Thyroid Function tests

Dr Danielle B Freedman
please see January 2015 PULSE p 50 - 51

April 2018
 Incidence of Thyroid disease
Hypothyroidism
Spontaneous 2%, 10 Females : 1 Male
Another 1% due to destructive treatment for
Hyperthyroidism

Congenital Hypothyroidism 1/4000 births

Hyperthyroidism
 0.5 – 2%, 10 Females :1 Male
 Important Clinical Manifestations

Hyperthyroidism
•5-10% of patients with thyrotoxicosis have Atrial
Fibrillation
•Correctable cause of osteoporosis
•Associated with menstrual irregularity, subfertility and
foetal loss

Hypothyroidism
•Well recognised secondary cause of hyperlipidaemia
•Associated with menstrual irregularity, subfertility and
foetal loss
 Causes of Hyperthyroidism
• Grave’s disease
• Account for
Toxic Mutinodular goitre
>90% cases
• Solitary toxic adenoma
• Thyroiditis
• Exogenous iodine and iodine-containing drugs eg
amiodarone
• Excessive T4 or T3 ingestion
• Ectopic thyroid tissue, eg struma ovarii, functioning
metastatic thryoid cancer
• hCG dependent: choriocarcinoma
• TSH dependent: pituitary tumour
 Causes of hypothyroidism
• Atrophic hypothyroidism (may
represent the end-stage of
Hashimoto’s disease)
• Automimmune hypothyroidism
Account for
(Hashimoto’s thyroiditis) >90% cases
• Post-surgery, radioactive iodine,
anti-thyroid drugs (eg carbimazole)
and other agents (eg lithium)
• Congenital
• Dyshormonogenic
• Secondary (pituitary or hypothalamic disease)
• Iodine deficiency
 Drugs and thyroid disease

Amiodarone
•Hyperthyroidism (iodine deficient) 10%
•Hypothyroidism (iodine replete) 20%

Lithium
•Hypothyroidism: Mild 34%
Overt 15%

Monitoring for patients taking either drug

•6 monthly TFT’s
•12 monthly review
 Patients on Levothyroxine
• Annual measurement TSH (+FT4)
• Starting dose 50 mcg
• Check TFT’s 6-8 weeks after commencing treatment and
following change of dose
• Dose increment 25 mcg
• Average dose 1.6 mcg/kg
• Caution with elderly patients – start @25mcg

In pregnancy
• Increase dose by 50 mcg
• Measure TFT’s each trimester
• TSH should be 1.0- 2.5 mU/L
 Patients on Carbimazole
• If patient toxic refer to Endocrine clinic /start
Cz 20mg bd, ? Beta blockers
• TFTs checked every 4 – 6 weeks
• Once stable ,every 2 – 3 months
• Other investigations, anti-TPO abs and US
• Duration, 18 months – 2 years
 Thyroid disorders in
pregnancy and the post
partum period
 Introduction
• 4% of pregnant women:
o Have a history of thyroid disease
o Develop thyroid disease during pregnancy
o 1st time develop thyroid disease within 5 years following pregnancy

• Beware ‘Gestational transient thyrotoxicosis’- hCG induced

hyperthryoidism – TSH receptor sensitivity to (appropriately) high hCG
concentrations

• Remember the reference range for Free T4 and Free T3 decreases approx
20% in the 2nd and 3rd trimesters

• During pregnancy TSH can be up to 50% lower in the 1st trimester and
within the non-pregnant reference range in the 2nd and 3rd trimesters,
while Free T4 can be up to 20% lower in the 2nd and 3rd trimesters and
within the non-pregnant reference range in the 1st trimester based on
current scientific evidence.

