ORIGINAL

ARTICLE

E n d o c r i n e

C a r e

A 2013 Survey of Clinical Practice Patterns in the

Management of Primary Hypothyroidism
Henry B. Burch, Kenneth D. Burman, David S. Cooper, and James V. Hennessey
Endocrinology Division (H.B.B.), Walter Reed National Military Medical Center, Bethesda, Maryland 20889, and
Uniformed Services University of Health Sciences, Bethesda, Maryland 20814; Endocrinology Section (K.D.B.),
Washington Hospital Center, Washington, DC 20010; Georgetown University Medical Center (K.D.B.),
Washington, DC 20007; Division of Endocrinology (D.S.C.), The Johns Hopkins University School of Medicine,
Baltimore, Maryland 21205; Division of Endocrinology (J.V.H.), Beth Israel Deaconess Medical Center, Boston,
Massachusetts 02215; and Harvard Medical School (J.V.H.), Boston, Massachusetts 02115
Context: In 2012, comprehensive clinical practice guidelines (CPGs) were published regarding the
management of hypothyroidism.
Objective: We sought to document current practices in the management of primary hypothyroidism and compare these results with recommendations made in the 2012 American Thyroid Association (ATA)/American Association of Clinical Endocrinologists (AACE) hypothyroidism CPGs. In
addition, we sought to examine differences in management among international members of
U.S.-based endocrine societies and to compare survey results with those obtained from a survey of
ATA members performed 12 years earlier.
Methods: Clinical members of The Endocrine Society (TES), the ATA, and the AACE were asked to take a
web-based survey consisting of 30 questions dealing with testing, treatment, and modulating factors in the
management of primary hypothyroidism.
Results: In total, 880 respondents completed the survey, including 618 members of TES, 582 AACE members,
and 208 ATA members. North American respondents accounted for 67.6%, Latin American 9.7%, European
9.2%, Asia and Oceania 8.1%, and Africa and Middle East 5.5%. Overt hypothyroidism would be treated using
L-T4 alone by 99.2% of respondents; 0.8% would use combination L-T4 and liothyronine (L-T3) therapy. Generic
L-T4 would be used by 49.3% and a brand name by 49.9%. The rate of replacement would be gradual (38.5%);
an empiric dose, adjusted to achieve target (33.6%); or a calculated full replacement dose (27.8%). A target
TSH of 1.0 to 1.9 mU/L was favored in the index case, but 3.0 to 3.9 mU/L was the most commonly selected TSH
target for an octogenarian. Persistent hypothyroid symptoms despite achieving a target TSH would prompt
testing for other causes by 84.3% of respondents, a referral to primary care by 11.3%, and a change to L-T4
plus L-T3 therapy by 3.6%. Evaluation of persistent symptoms would include measurement of T3 levels by
21.9% of respondents. Subclinical disease with a TSH 5.0 to 10.0 mU/L would be treated without further
justification by 21.3% of respondents, or in the presence of positive thyroid peroxidase antibodies (62.3%),
hypothyroid symptoms (60.9%), high low-density lipoprotein (52.9%), or goiter (46.6%). The TSH target for
a newly pregnant patient was 2.5 mU/L for 96.1% of respondents, with 63.5% preferring a TSH target 1.5
mU/L. Thyroid hormone levels would be checked every 4 weeks during pregnancy by 67.7% and every 8 weeks
by an additional 21.4%. A hypothyroid patient with TSH of 0.5 mU/L who becomes pregnant would receive
an immediate L-T4 dose increase by only 36.9% of respondents.

Conclusion: The current survey of clinical endocrinologists catalogs current practice patterns in the management
of hypothyroidism and demonstrates 1) a nearly exclusive preference for L-T4 alone as initial therapy, 2) the widespread use of age-specific TSH targets for replacement therapy, 3) a low threshold for treating mild thyroid failure,
4) meticulous attention to TSH targets in the pregnant and prepregnant woman, and 5) a highly variable approach
to both the rate and means of restoring euthyroidism for overt disease. Both alignment and focal divergence from
recent CPGs are demonstrated. (J Clin Endocrinol Metab 99: 20772085, 2014)

ISSN Print 0021-972X ISSN Online 1945-7197

Printed in U.S.A.
Copyright 2014 by the Endocrine Society
Received January 7, 2014. Accepted February 6, 2014.
First Published Online February 14, 2014

doi: 10.1210/jc.2014-1046

Abbreviations: Ab, antibody; CPG, clinical practice guideline; TPO, thyroid peroxidase.

