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Guideline Summary NGC-5884


Guideline Title
Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice
guideline.

Bibliographic Source(s)
The Endocrine Society. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society
clinical practice guideline. Chevy Chase (MD): The Endocrine Society; 2007. 79 p. [281 references]

Guideline Status
This is the current release of the guideline.

Scope
Disease/Condition(s)
Thyroid dysfunction during pregnancy and postpartum including:
l Hypothyroidism
l Hyperthyroidism
l Gestationalhyperemesisandhyperthyroidism
l Autoimmunethyroiddisease
l Thyroidnodulesandcancer
l Postpartumthyroiditis

Guideline Category
Diagnosis

Management

Treatment

Clinical Specialty
Endocrinology

Family Practice

Obstetrics and Gynecology

Intended Users
Physicians

Guideline Objective(s)
To provide clinical guidelines for the management of thyroid problems present during pregnancy and in the postpartum

Target Population
Pregnant women and women who are postpartum with thyroid dysfunction

Interventions and Practices Considered


Diagnosis/Management/Treatment
1.Targetedcasefindingofhypothyroidismatfirstprenatalvisit
2.Adjustmentofpreconceptionthyroxinedose
3.Thyroidfunctiontesting
4.Differentialdiagnosisofhyperthyroidism
5.Antithyroiddrugtherapy
l Propylthiouracil
l Methimazole
6.Thyroidectomy
7.Measurementofthyroidreceptorantibodies
8.Fetalultrasound
9.Umbilicalbloodsampling,asappropriate
10.
Assessmentofnewbornsforthyroiddysfunction
11.
Fineneedleaspiration(FNA)cytologyandultrasoundguidedFNA
12.
Thyroidhormoneadministration
13.
Avoidanceofradioactiveiodine(RAI)and131-I in pregnant women or women who are breast-feeding
14.
Ensuringanadequateiodineintake
7.Measurementofthyroidreceptorantibodies
8.Fetalultrasound
9.Umbilicalbloodsampling,asappropriate
10.
Assessmentofnewbornsforthyroiddysfunction
11.
Fineneedleaspiration(FNA)cytologyandultrasoundguidedFNA
12.
Thyroidhormoneadministration
13.
Avoidanceofradioactiveiodine(RAI)and131-I in pregnant women or women who are breast-feeding
14.
Ensuringanadequateiodineintake
15.
Measurementofurinaryiodineconcentration
16.
Measurementofthyroid-stimulating hormone (TSH) levels in women known to be thyroid peroxidase antibody
(TPO-Ab) positive
17.
Postpartumscreeningforthyroiditisinwomenwithtype1diabetesmellitus
18.
AnnualTSHlevelinwomenwithahistoryofpostpartumthyroiditis(PPT)
19.
MonitoringofTSHinasymptomaticwomenwithanabnormalTSHwhoarenotplanningasubsequentpregnancy
20.
LevothyroxinetherapyforsymptomaticwomenwithanabnormalTSHwhoareplanningpregnancy

Major Outcomes Considered


l Riskforandprevalenceofthyroiddysfunctioninpregnancyandthepostpartumperiod

l Incidenceoffetalhyperthyroidism
l Incidenceofmiscarriageandpretermdelivery
l Neuropsychologicaloutcomeofprogeny
l Adverseeffectsofantithyroiddrugsonfetaldevelopmentandfetalthyroid

Methodology
Methods Used to Collect/Select the Evidence
Searches of Electronic Databases

Description of Methods Used to Collect/Select the Evidence


Not stated

Number of Source Documents


Not stated

Methods Used to Assess the Quality and Strength of the Evidence


Weighting According to a Rating Scheme (Scheme Given)

Rating Scheme for the Strength of the Evidence


The United States Preventive Services Task Force (USPSTF) grades the overall evidence for a service on a three-point
scale (good, fair, or poor):
Good: Evidence includes consistent results from well designed, well conducted studies in representative populations
that directly assess effects on health outcomes.
Fair: Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the
number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the
evidence on health outcomes.
Poor: Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies,
important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health
outcomes.
Level of Evidence by GRADE System
High: ++++ or +++O
Moderate: ++OO
Low: +OOO
Very Low: OOOO