ATA & AACE do NOT recommend universal screening for

thyroid function in pregnancy
 Hypothyroidism in pregnancy
• 2-3% of iodine-sufficient pregnant women will have
undiagnosed hypothyroidism – mostly subclinical

• Main cause in iodine sufficient is chronic autoimmune

thyroiditis

• 10-20% of women of child bearing age have positive anti-TPO

antibodies

• Untreated overt hypothyroidism is associated with:

o Increased risk of miscarriage
o Preterm delivery
o PET
o Neonatal mortality
o Low birth weight
o Decreased IQ
 Treatment and monitoring in pregnancy
• ATA recommend diagnosis of hypothryoidism in all pregnant
women with; - a TSH > reference interval and a low FT4
- All with TSH > 10mU/L irrespective of FT4

• In women with subclinical hypothryoidism who are not initially

treated; ATA recommends monitoring FT4 and TSH every 4
weeks until 16-20/40 and once between 26/40 - 32/40 weeks
gestation

• Dosage of levothyroxine will go up during pregnancy ( 30-50%)

• Aim for TSH 1.0 – 2.5 mU/L, monitor TSH as above

• Post partum revert back to original dosage and check TFT’s 6

weeks post partum
 Thyrotoxicosis in pregnancy
• Grave’s disease occurs in 0.1-1% of all pregnancies

• Transient gestational hyperthyroidism can occur in the 1st

trimester (prevalence 2-3 %)

• In patients with Grave’s:

 Monitor TFT’s every 4-6 weeks
 TRAb at 24 weeks – can cross the placenta and cause foetal
and neontal hyperthryoidism (<1%)

• Uncontrolled Grave’s:
o Foetal loss
o PET
o Miscarriage
o Premature labour
o CCF
o Thyroid storm
 Treatment of thyrotoxicosis in pregnancy
• 1st trimester PTU
• 2nd and 3rd trimester PTU/CBZ
• Block replacement and I131: CONTRAINDICATED

• Aim to keep: FT4 in within or slightly above reference range

TSH within the reference range
• 30-40% of women are able to remain euthyroid without
treatment in the last few weeks of pregnancy

• Can relapse post partum

• Breast-feeding is ok if the dose of

PTU < 300mg/day
CBZ < 30 mg/day
 Post partum thyroiditis
• May be difficult to distinguish from Grave’s

• 4-9% of women develop post partum thyroiditis

• Positive Anti-TPO antibodies (which rise in titre 6 weeks PP)

• Can be transiently hyperthyroid (unless Grave’s) – do not treat with

antithyroid drugs

• Can become transiently hypothryoid or permanent (20 - 30%)

• If ‘transient’ check TFT’s annually – can recur with subsequent

pregnancy
Development of thyroid dysfunction in the
postpartum period
Adapted from the ACB/RCPath
‘Minimum Retesting Intervals’
2016
 Clinical
Recommendation
situation

Hyperthyroid- TFTs should be performed every 4–6 weeks

monitoring after commencing thioamides. Testing at 3
CBZ/PTU month intervals is recommended once
treatment maintenance dose achieved.

Hyperthyroid Assess TSH and fT4 at 4–6 week intervals, then

monitoring after a further 3 months once maintenance
‘block and dose achieved, and then 6 monthly thereafter
replace’
 Clinical
Recommendation
situation
Follow-up in first 1–2 months after radioactive iodine
Hyperthyroid treatment for Graves’ should include fT4 and TSH. If patient
- monitoring remains thyrotoxic then biochemical monitoring to
of treatment continue at 4–6 week intervals
in Graves’ Following thyroidectomy for Graves’ disease (and
disease commencement of levothyroxine), serum TSH to be
measured 6–8 weeks post-op
Hyperthyroid Follow-up in first 1–2 months after radioactive iodine
- monitoring treatment for toxic multinodular goitre and toxic adenoma
of treatment should include fT4 and TSH. Should be repeated at 1–2
in toxic month intervals until stable results, and then annually
multinodular thereafter. Following surgery for toxic multinodular goitre
goitre and and start of thyroxine therapy, TSH should be measured 1–
toxic 2 monthly until stable and annually thereafter. Following
adenoma surgery for toxic adenoma TSH and fT4 concentrations
should be measured 4–6 weeks post-op.
 Clinical
Recommendation
situation
The minimum period to achieve stable
concentrations after a change of dose of thyroxine
is 2 months and TFTs should not normally be
assessed before this period has elapsed.
Hypothyroidism
- monitoring Patients stabilised on long-term thyroxine therapy
treatment should have serum TSH checked annually.

