Explain that a patch test will help to determine the
BMJ 2007;335:399
doi: 10.1136/bmj.39252.524317.94 because of a worse prognosis in the allergic form if cause of her problem, and tell her what it involves.
exposure to the allergen is not eliminated. Patch testing to a hairdresser’s battery—which includes
How is the problem affecting her?—Her symptoms hair dyes, ammonium persulphate, aminophenol,
may be affecting her day to day life. She may be dis- and surfactant—in addition to the standard European
tressed and embarrassed and may fear for her future series is the investigation of choice; these tests are
employment. negative in irritant dermatitis. Skin prick tests or the
Take a detailed occupational history—Has she had skin radioallergosorbent test do not help. Arrange to see
problems before? Symptoms that develop after a her again once you get the results.
new job is started or that improve when she is away
copyright.
from work indicate an occupational problem. Which Avoiding the chemicals
solutions does she think might be responsible? Hair Explain that wearing gloves when mixing and apply-
bleaches and dyes that contain ammonium and potas- ing chemicals can help to reduce exposure (recom-
sium persulphates or paraphenylenediamine are com- mend non-latex plastic gloves to minimise risk of
mon triggers of allergic contact dermatitis and may latex allergy developing). As dermatitis is so common
also provoke respiratory problems such as asthma. among hairdressers, her employer is likely to be famil-
Management strategies—Is she using any protective iar with the problem and potential responses, so she
measures or treatments such as gloves or over the should discuss strategies for reducing exposure, such
counter creams? Ask whether she has raised the issue as using different products and asking colleagues to
with her employer and, if so, with what effect. A letter mix products or temporary redeployment to a differ-
from you to her employer may be helpful. ent type of work while awaiting patch test results.
What you should do Treatment

Examination Emollients are effective in keeping the skin moist and
Assess her hands for signs of dermatitis. Erythematous, should be used regularly. Acute reactions require treat-
This is part of a series of swollen skin indicates an acute reaction. In severe ment with moderate potency topical corticosteroids
occasional articles on common
problems in primary care. The cases blistering and oozing may also occur. Dryness, (such as betamethasone valerate (Betnovate)) and, if she
BMJ welcomes contributions fissuring, and scaling point to more chronic disease. has signs of infection, short term use of antibiotics.
from GPs Look for signs of supra-infection. Examine the rest of
Information and support
Useful resources for doctors and patients Explain the potential long term nature of the condi-
Arshad SH. Allergy: an illustrated colour text. Edinburgh: Churchill Livingstone, 2002. pp 82-3 tion. Discuss the need for her to be aware of exposure
Bourke J, Coulson I, English J. Guidelines for care of contact dermatitis. Br J Dermatol to solutions and the importance of continuing to use
2001;145:877-85 gloves and emollients. Advise her that acute flare-ups
Werfel T, Kapp A. Atopic dermatitis and allergic contact dermatitis. In: Holgate ST, Church MK, may occur with continued exposure and that if this
Lichtenstein LM, eds. Allergy. 2nd ed. London: Mosby, 2001:105-25 occurs she should seek advice. Encourage learning
National Library for Health. Dermatitis—Contact. ��
(Prodigy guidance) www.cks.library.nhs. about the condition: good practical advice on self-
uk/dermatitis_contact management is available from hairdressing organi-
Free factsheets on skin allergy are available from Allergy UK (www.allergyuk.org/info_ sations and occupational health websites, which she
factsheets.aspx) should be encouraged to pursue. She should familiar-
Information for employers and employees on occupational skin disease can be accessed on ise herself with information about her rights and her
the Health and Safety Executive’s website (www.hse.gov.uk/skin/information.htm and employer’s duties (available from the UK Health and
www.coshh-essentials.org.uk) Safety Executive.
19
BMJ | 25 August 2007 | Volume 335 399
M6 Reading 3
Ann Endocrinol 2021
Annales d’Endocrinologie 82 (2021) 161–162
PMID32204892
Disponible en ligne sur
ScienceDirect
www.sciencedirect.com
Klotz communications 2021: Heart and Hormones
“Is there any reason to treat subclinical hypo and hyperthyroidism?”

Bernadette Biondi
University of Naples Federico II, Department of Clinical Medicine and Surgery, Naples, Italy
a r t i c l e i n f o a b s t r a c t
Keywords: Subclinical thyroid disease represents an early stage of thyroid dysfunction, which is usually asymp-
Subclinical Hyperthyroidism tomatic and biochemically defined; its diagnosis can be performed thanks to the high sensitivity of the
Subclinical Hypothyroidism hypothalamic-pituitary-thyroid axis. The approach to this disorder requires correct diagnosis, clinical
Treatment
assessment and treatment. Cardiovascular diseases (e.g. atrial fibrillation, heart failure, and coronary
heart disease), bone loss and fractures, and dementia represent the main adverse events of severe subclini-
cal hyperthyroidism with undetectable TSH levels. Treatment of patients with subclinical hypothyroidism
with a serum TSH level above 10 mIU/L is justified in order to reduce the risks of coronary heart disease
and heart failure.
© 2020 Published by Elsevier Masson SAS.
Subclinical thyroid disease represents an early stage of thy- Prolonged exposure to thyroid hormone excess can induce
roid dysfunction, which is usually asymptomatic and biochemically cardiomyocyte hypertrophy and diastolic dysfunction even in
defined; its diagnosis can be performed thanks to the high sen- middle-aged patients with low serum TSH [1]. Population-based
sitivity of the hypothalamic-pituitary-thyroid axis. The approach studies, prospective observational studies and meta-analyses have
to this disorder requires correct diagnosis, clinical assessment and shown a significantly higher risk of atrial fibrillation, heart fail-
treatment. ure, death from coronary heart disease, death from any cause and
major adverse cardiovascular events among patients with serum
1. Subclinical Hyperthyroidism TSH levels below 0.10 mIU/L than among those with normal thyroid
function [2,3]. The risk of osteoporotic fractures is also significantly
Subclinical hyperthyroidism (SHyper) is characterised by serum increased among elderly patients with undetectable serum TSH
thyroid hormone levels within their respective reference range and [2,3]. Moreover, a strong association has been reported between
low or undetectable serum thyroid-stimulating hormone (TSH) lev- severe subclinical hyperthyroidism and cognitive impairment or
els [1,2]. The prevalence of this dysfunction increases with age, dementia [3].
especially in women and in iodine-deficient populations. Graves’ The available literature data provide sufficient and high-quality
disease is the most common cause of subclinical hyperthyroidism evidence that SHyper is associated with adverse events in elderly
in young patients, whereas toxic multinodular goiter and solitary patients with undetectable serum TSH. However, despite the neg-
autonomous nodules become more common causes with aging [3]. ative implications of this disorder, the appropriate management of
Serum TSH progressively decreases with the progression of this subclinical hyperthyroidism remains controversial because of the
dysfunction; the onset of overt hyperthyroidism occurs especially lack of large randomised controlled trials assessing the beneficial
when serum thyrotropin levels are less than 0.1 mU per litre; on effects of specific treatment. Therefore, most of the recommenda-
the contrary, low but detectable serum TSH usually normalises in tions of the guidelines on the management of SHyper have a low
more than 50% of the cases during follow-up [1–3]. level of evidence.
Subclinical hyperthyroidism can be associated with adverse out- Treatment of this disorder is multidisciplinary because of the
comes even without progression to overt hyperthyroidism [3]. need to take co-morbidities into account. Uncontrolled studies have
Cardiovascular diseases (e.g.: atrial fibrillation, heart failure, and shown improvements in various cardiac and bone parameters after
coronary heart disease), bone loss and fractures, and dementia anti-thyroid drug therapy or radioiodine therapy [3].
represent the main adverse events of severe SHyper and can be According to the available guidelines, methimazole could be
particularly dangerous in persons older than 65 years of age [3]. appropriate for adults with Graves’ disease who are 65 years of
age or younger, since this disease may remit after 12–18 months of
therapy [3,4]. Radioiodine is the preferred option in patients with
subclinical hyperthyroidism caused by toxic multinodular goiter
E-mail address: bebiondi@unina.it
https://doi.org/10.1016/j.ando.2020.03.003
0003-4266/© 2020 Published by Elsevier Masson SAS.
20
B. Biondi Annales d’Endocrinologie 82 (2021) 161–162
or toxic adenoma, and in patients with Graves’ disease who are systemic vascular resistance and arterial stiffness and by alter-
older than 65 years of age [3,4]. Surgery is usually reserved for ing endothelial function, thereby potentially increasing the risk
patients with large goiters and compressive symptoms, in presence of atherosclerosis and coronary artery disease [1,2]. Moreover,
of nodules suspicious of thyroid cancer or coexisting hyperparathy- SHypo has been associated with increased total and LDL choles-
roidism [3,4]. terol, triglycerides and lipoprotein (a). More severe cardiovascular
and metabolic adverse effects have been reported in SHypo patients
2. Subclinical hypothyroidism with serum TSH > 10 mIU/L [1,2]. Diastolic hypertension in con-
junction with dyslipidemia and increased arterial stiffness are
The diagnosis of subclinical hypothyroidism (SHypo) can be well-recognised risk factors for the development of atherosclerosis.
performed when serum TSH is persistently elevated in conjunc- A meta-analysis, which performed a pooled analysis of individ-
tion with free thyroxine levels within their reference range [1,2]. ual participant data from 11 prospective studies on subclinical
Subclinical hypothyroidism can be categorised as grade 1 when hypothyroidism, demonstrated a significant trend of increased risk
TSH levels are between the upper limit of the reference range and in both CHD events and mortality at higher serum TSH concentra-
9.9mU/L, and as grade 2 when serum TSH levels are 10mU/L or tions, particularly in participants with a TSH level of 10 mIU/L or
higher. Approximately 90% of patients with SHypo have serum TSH greater [5].
levels lower than 10mU/L [5]. These important meta-analyses provide evidence to justify
Grade 2 subclinical hypothyroidism is associated with increased treatment of patients with subclinical hypothyroidism with a
rates of progression to overt hypothyroidism, especially in women serum TSH level above 10 mIU/L in order to reduce the risks of CHD
and in patients with positive TPO antibodies; on the contrary in 60% and HF. Recent data support that mild subclinical hypothyroidism
of patients with grade 1 subclinical hypothyroidism, TSH levels can (TSH 5–10 mIU/L) may be associated with a greater cardiovascular
normalise over 5 years [5]. risk in young and middle-aged people and indicate that treatment
Important changes in cardiac structure and function have been of mild SHypo with L-T4 can be associated with better outcomes
reported in patients with SHypo, whose severity depends on in younger people [2,5]. Treatment of mild disease is not recom-
the degree and duration of thyroid hormone deficiency [1,2]. An mended in elderly and asymptomatic patients [5].
impairment of left ventricular diastolic function, characterised by Large randomised controlled studies will be required in order
slowed myocardial relaxation and impaired ventricular filling rep- to assess the importance of treatment in patients with subclinical
resents the most consistent cardiac abnormality, which has been hypothyroidism.
reported even in patients with mild subclinical hypothyroidism
[1]. Moreover, an impaired systolic function has been identified Disclosure of interest
with sensitive techniques such as Doppler echocardiography and
cardiac magnetic resonance imaging. Left ventricular systolic and The author declares that she has no competing interest.
diastolic dysfunction on effort have been documented by Doppler
echocardiography in SHypo patients in comparison with euthyroid References
controls [1]. Some studies indicate that SHypo may worsen car-
diovascular hemodynamic, leading to heart failure (HF). A recent [1] Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction.
Endocr Rev 2008;29:76–131.
meta-analysis performed a pooled analysis of individual partici- [2] Cooper DS, Biondi B. Subclinical thyroid disease. Lancet 2012;379:1142–54.
pant data from all the available prospective cohorts with thyroid [3] Biondi B, Cooper DS. “Subclinical Hyperthyroidism”. N Eng J Med
function tests and subsequent follow-up of HF events. It showed 2018;378:2411–9.
[4] Biondi B, Bartalena L, Cooper DS, Hegedüs L, Laurberg P, Kahaly GJ. “The 2015
that the risk of HF events is related to higher TSH levels with a sta- European Thyroid Association guidelines on diagnosis and treatment of endoge-
tistically significantly increased risk among those with TSH above nous subclinical hyperthyroidism”. Eur Thyroid J 2015;3:149–63.
10.0 mIU/L [2,5]. [5] Biondi B, Cappola AR, Cooper DS. Subclinical Hypothyroidism: a review. JAMA
2019;322:153–60.
Subclinical hypothyroidism may increase the risk for atheroscle-
rosis. It can impair vascular function by inducing an increase in
162
21
Focus | Clinical
M6 Reading 4
Thyroid disease
Aust J Gen Pract 2021
PMID: 33543160
Long-term management of
hyperthyroidism and hypothyroidism
Kiernan Hughes, Creswell Eastman HYPOTHYROIDISM AND HYPERTHYROIDISM found in the USA, where hypothyroidism
are commonly encountered problems in has been documented in 4.6% of the
clinical practice. General practitioners are population, with 0.3% being clinical and
Background
Hypothyroidism and hyperthyroidism
well placed to be the primary clinicians 4.3% being subclinical.3 Approximately
are commonly encountered in clinical overseeing the long-term management 10–20% of the Australian population have
practice. General practitioners have a of patients with thyroid function evidence of thyroid autoimmunity based
central role in the long-term management abnormalities. on the presence of circulating thyroid
of these conditions. autoantibodies,4 but prevalence may
Objective
vary with age, sex and ethnicity.
The aim of this review is to provide an What are the causes of
overview of the causes of thyroid function hypothyroidism?
disorders and guidance on management. The diagnosis of hypothyroidism relies Approach to management of
on confirmation by laboratory testing. subclinical hypothyroidism
Discussion
Optimal management of hypothyroidism Primary hypothyroidism, caused by failure Subclinical hypothyroidism, defined
relies on an understanding of the potential of the thyroid gland, is characterised by biochemically as an elevated TSH level
risks and benefits of therapy versus a decreased serum free thyroxine (FT4) accompanied by a normal FT4 level,
observation. If levothyroxine (LT4) level with an appropriately elevated serum is a very common finding in general
replacement is commenced in a person thyroid stimulating hormone (TSH) practice. It is useful to measure thyroid
with subclinical hypothyroidism on the
level. Secondary hypothyroidism is a rare peroxidase antibodies (anti-TPO) to
basis of the presence of possibly relevant
condition caused by hypothalamic or identify underlying Hashimoto’s disease
hypothyroid symptoms, consideration
should be given to ceasing LT4 if no pituitary disease and characterised by a as the cause. People with Hashimoto’s
symptomatic benefit is observed. Thyroid low serum FT4 level without an increased thyroiditis have an increased risk of other
stimulating hormone levels below the TSH level, which is low or even normal. autoimmune conditions including coeliac
reference range are associated with atrial Causes of hypothyroidism are listed disease, vitamin B12 deficiency and
fibrillation and osteoporosis, and should in Box 1. Globally, iodine deficiency Addison’s disease.
be avoided. Treatment modalities for
remains the most common cause of Most people with subclinical
hyperthyroidism include antithyroid
medications, radioactive iodine therapy
hypothyroidism.1 Hashimoto’s thyroiditis hypothyroidism will have minimal or no
and thyroidectomy. Each is satisfactory, (autoimmune thyroiditis) is the most specific symptoms. It can be challenging
but none is ideal. A patient-centred choice common cause of primary hypothyroidism to determine the extent to which mild
of treatment modality should be in Australia and most iodine-sufficient thyroid dysfunction is causing a patient’s
individualised, taking into consideration areas of the world.2 Hashimoto’s thyroiditis symptoms because of the high rate of
the underlying pathology, age, sex, patient is characterised by gradual thyroid failure, some complaints (eg cold intolerance,
preference and availability of expert thyroid
with or without goitre formation, due to weight gain, constipation, fatigue, hair loss
surgical care. Long-term management of
patients with hyperthyroidism requires autoimmune-mediated destruction of and dry skin) in the general population.
careful consideration of the likely the thyroid gland. The exact prevalence As subclinical hypothyroidism
outcomes of treatment including of primary hypothyroidism in Australia is progresses to overt hypothyroidism at
the risk of hypothyroidism. unknown, but it is probably similar to that a rate of approximately 5% per year,
36 Reprinted from AJGP Vol. 50, No. 1–2, Jan–Feb 2021 © The Royal Australian College of General Practitioners 2021
22
Thyroid disease: Long-term management of hyperthyroidism and hypothyroidism Focus | Clinical
asymptomatic patients with subclinical Restoration of a euthyroid state can be and unambiguously have not benefited
hypothyroidism can usually be observed readily accomplished in almost all patients from LT4. If the serum TSH level stays
with annual thyroid function tests (TFTs). by oral administration of LT4. The average within the reference range, replacing a
Most guidelines recommend full replacement dose of LT4 in adults is small fraction of the LT4 dose by LT3 once
levothyroxine (LT4) treatment if TSH is approximately 1.6 μg/kg body weight per or twice per day has not been associated
>10 mIU/L.5 A lower TSH threshold is day. Mildly elevated levels of FT4 may with adverse drug reactions.11 Combination
appropriate in younger individuals and be seen if blood is taken in the first few therapy should generally be initiated under
during pregnancy. A TSH >2.5 mIU/L hours after swallowing the medication. In specialist supervision with care to avoid
should prompt consideration of the need general, it is best to base dosing decisions
for LT4 therapy during pregnancy, and predominantly on TSH levels. Thyroxine
international guidelines recommend LT4 has a long half-life of approximately seven Box 1. Causes of hypothyroidism19
replacement when TSH is >4.0 mIU/L and days, and steady-state TSH concentrations • Autoimmune lymphocytic thyroiditis
the patient is anti-TPO positive.6 Based are therefore not achieved for at least (Hashimoto’s thyroiditis)
on the number of annual Pharmaceutical six weeks. Consequently, it is best not to • Post-ablative therapy
Benefits Scheme prescriptions for LT4 repeat TFTs sooner than this after initiating – Radioiodine therapy
replacement therapy, it is likely that LT4 therapy or changing the dose. The
– Thyroidectomy
approximately one million people are being long half-life also enables different doses
• Transient
treated for hypothyroidism in Australia. It to be given on different days to provide
– Subacute thyroiditis
is probable that the vast majority of these the required total weekly dose. In elderly
patients are being treated for subclinical patients and those with known cardiac – Postpartum thyroiditis
hypothyroidism. disorders, it is better to go ‘low and slow’, – Subtotal thyroidectomy