Methods Used to Analyze the Evidence


Review of Published Meta-Analyses

Systematic Review

Description of the Methods Used to Analyze the Evidence


The guideline committee undertook to review all material on guideline topics published in English during the past two
decades, or earlier at the working group's discretion. The committee concentrated on original reports and largely
excluded reviews from their references. At present, with the exception of studies on iodide supplementation, only two
prospective, randomized intervention trials have been published in this area. The guideline committee is aware of two
large-scale prospective intervention trials that are presently ongoing. Nevertheless, in the last 15 years, many high-
quality studies have modified older dogmas and profoundly changed the ways in which these patients are managed.
These studies are most often prospective or retrospective clinical evaluations of a particular patient population and
matched groups of control women. Such studies, when carefully performed, adequately matched, and appropriately
interpreted; provide the bulk of the evidence presented in the guidelines.

Methods Used to Formulate the Recommendations


Description of the Methods Used to Analyze the Evidence
The guideline committee undertook to review all material on guideline topics published in English during the past two
decades, or earlier at the working group's discretion. The committee concentrated on original reports and largely
excluded reviews from their references. At present, with the exception of studies on iodide supplementation, only two
prospective, randomized intervention trials have been published in this area. The guideline committee is aware of two
large-scale prospective intervention trials that are presently ongoing. Nevertheless, in the last 15 years, many high-
quality studies have modified older dogmas and profoundly changed the ways in which these patients are managed.
These studies are most often prospective or retrospective clinical evaluations of a particular patient population and
matched groups of control women. Such studies, when carefully performed, adequately matched, and appropriately
interpreted; provide the bulk of the evidence presented in the guidelines.

Methods Used to Formulate the Recommendations


Expert Consensus

Description of Methods Used to Formulate the Recommendations


An international task force was created, under the auspices of The Endocrine Society, to review the best evidence in
the field and develop evidence-based guidelines. Members of the task force included representatives from The
Endocrine Society, American Thyroid Association, Association of American Clinical Endocrinologists, European Thyroid
Association, Asia and Oceania Thyroid Association, and the Latin American Thyroid Society. The task force worked
during 2 years to develop the guidelines, had multiple phone conversations, and two 2-day retreats. Upon completion
of the guidelines, they were reviewed and approved by all of the participants.

Rating Scheme for the Strength of the Recommendations


The United States Preventive Services Task Force (USPSTF) grades its recommendations (level A, B, C, D or I) on the
basis of the strength of evidence and magnitude of net benefits (benefits minus harms):
A: The USPSTF strongly recommends that clinicians provide (the service) to eligible patients. The USPSTF found good
evidence that (the service) improves important health outcomes and concludes that benefits substantially outweigh
harms.
B: The USPSTF recommends that clinicians provide (the service) to eligible patients. The USPSTF found at least fair
evidence that (the service) improves important health outcomes and concludes that benefits outweigh harms.
C: The USPSTF makes no recommendation for or against routine provision of (the service). The USPSTF found at least
fair evidence that (the service) can improve health outcomes but concludes that the balance of benefits and harms is
too close to justify a general recommendation.
D: The USPSTF recommends against routinely providing (the service) to asymptomatic patients. The USPSTF found
good evidence that (the service) is ineffective or that harms outweigh benefits.
I: The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing (the service).
Evidence that (the service) is effective is lacking, or poor quality, or conflicting, and the balance of benefits and harms
cannot be determined.
Recommendation Level by GRADE System
1: Strong
2: Moderate
Note: There are no equivalents in the GRADE system for the recommendation levels C, D, and I used in the USPSTF
system.

Cost Analysis
A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation


Internal Peer Review

Description of Method of Guideline Validation


The manuscript was reviewed by the Society's Clinical Guideline's Subcommittee (CGS), Clinical Affairs Committee,
members of The Endocrine Society, and members of each of the collaborating societies. Many valuable suggestions
were received and incorporated into the final document. Each of the societies endorsed the guidelines.