An annual fT4 should be performed in all patients

with secondary hypothyroidism stabilised on
thyroxine therapy.
Clinical situation Recommendation

Patients with subclinical hypothyroidism should have the

pattern confirmed within 3–6 months to exclude
transient causes of elevated TSH. Subjects with
Monitoring adult
subclinical hypothyroidism who are Anti-TPO-Ab positive
sub-clinical
should have TSH and fT4 checked annually. Subjects with
hypothyroidism
subclinical hypothyroidism who are Anti-TPO-Ab negative
should have TSH and fT4 checked every 3 years.

If a serum TSH below ref range but >0.1 mU/L is found,

Monitoring Adult
then the measurement should be repeated 1–2 months
sub-clinical
later along with fT4 and fT3 after excluding non-thyroidal
hyperthyroidism
illness and drug interferences.
Clinical situation Recommendation

Secondary Care TSH and fT4 should be measured as dose of

levothyroxine increased (every 6 weeks) until
Follow up of the serum TSH is <0.1 mIU/L. Thereafter annually
patients who unless clinically indicated/pregnant.
have had
differentiated Samples for thyroglobulin (Tg) should not be
(papillary and collected sooner than 6 weeks post-
follicular) thyroid thyroidectomy or 131I ablation/therapy. TSH,
carcinoma and a fT4/fT3 (whichever is being supplemented) and
total Tg autoantibodies (TgAb) should be requested
thyroidectomy when Tg is measured. If TgAb are detectable,
and 131I ablation measurement should be repeated every 6
months.
 1
• 58 year old male with strong FHx of CHD. Non-
smoker with BMI = 26.5.
– Fasting glu = 4.6 mmol/L
– Chol = 8.4 mmol/L
– HDL = 1.1 mmol/L
– Trig = 2.1 mmol/L

• 1/52 – complaining of malaise

• CK = 850 U/L [<170]
What test(s) are required to investigate the
raised CK ?
a. Magnesium
b. FBC
c. TFT’s
d. HbA1c
e. U+E
a. TFT
 2.
• Which one of the following findings in a
patient with primary hypothyroidism could
not be explained by this condition ?
• a). Hyponatraemia
• b). Increased mean red cell volume
• c). Plasma cholesterol of 7.2 mmol/L
• d). Plasma ALP 2x the ULN
• e). Plasma CK 2x the ULN
• d). Plasma ALP 2x the ULN
 3.
25-year-old female with menorrhagia
FT4 = 11.5 pmol/L [10 – 20]
TSH = 8.3 mu/L [0.4 – 4.5]
What do you do next?

a. Repeat in 3 months
b. Measure serum anti-TPo abs
c. Treat with levothyroxine
d. Measure 9 am Cortisol
 Answer
a. Repeat in 3 months
b. Anti TPO abs
 4.
Mr DW Home visit
dob 20/8/41
LVF
A fibrillation
PMH CABG 1989
Angioplasty 2004
MI – 1998
Hypertension
Hypercholesterolaemia
Type 2 DM
DH Frusemide
Clopidogrel
Nicorandil
Amiodarone
Simvastatin
Ezetimibe
Warfarin
Ramipril
Bisoprolol
Allergies None
SH Ex smoker
Occasional alcohol
Lives with wife
FH none
O/E p = 130 AF
bp = 143/76
chest basal crackles
JVP  5 cm
No ankle oedema
HS I and II and 0
U = 10.7 mmol/l [2.5 – 6.5]
Cr = 124 mmol/l [60 – 120]
Na = 131 mmol/l
K = 3.6 mmol/l

FT4 = 100.2 pmol/l [12 – 23]

TSH = <0.06 mu/l [0.35 – 5.5]
 Question In addition to treating his AF and LVF, how do
you think the patient’s deranged thyroid function should be
treated? interactive

a. Do nothing
b. Stop Amiodarone
c. Start Propylthiouracil
d. Treat with radioactive iodine
 Answer
b. Stop Amiodarone
c. PTU
 5.
• 81 yr old female just discharged from hospital
with diagnosis of pneumonia.