A recent systematic review concluded starting with 25–50 μg per day. • Medication induced
that most non-pregnant individuals with Because co-administration of food with – Thionamide (carbimazole,
subclinical hypothyroidism do not benefit the medication can impair LT4 absorption, propylthiouracil)
from treatment.7 This review has further the medication should be taken while – Lithium
ignited debate regarding treatment fasting at least 30 minutes – and ideally – Amiodarone
thresholds and highlighted concerns about 60 minutes – before breakfast. For patients – Interferon
the potential for overtreatment. unable to comply, bedtime dosing can be – Immune checkpoint inhibitors
Age-specific local reference ranges considered (three or more hours after the – Medications that interfere with
for TSH should be considered when evening meal). Care should also be taken thyroxine absorption (eg iron, calcium,
establishing a diagnosis of subclinical not to co-administer with supplements cholestyramine, sulcralfate)
hypothyroidism, particularly in older such as iron and calcium, which may • Iodine associated
people. Unfortunately, these reference reduce absorption. It is generally – Iodine deficiency
ranges are not generally available in appropriate to target a TSH level within – Iodine induced (eg contrast load,
Australia. A recent placebo-controlled, the reference range. The most common Lugol’s iodine)
randomised, double-blind study failed cause of failure to achieve normal TSH • Infiltrative
to find any benefit from treatment of levels despite escalation of thyroxine – Riedel’s thyroiditis
subclinical hypothyroidism (mean baseline doses is non-adherence with therapy. If a – Amyloid
TSH 6.4 mU/L) in 737 elderly patients.8 patient has ongoing symptoms suggestive – Haemochromatosis
Most elderly patients with subclinical of hypothyroidism and the serum TSH is
– Scleroderma
hypothyroidism should be carefully confirmed by repeat measurement to be
• Neonatal/congenital
followed up with a ‘wait and see’ strategy, at the upper limits or above the reference
– Thyroid agenesis/ectopia
generally avoiding replacement therapy. range, it is reasonable to increase the dose
Figure 1 provides an algorithm to assist and to aim for a serum TSH value in the – Genetic disorders of thyroid
stimulating hormone (TSH),
in decision making for LT4 replacement lower half of the reference range. Some
TSH receptor, thyroid peroxidase,
therapy for those with either overt or studies have suggested psychological thyroglobulin, pendrin
subclinical hypothyroidism.9 wellbeing is better in patients with lower – Transplacental passage of blocking
serum TSH concentrations.10 TSH receptor antibody
Combination thyroxine/triiodothyronine
• Secondary
Goals of hypothyroidism treatment (T4/T3) therapy may have a limited role in
– Hypothalamic or pituitary disease
The goals of therapy for hypothyroidism the minority of patients who are dissatisfied
• Other
include: with T4 monotherapy. Professional
• amelioration of hypothyroid symptoms guidelines support the use of liothyronine – Thyroid hormone resistance
• restoration of a euthyroid state (LT3) in combination with LT4 for those – Factitious (eg falsely elevated TSH due
to heterophile antibodies)
• avoidance of overtreatment. patients who have been properly screened
23
© The Royal Australian College of General Practitioners 2021 Reprinted from AJGP Vol. 50, No. 1–2, Jan–Feb 2021 37
Focus | Clinical Thyroid disease: Long-term management of hyperthyroidism and hypothyroidism
overtreatment. The European Thyroid patients often think that their LT4 dose fracture (relative hazard: 3.6; 95%
Association has published guidelines is inadequate, such as when they feel confidence interval [CI]: 1.0, 12.9]) and
with the intent of enhancing the safety of excessively tired or gain weight. This a fourfold increased risk for vertebral
combination therapy.12 Desiccated thyroid can lead to an individual requesting an fracture (odds ratio: 4.5; 94% CI: 1.3,
extract has been extensively used in the LT4 dose escalation or self-escalating 15.6) when compared with women who
past and is widely promoted on social their dose, causing a suppressed serum had normal TSH levels (0.5–5.5 mU/L).15
media sites, but it is not recommended TSH level. In another prospective cohort study of
by any of the current specialist society TSH levels of <0.4 mIU/L have been >230,000 women, there was an increased
guidelines. Typically it has a T4-to-T3 ratio associated with osteoporosis and atrial incidence of major osteoporotic fracture
of 4:1 – providing much more T3 than the fibrillation in people aged >60 years (hip, spine, humerus, forearm) in patients
physiological ratio of approximately 13:1 to of age.13 In one study, patients aged with low TSH levels (<0.3 mU/L; 13.5%,
16:1. The result is that thyroid extract will >65 years with serum TSH levels compared with 6.9% in those with normal
often produce supraphysiological T3 levels <0.1 mIU/L, the majority of whom were TSH levels).16
that may be associated with harm; it is taking LT4, had a threefold increase in
contraindicated in pregnant patients or the the risk of atrial fibrillation over a 10-year
elderly with cardiac disorders. observation period when compared with Potential adverse effects of
euthyroid controls.14 inadequate thyroid hormone
The risk for low bone density replacement
Potential adverse effects of and fractures is also elevated in The adverse effects of thyroid hormone
excessive thyroid hormone postmenopausal women taking excessive deficiency are often nonspecific and
replacement LT4. In a cohort of women aged >65 years, may include cognitive impairment,
Because many symptoms of women with a low TSH level (≤0.1 mU/L) hyperlipidaemia and progression of
hypothyroidism are nonspecific, had a threefold increased risk for hip cardiovascular disease. Patients with overt
Patient is diagnosed with subclinical hypothyroidism due to Hashimoto’s thyroiditis
TSH 4.0 to 6.9 mU/L TSH 7.0 to 9.9 mU/L TSH ≥10.0 mU/L
Age ≥65 years Age <65 years Age ≥65 years Age <65 years Treat with LT4
Observe and Consider therapeutic trial of LT4 if Treat with LT4 if not
monitor as symptomatic* contraindicated
TSH level
may be age
appropriate
Figure 1. Algorithm for thyroid hormone replacement in adults with subclinical hypothyroidism due to Hashimoto’s thyroiditis9
*Patients who commence LT4 therapy for symptoms attributed to subclinical hypothyroidism should be reviewed after three or four months to assess
response to treatment once the serum TSH returns to the reference range. If symptoms have not improved then LT4 therapy should generally be
discontinued and the patient reviewed for other disorders.
LT4, levothyroxine; TSH, thyroid stimulating hormone
Reproduced with permission of Medicine Today from Hughes K, Eastman CJ, Hashimoto’s thyroiditis: How to spot the diagnosis and how to manage it,
Med Today 2017;18(9):27–32.
24
hypothyroidism should generally have the first half of gestation, to adjust the LT4 sonography has a limited role in evaluation
LT4 dose adjusted to achieve a normal dosage to maintain these parameters of patients with thyrotoxicosis and is not
TSH level to avoid these potential adverse within the normal pregnancy reference necessary as part of routine assessment.
effects. In extreme situations, myxoedema range (0.1–2.5 mIU/L). A therapeutic
coma could eventuate. and monitoring regimen should apply
to women diagnosed with either overt Management of Graves’ disease
or subclinical hypothyroidism during Graves’ disease has three different
Management of hypothyroidism pregnancy. Soon after delivery, the LT4 treatment modalities:
during pregnancy dosage must be reduced to the original • antithyroid medications (thionamides)
Thyroxine production increases early prepartum replacement dosage. that block the synthesis of thyroid
in gestation by 25–50% in response to hormones
human chorionic gonadotrophin (hCG) • radioactive iodine ablation (I-131)
stimulation of the normal thyroid gland What are the causes of • thyroidectomy.
and increased oestrogen-stimulated hyperthyroidism? Each of these modalities of therapy is a
synthesis of thyroid hormone–binding Common causes of hyperthyroidism are satisfactory treatment but none is ideal.
proteins. Accordingly, patients with listed in Table 1. Investigations to determine The advantages and disadvantages of
hypothyroidism who are maintained the cause of thyrotoxicosis should routinely different types of treatment are listed
on LT4 therapy should increase the include TSH, FT4, FT3 and thyroid in Table 2. Individual patient factors
dosage of their medication initially by antibodies including thyroid receptor will influence the choice of therapy, and
approximately 25% as soon as pregnancy antibodies (TRAb). C-reactive protein management decisions should involve
has been confirmed. This increase can should be checked if subacute thyroiditis discussion of the values and preferences
often be easily achieved with an extra is suspected (indicated by a painful, tender of the patient. Administration of
two daily doses each week. Regular thyroid). Thyroid uptake scans are useful beta-blocker medication (eg propranolol,
monitoring of serum TSH and FT4 levels if the diagnosis is not clear based on atenolol, metoprolol) is recommended as
is recommended, particularly during the clinical features and bloods tests. Thyroid initial, short-term symptomatic therapy
Table 1. Common causes of thyrotoxicosis and main diagnostic features
Laboratory thyroid
Cause Aetiology Uptake scan finding autoantibody results
Graves’ disease TRAb stimulate thyroid hormone Normal or diffusely increased Presence of TRAb is diagnostic
production and development of a isotope uptake
diffuse goitre
Toxic multinodular goitre or Autonomous nodules produce thyroid Increased isotope uptake into Typically, a gradual progression
toxic adenoma hormone without TSH stimulation; toxic nodules with reduced towards the hyperthyroid state
hyperthyroidism may be precipitated uptake into surrounding over several years and thyroid
or exacerbated by exposure to excess normal thyroid tissue autoantibody negative
amounts of iodine
Painless thyroiditis or Release of preformed thyroid hormone Reduced or absent isotope Anti-TPO antibodies and/or
postpartum thyroiditis due to autoimmune destruction of uptake antithyroglobulin antibodies
thyroid tissue are present
Painful, subacute thyroiditis Release of preformed thyroid hormone Reduced or absent isotope Anti-TPO and antithyroglobulin
due to virally mediated destruction of uptake antibodies usually not detected
thyroid tissue and CRP/ESR elevated
Amiodarone-induced Type 1 – iodine induced in people with Usually reduced or absent Nil characteristic laboratory
thyrotoxicosis underlying autonomous nodules or isotope uptake, but often not results; recommend checking
Graves’ disease; Type 2 – destructive helpful anti-TPO antibodies and TRAb
thyroiditis to look for competing causes
Exogenous thyroid hormone Excess ingestion of thyroid hormone Reduced or absent isotope Nil characteristic laboratory
excess: Iatrogenic, intentional uptake results
or factitious
Anti-TPO, thyroid peroxidase antibodies; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; TRAb, thyroid receptor antibodies; TSH, thyroid
stimulating hormone
25
in all patients with moderate-to-severe and liver function. It is worth discussing of I-131 ablation on fertility in women
symptomatic thyrotoxicosis. the risk of agranulocytosis when and a potential small increased risk of
Antithyroid medications are the prescribing thionamides so patients are malignancy associated with radiation
usual first-line treatment for patients aware to attend for a blood test if infective exposure. Radioiodine carries the risk of
with Graves’ disease and are generally symptoms develop. exacerbating Graves’ orbitopathy and so
favoured because they allow the Long-term thionamide medication has is best avoided in patients with significant
possibility of achieving a durable generally been discouraged because of thyroid eye disease. Corticosteroids
remission without the need for lifelong challenges with compliance and potential should be given prophylactically at the
thyroid hormone replacement. Patients side effects; however, some patients time of radioiodine therapy to reduce the
with mild hyperthyroidism, a minimally and clinicians express a preference for risk of a flare of orbitopathy in individuals
enlarged thyroid and/or only modestly thionamide, wanting to avoid permanent with mild orbitopathy.
elevated TRAb levels are particularly hypothyroidism from either radioactive Thyroidectomy is generally the
good candidates for a trial of thionamide iodine ablation or thyroidectomy.17 preferred option in the following settings:
therapy as they have the best chance A course of antithyroid medication is • moderate-to-severe Graves’
of achieving a durable remission. Most recommended to achieve euthyroidism orbitopathy
individuals will need treatment for before the patient is treated definitively • women who desire a pregnancy within
12–18 months, with treatment continuing with either radioiodine or thyroidectomy. the next 6–12 months
until the TRAb becomes undetectable. Definitive treatment with radioiodine • large goitres causing compressive
Carbimazole is the favoured thionamide is generally considered in the following symptoms or goitres with significant
as it has less hepatotoxicity than settings: retrosternal extension
propylthiouracil (PTU). However, PTU • failure to achieve a durable remission • where thyroid malignancy is suspected
is preferred during the first trimester of despite prolonged or recurrent courses • when patients are fearful of taking
pregnancy and in treatment of thyroid of thionamide therapy radioactive medication.
storm because it inhibits conversion of T4 • recurrent Graves’ disease Thyroidectomy should only be performed
to T3. PTU may also be used for people • individuals who are unable to tolerate by a high-volume surgeon as complication
with adverse reactions to carbimazole. thionamides because of adverse effects. rates are lower in the hands of an
Agranulocytosis is a rare but serious The cure rate (achieving euthyroid or experienced surgeon.
adverse effect of thionamide medications. hypothyroid state) following the oral None of the available therapeutic
Before commencing thionamides, administration of a 555 Mbq dose of options for the management of Graves’
all patients should have baseline full radioactive iodine is approximately 75% disease has been able to re-establish
blood examination and liver function at 12 months. Radioiodine typically takes normal thyroid function in all patients.
tests performed. Any patient taking 3–6 months to induce a hypothyroid Regardless of the treatment chosen, up
thionamides who develops fever, sore state, and some individuals will need to 25% of patients report not feeling fully
throat or other signs of sepsis should have more than one dose. There is lingering recovered after their treatment, mostly
an urgent assessment of white cell count concern about possible adverse effects because of persistent fatigue and eye
Table 2. Advantages and disadvantages of Graves’ disease treatment options
Treatment Advantages Disadvantages
Thionamides • Allows possibility of a durable remission and • Side effects – rash, pruritus, gastrointestinal, agranulocytosis
preservation of endogenous thyroid function and hepatitis, usually occurring early in the course of therapy
• Low cost • Risk of birth defects if pregnant
• Frequent monitoring required
Radioiodine • Permanent resolution of hyperthyroidism • Permanent hypothyroidism in most cases