Recommendations
Major Recommendations
Definitions for the quality of the evidence based on the United States Preventative Services Task Force [USPSTF] levels
(good, fair, and poor) and Grading of Recommendations Assessment, Development and Evaluation [GRADE] levels
(+OOO, ++OO, +++O, and ++++) and the strength of the recommendation (USPSTF: A, B, C, D, I and GRADE: 1 or 2)
are provided at the end of the "Major Recommendations" field.
Hypothyroidism and Pregnancy: Maternal and Fetal Aspects
Both maternal and fetal hypothyroidism are known to have serious adverse effects on the fetus. Therefore maternal
hypothyroidism should be avoided. For overt hypothyroidism (OH), The United States Preventive Service Task Force
(USPSTF) recommendation level is A; evidence is fair. Targeted case finding is recommended at the first prenatal visit.
The USPSTF recommendation level is B; evidence is fair (GRADE 2 | ++OO) (Abalovich et al., 2002; Klein et al., 1991;
Haddow et al., 1999; Glinoer et al., 1994).
If hypothyroidism has been diagnosed before pregnancy, the guideline panel recommends adjustment of the
preconception thyroxine dose to reach before pregnancy a thyroid-stimulating hormone (TSH) level not higher than 2.5
mIU/liter. The USPSTF recommendation level is I; evidence is poor (GRADE 2 | +OOO) (Demers & Spencer, 2002;
Baloch et al., 2003; Panesar, Li, & Rogers, 2001).
The thyroxine dose often needs to be incremented by 4 to 6 weeks gestation and may require a 30 to 50% increment in
dosage. The USPSTF recommendation level is A; evidence is good (GRADE 1 | +++O) (Mandel et al., 1990; Kaplan,
1992).
If OH is diagnosed during pregnancy, thyroid function tests should be normalized as rapidly as possible. Thyroxine
Haddow et al., 1999; Glinoer et al., 1994).
If hypothyroidism has been diagnosed before pregnancy, the guideline panel recommends adjustment of the
preconception thyroxine dose to reach before pregnancy a thyroid-stimulating hormone (TSH) level not higher than 2.5
mIU/liter. The USPSTF recommendation level is I; evidence is poor (GRADE 2 | +OOO) (Demers & Spencer, 2002;
Baloch et al., 2003; Panesar, Li, & Rogers, 2001).
The thyroxine dose often needs to be incremented by 4 to 6 weeks gestation and may require a 30 to 50% increment in
dosage. The USPSTF recommendation level is A; evidence is good (GRADE 1 | +++O) (Mandel et al., 1990; Kaplan,
1992).
If OH is diagnosed during pregnancy, thyroid function tests should be normalized as rapidly as possible. Thyroxine
dosage should be titrated to rapidly reach and thereafter maintain serum TSH concentrations of less than 2.5 mI/liter
in the first trimester (or 3 mIU/liter in second and third trimesters) or to trimester-specific normal TSH ranges. Thyroid
function tests should be remeasured within 30 to 40 days. The USPSTF recommendation level is A; evidence is good
(GRADE 1 | ++++) (Soldin et al., 2004; Sapin, D'Herbomez, & Schlienger, 2004; Panesar, Li, & Rogers, 2001).
Women with thyroid autoimmunity (TAI) who are euthyroid in the early stages of pregnancy are at risk of developing
hypothyroidism and should be monitored for elevation of TSH above the normal range. The USPSTF recommendation
level is A; evidence is fair (GRADE 1 | +++O) (Alexander et al., 2004; Glinoer et al., 1994).
Subclinical hypothyroidism (SCH) (serum TSH concentration above the upper limit of the reference range with a normal
free T 4) has been shown to be associated with an adverse outcome for both the mother and offspring. Thyroxine
treatment has been shown to improve obstetrical outcome, but has not been proved to modify long-term neurological
development in the offspring. However, given that the potential benefits outweigh the potential risks, the panel
recommends thyroxine replacement in women with subclinical hypothyroidism. For obstetrical outcome, the USPSTF
recommendation level is B; evidence is fair (GRADE 1 | ++OO); for neurological outcome, the USPSTF recommendation
level is I; evidence is poor (OOOO) (Abalovich et al., 2002; Leung et al., 1993; Casey et al., 2005; Glinoer, 1997).
After delivery, most hypothyroid women need to decrease the thyroxine dosage they received during pregnancy. The
USPSTF recommendation level is A; evidence is good (GRADE 1 | ++++) (Caixas et al., 1999).
Management of Maternal Hyperthyroidism: Maternal Aspects
If a subnormal serum TSH concentration is detected during gestation, hyperthyroidism must be distinguished from both