• FT4 = 9 pmol/l (10-20)

• TSH = 0.10 mu/l (0.4-4.5)
• FT3 = 1.8 pmol/l (3.0-8.0)
 What would you do next ?
• a) Nothing

• b) Treat with carbimazole

• c) Treat with levothyroxine

• d) repeat TFTs in 4 weeks

 6.
• 45 yr old female on 125mcg levothyroxine
c/o TAT

• FT4 = 13pmol/l ( 12-23)

• TSH = 4.3 mu/l ( 0.35 – 5.5 )

• What would you do?

• a) Nothing
• b) reduce T4 to 100mcg
• c) Increase T4 to 150mcg
• d) rpt TFTs in 2 months
 7.
• 65-year old man
• c/o TATT, muscle aches, loss of libido
• DH nil

Sodium 137 mmol/L

Potassium 4.2 mmol/L
Creatinine 76 umol/L
eGFR >60 ml/min/1.73m2
TSH 1.32 mU/L
Testosterone 0.5 nmol/L
Creatine Kinase 223 U/L
Hb 138 g/L
 Free T4 5.5 pmol/L

Duty Biochemist added:

•Cortisol 52 nmol/L
• LH 1.2 U/L
• FSH 0.8 U/L

Diagnosis?
What most determines a clinician’s test
ordering?

1. Fear of litigation
2. Cost of test
3. Evidence based guidelines
4. Patient went to Lab Tests Online
5. Watched an episode of ‘House’ last night
ACB SPOTLIGHT MEETING
 Analysis of malpractice claims – US
Ann Intern Med 2006; 145: 488-496
Faulty process leading to missed diagnosis:

• Failure to order appropriate dx /lab test 55%

• Inappropriate/inadequate follow-up 45%
• Failure to obtain adequate history/exam 42%
• Incorrect interpretation of diag. test 37%
• Failure to refer 26%
• Provider did not receive test results 13%
• Tests ordered but not done 9%
• Tests performed incorrectly 8%
 Patient Safety and Laboratory Medicine
Pre Analytical right test
right patient
right label
‘request form’
right sample

Analytical right lab

EQA right conditions -
Accreditation (CPA) temperature

Post Analytical right result

right patient
right clinician
right communication
right interpretation
right Mx and further investigations
 How much is spent in the US on unnecessary testing and
procedures

a. $ 1.5 billion
b. $ 3.0 billion
c. $ 6.8 billion
d. $ 18.0 billion

17.4 % of US GDP was spent on health care in 2009

$65 billion per annum on > 4.3 billion laboratory tests

50
 Some Causes of Overutilization

•Patient pressure
•Duplicate requesting
•Lack of understanding of the diagnostic value of a test
•“just in case”
•Ordering ‘wrong’ test
•Failure to understand the consequences of overutiliz’n

•Defensive testing
•Perverse financial incentives (more tests = more £ )
•“Availability creates demand “
• Laboratory investigations £2.5 billion / year
• Approximately 4% of total NHS expenditure
• Annual increase in workload 8-10%
• 25% of pathology tests unnecessary
• Department of Health Independent Review of Pathology
Services 2009
• BUT same amount of under requesting?
• 30% “Consensus” estimate AACC Webinar 26th
Oct 2010
• ”
Which points in the
process have the highest
incidence of errors?

Test selection by clinicians?