J Clin Endocrinol Metab, June 2014, 99(6):20772085

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2078

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Hypothyroidism Management Survey

evothyroxine therapy (L-T4) results in a resolution of

signs and symptoms in most patients with overt hypothyroidism. Still, a number of controversies remain, including 1) the treatment threshold in patients with mild or
subclinical disease (1, 2), 2) the need for age-specific targets for serum TSH levels (35), 3) whether administration
of L-T4 alone provides adequate tissue-level triiodothyronine (T3) levels (6, 7); 4) optimal control of thyroid function during pregnancy (8, 9); and 5) screening indications
for the detection of hypothyroidism in the general population and in women planning pregnancy (10, 11).
In 2012, a joint task force of the American Association
of Clinical Endocrinologists (AACE) and American Thyroid Association(ATA) published clinical practice guidelines (CPGs) dealing with diagnostic evaluation and treatment strategies for adults with hypothyroidism (1).
Clinicians were encouraged to use the 52 recommendations contained in those guidelines in conjunction with
their own clinical judgment and within the context of individual patient circumstances. It is not clear to what extent current practices differ from recommendations made
in the 2012 AACE/ATA hypothyroidism CPG, because
the only existing survey of clinical management practices
for patients with hypothyroidism was published more
than a decade ago (12).
The objectives of the current study were 1) to document
current practices in the management of primary hypothyroidism; 2) to evaluate management modifications in unique

Table 1.

R22.1
R22.2
R22.4
R22.7.2
R25.1
R25.3
R27
R28
R29

clinical circumstances such as subclinical hypothyroidism,

pregnancy, and old age; 3) to compare current practice with
that recommended in the 2012 AACE/ATA hypothyroidism
guidelines; and 4) to assess for any international differences
in the management of hypothyroidism.

Materials and Methods

Survey design
The survey was designed in a manner similar to our recently
published Graves disease management survey (13). A commercial web-based, survey management service (Survey Monkey,
Palo Alto, CA) was used to administer the survey. The survey
included questions pertaining to diagnostic evaluation, choice of
therapy, and follow-up for an index case (see below) of primary
overt hypothyroidism followed by 3 clinical variants including a
patient with persistent symptoms of hypothyroidism despite
having achieved target thyroid hormone levels, a patient anticipating pregnancy, and a patient with subclinical hypothyroidism (Table 1).

Index case
A 52-year old woman presents with a 9 month history of
fatigue, cold intolerance, poor concentration, and constipation.
She is otherwise healthy, takes no medications, and does not
smoke cigarettes. She has a blood pressure of 135/90, a pulse rate
of 55 beats per minute, and weighs 132 pounds (60 kilograms).
She has a firm goiter, approximately twice normal size. Serum
TSH is 20 mU/L (normal 0.4 4.5 mU/L), and free T4 is 0.7 ng/dL
(normal 0.8 1.8 ng/dL).

Comparison of CPG Recommendations With Survey Response

Recommendation
No.
R1
R8
R10
R13
R14.1
R 14.2
R15
R16
R17
R19.3

J Clin Endocrinol Metab, June 2014, 99(6):20772085

CPG Recommendation (Abbreviated)

Measure TPO Ab in subclinical hypothyroidism
Use both free T4 and TSH to monitor L-T4 treatment
Do not use T3 to diagnose hypothyroidism
Measure TSH 4 8 wk after starting or adjusting L-T4
Use age-specific normal ranges for TSH when available
Use pregnancy-specific normal ranges for TSH when available
Treat patients with TSH above 10 mIU/L
Consider other factors before treating patients with TSH 510 mU/L
Target TSH should be within the normal range when treating hypothyroidism
Treat pregnant women or those planning pregnancy when TPO Ab positive and
serum TSH is 2.5 mIU/L
Use L-T4 alone to treat hypothyroidism
Do not use L-T4 and L-T3 combinations to treat hypothyroidism
Do not use desiccated thyroid hormone to treat hypothyroidism
Gradually restore euthyroidism in patients older than 50 60 y of age
Adjust L-T4 to give TSH 2.5 mU/L when pregnancy is diagnosed
Check thyroid laboratory studies every 4 wk for the first half of pregnancy
Do not adjust L-T4 therapy to give low-normal TSH values in hypothyroid patients
who are not pregnanta
Endocrinologists should be consulted for a subset of hypothyroid patientsb
Do not treat symptoms suggestive of hypothyroidism if thyroid laboratory studies
are normal

Survey
Concordance (%)
91.9
59.9
86.3
74.9
84.2
96.1
98.9
78.7
99.5
95.1
99.2
99.2
100
38.3
95.1
70.6
43.6
34.9
99.4

Assessed by calculating the percentage of respondents accepting a TSH value 2 to 4.9 mU/L.