• Low cost • Radiation exposure to salivary glands
• Potential adverse effects on fertility
• Risk of exacerbation of Graves’ orbitopathy
Thyroidectomy • Rapid, permanent resolution of hyperthyroidism • Permanent hypothyroidism

• May help improve Graves’ orbitopathy • Risks of surgery and anaesthesia
• Provides relief of compressive symptoms if large • Risk of hypoparathyroidism and recurrent laryngeal nerve injury
goitre is present • High cost in comparison to other treatments
40 Reprinted from AJGP Vol. 50, No. 1–2, Jan–Feb 2021 © The Royal Australian College of General Practitioners 2021 26
symptoms.18 Weight loss is a common Radioiodine is generally the preferred Conclusion

feature of hyperthyroidism, and many treatment for toxic nodules as it provides Thyroid function disorders are commonly
patients gain considerable weight after the best chance of achieving the euthyroid encountered in general practice.
treatment of their hyperthyroidism. state without the need for medication. Long-term management requires an
Patients should be counselled regarding Surgery is preferable in patients with understanding of the range of causes and
the risk of weight gain; appropriate early very large goitres and/or significant benefits from a shared decision-making
dietary modification may help to minimise compressive symptoms and for those who approach, with discussion about potential
weight gain. do not want to have radiation therapy. risks and benefits of therapy.
Long-term thionamide therapy is an
option, particularly in elderly people or in
Management of toxic nodules individuals who prefer to avoid radiation Key points
Toxic nodules are a common cause or surgery. Percutaneous ethanol therapy • Thyroid function abnormalities are
of mild hyperthyroidism, generally or laser therapy are available in some commonly encountered in general
progressing slowly over many years. parts of the world, but their availability in practice, occurring much more often
In the early stages, a subnormal TSH Australia is very limited currently. in females than males, with close to
level is frequently the only biochemical a million people being treated for
abnormality. Risks of osteoporotic hypothyroidism.
fractures and atrial fibrillation increase, Management of thyroiditis • Treatment of established
particularly in the elderly, as the TSH Thyroiditis may have multiple different hypothyroidism should be with LT4,
levels falls below 0.1 mIU/L; therefore, causes, including autoimmune in preference to other forms of thyroid
this is a common threshold for considering (eg painless lymphocytic and postpartum hormone replacement, with goals of
treatment (even when the FT4 and thyroiditis), viral (eg subacute thyroiditis) ameliorating symptoms, achieving
FT3 concentrations remain within the and medication induced (eg amiodarone). the euthyroid state and avoiding
reference range). Exposure to large iodine Thyrotoxicosis associated with thyroiditis overtreatment.
loads, as occurs with iodinated contrast, is typically self-limited. Antithyroid • Decisions about who and when to treat
may precipitate a transient increase in (thionamide) medication therapy is for hypothyroidism can be challenging
severity of hyperthyroidism. Diagnosis is generally ineffective and inappropriate. and may benefit from a shared decision-
usually confirmed by the appearance on a Beta-blockers are indicated for making approach with discussion about
radionuclide scan (Figure 2). symptomatic relief in patients with potential risks and benefits of therapy.
significant palpitations, tachycardia • Hyperthyroidism, even when
and tremor. Corticosteroids may have subclinical, carries long-term risks of
a role in people with persistent, painful osteoporosis and atrial fibrillation,
A B subacute thyroiditis and in people with particularly in the elderly, and generally
type 2 destructive thyroiditis associated should not be left untreated.
with amiodarone therapy. • Choice of treatment modality for
Hyperthyroidism associated with hyperthyroidism should be patient
thyroiditis is attributable to the release centred and dependent on underlying
of preformed thyroid hormone from the pathology, patient preference and
C D inflamed thyroid. The thyrotoxic phase availability of expert surgical care.
may be followed by a hypothyroid phase,
so monitoring of thyroid function tests
Authors
is prudent. The hypothyroid phase is
Kiernan Hughes MBBS (Hons), MSc, FRACP,
Sternal notch
usually transient; therefore, thyroxine Consultant Endocrinologist, St Vincent’s Hospital,
replacement may not be required. If NSW
Sternal notch Creswell Eastman AO MBBS, MD, FRACP, FRCPA,
LT4 is considered necessary, it can
FAFPHM, Principal, Sydney Thyroid Clinic, NSW;
usually be weaned within 3–6 months. Professor, Sydney Medical School, University of
The rate of permanent hypothyroidism Sydney, NSW
Competing interests: None.
Figure 2. Uptake scan appearances of thyroid associated with thyroiditis will depend
Funding: None.
conditions20 on the underlying cause. Females
Provenance and peer review: Commissioned,
a. Graves’ disease; b. Multinodular goitre; with a history of thyroiditis should be externally peer reviewed.
c. Thyroiditis; d. Autonomous nodule encouraged to have TSH checked prior Correspondence to:
Reproduced with permission of The Royal kiernanhughes@northernendocrine.com.au
to attempting conception and during
Australian College of General Practitioners from
Lee JC, Harris AM, Khafagi FA, Thyroid scans, the first trimester of pregnancy as they
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2012;97(8):2543–65. doi: 10.1210/jc.2011-2803.
7. Bekkering GE, Agoritsas T, Lytvyn L, et al.
Thyroid hormones treatment for subclinical
hypothyroidism: A clinical practice guideline.
BMJ 2019;365:l2006. doi: 10.1136/bmj.l2006.
8. Stott DJ, Rodondi N, Kearney PM, et al.
Thyroid hormone therapy for older adults
with subclinical hypothyroidism. N Engl J
Med 2017;376(26):2534–44. doi: 10.1056/
NEJMoa1603825.
9. Hughes K, Eastman CJ. Hashimoto’s thyroiditis:
How to spot the diagnosis and how to manage it.
Med Today 2017;18(9):27–32.
10. Saravanan P, Visser TJ, Dayan CM. Psychological
well-being correlates with free thyroxine but not free
3,5,3’-triiodothyronine levels in patients on thyroid
hormone replacement. J Clin Endocrinol Metab
2006;91(9):3389–93. doi: 10.1210/jc.2006-0414.
11. Ettleson MD, Bianco AC. Individualized therapy
for hypothyroidism: Is T4 enough for everyone?
J Clin Endocrinol Metab 2020;105(9):e3090–e104.
doi: 10.1210/clinem/dgaa430.
12. Wiersinga WM, Duntas L, Fadeyev V, Nygaard B,
Vanderpump MP. 2012 ETA guidelines:
The use of L–T4 + L–T3 in the treatment of
hypothyroidism. Eur Thyroid J 2012;1(2):55–71.
doi: 10.1159/000339444.
13. Uzzan B, Campos J, Cucherat M, Nony P, Boissel JP,
Perret GY. Effects on bone mass of long term
treatment with thyroid hormones: A meta-analysis.
J Clin Endocrinol Metab 1996;81(12):4278–89.
doi: 10.1210/jcem.81.12.8954028.
14. Sawin CT, Geller A, Wolf PA, et al. Low serum
thyrotropin concentrations as a risk factor
for atrial fibrillation in older persons. N Engl
J Med 1994;331(19):1249–52. doi: 10.1056/
NEJM199411103311901.
15. Bauer DC, Ettinger B, Nevitt MC, Stone KL. Risk
for fracture in women with low serum levels of
thyroid-stimulating hormone. Ann Intern Med
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7-200104030-00009.
16. Abrahamsen B, Jørgensen HL, Laulund AS,
Nybo M, Brix TH, Hegedüs L. Low serum
thyrotropin level and duration of suppression as
a predictor of major osteoporotic fractures – the
OPENTHYRO register cohort. J Bone Miner Res
2014;29(9):2040–50. doi: 10.1002/jbmr.2244. correspondence ajgp@racgp.org.au
28
M6 Reading R4
Am Fam Physician 2016
PMID: 27929275
Erectile Dysfunction
KARL T. REW, MD, and JOEL J. HEIDELBAUGH, MD, University of Michigan Medical School, Ann Arbor, Michigan
Erectile dysfunction (ED) is the inability to achieve or maintain an erection sufficient for satisfactory sexual perfor-
mance. It is common, affecting at least 12 million U.S. men. The five-question International Index of Erectile Func-
tion allows rapid clinical assessment of ED. The condition can be caused by vascular, neurologic, psychological, and
hormonal factors. Common conditions related to ED include diabetes mellitus, hypertension, hyperlipidemia, obe-
sity, testosterone deficiency, and prostate cancer treatment. Performance anxiety and relationship issues are common
psychological causes. Medications and substance use can cause or exacerbate ED; antidepressants and tobacco use are
the most common. ED is associated with an increased risk of cardiovascular disease, particularly in men with meta-
bolic syndrome. Tobacco cessation, regular exercise, weight loss, and improved control of diabetes, hypertension,
and hyperlipidemia are recommended initial lifestyle interventions. Oral phosphodiesterase-5 inhibitors are the first-
line treatments for ED. Second-line treatments include alprostadil and vacuum devices. Surgically implanted penile
prostheses are an option when other treatments have been ineffective. Counseling is recommended for men with psy-
chogenic ED. (Am Fam Physician. 2016;94(10):820-827. Copyright © 2016 American Academy of Family Physicians.)
E
More online rectile dysfunction (ED) is the reuptake inhibitors citalopram (Celexa),
at http://www. inability to achieve or maintain an fluoxetine (Prozac), paroxetine (Paxil),
aafp.org/afp.
erection sufficient for satisfactory and sertraline (Zoloft), and the serotonin-
CME This clinical content
sexual performance.1 ED becomes norepinephrine reuptake inhibitor venlafax-
conforms to AAFP criteria
for continuing medical
more common as men age (Figure 1).2 At ine. Bupropion (Wellbutrin), mirtazapine
education (CME). See least 12 million U.S. men 40 to 79 years of (Remeron), and fluvoxamine are less likely
CME Quiz Questions on age have ED.3 to cause ED.11 Tobacco, alcohol, and illicit
page 791. drugs can cause ED.13,14 Marijuana use may
Author disclosure: No rel- Diagnosis cause ED, although further study is needed.15
evant financial affiliations. The five-question International Index of
METABOLIC SYNDROME
Patient information: Erectile Function (IIEF-5) allows rapid