Interpretation of test results by
clinicians?
Yes
Laposata,2008
 Types and frequency of errors in the different
phases of the TTP
Phase of the TTP Relative
Frequency (%)

Pre-pre-analytic 46 – 68.2

Wrong test choice accounts for up to 50 – 60% of missed /

delayed diagnoses
Approx 30% of total laboratory medicine errors have direct impact
on patient care, and 2.7%-12% cause an adverse event.

Plebani Ann Clin Biochem 2010,47:101-110

UK junior hospital doctors:
“How confident are you in requesting
laboratory tests?”

(Khromova & Gray, 2008)56

How confident are you in interpreting laboratory
tests?

LFT

U&E

Proteins
Mg, PO4

Haematinics
PTH

Short Synacthen Test

Urine sodium and osmolality

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Confident Usually Confident Not Confident

 Questions Answer Options Correct %
Oxford ,2010 Answer
Correct
1. Which of the following blood O Rh positive
groups would it be unsafe to
transfer to a man of blood
77
O Rh negative
group O Rhesus positive? A Rh positive

A Rh positive
2. In a patient on Warfarin in 3
whom there is no, or only 5
minor bleeding, at what INR 36
7 8
would you consider
administering Vitamin K? 8
10
3. The following test result A low serum iron
would confirm a diagnosis of
iron deficiency:
Both a low serum A low serum
iron and low ferritin 61
transferrin
A low serum ferritin
Strategies for Changing Physician
Behaviour in Ordering Lab Tests

• Bandolier Review of 49 articles between 1966 and

1998
• Strategies that don’t work by themselves
• Physician consensus building
• Test guideline dissemination
• Traditional education
• Utilisation audits
• Inform physicians of lab test charges
Published:
J Clin Path
B M JMJ
 National Minimum Re-testing Interval Project 2013:
A final report detailing consensus recommendations for
minimum re-testing intervals for use in Clinical Biochemistry

Box 1 Minimum Re-testing Interval Work Streams

Renal
Liver and Bone
Endocrine
Lipids and Diabetes
Specific Proteins
Cardiac
Tumour Markers
Gastro-Intestinal The Association for
Occupational/Toxicology Clinical Biochemistry
Therapeutic Drug Monitoring
Pregnancy and Paediatrics
 Unnecessary testing
• Australia – Vit D requests increased by 4,600 % from
2002/3 to 2011/12 !!

• 73,000 requests pa to 3.5million requests pa

Vasikaran,Ann Clin Biochem 2013: 50: 283-4

Ordering by clinical condition with defined options for primary care reduce
inappropriate tests and reduce variation in practice.
 Tests linked to diagnostic algorithms at time of order promote appropriate
investigations, ensure adequate investigation and improve compliance with
care pathways.
Need to minimize variation in test ordering

• Guidelines, education and audit

• Use of Formularies
• Electronic order systems (CPOE)
• Diagnostic algorithms
• Minimum retesting intervals
• Request vetting and restrictions
• Feedback to users – activity data and costs
• Multiple interventions
• MUST stay in place otherwise behaviour will drift back
to the unwanted condition
‘Better do a few lab tests…’

‘I could give you a copy of

your lab report but…

…I doubt you’d understand

it.’
Language confusing
FBC
LFT
TFT
IgE
 Why do I need this blood test?

What does this laboratory result mean?

www.labtestsonline.org.uk

“Laboratory medicine empowering patients”

Peer-reviewed - Practicing laboratory doctors and
scientists

Non-
commercial

Patient - Language that’s easy to understand

centered - Access for all
 Lab Tests Online-UK provides:
• Detailed descriptions of 302 laboratory tests

• Descriptions of 114 conditions and diseases,

cross-referenced to the relevant tests

• News on advances in laboratory testing

• Links to other relevant and useful websites that

can help answer any further questions
www.labtestsonline.org.uk
 Top ten tests
UE ESR Platelet
LFT Count
CRP