normal physiology of pregnancy and hyperemesis gravidarum because of the adverse effects of OH on the mother and
fetus. Differentiation of Graves' disease from gestational thyrotoxicosis is supported by presence of clinical evidence of
autoimmunity, a typical goiter, and presence of TSH-receptor antibodies (TRAb). The USPSTF recommendation level is
A; evidence is good (GRADE 1 | ++++) (Mestman, 2004; Goodwin, Montoro, & Mestman, 1992; Tan et al., 2002; Davis
et al., 1989; Millar et al., 1994).
For OH due to Graves' disease or thyroid nodules, antithyroid drug (ATD) therapy should be either initiated (for those
with new diagnoses) or adjusted (for those with a prior history) to maintain the maternal thyroid hormone levels for
free T4 in the upper nonpregnant reference range. The USPSTF recommendation level is A; evidence is good (GRADE 1 |
++++) (Momotani et al., 1986; Mortimer et al., 1990).
Because available evidence suggests that methimazole (MMI) may be associated with congenital anomalies,
propylthiouracil (PTU) should be used as a first-line drug, if available, especially during first-trimester organogenesis.
MMI may be prescribed if propylthiouracil is not available, or if a patient cannot tolerate or has an adverse response to
propylthiouracil. The USPSTF recommendation level is B; evidence is fair (GRADE 1 | ++OO) (Mandel, Brent, & Larsen,
1994; Martinez-Frias et al., 1992; Clementi et al., 1999; Johnsson, Larsson, & Ljunggren, 1997; Di Gianantonio et al.,
2001; Greenberg, 1987; Wilson et al., 1998).
Subtotal thyroidectomy may be indicated during pregnancy as therapy for maternal Graves' disease if 1) a patient has a
severe adverse reaction to ATD therapy, 2) persistently high doses of ATD are required, or 3) a patient is nonadherent
to ATD therapy and has uncontrolled hyperthyroidism. The optimal timing of surgery is in the second trimester. The
USPSTF recommendation level is I; evidence is poor (+OOO) (Stice et al., 1984; Burrow, 1985; Brodsky et al., 1980).
There is no evidence that treatment of subclinical hyperthyroidism improves pregnancy outcome, and treatment could
potentially adversely affect fetal outcome. The USPSTF recommendation level is I; evidence is poor (+OOO) (Goodwin,
Montoro, & Mestman, 1992; Tan et al., 2002; Casey et al., 2006; Momotani et al., 1986).
Management of Maternal Hyperthyroidism: Fetal Aspects
Because thyroid receptor antibodies (thyroid receptor stimulating, binding, or inhibiting antibodies) freely cross the
placenta and can stimulate the fetal thyroid, these antibodies should be measured by the end of the second trimester
in mothers with current Graves' disease or with a history of Graves' disease and treatment with 131-I or thyroidectomy
before pregnancy, or with a previous neonate with Graves' disease. Women who have a negative TSH-receptor
antibodies (TRAb) and do not require ATD have a very low risk of fetal or neonatal thyroid dysfunction. The USPSTF
recommendation level is B; evidence is fair (GRADE 1 | +++O) (Nachum et al., 2003; Peleg et al., 2002; McKenzie &
Zakarija, 1992; Laurberg et al., 1998; Luton et al., 2005).
131-I should not be given to a woman who is or may be pregnant. If inadvertently treated, the patient should be
promptly informed of the radiation danger to the fetus, including thyroid destruction if treated after the 12th week of
gestation. The USPSTF recommendation level is A; evidence is good (GRADE 1 | +OOO). There are no data for or
against recommending termination of pregnancy after 131-I exposure. The USPSTF recommendation level is I; evidence
is poor (+OOO) (Zanzonico, 1997; Berg et al., 1998; Lowe, 2004; Bydder et al., 2005; Gorman, 1999).
In women with elevated TRAb or in women treated with ATD, fetal ultrasound should be performed to look for evidence
of fetal thyroid dysfunction, which could include growth restriction, hydrops, presence of goiter, advanced bone age, or
cardiac failure. The USPSTF recommendation level is B; evidence is fair (GRADE 1 | +++O) (Nachum et al., 2003;
McKenzie & Zakarija, 1992; Laurberg et al., 1998; Mitsuda et al., 1992; Luton et al., 2005).
Umbilical blood sampling should be considered only if the diagnosis of fetal thyroid disease is not reasonably certain
from the clinical data and the information gained would change the treatment. The USPSTF recommendation level is B;
evidence is fair (GRADE 2 | +OOO) (Davidson et al., 1991; Nachum et al., 2003; Porreco & Bloch, 1990; Wenstrom et