▲
A handout on this topic, clinical assessment of ED and can mea- ED has been linked to each component of the
written by the authors of sure the effectiveness of ED treatments (see metabolic syndrome (eTable A), including
this article, is available
at http://www.aafp.org/ http://www.aafp.org/afp/2010/0201/p305. increased fasting serum glucose levels, dia-
afp/2016/1115/p820-s1. html#afp20100201p305-t3). Other diagnos- betes, hypertension, and abdominal obesity,
html. tic options include a single-question self- as well as to an increased risk of cardiovascu-
assessment (Table 1) 4 and the Brief Male lar disease (CVD).16-22
Sexual Function Inventory.5 Low serum testosterone levels are one fac-
tor that may explain the relationship between
Causes and Related Conditions metabolic syndrome and ED.23 The adipose
ED has vascular, neurologic, psychologi- tissue enzyme aromatase prevalent in obese
cal, and hormonal causes. Conditions com- men converts testosterone into estradiol, a
monly associated with ED include diabetes significant cause of hypogonadism.24-26 Adi-
mellitus, hypertension, hyperlipidemia, pocytes also generate inflammatory cyto-
obesity, testosterone deficiency, and prostate kines associated with impaired endothelial
cancer treatment (Table 2).6-8 Performance function, cardiovascular events, and ED.27-29
anxiety and relationship issues are common Patients with diabetes are three times more
psychological causes. likely to develop ED, and a longer duration of
diabetes is strongly associated with ED.18,30,31
MEDICATIONS AND SUBSTANCE USE Metabolic syndrome is associated with a 2.6-
Many medications cause or exacerbate ED fold increase in the incidence of ED, and the
(Table 3).9-12 Antidepressants are a com- fasting blood glucose level is the component
mon cause, especially the selective serotonin associated with the highest risk of ED.32,33
820 American
Downloaded Family
from the Physician
American www.aafp.org/afp
Family Physician website at www.aafp.org/afp.
Copyright © 2016 Volume
American Academy 94, Number
of Family 10 ForNovember
Physicians. the private, 15,
◆ 2016
noncom-
mercial use of one individual user of the website. All other rights reserved. Contact copyrights@aafp.org for copyright questions and/or permission requests.
29
BEST PRACTICES IN UROLOGY: RECOMMENDATIONS
FROM THE CHOOSING WISELY CAMPAIGN
Sponsoring
Recommendation organization
mass index, and waist circumference to assess abdomi-
Do not prescribe testosterone to men American nal obesity; a genital examination; and an assessment of
with erectile dysfunction who have Urological
normal testosterone levels. Association
male secondary sex characteristics.
Source: For more information on the Choosing Wisely Campaign, Laboratory Evaluation
see http://www.choosingwisely.org. For supporting citations and to The A1C or fasting glucose level can be used to assess for
search Choosing Wisely recommendations relevant to primary care,
see http://www.aafp.org/afp/recommendations/search.htm.
diabetes. A lipid panel can assess for hyperlipidemia. A
thyroid-stimulating hormone level is recommended for
men with signs or symptoms of hypothyroidism.
The probability of having undiagnosed diabetes is one in
50 among men 40 to 59 years of age who do not have ED,
but increases to one in 10 for those with ED.34 Low Median High
100
CVD
90
ED and CVD share similar risk factors, including older
Prevalence of erectile dysfunction (%)

age, hypertension, dyslipidemia, smoking, obesity, and 80
74
diabetes. ED is associated with an increased risk of CVD, 70
76
coronary artery disease (CAD), stroke, and all-cause
mortality, and it is probably an independent risk factor 60
50
for CVD.35 50
44
ED typically occurs two to five years before CAD, pro-
viding a potential window during which men diagnosed 40
32
with ED can make lifestyle changes to prevent CAD.36 30
29
Men with ED are at higher risk of angina, myocardial
26
infarction, stroke, transient ischemic attack, congestive 20
heart failure, and cardiac arrhythmias compared with 16

10
6 3
men who do not have ED.37 Men with ED have a 75% 1 7
increased risk of developing peripheral vascular disease.38 0
40 to 49 50 to 59 60 to 69 70 to 79
ED has a positive predictive value for the development
of CVD that is equal to or greater than that for smoking, Age (years)
hyperlipidemia, or a family history of myocardial infarc-

Figure 1. The prevalence of erectile dysfunction increases
tion.37,39 ED can accurately predict silent CAD.40-45 ED in with age.
men 40 to 49 years of age is more predictive of CAD than Information from reference 2.
in older men.36 In one study, the incidence of CAD in
men younger than 40 years who had ED was seven times
that in the control population.46 ED is a useful marker Table 1. Single-Question Assessment
for assessing cardiovascular risk, particularly in younger of Erectile Dysfunction
men and minorities, for whom global risk assessment
calculators may underestimate actual risk.47,48 Impotence means not being able to get and keep an
Management of cardiovascular risk factors is recom- erection that is rigid enough for satisfactory sexual activity.
mended in men who have ED but no known CVD.49,50 How would you describe yourself?
Because diagnosing ED can help identify men at higher A. N ot impotent: always able to get and keep an erection
risk of CVD, use of the IIEF-5 is also recommended dur- good enough for sexual intercourse.
ing CVD risk assessment. B. Minimally impotent: usually able to get and keep an
erection good enough for sexual intercourse.
History and Physical Examination C. Moderately impotent: sometimes able to get and keep
an erection good enough for sexual intercourse.
Medical and surgical history, sexual history, use of medi- D. Completely impotent: never able to get and keep an
cations and other substances, and an assessment of psy- erection good enough for sexual intercourse.
chological and relationship health are key components of
the patient history. Essential parts of the physical exami- Information from reference 4. 30
nation include measurement of blood pressure, body
November 15, 2016 ◆ Volume 94, Number 10 www.aafp.org/afp American Family Physician 821
Table 2. Erectile Dysfunction: Related Conditions and
Approaches to Evaluation
Related condition Approach to evaluation

Routine measurement of testoster-
Cardiovascular disease History and physical examination
one levels is controversial. As part of the
Diabetes mellitus A1C or fasting glucose level
Choosing Wisely campaign, the Ameri-
Endocrine disorders (e.g., hypo- History and physical examination; if
can Urological Association recommends
gonadism, hyperprolactinemia, an endocrine disorder is suspected,
thyroid disorders) consider laboratory testing that physicians not prescribe testoster-
Genital pain History one to men with ED who have normal
Hyperlipidemia Lipid panel testosterone levels. A diagnosis of hypo-
Hypertension Blood pressure gonadism must be based on more than
Metabolic syndrome Blood pressure; fasting glucose, just an abnormal laboratory test result.51
high-density lipoprotein, Measurement of morning total testos-
and triglyceride levels; waist terone may be considered for men with
circumference small testes, lack of male secondary sex
Neurologic conditions (e.g., multiple History and physical examination characteristics, significantly low libido,
sclerosis, Parkinson disease, spinal
or a history of inadequate response to
cord injury, stroke)
phosphodiesterase-5 (PDE-5) inhibi-
Obesity Body mass index, waist circumference
tors; if the initial result is abnormal, the
Peyronie disease History and physical examination
test should be repeated in a few months.
Prostate cancer treatment History
(e.g., surgery, radiation, hormone
Free testosterone levels vary widely across
therapy) laboratories and are not uniformly rec-
Psychological conditions (e.g., anxiety, History ommended for screening. However,
depression, guilt, history of sexual when hypogonadism is clinically sus-
abuse, marital or relationship pected but the morning total testosterone
problems, stress) level is repeatedly normal, bioavailable
Sedentary lifestyle History testosterone or free testosterone may
Tobacco use History account for the effects of sex hormone–
Trauma History binding globulin levels on testosterone
Venous leakage History and physical examination; activity. Levels of follicle-stimulating
if venous leakage is suspected,
consider urology consultation for
hormone, luteinizing hormone, sex hor-
venous flow testing mone–binding globulin, estradiol, and
prolactin can help differentiate between
Information from references 6 through 8. primary and secondary causes of testicu-
lar hypogonadism.52
Table 3. Medications and Substances That May Cause or Contribute to Erectile Dysfunction
Alcohol, nicotine, and illicit drugs (e.g., amphetamines, Antipsychotics (e.g., chlorpromazine, haloperidol, pimozide
barbiturates, cocaine, marijuana, opiates) [Orap], thioridazine, thiothixene)
Analgesics (e.g., opiates) Cardiovascular agents (e.g., digoxin, disopyramide
Anticonvulsants (e.g., phenobarbital, phenytoin [Dilantin]) [Norpace], gemfibrozil [Lopid])
Antidepressants (e.g., lithium, monoamine oxidase inhibitors, Cytotoxic agents (e.g., methotrexate)
selective serotonin reuptake inhibitors, serotonin- Diuretics (e.g., spironolactone, thiazides)
norepinephrine reuptake inhibitors, tricyclic antidepressants) Hormones and hormone-active agents (e.g., 5-alpha-
Antihistamines (e.g., dimenhydrinate, diphenhydramine reductase inhibitors, androgen receptor blockers,
[Benadryl], hydroxyzine, meclizine [Antivert], promethazine) androgen synthesis inhibitors, corticosteroids, estrogens,
Antihypertensives (e.g., alpha blockers, beta blockers, calcium gonadotropin-releasing hormone analogs, progesterones)
channel blockers, clonidine, methyldopa, reserpine) Immunomodulators (e.g., interferon alfa)
Antiparkinson agents (e.g., bromocriptine [Parlodel], levodopa, Tranquilizers (e.g., benzodiazepines)
trihexyphenidyl)
Information from references 9 through 12.
822 American Family Physician www.aafp.org/afp Volume 94, Number 10 ◆ November 15, 2016
31
Treatment of other agents are expected to be available in 2017 to 2019.