Calprotectin
RBC Thyroid
function D-dimer GGT
tests
Lab Tests Online-UK monthly stats
www.labtestsonline.org.uk

240,050 UK website hits per

month 2017
App downloads reached 23,294
by Dec 2017
Annual visitors > three million
 Links to Lab Tests Online-UK
(existing or working towards)

Websites: • NHS Choices •

UCLH OCS project
• Microtest • Many More!!
• DrDoctor
• Welsh specialist virology unit
• Choosing Wisely UK
• TPP(System • InPS
GP systems:
One) • i-Patient
• HealthFabric • OMNI lab
• iSOFT • Manage your
health
 Some comments from users 2016/17
• Nicely presented and well written. A good
educational resource for a retired GP
• As a nurse just starting to learn how to interpret
blood tests ..the site is amazing…love it. Thank
you.
• Very helpful to be able to see differences between
one test and another. I am noting INR kidney
filtration rate potassium and blood sugar levels.
Thanks for info.
• Excellent and easy to understand
• Loved the sumple explanations of what the test
means, what it measures and what it can be used to
indicate eg high ESR and inflammation
• Brilliant & reliable. The mobile app is excellent, too.
Volume: 53 issue: 6, page(s): 669-679
Article first published online: March 24, 2016;Issue published: November 1, 2016
DOI: https://doi.org/10.1177/0004563216631774
 Who uses the Lab Tests Online-UK
website?
• Patients, their carers and health care professionals

In our 2014 survey (661 responders):

• 40% of respondents were healthcare
professionals
• 60% were patients or carers
 2014 Survey results
Patients and carers
• 71% found what they were looking for when
visiting the website

• 71% found the information was written at the

right level for them

• 93% found the information very easy or fairly

easy to understand

• 87% understood their test/diagnosis/condition

better after visiting our website
Q3. Which of these best describes your reason
for visiting Lab Tests Online-UK?
Q 13. Which of these best describes what you are looking
for today on this website?

• I have been told my white blood count is low

• Doctors lack of time/complacency etc
• Trying to understand what raised white blood cells means
• My wife desires to know what poisoned her. Current doctors
are monitoring her recovery but are not finding the source
 Q16. You stated that you did not find what you were
looking for on the website (11%)
Please could you state what was missing on the site
• I’m suffering from joint pain in my hands and feet and was
wondering if this would be a consequence of taking statins over
a period of years
• Wanted to find test results online
• Why I have high plate count
• What is a normal cholesterol
• I am suffering from a sewage leak over a year and want to test
for ammonia inhalation if possible (local water board not
repairing) and possibly other V.O.C.s Also any precautions or
cures I need to take.
• Home testing for mercury
• Was looking to find out if HRT for menopause safe to take after
radioiodine
• Testosterone cream for women
 Q23. Only 4% would NOT like to see their laboratory
test results, at the same time as their doctor/nurse

Please may we ask why you do not want to view your

laboratory results

• They know how to interpret them, I’d just worry

• I wouldn’t know what I’m looking at and it would probably make
patient feel they know better than their GPs who are the
experts
• Doctor can interpret the results, I can’t
• Would not understand them. The consultant provides me with
a copy of his letter to my GP. I therefore have info for
discussion with GP
• it's v good
• Excellent, doesn't need improvement
• Very good and informative web site
• love it
• it is better If you are able to add drugs information relevant to
the specific conditions if drugs are involved with the condition.
 Summary / Key Findings
• 661 users responded but not all surveys were completed
• Liked / Loved website – right level of information / very useful
• Patients WANT to see their lab results and want to
know what they mean
• Professionals like the information – right level
• Large number of users from outside the UK [Asia and America]
• Editorial comments: cluttered front page / font size
• Users unaware LTOL - UK Team are working voluntarily
• App rated 4.35/5
William Osler
(adapted)

Laboratories are … to the GP as the knife and

scalpel are to the surgeon.