al., 1990; Cohen et al., 2003; Fisher, 1997; Polak et al., 1997; Wallace, Couch, & Ginsberg, 1995; Luton et al., 2005;
Van Kamp et al., 2005; Polak et al., 2004).
All newborns of mothers with Graves' disease should be evaluated by a medical care provider for thyroid dysfunction
and treated if necessary. The USPSTF recommendation level is B; evidence is fair (GRADE 1 | +++O) (McKenzie &
Zakarija, 1992, Mitsuda et al., 1992; Luton et al., 2005).
Gestational Hyperemesis and Hyperthyroidism
Thyroid function tests should be measured in all patients with hyperemesis gravidarum (5% weight loss, dehydration,
and ketonuria). The USPSTF recommendation level is B; evidence is poor (GRADE 2 | +OOO) (Goodwin, Montoro, &
Mestman, 1992; Tan et al., 2002; Goodwin et al., 1992; Lazarus, 2005).
Few women with hyperemesis gravidarum will require ATD treatment. The USPSTF recommendation level is A; evidence
is good (GRADE 1 | ++++). Overt hyperthyroidism believed to be due to coincident Graves' disease should be treated
Van Kamp et al., 2005; Polak et al., 2004).
All newborns of mothers with Graves' disease should be evaluated by a medical care provider for thyroid dysfunction
and treated if necessary. The USPSTF recommendation level is B; evidence is fair (GRADE 1 | +++O) (McKenzie &
Zakarija, 1992, Mitsuda et al., 1992; Luton et al., 2005).
Gestational Hyperemesis and Hyperthyroidism
Thyroid function tests should be measured in all patients with hyperemesis gravidarum (5% weight loss, dehydration,
and ketonuria). The USPSTF recommendation level is B; evidence is poor (GRADE 2 | +OOO) (Goodwin, Montoro, &
Mestman, 1992; Tan et al., 2002; Goodwin et al., 1992; Lazarus, 2005).
Few women with hyperemesis gravidarum will require ATD treatment. The USPSTF recommendation level is A; evidence
is good (GRADE 1 | ++++). Overt hyperthyroidism believed to be due to coincident Graves' disease should be treated
with ATDs. The USPSTF recommendation level is B; evidence is fair (GRADE 1 | ++OO). Gestational hyperthyroidism
with clearly elevated thyroid hormone levels (free T 4 above the reference range or total T 4 >150% of top normal
pregnancy value and TSH <0.1 microU/ml) and evidence of hyperthyroidism may require treatment as long as clinically
necessary. The USPSTF recommendation level is I; evidence is poor (+OOO) (Goodwin, Montoro, & Mestman, 1992; Tan
et al., 2002; Goodwin et al., 1992; Lazarus, 2005).
Autoimmune Thyroid Disease and Miscarriage
Although a positive association exists between the presence of thyroid antibodies and pregnancy loss, universal
screening for antithyroid antibodies, and possible treatment, cannot be recommended at this time. As of this date, only
one adequately designed intervention trial has demonstrated a decrease in the miscarriage rate in thyroid antibody-
positive euthyroid women. The USPSTF recommendation level is C; evidence is fair (GRADE | +OOO) (Stagnaro-Green
et al., 1990; De Carolis et al., 2004; Sher et al., 1998).
Thyroid Nodules and Cancer
Fine needle aspiration (FNA) cytology should be performed for single or dominant thyroid nodules larger than 1 cm
discovered in pregnancy. Ultrasound guided FNA may have an advantage for minimizing inadequate sampling. The
USPSTF recommendation level is B; evidence is fair (GRADE 1 | +++O) (Kung et al., 2002; Mazzaferri & Jhiang, 1994;
Moosa & Mazzaferri, 1997; Vini et al., 1999).
When nodules are discovered in the first or early second trimester to be malignant on cytopathological analysis or
exhibit rapid growth, pregnancy should not be interrupted but surgery should be offered in the second trimester, before
fetal viability. Women found to have cytology indicative of papillary cancer or follicular neoplasm without evidence of
advanced disease, who prefer to wait until the postpartum period for definitive surgery, may be reassured that most
well-differentiated thyroid cancers are slow growing and that surgical treatment soon after delivery is unlikely to
change prognosis. The USPSTF recommendation level is B; evidence is fair (GRADE 1 | ++OO) (Mazzaferri & Jhiang,
1994; Moosa & Mazzaferri, 1997; Vini et al., 1999; Herzon et al., 1994).
It is appropriate to administer thyroid hormone to achieve a suppressed but detectable TSH in pregnant women with a
previously treated thyroid cancer, or a FNA positive for or suspicious for cancer, and those who elect to delay surgical