Expressed as the percentage of respondents who would return an uncomplicated hypothyroidism case to the primary care physician.

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doi: 10.1210/jc.2014-1046

Strategy for question design

Most questions required a single best response to be selected
from multiple choices. Diagnostic preference questions allowed
multiple items to be simultaneously selected. To limit bias, questions were constructed to omit phrasing that could influence
respondents answers, and a broad range of answers were included, arranged alphabetically, numerically, or in an order randomized by the survey tool (14). The survey was designed and
tested to allow a completion time of approximately 10 to 15
minutes. Before general release, the survey was vetted through
council members of the 3 societies and the research committee of
the ATA.

Contact of potential respondents

The target groups for the survey were clinically active international members of The Endocrine Society (TES), the ATA, and
the AACE. Clinically active members of these 3 societies received
an e-mail invitation for participation in the survey from society
administrators, which described the survey and contained an
electronic link to the survey website. The authors did not contact
potential respondents directly, and no reminders were sent to
nonrespondents; a second general e-mail was sent to the ATA
membership 1 month after the initial invitation.

Collection and summary of responses

Survey responses were anonymously collected and stored
electronically by the survey service, accessible in a passwordprotected manner. Repeat submissions from the same IP address
were automatically blocked by the survey service. The survey
website was open for the 2-month period from August 1, 2013,
through September 30, 2013.

Geographical region of respondents

The geographical location was localized to country of the
respondents clinical practices. To preserve anonymity, the city
or town of origin of individual respondents was not requested.
Respondents were grouped according to the United Nations
country grouping of the following geographical regions: Africa,
Asia, Europe and Eastern Europe, Central America, South America, Caribbean, the Middle East, North America (United States
and Canada), and Oceania (principally Australia and New Zealand). Responses from Central America, South America, and the
Caribbean were pooled as were responses from Asia and Oceania
and responses from Africa and the Middle East.

Statistical analysis
Summary statistics were prepared for responses to each question. Because not every participant answered all questions, the
percentage of respondents providing a given answer was calculated individually for each question, using the number of respondents to that question as the denominator. Statistical analysis
explored the relationship between respondent demographics and
key diagnostic or treatment preferences for the index case. Fishers exact test (two-tailed) was used to compare gender and the
geographical region of respondents to preferred treatment strategy. ANOVA was used to compare year of medical school graduation between groups with a Bonferroni correction to adjust for
multiple comparisons. Data were analyzed using IBM SPSS Statistics version 19 software.

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Results
Professional society membership
Of 880 respondents participating in the survey, 815
(92.6%) completed all sections. The 809 respondents providing society membership consisted of 618 TES members,
582 AACE members, and 208 ATA members. Multiple
society membership was commonly reported. One hundred fifty-seven (19.4%) belonged only to TES, 151
(18.7%) belonged only to AACE, and 27 (3.3%) belonged
solely to the ATA. Dual membership in TES and AACE
was noted by 293 respondents (36.2%), TES and ATA in
43 respondents (5.3%), and ATA and AACE in 13 (1.6%)
respondents. Membership in all 3 societies was noted by
125 respondents (15.5%).
Response rate
Among TES members, 5650 physicians were sent the
e-mail, of which 5398 were successfully delivered and
1762 (32.6%) opened. For ATA members, an initial email was sent to 1478 members, 407 (27.5%) of whom
opened the e-mail. A second mailing to ATA members 1
month later resulted in an additional 162 unique e-mail
openings (among 1533 recipients), for a final ATA member opening rate of 37.1% (569 of 1533). Among AACE
members, 6444 were sent an e-mail invitation; opening
rates were not available. The approximate response rates
for society members opening the e-mail was 35.1% (618
of 1762) for TES, and 51.1% (208 of 407) for ATA members. The percentage of clinically active society members
represented by survey respondents was 208 of 1533
(13.6%) for the ATA, 618 of 5650 (10.9%) for TES, and
582 of 6444 (9.0%) for AACE.
Respondent demographics
The type of medical practice reported by respondents
was adult endocrinology (90.7%), either alone (83.8%) or
combined with another specialty such as internal medicine
(6.9%), pediatric endocrinology alone (3.0%), general internal medicine (1.5%), general surgery (1.5%), nuclear
medicine (1.0%), and other (2.1%).
The geographical regions of the respondents practices
were diverse, including North America (67.5%: United
States, 65.0%; Canada, 2.5%), Latin America (9.7%),
Europe (9.2%), Asia and Oceania (8.1%), and the Middle
East and Africa (5.5%). Gender was reported by 801 respondents, among whom 62.9% (504 of 801) were men,
and 37.1% (297 of 801) were women. The median year of
graduation from medical school was 1987 (mean, 1986
13 years). The number of new hypothyroidism cases
seen on a monthly basis was 1 to 5 for 40.9% of respondents, 6 to 10 for 28.3% of respondents, and 10 for
29.1% of respondents.