An algorithm for the diagnosis and management of ED is Insurance coverage for these medications is limited, and
shown in Figure 2.6-17,33,49-68 prescriptions may require prior authorization.
LIFESTYLE MODIFICATIONS SURGICAL AND PROCEDURAL THERAPY
Lifestyle modifications can improve IIEF-5 scores in Second-line treatments for ED include alprostadil
men with ED.53 Regular exercise, weight loss in obese (Caverject) and vacuum devices. These treatments can
or overweight men, and improved control
of diabetes, hypertension, and hyperlipid-
emia are recommended. Weight loss can Diagnosis and Management of Erectile Dysfunction
modestly improve low testosterone levels,
Have patient complete the five-item International
although the extent of the benefit on ED is Index of Erectile Function questionnaire.
unclear.54 Statin use seems to improve ED,
as measured by IIEF-5 scores.55 Tobacco ces-
Perform a focused history and physical examination: medical and surgical history,
sation is highly recommended. Compared
sexual history, use of medications and substances, psychological and relationship
with men who have never smoked, the risk health. Measure blood pressure, body mass index, and waist circumference.
of ED is increased by 51% in current smok- Perform a genital examination and assess for secondary sex characteristics.
ers and 20% for ex-smokers.14
Obtain appropriate laboratory tests: fasting glucose or A1C, lipid panel. Consider
MEDICATIONS
morning total testosterone level and other laboratory tests if clinically indicated.
Oral PDE-5 inhibitors are first-line treat-
ments for ED.57 Sexual stimulation is needed
Common causes present Common causes not present
to produce an erection; the PDE-5 inhibitor
helps to maintain the erection by enhancing
the vasodilatory effects of endogenous nitric Optimize management of: Consider:
oxide. Four PDE-5 inhibitors with similar Cardiovascular disease Stress test or cardiology consultation to
effectiveness and safety profiles are currently Diabetes mellitus assess for undetected cardiovascular
approved by the U.S. Food and Drug Admin- disease
Hyperlipidemia
Evaluation for possible endocrine,
istration (FDA) for treatment of ED: avana- Hypertension
neurologic, or psychological causes
fil (Stendra), sildenafil (Viagra), tadalafil Hypogonadism (Table 2)
(Cialis), and vardenafil (Levitra). Table 4 Metabolic syndrome Nocturnal penile tumescence testing
summarizes these medications.56-58 All are Overweight or obesity Sexual health evaluation and counseling
Psychogenic causes
effective within about one hour of dosing
Tobacco use cessation
and are typically used on an as-needed basis.
The effects may be delayed or decreased if
the patient has recently eaten a fatty meal,
First-line therapies:
particularly for sildenafil and vardenafil.69
Lifestyle modifications
PDE-5 inhibitors are ineffective in some Medication changes if needed (Table 3)
men, particularly those with severe ED. Oral phosphodiesterase-5 inhibitor (if not contraindicated)
Headache, flushing, and dyspepsia are com-
mon adverse effects.58 PDE-5 inhibitors are
contraindicated in men using nitroglycerin Second-line therapies:
or other nitrates because of the risk of cata- Intraurethral or intracavernosal alprostadil (Caverject)
strophic low blood pressure. Tadalafil has a Vacuum device
longer half-life, which gives men the option
of taking it up to 12 hours before sex or as a
lower-dose, once-daily medication; however, Consider urology consultation for possible penile prosthesis implantation.
adverse effects also last longer. Vardenafil is

available as a 10-mg oral disintegrating tab- Figure 2. Algorithm for the diagnosis and management of erectile
let. Sildenafil is the only PDE-5 inhibitor that dysfunction.
is available generically; generic formulations Information from references 6 through 17, 33, and 49 through 68.
32
Table 4. PDE-5 Inhibitors for Treatment of Erectile Dysfunction
Minimum time
from dosing to
Medication* Dosage sexual activity Elimination half-time Cost for 10 tablets†
Avanafil (Stendra) 50, 100, or 200 mg once daily 15 minutes Five to 10 hours NA ($350)
as needed
Sildenafil (Viagra) 20, 25, 50, or 100 mg once daily 30 minutes Three to five hours $10 ($475)
as needed
Tadalafil (Cialis) 10 or 20 mg once daily as needed 30 minutes 17.5 hours NA ($525)

2.5 or 5 mg once daily NA NA NA ($280 for 30 tablets)
Vardenafil (Levitra) 10 or 20 mg once daily as needed 60 minutes Four to five hours NA ($465)
NOTE: Contraindications include concomitant use of nitrates, stroke or myocardial infarction in the past six to eight weeks, significantly low blood
pressure, uncontrolled high blood pressure, unstable angina, severe cardiac failure, severe liver impairment, and end-stage kidney disease requiring
dialysis. Lower doses should be used in patients with chronic kidney disease or moderate liver impairment.
NA = not available or not applicable; PDE-5 = phosphodiesterase-5.
*—Other PDE-5 inhibitors not currently approved by the U.S. Food and Drug Administration include lodenafil, mirodenafil, and udenafil.
†—Estimated retail cost based on information from http://www.goodrx.com (accessed July 27, 2016). Generic price listed first; brand price in
parentheses.
Information from references 56 through 58.
be used to establish an erection before sexual stimula- left in place for more than 30 minutes. Vacuum devices
tion. They should be avoided in men who are receiving can be cumbersome, require several minutes to produce
anticoagulants or who have sickle cell disease or other an erection, may lead to bending at the base of the penis
bleeding or clotting disorders.
Alprostadil causes penile vasodilation by relaxing
arterial smooth muscle; it is available in injectable and
intraurethral forms and can be used in combination
with PDE-5 inhibitors. Injectable alprostadil is adminis-
tered intracavernosally into one side of the penis. Intra-
urethral alprostadil is a dissolvable pellet that is placed
into the urethra with an applicator.59 The injectable form
is more effective.60 The lowest effective dose should be
used, and the patient should be instructed on proper
technique by administering a test dose in the physician’s
office. Fear of needles or pain can limit patient accep-
tance of alprostadil. Patients should be warned to seek
emergency urologic treatment if an erection lasts four
hours or longer. Penile fibrosis is another possible adverse
effect; in one study, persistent fibrotic changes occurred
in 4.9% of patients using intracavernosal alprostadil for
four years.61 A similar ED treatment that has not been
approved by the FDA is intracavernosal injection of
compounded mixtures of alprostadil, papaverine, and
phentolamine.60
Vacuum devices consist of a tube that is placed
over the penis and sealed at the base with lubricant
(Figure 3).62 A vacuum pump removes air from the tube,
pulling blood into the penis and creating an erection. A
constricting ring is then slid off the base of the tube onto Figure 3. Erec-Tech vacuum therapy system.
the penis to maintain the erection. To prevent ischemic Reprinted with permission from Heidelbaugh JJ. Management of erectile
damage, the constricting ring should generally not be dysfunction. Am Fam Physician. 2010;81(3):310.
33
history can elicit potential causes such as

SORT: KEY RECOMMENDATIONS FOR PRACTICE performance anxiety and relationship con-
flicts, which distract attention and impair
Evidence
Clinical recommendation rating References sexual arousal. Problems such as premature
ejaculation, genital pain, or dyspareunia can
Current smoking is significantly associated with A 13, 14 lead to psychogenic ED, as can cultural or
ED, and smoking cessation has a beneficial religious taboos or a history of sexual abuse.
effect on the restoration of erectile function.
Although men and their partners may resist
Men with metabolic syndrome should be B 33
counseled to make lifestyle modifications to a psychological explanation for ED, coun-
reduce the risk of cardiovascular events and ED. seling can be effective.60
Phosphodiesterase-5 inhibitors are the first-line A 57 ED of mixed organic and psychogenic ori-
treatment for ED. gin is common. Psychogenic causes are more
likely when the patient has normal erections
ED = erectile dysfunction.
with masturbation or when nocturnal penile
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited- tumescence is normal. Devices are available
quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual
practice, expert opinion, or case series. For information about the SORT evidence to measure the number, duration, and rigid-
rating system, go to http://www.aafp.org/afpsort. ity of erections during sleep. However, normal
nocturnal erections do not always correlate
with sexually relevant erections, and this test
where the ring is in place, and will cause the erect penis may be unreliable in older or anxious patients.66
to seem cool or cold because of restricted blood flow. When ED coexists with depression or anxiety, treat-
However, success and satisfaction rates are fairly high.63 ment of the mood disorder may be the most appropri-
Vacuum devices can be used in combination with an ate first step. If antidepressants are used, the specific
oral PDE-5 inhibitor or with alprostadil for men who agent should be one that is less likely to worsen ED (e.g.,
have not had success with single-component treat- bupropion, mirtazapine, fluvoxamine). PDE-5 inhibi-
ment. These devices are also useful in men receiving tors are effective in men with depression and can be used
daily nitroglycerin or other long-term nitrate therapy, in combination with treatments for mood disorders.67
in whom PDE-5 inhibitors are contraindicated. Patients This article updates previous articles on this topic by Heidelbaugh,62
can obtain vacuum devices at medical supply compa- Miller,70 and Viera, et al.71
nies by presenting a physician’s prescription. Insurance
Data Sources: A computerized literature search was performed using the
coverage varies. PubMed Clinical Query function to identify publications using the follow-
ing terms: erectile dysfunction, male sexual dysfunction, cause/etiology,
PROSTHESES treatment, phosphodiesterase type-5 inhibitors, metabolic syndrome.
Surgically implanted penile prostheses are a third-line The search included meta-analyses, randomized controlled trials, clinical
trials, and reviews. Additional sources searched included the Agency for
treatment option for ED when other treatments have Healthcare Research and Quality, Cochrane database, Essential Evidence,
been ineffective. Semirigid malleable prostheses are the National Guideline Clearinghouse, and U.S. Preventive Services Task Force.
simplest and easiest to implant, but they can be difficult The search was limited to English-language studies involving human
to conceal because the penis is always erect. Inflatable subjects. Abstracts, book chapters, and case studies were excluded. Bibli-
ographies from index citations were also reviewed for additional relevant
prostheses typically consist of two tubes that replace the studies. Search dates: March 27, 2016, and June 20, 2016.
corpora cavernosa, plus a pump in the scrotum and an
intra-abdominal reservoir (eFigure A). Mechanical fail-
The Authors
ure or infection may require removal of the prosthesis.
Risks include scarring, penile shortening, and recurrent KARL T. REW, MD, is an assistant professor in the Departments of Family
Medicine and Urology at the University of Michigan Medical School, Ann
infections. Prostheses coated with antibiotics have been
Arbor.
used to reduce the risk of infection.64
JOEL J. HEIDELBAUGH, MD, FAAFP, FACG, is a professor in the Depart-
Managing Psychogenic ED ments of Family Medicine and Urology at the University of Michigan Medi-
cal School.
Many men have ED that is predominantly or exclu-
Address correspondence to Karl T. Rew, MD, University of Michigan
sively caused by psychological or interpersonal fac- Medical School, 24 Frank Lloyd Wright Dr., Lobby H, Ann Arbor, MI
tors.65 Psychogenic ED occurs at all ages but is most 48105 (e-mail: karlr@med.umich.edu). Reprints are not available from
common in men younger than 40 years. A thorough the authors.
34
ment in patients with erectile dysfunction? The role of body fat mass
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18. Aslan Y, Sezgin T, Tuncel A, Tekdogan UY, Guler S, Atan A. Is type 2 39. Araujo AB, Travison TG, Ganz P, et al. Erectile dysfunction and mortality.
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19. Saigal CS, Wessells H, Pace J, Schonlau M, Wilt TJ; Urologic Diseases in erectile dysfunction and silent myocardial ischemia in apparently
America Project. Predictors and prevalence of erectile dysfunction in a uncomplicated type 2 diabetic patients. Circulation. 2004;110(1):22-26.
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20. Al-Hunayan A, Al-Mutar M, Kehinde EO, Thalib L, Al-Ghorory M. The dysfunction to angiographic coronary artery disease. Am J Cardiol.
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21. Tomada N, Tomada I, Botelho F, Cruz F, Vendeira P. Are all metabolic atic coronary artery disease in men with vasculogenic erectile dysfunc-
syndrome components responsible for penile hemodynamics impair- tion: a prospective angiographic study. Eur Urol. 2005;48(6):996-1002.
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Eur Heart J. 2006;27(22):2632-2639. 58. Ückert S, Kuczyk MA, Oelke M. Phosphodiesterase inhibitors in clinical
4 4. Montorsi F, Briganti A, Salonia A, et al. Erectile dysfunction prevalence, urology. Expert Rev Clin Pharmacol. 2013;6(3):323-332.
time of onset and association with risk factors in 300 consecutive 59. Costa P, Potempa AJ. Intraurethral alprostadil for erectile dysfunction: a
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4 6. Chew KK, Finn J, Stuckey B, et al. Erectile dysfunction as a predictor alprostadil alfadex—an effective and well tolerated treatment for erec-
for subsequent atherosclerotic cardiovascular events: findings from a tile dysfunction. Results of a long-term European study. Int J Impot Res.
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47. Marma AK, Berry JD, Ning H, Persell SD, Lloyd-Jones DM. Distribution 62. Heidelbaugh JJ. Management of erectile dysfunction. Am Fam Physi-
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52. Shabsigh R, Kaufman JM, Steidle C, Padma-Nathan H. Randomized study 67. Makhlouf A, Kparker A, Niederberger CS. Depression and erectile dys-
of testosterone gel as adjunctive therapy to sildenafil in hypogonadal function. Urol Clin North Am. 2007;34(4):565-574, vii.
men with erectile dysfunction who do not respond to sildenafil alone. 68. Rosen RC, Cappelleri JC, Smith MD, et al. Development and evaluation of an
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53. Gupta BP, Murad MH, Clifton MM, Prokop L, Nehra A, Kopecky SL. The diagnostic tool for erectile dysfunction. Int J Impot Res. 1999;11(6):319-326.
effect of lifestyle modification and cardiovascular risk factor reduction 69. Hawksworth DJ, Burnett AL. Pharmacotherapeutic management of