treatment until postpartum. High-risk patients may benefit more from a greater degree of TSH suppression compared
with low-risk patients. The free T 4 or total T 4 levels should ideally not be increased above the normal range for
pregnancy. The USPSTF recommendation level is I; evidence is poor (+OOO) (Rosen, Korman, & Walfish, 1997).
Radioactive iodine (RAI) with 131-I should not be given to women who are breast-feeding. The USPSTF
recommendation level is B; evidence is fair. Furthermore, pregnancy should be avoided for 6 months to 1 year in
women with thyroid cancer who receive therapeutic RAI doses to ensure stability of thyroid function, and confirm
remission of thyroid cancer. The USPSTF recommendation level is B; evidence is fair (GRADE 1 | ++OO) (Choe &
McDougall, 1994; Schlumberger et al., 1995; Chow et al., 2004).
Iodine Nutrition during Pregnancy
Women in the childbearing age should have an average iodine intake of 150 micrograms/day. During pregnancy and
breast-feeding, women should increase their daily iodine intake to 250 micrograms on average. The USPSTF
recommendation level A; evidence is good (GRADE 1| +++O) (Glinoer, 2001; Glinoer, 2003; World Health Organization,
2005; Hollowell et al., 1998).
Iodine intake during pregnancy and breastfeeding should not exceed twice the daily recommended nutrient intake (RNI)
for iodine (i.e. 500 micrograms iodine/day). The USPSTF recommendation level is I; evidence is poor (+OOO) (Glinoer,
2001; Glinoer, 2003; World Health Organization, 2005; Hollowell et al., 1998).
To assess the adequacy of the iodine intake during pregnancy in a population, urinary iodine concentration (UIC) should
be measured in a representative cohort of the population. UIC should ideally range between 150 and 250
micrograms/liter. The USPSTF recommendation level A; evidence is good (GRADE 1 | ++++) (Delange, 2004).
To reach the daily RNI for iodine, multiple means must be considered, tailored to the iodine intake level in a given
population. Different situations must therefore be distinguished: 1) countries with iodine sufficiency and/or with a well-
established universal salt iodinization (USI) program, 2) countries without a USI program or with an established USI
program where the coverage is known to be only partial, and 3) remote areas with no accessible USI program and
difficult socioeconomic conditions. The USPSTF recommendation level is A; evidence is good (GRADE 1 | ++++)
(Glinoer et al., 1995; Chaouki & Benmiloud, 1994; Liesenkotter et al., 1996; Nohr & Laurberg, 2000; Romano et al.,
1991).
Postpartum Thyroiditis
There are insufficient data to recommend screening of all women for postpartum thyroiditis (PPT). The USPSTF
recommendation level is I; evidence is poor (+OOO) (Stagnaro-Green, 2002; Muller, Drexhage, & Berghout, 2001).
Women known to be thyroid peroxidase antibody (TPO-Ab)-positive should have a TSH performed at 3 and 6 months
postpartum. The USPSTF recommendation level is A; evidence is good (GRADE 1 | +++O) (Stagnaro-Green, 2002;
Premawardhana et al., 2004).
The prevalence of PPT in women with type 1 diabetes mellitus (DM) is 3-fold greater than in the general population.
Postpartum screening (TSH determination) is recommended for women with type 1 DM at 3 and 6 months postpartum.
The USPSTF recommendation level is B; evidence is fair (GRADE 1 | ++OO) (McCanlies et al., 1998; Alvarez-Marfany et
al., 1994; Gerstein, 1993).
Women with a history of PPT have a markedly increased risk of developing permanent primary hypothyroidism in the 5-
to 10-year period following the episode of PPT. An annual TSH level should be performed in these women. The USPSTF
recommendation level is A; evidence is good (GRADE 1 | +++O) (Azizi, 2005; Othman et al., 1990; Premawardhana et
al., 2000; Tachi et al., 1988).
Asymptomatic women with PPT who have a TSH above the reference range but less than 10 U/ml and who are not
planning a subsequent pregnancy do not necessarily require intervention, but should, if untreated, be remonitored in 4
to 8 weeks. Symptomatic women and women with a TSH above normal and who are attempting pregnancy should be
treated with levothyroxine. The USPSTF recommendation level is B; evidence is fair (GRADE 1 | ++OO) (Stagnaro-
Green, 2002).
Postpartum screening (TSH determination) is recommended for women with type 1 DM at 3 and 6 months postpartum.
The USPSTF recommendation level is B; evidence is fair (GRADE 1 | ++OO) (McCanlies et al., 1998; Alvarez-Marfany et