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Hypothyroidism Management Survey

An-TPO

J Clin Endocrinol Metab, June 2014, 99(6):20772085

4 weeks (23.0%), 2 weeks (20.5%), 8 weeks (18.0%), and

12 weeks (2.8%). Gender had no significant impact on
choice of correction technique. An earlier year of graduation from medical school was positively associated with
a gradual approach (P .001).

79.6%

Repeat TSH

52.1%

Thyroid US

44.4%

An-Tg

35.1%

Repeat Free T4

33.6%

Lipid panel

31.6%

Free T3

9.3%

Total T3

4.4%
0

100

200

300
400
500
600
Number of Respondents

700

800

Figure 1. Percentage of participants who would request the listed

testing in a patient with overt hypothyroidism.

Diagnostic evaluation of the index case

Figure 1 shows the percentage of respondents ordering
the listed laboratory tests for the index case. Regional differences were noted, with a higher use of ultrasound examination in hypothyroid patients undergoing initial evaluation in regions outside of North America. Specifically,
whereas 37.9% of North American endocrinologists
would obtain a thyroid ultrasound in this setting, the rate
was 58.0% in Latin America (P .001 vs North America),
58.8% in Europe (P .001), 58.2% in Asia-Oceania (P
.001), and 56.3% in Middle East-Africa (P .014). Thyroid peroxidase (TPO) antibody (Ab) testing was similar
across regions.
Therapy for overt hypothyroidism
Decision to treat
Among 870 respondents, 860 (98.9%) would initiate
thyroid hormone therapy in the index case of overt
hypothyroidism.
Rate of correction
We queried respondents about their usual technique for
correcting overt hypothyroidism. Among 851 respondents to this question, 328 (38.5%) would gradually restore euthyroidism, 286 (33.6%) would select an empiric
dose adjusted to achieve target levels, and 237 (27.8%)
would start with a calculated full-replacement dose. There
were regional differences, with a greater use of a gradual
approach outside of North America. Whereas 30.5% of
North American respondents would use a gradual approach, the latter was favored in all other regions, including Latin America (60.5%, P .001 vs North America),
Europe (55.8%, P .001), Asia-Oceania (55.1%, P
.001), and Middle East-Africa (46.8%, P .081). For
respondents preferring a gradual restoration of euthyroidism, most (61.1%) would increase in increments of 25 g,
followed by 50 g (26.9%), and 12.5 g (12.0%). The
frequency of incremental increases was 6 weeks (35.7%),

Preferred initial thyroid hormone preparation

Among 743 respondents, 371 (49.9%) would use a
brand name of L-T4, and 366 (49.3%) would use a generic
formulation for the initial therapy of overt hypothyroidism. There was a significantly lower use of brand-name
formulations in North America (37.9%) compared with
Latin America (58.0%, P .001) and Europe (58.8%, P
.001). The percentage of respondents using a brand-name
formulation in Asia-Oceania (58.2%) and in the Middle
East-Africa (56.3%) was similar to that of Europe and
Latin America, but did not achieve significance vs North
America.
Combined L-T4/L-T3 or thyroid extract as initial
therapy
Only 13 respondents (0.8%) selected combined L-T4/
L-T3 as initial therapy in the index case. Among these respondents, 4 would add 10 g daily of L-T3, and 2 each
would add 5 g of L-T3 once, twice, or 3 times daily. No
respondents selected thyroid extract as initial therapy.
Follow-up testing and dose adjustment
Among 859 respondents, 423 (49.2%) would recheck
thyroid hormone levels 6 weeks after starting thyroid hormone therapy, followed by 8 weeks (25.7%), 4 weeks
(16.0%), 12 weeks (8.0%), and 2 weeks (1.1%). Specific
testing at the time of follow-up included TSH for 845 of
856 (98.7%) respondents, free T4 in 513 respondents
(59.9%), free T3 (7.8%), or total T3 (3.4%).
TSH targets in primary hypothyroidism
Among 856 respondents, the target TSH in the 52-yearold index case was 1.0 to 1.9 mU/L for 408 respondents
(47.7%), 2.0 to 2.9 mU/L in 284 respondents (33.2%), 0.5
to 0.9 mU/L in 66 respondents (7.7%), and 3.0 to 3.9
mU/L in 66 respondents (7.7%). When asked what the
TSH target would be in a 25-year-old patient, there was a
shift toward lower TSH values, with 61.6% now selecting
1.0 to 1.9 mU/L, followed by 2.0 to 2.9 mU/L (18.1%) and
0.5 to 0.9 mU/L (14.4%). Conversely, in an 85-year-old
patient, 29.5% would select a TSH from 3.0 to 3.9 mU/L,
followed by 2.0 to 2.9 mU/L (25.8%), 4.0 to 4.9 mU/L
(22.5%), and 5.0 to 9.9 mU/L (10.4%). A comparison of
TSH targets for the 3 age variants is shown in Figure 2.