on erectile dysfunction: a systematic review and meta-analysis. Arch erectile dysfunction. Clin Pharmacol Ther. 2015;98(6):602-610.
Intern Med. 2011;171(20):1797-1803.
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meta-analysis. Eur J Endocrinol. 2013;168(6):829-843.
cologic alternatives for erectile dysfunction [published correction
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meta-analysis of randomized trials. J Sex Med. 2014;11(7):1626-1635. 1999;60(4):1159-1166.
56. Brant WO, Bella AJ, Lue TF. Treatment options for erectile dysfunction.
Endocrinol Metab Clin North Am. 2007;36(2):465-479.
36
eTable A. Diagnostic Criteria for Metabolic Syndrome
Clinical measure Criteria*
Blood pressure† Systolic ≥ 130 mm Hg or diastolic ≥ 85 mm Hg

Fasting blood glucose level ≥ 100 mg per dL (5.6 mmol per L)
High-density lipoprotein level† Men < 40 mg per dL (1.04 mmol per L); women < 50 mg per dL (1.29 mmol per L)
Triglyceride level† ≥ 150 mg per dL (1.7 mmol per L)
Waist circumference‡ Asians: men ≥ 35.5 inches (90 cm); women ≥ 31.5 inches (80 cm)
Blacks: men ≥ 37 inches (94 cm); women ≥ 31.5 inches
Hispanics: men ≥ 35.5 inches; women ≥ 31.5 inches
Whites: men ≥ 37 inches; women ≥ 31.5 inches§
*—Criteria listed are the harmonized criteria proposed by the joint statement from the International Diabetes Federation Task Force on Epidemiology
and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society;
and International Association for the Study of Obesity. At least three criteria must be present to diagnose metabolic syndrome.
†—Patients currently receiving drugs to manage lipid disorders or high blood pressure are considered positive for these criteria.
‡—Thresholds according to International Diabetes Federation recommendations.
§—Thresholds for white patients differ significantly according to the recommending organization. Thresholds listed are from the International Diabe-
tes Federation. However, the American Heart Association and National Heart, Lung, and Blood Institute set thresholds of 40 inches (102 cm) for U.S.
men and 34.5 inches (88 cm) for U.S. women, noting that there is increased risk at the lower International Diabetes Federation values.
Adapted with permission from Mayans L. Metabolic syndrome: insulin resistance and prediabetes. FP Essent. 2015;435:12.
eFigure A. Coloplast Alpha-1 inflatable penile prosthesis.

Reprinted with permission from Heidelbaugh JJ. Management of erectile
dysfunction. Am Fam Physician. 2010;81(3):310.
November 15,
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M6 Reading 5
J Urol 2020
PMID: 32698717
Trauma/Reconstruction/Diversion
Microhematuria: AUA/SUFU Guideline

Daniel A. Barocas,*,† Stephen A. Boorjian,* Ronald D. Alvarez, Tracy M. Downs, Cary P. Gross,
Blake D. Hamilton, Kathleen C. Kobashi, Robert R. Lipman, Yair Lotan, Casey K. Ng,
Matthew E. Nielsen, Andrew C. Peterson, Jay D. Raman, Rebecca Smith-Bindman
and Lesley H. Souter
Vanderbilt University Medical Center (DAB, RDA), Nashville, Tennessee, Mayo Clinic (SAB), University of Wisconsin (TMD), Yale University (CPG), University of Utah
(BDH), Virginia Mason (KCK), Bladder Cancer Advocacy Network (RRL), University of Texas, Southwestern (YL), Kaiser Permanente (CKN), University of North Carolina
(MEN), Chapel Hill, North Carolina, Duke University (ACP), Penn State Health (JDR), University of California (RS-B), San Francisco, California
Purpose: Patients presenting with microhematuria represent a heterogeneous

Abbreviations
population with a broad spectrum of risk for genitourinary malignancy. Recognizing
and Acronyms
that patient-specific characteristics modify the risk of underlying malignant etiol-
CIS [ carcinoma in situ ogies, this guideline sought to provide a personalized diagnostic testing strategy.
GRADE [ Grading of Recom- Materials and Methods: The systematic review incorporated evidence published
mendations, Assessment, Devel-
from January 2010 through February 2019, with an updated literature search to
opment, and Evaluation
include studies published up to December 2019. Evidence-based statements were
MH [ microhematuria developed by the expert Panel, with statement type linked to evidence strength,
RBC/HPF [ red blood cells per level of certainty, and the Panel’s judgment regarding the balance between
high-power field benefits and risks/burdens.
RCC [ renal cell carcinoma Results: Microhematuria should be defined as 3 red blood cells per high power
UA [ urinalysis field on microscopic evaluation of a single specimen. In patients diagnosed with
UTUC [ upper tract urothelial gynecologic or non-malignant genitourinary sources of microhematuria, clinicians
carcinoma should repeat urinalysis following resolution of the gynecologic or non-malignant
genitourinary cause. The Panel created a risk classification system for patients
Accepted for publication July 15, 2020. with microhematuria, stratified as low-, intermediate-, or high-risk for genito-
This document is being printed as submitted,
independent of standard editorial or peer review
urinary malignancy. Risk groups were based on factors including age, sex,
by the editors of The Journal of Urology. smoking and other urothelial cancer risk factors, degree and persistence of
* Equal author contribution. microhematuria, as well as prior gross hematuria. Diagnostic evaluation with
†Correspondence: Vanderbilt University
Medical Center, Nashville, Tennessee (email:
cystoscopy and upper tract imaging was recommended according to patient risk
dan.barocas@vumc.org). and involving shared decision-making. Statements also inform follow-up after a
negative microhematuria evaluation.
Conclusions: Patients with microhematuria should be classified based on their
risk of genitourinary malignancy and evaluated with a risk-based strategy.
Future high-quality studies are required to improve the care of these patients.
Key Words: hematuria, cystoscopy, CT Urogram, bladder cancer, urothelial

carcinoma, urine markers
HEMATURIA is one of the most common The differential diagnosis of MH

urologic diagnoses, estimated to ac- encompasses a wide range of urologic,
count for over 20% of urology evalua- nephrologic, as well as gynecologic
tions.1 Indeed, screening studies have conditions. Importantly, while genito-
noted a prevalence range of micro- urinary malignancy has been diag-
hematuria (MH) among healthy vol- nosed in approximately 3% of patients
unteers of 2.4%-31.1% depending on evaluated for MH,2,3 the risk of
the specific population evaluated.2 detecting an underlying cancer has
0022-5347/20/2044-0778/0 https://doi.org/10.1097/JU.0000000000001297
THE JOURNAL OF UROLOGY® Vol. 204, 778-786, October 2020
Ó 2020 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC. Printed in U.S.A.
778 j www.auajournals.org/jurology 38
Copyright © 2020 American Urological Association Education and Research, Inc. Unauthorized reproduction of this article is prohibited.
MICROHEMATURIA: AUA/SUFU GUIDELINE 779
been found to be highly dependent on factors such as Determination of Evidence Strength

sex, age, smoking history, and degree of hematuria.4 Certainty of evidence underpinning the recommendation
As the aggregate likelihood of identifying a ma- statements were defined using the Grading of Recommen-
lignancy among patients with MH is relatively low, dations, Assessment, Development, and Evaluation (GRADE)
the benefits and potential harms of diagnostic system. The AUA employs a three-tiered strength of evidence
system to inform evidence-based guideline statements.16 In
evaluation must be considered both at the patient
short, high certainty by GRADE translates to AUA A-
and health system level.
category strength of evidence, moderate to B, and both low
At the same time, practice-pattern assessments and very low to C (table 1).
have demonstrated significant deficiencies in the
evaluation of patients presenting with hematuria. For AUA Nomenclature: Linking Statement Type to
example, one study found that less than 50% of pa- Evidence Strength
tients with hematuria diagnosed in a primary care The AUA nomenclature system explicitly links statement
type to the body of evidence strength, level of certainty,
setting were subsequently referred for urologic eval-
magnitude of benefit or risk/burdens, and the Panel’s
uation.5 Furthermore, performance of both cystoscopy judgment regarding the balance between benefits and risks/
and imaging occurs in less than 20% of patients in burdens (table 2).
most series, and varies to some degree by sex and A full description of the AUA methodology system can be
race.6e8 The underuse of cystoscopy, and the tendency found in the unabridged version of this guideline available
to rely solely on imaging for evaluation, is particularly at www.auanet.org/guidelines.
concerning since the vast majority of cancers diag-
nosed among persons with hematuria are bladder Guideline Statements
cancers, optimally detected with cystoscopy.4,6e14 Diagnosis and Definition of Microhematuria (MH)
As such, there is a need for updated, evidence- 1. Clinicians should define MH as >3 red blood cells per
based guideline recommendations for evaluation of high-power field (RBC/HPF) on microscopic evaluation
hematuria that limit the unnecessary risks and costs of a single, properly collected urine specimen. (Strong
associated with the over-evaluation of patients who Recommendation; Evidence Level: Grade C)
are at low risk for malignancy, while at the same time 2. Clinicians should not define MH by positive dipstick
clearly identifying clinical scenarios in which work- testing alone. A positive urine dipstick test (trace
up is warranted in order to address the delays in blood or greater) should prompt formal microscopic
diagnosis of important urologic conditions. In addi- evaluation of the urine. (Strong Recommendation; Ev-
idence Level: Grade C)
tion, since deciding how aggressively to pursue an
The literature review from the 2012 guideline and more
etiology for MH involves tradeoffs at the individual
recent data support the definition of MH as > 3 RBC/HPF
level (risk of malignancy versus harms of evaluation), on microscopic evaluation of a single urine specimen.2,17
it is necessary for the clinician and patient to engage Dipstick testing remains insufficient as it measures
in shared decision-making, particularly in situations peroxidase activity, which can be confounded by factors
where the ratio of benefits to harms is uncertain, including (but not limited to) the use of povidone iodine,
equivalent, or “preference sensitive.”15 The purpose of myoglobinuria, and dehydration. In order to inform clini-
this guideline and the associated algorithm (figure 1) cians of the degree of hematuria a patient has with suffi-
is, therefore, to provide a clinical framework for the cient detail to determine whether further evaluation is
diagnosis, evaluation, and follow-up of MH. warranted, the Panel emphasizes the importance of uti-
lizing laboratories reporting RBC/HPF quantitatively.
Initial Evaluation.
METHODOLOGY 3. In patients with MH, clinicians should perform a his-
Searches and Article Selection tory and physical examination to assess risk factors
A systematic review was conducted to inform on appropriate for genitourinary malignancy, medical renal disease,
diagnosis, evaluation, and follow-up in patients with sus- gynecologic and non-malignant genitourinary causes
pected and confirmed MH. The methodologist, in consulta- of MH. (Clinical Principle)
tion with the expert panel, developed criteria for inclusion Careful consideration should be given to risk factors for
and exclusion of studies based on the Key Questions and the malignancy (tables 3 and 4). Physical examination should
populations, interventions, comparators, and outcomes of include measurement of blood pressure and a genitourinary
interest. OVID was used to systematically search MED- examination as dictated by the clinical history. For
LINE and EMBASE databases for articles evaluating he- example, in women, examination of the external genitalia,
maturia using the criteria determined by the expert panel. introitus, and periurethral tissue may identify urethral
Five systematic reviews and 91 primary literature studies pathology or other gynecologic pathology to explain the MH.
met the study selection criteria and were chosen to form the 4. Clinicians should perform the same evaluation of pa-
evidence base. The initial draft evidence report included tients with MH who are taking antiplatelet agents
evidence published from January 2010 through February or anticoagulants (regardless of the type or level of
2019. A second search was conducted to update the report to therapy) as patients not on these agents. (Strong
include studies published up to December 2019. Recommendation; Evidence Level: Grade C)
39
780 MICROHEMATURIA: AUA/SUFU GUIDELINE
Figure 1.
Patients on anticoagulants should be assessed in the non-malignant genitourinary cause. If MH persists or