al., 1994; Gerstein, 1993).
Women with a history of PPT have a markedly increased risk of developing permanent primary hypothyroidism in the 5-
to 10-year period following the episode of PPT. An annual TSH level should be performed in these women. The USPSTF
recommendation level is A; evidence is good (GRADE 1 | +++O) (Azizi, 2005; Othman et al., 1990; Premawardhana et
al., 2000; Tachi et al., 1988).
Asymptomatic women with PPT who have a TSH above the reference range but less than 10 U/ml and who are not
planning a subsequent pregnancy do not necessarily require intervention, but should, if untreated, be remonitored in 4
to 8 weeks. Symptomatic women and women with a TSH above normal and who are attempting pregnancy should be
treated with levothyroxine. The USPSTF recommendation level is B; evidence is fair (GRADE 1 | ++OO) (Stagnaro-
Green, 2002).
There is insufficient evidence to conclude whether an association exists between postpartum depression (PPD) and
either PPT or thyroid antibody positivity (in women who did not develop PPT). The USPSTF recommendation level is I;
evidence is poor (Kuijpens et al., 1998; Lucas et al., 2000; Cox, Murray, & Chapman, 1993; Stamp & Crowther, 1994;
Harris et al., 1992; Pop et al., 1993). However, as hypothyroidism is a potentially reversible cause of depression,
women with postpartum depression should be screened for hypothyroidism and appropriately treated. The USPSTF
recommendation level is B; evidence is fair (GRADE 2 | ++OO) (Cleare et al., 1996).
Screening for Thyroid Dysfunction during Pregnancy
Although the benefits of universal screening for hypothyroidism may not be justified by current evidence, as presented
in Sections 1 to 7 in the original guideline document, we recommend case finding among the following groups of
women at high risk for thyroid dysfunction:
1.Womenwithahistoryofhyperthyroidorhypothyroiddisease,PPT,orthyroidlobectomy
2.Womenwithafamilyhistoryofthyroiddisease
3.Womenwithagoiter
4.Womenwiththyroidantibodies(whenknown)
5.Womenwithsymptomsorclinicalsignssuggestiveofthyroidunderfunctionoroverfunction,includinganemia,
elevated cholesterol, and hyponatremia
6.WomenwithtypeIdiabetes
7.Womenwithotherautoimmunedisorders
8.WomenwithinfertilityshouldhavescreeningwithTSHaspartoftheirinfertilitywork-up
9.Womenwithpriortherapeuticheadorneckirradiation
10.
Womenwithapriorhistoryofmiscarriageorpretermdelivery
The USPSTF recommendation level is B; evidence is fair (GRADE 1 | ++OO).
Definitions:
Strength of Evidence
The United States Preventive Services Task Force (USPSTF) grades the overall evidence for a service on a three-point
scale (good, fair, or poor):
Good: Evidence includes consistent results from well designed, well conducted studies in representative populations
that directly assess effects on health outcomes.
Fair: Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the
number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the
evidence on health outcomes.
Poor: Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies,
important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health
outcomes.
Strength of Recommendation
A: The USPSTF strongly recommends that clinicians provide (the service) to eligible patients. The USPSTF found good
evidence that (the service) improves important health outcomes and concludes that benefits substantially outweigh
harms.
B: The USPSTF recommends that clinicians provide (the service) to eligible patients. The USPSTF found at least fair
evidence that (the service) improves important health outcomes and concludes that benefits outweigh harms.
C: The USPSTF makes no recommendation for or against routine provision of (the service). The USPSTF found at least
fair evidence that (the service) can improve health outcomes but concludes that the balance of benefits and harms is
too close to justify a general recommendation.
D: The USPSTF recommends against routinely providing (the service) to asymptomatic patients. The USPSTF found
good evidence that (the service) is ineffective or that harms outweigh benefits.
I: The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing (the service).
Evidence that (the service) is effective is lacking, or poor quality, or conflicting, and the balance of benefits and harms
cannot be determined.
Evidence Level by GRADE System
High: ++++ or +++O
Moderate: ++OO
Low: +OOO
Very Low: OOOO
Recommendation Level by GRADE System
1: Strong
2: Moderate