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doi: 10.1210/jc.2014-1046

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500

25-year-old
52-year-old

400

85-year-old

300
200

is planning pregnancy and has a serum TSH of 3.5 mU/L

on L-T4 therapy (for full case description, see Supplemental Table 1, published on the Endocrine Societys Journals
Online web site at http://press.endocrine.org/journal/jcem).
For the prepregnant patient, the preferred TSH target for 824
respondents was 1.0 to 1.4 mU/L (36.3%), followed by 0.5
to 0.9 mU/L (23.9%), 1.5 to 1.9 mU/L (19.8%), 2.0 to 2.4
mU/L (14.1%), and 2.5 mU/L (4.9%).

100
L-T4

0
0.1-0.4 0.5-0.9 1.0-1.9 2.0-2.9 3.0-3.9 4.0-4.9 5.0-9.9
Target TSH (mU/L)

Figure 2. Age-specific TSH targets among survey participants.

Long-term follow-up
After achieving stable target TSH values, respondents
were asked how often they would repeat thyroid laboratory testing. Among 847 respondents, 55.5% would obtain laboratory studies at 6-month intervals, followed by
12 months (34.0%), 3 months (9.3%), and 3 months
(1.2%). The manner in which asymptomatic patients at
target TSH values would be followed was by laboratory
studies plus office visits by 56.2% of 849 respondents,
return to the primary care physician by 34.9%, or laboratory studies plus a phone call by 9.0% of respondents.
There was a lower rate of return to primary care in Latin
America (23.8%, P .020 vs North America) and a higher
rate of return to primary care physicians in Europe
(54.5%) vs North America (34.9%, P .001).
Variation 1: Persistent hypothyroid symptoms
We queried respondents about their response to a patient who despite achieving target TSH values on L-T4
therapy still has persistent hypothyroid symptoms.
Among 843 respondents, 84.3% would perform testing
for other sources of the patients symptoms, 11.3% would
refer the patient back to their primary care physician for
further evaluation, 3.6% would add L-T3 therapy to L-T4,
and fewer than 1% would either refer the patient to behavioral health or increase the dose of the patients L-T4.
Additional testing requested in patients with persistent
unexplained hypothyroid symptoms would include a
complete cell count by 90.3% of 723 respondents, a complete metabolic panel (82.4%), morning cortisol level
(58.5%), B-12 levels (57.4%), or T3 levels (21.9%). Free
text responses included measurement of 25-hydroxyvitamin D levels (4.7%), and evaluation for a sleep disorder
(2.2%).
Variation 2: hypothyroidism management in a
patient planning pregnancy
Prepregnancy TSH target
Respondents were queried regarding their approach to
a 25-year-old woman with Hashimotos thyroiditis, who

changes with confirmed pregnancy

Respondents were next asked about immediate
changes in L-T4 dose after a confirmed pregnancy in a
woman with a recent TSH value of 0.5 mU/L. Among 821
respondents, 57.1% would continue the current dose of
L-T4, 34.6% would increase the dose by one-third, 5.1%
would decrease the dose by one-third, and 2.3% would
increase the dose by 50%.
Target TSH value during pregnancy
The preferred TSH range during pregnancy was similar
to the prepregnant patient, with a TSH target of 1.0 to 1.4
mU/L among 33.5% of 822 respondents, 0.5 to 0.9 mU/L
(25.5%), 1.5 to 1.9 mU/L (19.1%), 2.0 to 2.4 mU/L
(13.5%), 0.1 to 0.4 mU/L (4.5%), and 2.5 mU/L (3.9%)
(Figure 3).
Frequency of monitoring during pregnancy
Among 821 respondents, 67.7% would check thyroid
laboratory studies every 4 weeks during pregnancy,
21.4% every 8 weeks, 7.9% every 12 weeks, and 2.9%
every 2 weeks.
Variation 3: subclinical hypothyroidism
management
Survey participants were next presented with a case of
subclinical hypothyroidism in an asymptomatic 52-year-