same fashion as patients who are not anticoagulated the etiology cannot be identified, clinicians should perform
because these patients have a malignancy risk similar to risk-based urologic evaluation. (Clinical Principle)
other populations.18e20 7. In patients with hematuria attributed to a urinary
5. In patients with findings suggestive of a gynecologic tract infection, clinicians should obtain a UA with
or non-malignant urologic etiology, clinicians should microscopic evaluation following treatment to ensure
evaluate the patients with appropriate physical exam- resolution of the hematuria. (Strong Recommenda-
ination techniques and tests to identify such an etiol- tion; Evidence Level: Grade C)
ogy. (Clinical Principle) If the history and physical examination suggest the
6. In patients diagnosed with gynecologic or non-malignant presence of a gynecologic or non-malignant source of MH,
genitourinary sources of MH, clinicians should repeat uri- the clinician should perform a directed evaluation to rule
nalysis (UA) following resolution of the gynecologic or in or rule out such an etiology.
40
Table 1: Strength of Evidence Definitions

AUA Strength of Evidence Category GRADE Certainty Rating Definition
A High We are very confident that the true effect lies close to that of the estimate of the effect
B Moderate We are moderately confident in the effect estimate
The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is
substantially different
C Low Our confidence in the effect estimate is limited
Very Low The true effect may be substantially different from the estimate of the effect
We have very little confidence in the effect estimate
The true effect is likely to be substantially different from the estimate of effect
In light of noted practice patterns, the Panel believes it Recognizing that there remains variability in risk within
is important to emphasize the need for a follow-up UA each risk group and that this classification system will
following resolution of a presumed gynecologic or non-ma- require validation, several strengths merit highlighting.
lignant urologic cause of MH, particularly urinary tract First, the stratification incorporates age-specific thresholds
infection, to confirm resolution of the MH. If the MH perfor men and women, drawing on observations of greater risk
sists, a risk-based urologic evaluation should be performed. for malignancy for male patients at younger ages than their
The Panel acknowledges that there are some non-ma- female counterparts.4,9,22e27 Additionally, this system in-
lignant urologic and gynecologic conditions, such as non- corporates stratification based on degree of MH, as large
obstructing nephrolithiasis or pelvic organ prolapse, series have found increased risks associated with higher
which will not merit treatment or in which the MH may numbers of RBC/HPF on microscopic UA.23,26 With respect
not resolve completely even with appropriate manage- to tobacco exposure, this system incorporates considerations
ment. In these cases, clinicians must use careful judgment of duration and intensity of tobacco exposure, in accord
and shared decision-making to decide whether to pursue with standards from the cancer screening literature.28,29
MH evaluation. Attention to the patient’s risk factors for Further, the framework provides guidance to recategorize
urologic malignancy should guide these decisions. initially low-risk patients with persistent hematuria on
8. Clinicians should refer patients with MH for nephro- follow-up evaluations. Finally, the AUA Guideline Risk
logic evaluation if medical renal disease is suspected. Stratification System explicitly incorporates recognized risk
However, risk-based urologic evaluation should still factors for urothelial cancer (table 3) into the considerations
be performed. (Clinical Principle) for recommending diagnostic evaluation.
Patients with proteinuria, dysmorphic RBCs, cellular
casts, or renal insufficiency may have medical renal dis- Urinary Tract Evaluation
ease, which can cause hematuria. Therefore, patients with Low-Risk.
these features should be referred to a nephrologist. While 10. In low-risk patients with MH, clinicians should
evaluation for medical renal disease should be performed, engage patients in shared decision-making to decide
this does not preclude the need for risk-based urologic between repeating UA within six months or
evaluation to identify coexistent urologic pathology. proceeding with cystoscopy and renal ultrasound.
(Moderate Recommendation; Evidence Level: Grade C)
Risk Stratification. The Panel acknowledges that the likelihood of diag-
9. Following initial evaluation, clinicians should catego- nosing malignancy in a low-risk MH patient is very low;
rize patients presenting with MH as low-, intermedi- therefore, the diagnostic yield in such patients must be
ate-, or high-risk for genitourinary malignancy based balanced against the potential harms of obtaining imaging,
on the accompanying tables (tables 3 and 4). (Strong including the implications of false positive detection.30
Recommendation; Evidence Level: Grade C) Further, while cystoscopy represents the current stan-
Patients presenting with hematuria represent a het- dard for diagnosing bladder tumors31e34 it does involve a
erogeneous population with a broad spectrum of risk for relatively invasive procedure, with potential patient
underlying malignancy based on clinical and demographic discomfort and anxiety, as well as a low risk of UTI, and,
features. The Panel, therefore, created categories, sum- from a healthcare system vantage point, cost.35,36
marized as ‘low-,’ ‘intermediate-,’ and ‘high-’ risk for a Understanding then that some low-risk patients may
diagnosis of genitourinary malignancy (table 4), in order choose to repeat a UA rather than undergo evaluation at
to facilitate patient-centered testing strategies. the time of initial MH diagnosis, the Panel advises a
Several available risk stratification systems were repeat UA within six months to limit the likelihood of
considered, which, broadly stated, estimate risk of uro- delayed diagnosis of a treatable urologic condition.
thelial carcinoma as <1% for those deemed low-risk, 1-2%
for intermediate-risk, and 10% or greater for high-risk.4,21 Initially Low-Risk With Hematuria on Repeat Urinalysis
The Panel also considered the contribution to patient risk (UA).
of each individual risk factor for urothelial carcinoma 11. Low-risk patients who initially elected not to undergo
based on an extensive literature review. The risk strati- cystoscopy or upper tract imaging and who are found
fication system designed for this guideline was based on to have MH on repeat urine testing should be
this systematic review and received unanimous approval reclassified as intermediate- or high-risk. In such
from members of the Panel. patients, clinicians should perform cystoscopy and
41
upper tract imaging in accordance with
A Clinical Principle is a statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical
-Applies to most patients in most circumstances but better
-Applies to most patients in most circumstances but better
-Net benefit (or net harm) comparable to other options

recommendations for these risk strata. (Strong
-Balance between Benefits & Risks/Burdens unclear

Recommendation; Evidence Level: Grade C)
-Alternative strategies may be equally reasonable
Expert Opinion refers to a statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge, and judgment.
In one large study, patients who had persistent MH
Evidence Strength C (Low Certainty)
-Net benefit (or net harm) appears substantial
-Net benefit (or net harm) appears moderate
-Better evidence likely to change confidence

on repeat urine testing had a higher rate of malignancy
-Benefits > Risks/Burdens (or vice versa)
on subsequent evaluation as compared with those who

evidence is likely to change confidence
evidence is likely to change confidence

had negative repeat urine testing.37 According to the
risk stratification schema above, patients with persis-
tent MH are, therefore, re-classified as either interme-
diate- or high-risk for malignancy, in part dependent
upon the degree of MH present at the repeat UA (table
4). Such re-classification ensures that patients
Table 2: AUA Nomenclature Linking Statement Type to Level of Certainty, Magnitude of Benefit or Risk/Burden, and Body of Evidence Strength
with recurrent or persistent hematuria undergo a risk-

stratified evaluation.
Intermediate-Risk.
12. Clinicians should perform cystoscopy and renal ultra-
sound in patients with MH categorized as intermediate-
-Best action appears to depend on individual patient
-Applies to most patients in most circumstances but
-Applies to most patients in most circumstances but
risk for malignancy. (Strong Recommendation;

Evidence Strength B (Moderate Certainty)
Evidence Level: Grade C)

Studies of MH patients have consistently demonstrated
-Better evidence could change confidence

better evidence could change confidence
better evidence could change confidence

-Net benefit (or net harm) is substantial
that when a urologic malignancy is detected during eval-

-Net benefit (or net harm) is moderate
uation, the most frequent cancer found is bladder

literature.
cancer.4,6e14, Whereas imaging has poor sensitivity for

identifying bladder cancer,4 cystoscopy is 98% sensitive.38
-Benefits[ Risks/Burdens
As such, cystoscopy should be performed in intermediate-

risk MH patients. Regarding the choice of upper tract im-
aging, renal ultrasound has adequate sensitivity and
circumstances
specificity for renal cortical tumors compared to axial im-

aging, at lower cost and with less risk (e.g., ionizing radi-
ation, intravenous contrast reactions, and false-positive
results).30,39e41 While the reported sensitivity of renal ul-
trasound for upper tract urothelial carcinoma (UTUC) is
-Applies to most patients in most circumstances and future
-Applies to most patients in most circumstances and future
-Best action depends on individual patient circumstances
poor (14%), the Panel’s recommendation here is based on

the low incidence of this diagnosis,24 and, therefore, limited
-Future Research is unlikely to change confidence
benefit of axial imaging over ultrasound.

Evidence Strength A (High Certainty)
High-Risk.
research is unlikely to change confidence
research is unlikely to change confidence

Moderate Recommendation (Net benefit or harm -Benefits > Risks/Burdens (or vice versa)
-Net benefit (or net harm) is substantial
-Net benefit (or net harm) is moderate
13. Clinicians should perform cystoscopy and axial upper

tract imaging in patients with MH categorized as
high-risk for malignancy. (Strong Recommendation;
Evidence Level: Grade C)
-Benefits[Risks/Burdens
Options for Upper Tract Imaging in High-Risk

Patients:
a. If there are no contraindications to its use, clinicians
should perform multiphasic CT urography (including
imaging of the urothelium). (Moderate Recommenda-
tion; Evidence Level: Grade C)
b. If there are contraindications to multiphasic CT urog-
raphy, clinicians may utilize MR urography. (Moder-
Strong Recommendation (Net benefit or harm
Conditional Recommendation (Net benefit or
ate Recommendation; Evidence Level: Grade C)

c. If there are contraindications to multiphasic CT urogra-
harm comparable to other options)
phy and MR urography, clinicians may utilize retrograde

pyelography in conjunction with non-contrast axial im-
aging or renal ultrasound. (Expert Opinion)
Cystoscopy is a critical component of the work-up of
patients with MH identified as high-risk for malignancy
because of the risk of bladder cancer in this population.
Clinical Principle
Evidence Grade
Expert Opinion
substantial)
The Panel concluded that patients who meet the high-

moderate)
risk criteria are at a sufficient risk for harboring an

upper tract malignancy to also warrant multiphasic cross-
sectional imaging to evaluate both the renal parenchyma
42
Table 3: Urothelial Cancer Risk Factors

Risk Factors Included in AUA Microhematuria Risk Stratification System Additional Urothelial Cancer Risk Factors*
Age Irritative lower urinary tract symptoms