350
300
Number of Respondents

Number of Respondents

600

2081

Prepregnancy
Pregnancy

250
200
150
100
50
0

0.1-0.4 0.5-0.9 1.0-1.4 1.5-1.9 2.0-2.4 2.5-2.9 3.0-3.4

Target TSH (mU/L)
Figure 3. TSH targets in the pregnant and prepregnant patient.

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old woman with a serum TSH of 7.7 mU/L (for full case
description, see Supplemental Table 2).
Testing in subclinical hypothyroidism
Among 795 respondents, 91.9% would perform TPO
Ab testing, 50.6% would obtain a lipid panel, 50.4%
would request a thyroid ultrasound, 41.5% would obtain
antithyroglobulin Ab, and 19.7% would order either a
free T3 or total T3 level. For respondents selecting more
than one laboratory test, TPO Ab testing and a lipid panel
were requested most frequently (46.7%).
Factors influencing the decision to treat subclinical
hypothyroidism
Among 802 respondents, the percentage that would
start L-T4 therapy for subclinical hypothyroidism in the
presence of the listed clinical factors is shown in Figure 4.
Most respondents (73.8%) indicated more than one potential indication for treatment. Treatment without additional justification was selected more frequently in North
America (24.7%) compared with Latin America (10.8%,
P .008), Europe (14.3%, P .045), or Asia-Oceania
(9.3%, P .005), but at a similar frequency to Middle
East-Africa (20.0%, P .589). Free text responses indicated a desire to wait 3 to 6 months and repeat testing
before treating (5 respondents), treating only if TSH increased further (5 respondents), or defer the treatment
decision to the patient (3 respondents).

Discussion
The current report provides results from a large modern
survey of clinical practices in the management of primary
hypothyroidism. It includes a demographically diverse
collection of endocrinologists, representing members
from 3 major endocrine societies and 76 different coun-

Posive TPO anbodies

62.3%

Hypothyroidism symptoms

60.9%

LDL-cholesterol elevaon

52.9%

Goiter

46.6%

Known CAD

26.3%

Treat without juscaon

21.3%

Risk factors for CAD

20.7%
0

100

200

300

400

500

600

Number of Respondents

Figure 4. Percentage of participants who would initiate treatment of

subclinical hypothyroidism in the presence of the listed circumstance.

tries. Key findings include 1) a nearly exclusive preference

for L-T4 alone as initial therapy, 2) the widespread use of
age-specific TSH targets for replacement therapy, 3) a low
threshold for treating mild thyroid failure, 4) meticulous
attention to TSH targets in the pregnant and prepregnant
woman, and 5) a highly variable approach to both the rate
and means of restoring euthyroidism for overt disease.
International differences in management techniques and
changes in management trends over the past 12 years were
also identified.
The rate of overt hypothyroidism correction preferred
by respondents was highly variable, with a slightly higher
percentage using a start low and go slow approach, compared with an empiric dose adjusted to achieve target TSH
values or a calculated full replacement dose. This diversity
demonstrates that the optimal rate of correction of overt
hypothyroidism remains controversial (15), although a
recent randomized controlled trial showed that full replacement therapy was safe in otherwise healthy individuals who were free of cardiovascular disease (16). Repeat
laboratory studies would generally be obtained at 6 or 8
weeks, and L-T4 adjustments made using 25 g increments, to achieve a target TSH value of 1 to 2 mU/L in
younger patients and 2 to 5 mU/L in an octogenarian.
The approach to a patient with persistent hypothyroid
symptoms despite having target TSH values has received
considerable attention in the past decade (17). Only 1 in 5
respondents would also assess T3 levels in this circumstance, and fewer than 4% would switch to combination
L-T4/L-T3 therapy. The low level of interest in combination
L-T4/L-T3 therapy among survey respondents, either as initial therapy or in the management of patients with poor
symptomatic relief on L-T4, likely reflects several factors,
including the absence of long-acting preparations of L-T3,
which would therefore presently require 3 times daily dosing (18), concerns over potential adverse effects associated
with unregulated T3 availability at the tissue level, and
most importantly, the lack of evidence showing beneficial
effects of combination therapy (1, 6). Although the use of
combination L-T4/L-T3 therapy was low among our respondents, it is possible that this underestimates the prevalent use of combination therapy among primary care
physicians.
Patients with subclinical hypothyroidism and TSH values in the 5- to 10-mU/L range represent a subset in which
treatment with thyroid hormone is of unproven benefit,
yet more than 20% of respondents would treat such a
patient with thyroid hormone without further justification. The poor selectivity of current criteria for treatment
of subclinical hypothyroidism has been noted recently in
a retrospective review in which 92% of such patients
would meet at least one of the criteria for treatment ac-

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doi: 10.1210/jc.2014-1046

cording to the ATA/AACE hypothyroidism guidelines

(19). Because overtreatment with thyroid hormone is a
frequent finding in patients intended for replacement therapy (20, 21), and the resultant subclinical thyrotoxicosis
is linked to adverse consequences such as atrial fibrillation
(22, 23) and osteoporosis (22), the tendency among survey
respondents to treat mild subclinical hypothyroidism
likely reflects confidence in their ability to achieve and
maintain proper TSH targets in this patient subset.
Management of established hypothyroidism in the
pregnant or prepregnant woman has been addressed in
recent CPGs (24, 25). Although some variation exists in
recommendations among CPGs in this area (26), there is
general agreement that L-T4 requirements increase in most
pregnant women, often by up to 50% above baseline requirements (27, 28). Furthermore, due to concerns regarding adverse neurodevelopmental consequences associated
with maternal hypothyroidism during early pregnancy
(29, 30), lower TSH targets are recommended in this setting. Respondents to the current survey preferred to keep
TSH values well beneath the recommended first-trimester
upper limit of 2.5 mU/L in both pregnant and prepregnant
patients, with most respondents selecting TSH values of
0.5 to 1.4 mU/L. Despite the current recommendation to
increase the dose of L-T4 by 2 pills per week at pregnancy
confirmation in the hypothyroid patient (9, 27), our patient with a TSH value of 0.5 mU/L at pregnancy diagnosis
would be maintained on the same dose by more than half
of respondents.
The management practices for hypothyroidism identified in the current study mirror the 2012 AACE/ATA Hypothyroidism CPG in many areas although diverging significantly in others (Table 1). Because the survey was
conducted shortly after the release of the CPGs, it is unlikely that recommendations contained in the CPGs would
already have been incorporated into clinical practice. Regarding diagnostic evaluation, a reliance on TPO Ab testing was recommended in the CPG for the purpose of predicting progression of subclinical hypothyroidism. More
than 90% of respondents would obtain TPO Ab testing in
this circumstance, as would 80% in patients presenting
with overt hypothyroidism. Similarly, the CPG recommended against the use of T3 measurement in making the
diagnosis of hypothyroidism, and nearly 90% of respondents agreed. Thyroid ultrasound was not recommended
routinely in the hypothyroid patient in the ATA/AACE
guidelines, but more than 40% of respondents would obtain this study in patients with overt hypothyroidism and
50% in patients with subclinical disease. This may represent the prevalent use of thyroid ultrasound in the endocrine clinic to augment the physical examination, assess
for diffuse heterogeneity typical of Hashimotos thyroid-

jcem.endojournals.org

2083

itis, and exclude concurrent thyroid nodules in these patients. The use of T4 monotherapy was recommended in
the CPG, and nearly 100% of respondents agreed. Our
survey showed an equivalent use of generic and brandname preparations of L-T4 among respondents. The CPG
did not compare generic and brand names of L-T4 but
emphasized the need for a consistent preparation. Several
areas of current clinical practice appear to deviate from
that recommended in the guidelines. First, although a
gradual correction of hypothyroidism was suggested for
all patients over 50 to 60 years of age, only 39% of respondents selected this approach, the remaining selecting
more rapid correction. Second, the guidelines discourage
the use of specific TSH targets within the normal range in
nonpregnant patients, yet most respondents preferred
TSH values below 2 mU/L in the index case. Third, the
measurement of both free T4 and TSH was recommended
to monitor thyroid hormone replacement therapy, but
40% of respondents use TSH alone. Finally, the guidelines
provide specific referral criteria, implying that many hypothyroid patients do not require subspecialty care. However, only 35% of respondents would return the index case
to the primary care physician after attaining target TSH
values.
The current survey uncovered some interesting differences among international endocrinologists in the management of primary hypothyroidism. North American endocrinologists (largely U.S.-based) performed less
auxiliary testing, were more likely to use a generic preparation of L-T4, were more likely to correct overt hypothyroidism rapidly, and were more likely to treat mild
thyroid failure than in other geographical regions. It is not
clear to what extent differences in healthcare systems contribute to these dissimilarities.
In comparison with an earlier survey of hypothyroidism management practices published in 2001 (12), several
differences were noted. First, in 2001, 73% of ATA respondents indicated a preference for a gradual replacement approach to a 73-year-old patient with overt hypothyroidism, whereas only 39% of current respondents
would select a gradual approach in our 52-year-old patient. However, it is likely that at least some of this difference is attributable to the different ages of the 2 index
cases in these surveys. Second, in the earlier survey, 65%
of ATA members would have treated a patient with mild
fatigue and negative TPO Ab, and 92% would have
treated in the presence of TPO Ab. In contrast, only 21%
of our survey respondents would treat an asymptomatic
patient with subclinical hypothyroidism without further
justification, and 62% would treat in the presence of TPO
Ab, suggesting a lower tendency to treat mild thyroid failure in 2013 compared with 2001. This is contrary to a