Male sex Prior pelvic radiation therapy
Smoking history Prior cyclophosphamide/ifosfamide chemotherapy
Degree of microhematuria Family history of urothelial cancer or Lynch Syndrome
Persistence of microhematuria Occupational exposures to benzene chemicals or aromatic amines
(e.g., rubber, petrochemicals, dyes)
History of gross hematuria Chronic indwelling foreign body in the urinary tract
* The Panel recognizes that this list is not exhaustive.
and the urothelium, using CT urography if there are no RCC is associated with several genetic syndromes
contraindications to its use. (table 5)45e48 and with a family history of RCC;49 therefore,
In patients with contraindications to contrast-enhanced such patients who have MH should undergo upper tract
CT, such as chronic kidney disease or allergy to iodine- imaging. Insufficient evidence exists regarding the
based contrast, the Panel recommends MR urography. preferred modality in this scenario.
For patients with contraindications to both CT and MR
urography, either non-contrast CT or renal ultrasound may Urinary Markers.
be used to assess the renal cortex with the addition of 17. Clinicians should not use urine cytology or urine-based
retrograde pyelography to assess the upper urinary tracts. tumor markers in the initial evaluation of patients with
MH. (Strong Recommendation; Evidence Level: Grade C)
14. Clinicians should perform white light cystoscopy in
18. Clinicians may obtain urine cytology for patients with
patients undergoing evaluation of the bladder for
persistent MH after a negative workup who have irri-
MH. (Moderate Recommendation; Evidence Level:
tative voiding symptoms or risk factors for carcinoma
Grade C)
in situ. (Expert Opinion)
White light cystoscopy remains the standard for evalua-
The Panel does not recommend using urine cytology or
tion of MH.42 The Panel acknowledges the development of
urine-based tumor markers in the initial evaluation of
enhanced cystoscopic techniques such as blue light cystoscopy
MH because, to date, markers have not demonstrated
to improve bladder cancer detection and resection among
incrementally additive information to cystoscopy in the
patients previously diagnosed with bladder cancer.43,44
MH population, nor have they been found to be of suffi-
Nevertheless, blue light cystoscopy studies to date have been
cient predictive value to obviate cystoscopy.
reported among patients with an established diagnosis of
One area for which cytology may have a role is in
bladder cancer rather than MH cohorts being screened for
improving detection of carcinoma in situ (CIS), which oc-
bladder cancer. As such, the generalizability of this approach
casionally may evade detection by white light cystoscopy.50
to MH patients remains uncertain.
As such, there may be a role for cytology in patients with
15. In patients with persistent or recurrent MH previously
persistent MH in patients who have irritative voiding
evaluated with renal ultrasound, clinicians may
symptoms or other risk factors for CIS.
perform additional imaging of the urinary tract. (Condi-
tional Recommendation; Evidence Level: Grade C) Follow-Up.
The patient with persistent or recurrent MH who has 19. In patients with a negative hematuria evaluation, clini-
undergone prior renal ultrasound represents a clinical cians may obtain a repeat UA within 12 months. (Con-
scenario in which the diagnosis of UTUC is possible, ditional Recommendation; Evidence Level: Grade C)
although admittedly still uncommon. In these cases, cli- 20. For patients with a prior negative hematuria evalua-
nicians may choose to obtain further imaging to include tion and subsequent negative UA, clinicians may dis-
delineation of the urothelium such as CT urography, MR continue further evaluation for MH. (Conditional
urography, or retrograde pyelography. Recommendation; Evidence Level: Grade C)
16. In patients with MH who have a family history of 21. For patients with a prior negative hematuria evalua-
renal cell carcinoma (RCC) or a known genetic renal tion who have persistent or recurrent MH at the
tumor syndrome, clinicians should perform upper time of repeat UA, clinicians should engage in shared
tract imaging regardless of risk category. (Expert decision-making regarding need for additional evalua-
Opinion) tion. (Expert Opinion)
Table 4: AUA Microhematuria Risk Stratification System

High (patient meets any one of
Low (patient meets all criteria) Intermediate (patient meets any one of these criteria) these criteria)
Women age <50 years; Men age <40 years Women age 50-59 years; Men age 40-59 years Women or Men age 60 years
Never smoker or <10 pack years 10-30 pack years >30 pack years
3-10 RBC/HPF on a single urinalysis 11-25 RBC/HPF on a single urinalysis >25 RBC/HPF on a single urinalysis
No risk factors for urothelial cancer (see Table 3) Low-risk patient with no prior evaluation and 3-10 RBC/HPF History of gross hematuria
on repeat urinalysis
Additional risk factors for urothelial cancer (see Table 3)
43
Table 5: Known Genetic Renal Tumor Syndromes* Disclaimer: This document was written by the
Known genetic renal tumor syndrome Microhematuria Guideline Panel of the American
Urological Association Education and Research, Inc.,
1. von Hippel-Lindau
2. Birt-Hogg-Dube which was created in 2018. The Practice Guidelines
3. Hereditary Papillary Renal Cell Cancer Committee (PGC) of the AUA selected the committee
4. Hereditary Leiomyomatosis Renal Cell Cancer chair. Panel members were selected by the chair.
5. Tuberous sclerosis
Membership of the Panel included specialists in
* The Panel recognizes that this list is not exhaustive. urology, gynecology, and primary care with specific
expertise on this disorder. The mission of the panel
was to develop recommendations that are analysis
22. For patients with a prior negative hematuria evalua-
based or consensus-based, depending on panel pro-
tion who develop gross hematuria, significant increase
in degree of MH, or new urologic symptoms, clinicians cesses and available data, for optimal clinical prac-
should initiate further evaluation. (Moderate Recom- tices in the evaluation of microhematuria. Funding of
mendation; Evidence Level: Grade C) the panel was provided by the AUA. Panel members
The intensity of follow-up after completion of a negative received no remuneration for their work. Each
hematuria evaluation must balance the small risk of a member of the panel provides an ongoing conflict of
false-negative initial evaluation with the anxiety, cost, interest disclosure to the AUA, and the Panel Chair,
inconvenience, and risks of ongoing monitoring and repeat with the support of AUA Guidelines staff and the
investigation. PGC, reviews all disclosures and addresses any po-
The very limited diagnostic yield of repeated evalua- tential conflicts per AUA’s Principles, Policies and
tions noted to date from studies of patients followed after
Procedures for Managing Conflicts of Interest. While
a negative hematuria evaluation must be recognized.
these guidelines do not necessarily establish the
However, the Panel recognizes that select patients may
benefit from and/or request follow-up after a negative standard of care, AUA seeks to recommend and to
hematuria evaluation, or after a negative follow-up UA in encourage compliance by practitioners with current
a low-risk patient who has not been evaluated. A repeat best practices related to the condition being treated.
UA represents an initial, non-invasive modality for As medical knowledge expands and technology ad-
continued monitoring. Patients with a negative follow-up vances, the guidelines will change. Today these
UA may be discharged from further hematuria evaluation evidence-based guidelines statements represent not
given the very low risk of malignancy, while patients with absolute mandates but provisional proposals for
persistent MH merit shared decision-making regarding treatment under the specific conditions described in
next steps in care. Importantly, changes in a patient’s each document. For all these reasons, the guidelines
clinical status, particularly the development of gross he-
do not pre-empt physician judgment in individual
maturia, should prompt clinical review.
cases. Treating physicians must take into account
variations in resources, and patient tolerances,
FUTURE DIRECTIONS needs, and preferences. Conformance with any clin-
The goal of this guideline is to improve the evaluation ical guideline does not guarantee a successful
and management of patients with hematuria. Due to outcome. The guideline text may include information
the combination of a relatively high prevalence of MH or recommendations about certain drug uses (‘off
in the adult population with a low prevalence of label’) that are not approved by the Food and Drug
clinically-significant disease, this guideline aims to Administration (FDA), or about medications or sub-
provide a risk-based framework for testing. Moreover, stances not subject to the FDA approval process.
it is recognized that, in the current state, many pa- AUA urges strict compliance with all government
tients with hematuria do not undergo evaluation. regulations and protocols for prescription and use of
Accordingly, an important goal of risk-based recom- these substances. The physician is encouraged to
mendations is to provide guidance for patients and carefully follow all available prescribing information
clinicians regarding appropriate evaluation. Neverthe- about indications, contraindications, precautions and
less, the Panel recognizes the paucity of high-level warnings. These guidelines and best practice state-
supporting evidence for the guideline statements and ments are not intended to provide legal advice about
acknowledges several notable areas where gaps in use and misuse of these substances. Although
knowledge exist. These represent opportunities for guidelines are intended to encourage best practices
future investigation to meaningfully enhance care. and potentially encompass available technologies
Such areas include the use of new automated in- with sufficient data as of close of the literature re-
struments for UA, validation of risk groups, utility of view, they are necessarily time-limited. Guidelines
urinary biomarkers and enhanced cystoscopy for MH, cannot include evaluation of all data on emerging
refinement of imaging techniques to reduce radiation technologies or management, including those that
exposure, and further investigation of the natural his- are FDA-approved, which may immediately come to
tory of patients with MH following negative evaluation. represent accepted clinical practices. For this reason,
44
the AUA does not regard technologies or manage- Inc., American College of Physicians, American
ment which are too new to be addressed by Urological Association; Andrew Peterson, BSCI:
this guideline as necessarily experimental or American Medical Systems, Inc.; Jay Raman, Uro-
investigational. gen Pharma. Meeting Participant or Lecturer:
Tracy Downs, Photocure; Cary Gross, Flatiron, Inc.
CONFLICT OF INTEREST DISCLOSURES Scientific Study or Trial: Stephen Boorjian, SUO-
All panel members completed COI disclosures. CTC Organized Trial; Cary Gross, NCCN/Pfizer,
Disclosures listed include both topic- and non-topic- NCCN/Astra Zeneca; Yair Lotan, Cepheid, Pacific
related relationships. Panel members not listed Edge, FKD, MDxHealth, Anchiano, GenomeDx
below have nothing to disclose. Consultant/Advisor: Biosciences, Inc.; Andrew Peterson, Movember
Ronald Alvarez, Abbvie, Esai, Genentech, Unleash, Foundation; Jay Raman, MDx Health, Pacific Edge
Vaccitech; Stephen Boorjian, ArTara, Ferring, Biotechnologies. Investment Interest: Blake Ham-
Sanofi; Blake Hamilton, NextMed, Inc., Dornier ilton, StreamDx; Jay Raman, American Kidney
MedTech, Ambu; Kathleen Kobashi, Allergan, Stone Management, United Medical Systems, Inc.
Medtronic, Contura; Yair Lotan, Photocure, Astra Leadership Position: Yair Lotan, Vessi Medical.
Zeneca, Nucleix, Merck, Engene, Zymo Research, Other: Cary Gross, Johnson & Johnson; Yair Lotan,
CAPs Medical; Matthew Nielsen, Grand Rounds, Urogen, Synergo.
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46

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2021 GDFM Tutorial 6 -- TRAINEES

2021 GDFM Tutorial 6 -- TRAINEES

2021 GDFM Tutorial 6 -- TRAINEES

Free T4 34pmol/L (10.3- 31.0)

2021 GDFM Tutorial 6 -- TRAINEES

Physical examination reveals:-

2021 GDFM Tutorial 6 -- TRAINEES

He has no past medical history of note. He does not exercise. He smokes 20

The urinalysis results:

2021 GDFM Tutorial 6 -- TRAINEES

2021 GDFM Tutorial 6 -- TRAINEES

INTRODUCTION history, perform a thorough physical examination,

Dermatol Clin 38 (2020) 329–338

Feature ICD ACD

Ointments and barrier creams diagnosis is made, identification of the hazard so

currently only approved by the US Food and Drug DISABILITY

10-minute consultation BMJ 2007

Occupational dermatitis in a hairdresser PMID: 1771371

Allison Worth,1 S Hasan Arshad,2 Aziz Sheikh1

What you should do Treatment

Disponible en ligne sur

Klotz communications 2021: Heart and Hormones

“Is there any reason to treat subclinical hypo and hyperthyroidism?”

hypothyroidism. disorders, it is better to go ‘low and slow’, – Subtotal thyroidectomy

Patient is diagnosed with subclinical hypothyroidism due to Hashimoto’s thyroiditis

Table 1. Common causes of thyrotoxicosis and main diagnostic features

Table 2. Advantages and disadvantages of Graves’ disease treatment options

Treatment Advantages Disadvantages

Radioiodine • Permanent resolution of hyperthyroidism • Permanent hypothyroidism in most cases

Thyroidectomy • Rapid, permanent resolution of hyperthyroidism • Permanent hypothyroidism

symptoms.18 Weight loss is a common Radioiodine is generally the preferred Conclusion

Prevalence of erectile dysfunction (%)

heart failure, and cardiac arrhythmias compared with 16

hyperlipidemia, or a family history of myocardial infarc-

Related condition Approach to evaluation

Information from references 9 through 12.

Treatment of other agents are expected to be available in 2017 to 2019.

LIFESTYLE MODIFICATIONS SURGICAL AND PROCEDURAL THERAPY

adverse effects also last longer. Vardenafil is

Tadalafil (Cialis) 10 or 20 mg once daily as needed 30 minutes 17.5 hours NA ($525)

history can elicit potential causes such as

eTable A. Diagnostic Criteria for Metabolic Syndrome

Clinical measure Criteria*

Blood pressure† Systolic ≥ 130 mm Hg or diastolic ≥ 85 mm Hg

eFigure A. Coloplast Alpha-1 inflatable penile prosthesis.

Microhematuria: AUA/SUFU Guideline

Purpose: Patients presenting with microhematuria represent a heterogeneous

Key Words: hematuria, cystoscopy, CT Urogram, bladder cancer, urothelial

HEMATURIA is one of the most common The differential diagnosis of MH

been found to be highly dependent on factors such as Determination of Evidence Strength

Patients on anticoagulants should be assessed in the non-malignant genitourinary cause. If MH persists or

Table 1: Strength of Evidence Definitions

upper tract imaging in accordance with

-Applies to most patients in most circumstances but better

-Net benefit (or net harm) comparable to other options

-Balance between Benefits & Risks/Burdens unclear

-Alternative strategies may be equally reasonable

-Net benefit (or net harm) appears substantial

-Net benefit (or net harm) appears moderate

-Better evidence likely to change confidence