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2084

Burch et al

Hypothyroidism Management Survey

report from the United Kingdom in which a trend toward

a lower threshold for treating subclinical hypothyroidism
occurred from 2001 to 2009, with the median TSH of
patients selected for therapy dropping from 8.7 mU/L in
2001 to 7.9 mU/L in 2009 (31). Third, an increase in the
use of generic L-T4 has occurred, with 17% of ATA members using generic brands in the 2001 survey, compared
with 62% of North American endocrinologists in 2013.
This likely reflects the wider availability of approved generic brands and perhaps a greater attention to cost containment at the time of the current survey.
Our study has both strengths and limitations. The number of respondents was large and represented a diverse
international group of endocrinologists. The electronic
mail invitation to participate provided an opportunity for
more than 10 000 potential respondents to learn about the
survey. A limitation of the current study is the relatively
low percentage of active society membership participating, accounting for 9% to 14% of clinically active members. Another limitation is an underrepresentation of non
U.S.-based endocrinologists and potential selection bias
when including international members of U.S.-based endocrine societies. Therefore, the international differences
noted in management practices may underestimate those
obtained using independent surveys in those regions. In
addition, it is possible that respondents to management
surveys are more likely to be aware of CPGs and potentially adhere to their recommendations, although we are
not aware of evidence to support that possibility.
In summary, our survey of clinical endocrinologists on
the management of primary hypothyroidism catalogs current practice patterns and demonstrates both alignment
and focal deviation from recent CPGs. Both international
differences and a change in practice patterns over the past
decade are demonstrated.

Acknowledgments
We thank Ms Robin Howard for assistance with the statistical
analysis, and AACE (Dr Jeffrey I. Mechanick, President; Mr
Donald C. Jones, CEO; and Ms Xiomara Villanueva, Executive
Assistant), ATA (Dr John C. Morris, Secretary; and Ms Barbara
R. Smith, Executive Director), and TES (Ms Meredith Dyer, Associate Director, Health Policy; and Ms. Stephanie Kutler, Director, Government Affairs) for their expert assistance in reviewing and vetting the survey and forwarding it to society
membership. We also thank the many national and international
colleagues who took the time to participate in this survey.
Address all correspondence and requests for reprints to:
Henry B. Burch, MD, COL MC U.S. Army, Endocrinology Division, Walter Reed National Military Medical Center, 8901
Wisconsin Avenue, Building 19, Room 5053, Bethesda, MD

J Clin Endocrinol Metab, June 2014, 99(6):20772085

20889 5600. E-mail henry.b.burch.mil@health.mil or

hankburch@gmail.com.
The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of
the Army, Navy, the Department of Defense or the U.S. Government. One or more authors are military service members (or
employees of the U.S. Government). This work was prepared as
part of our official duties. Title 17 U.S.C. 105 provides that the
Copyright protection under this title is not available for any
work of the United States Government. Title 17 U.S.C. 101
defines a U.S. Government work as a work prepared by a military
service member or employee of the U.S. Government as part of
that persons official duties. We certify that all individuals who
qualify as authors have been listed; each has participated in the
conception and design of this work, the analysis of data (when
applicable), the writing of the document, and/or the approval of
the submission of this version; that the document represents valid
work; that if we used information derived from another source,
we obtained all necessary approvals to use it and made appropriate acknowledgments in the document; and that each takes
public responsibility for it.
Disclosure Summary: The authors have nothing to disclose.

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