Clinical Algorithm(s)
Moderate: ++OO
Low: +OOO
Very Low: OOOO
Recommendation Level by GRADE System
1: Strong
2: Moderate

Clinical Algorithm(s)
None provided

Evidence Supporting the Recommendations


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Type of Evidence Supporting the Recommendations


The type of evidence supporting the recommendations is specifically stated for each recommendation.

Benefits/Harms of Implementing the Guideline Recommendations


Potential Benefits
Appropriate diagnosis and management of thyroid dysfunction during pregnancy and postpartum

Potential Harms
l Subclinicalhypothyroidism(SCH)(serumthyroid-stimulating hormone [TSH] concentration above the upper limit of
the reference range with a normal free T4) has been shown to be associated with an adverse outcome for both the
mother and offspring.
l Overtreatmentofthemotherwiththioamidescanresultiniatrogenicfetalhypothyroidism.
l Treatmentofmaternalsubclinicalhyperthyroidismhasnotbeenfoundtoimprovepregnancyoutcomeandmayrisk
unnecessary exposure of the fetus to antithyroid drugs (ATDs).
l Therehavebeenreportsoftwodistinctteratogenicpatternsassociatedwithmethimazole(MMI):aplasiacutis
and choanal/esophageal atresia.
l Useofpropranololinlatepregnancyhasbeenassociatedwithmildandtransitoryneonatalhypoglycemia,apnea,
and bradycardia. Finally, there are case reports suggesting an association between propranolol use and intrauterine
growth restriction, but this remains controversial.
l Fetalexposuretohighdosesofradiationbeforeorganogenesis(before4to6weeksgestation)canleadto
miscarriage or have no effect. Radiation exposure later in gestation can be associated with malformations, growth
restriction, developmental delay and induction of malignancies.
l Exposureafter12weekscaninducethyroidablation,requiringintrauterinethyroidhormonereplacementand
lifelong therapy for hypothyroidism.
l Ifsurgeryiselectedinpregnancy,itisbestavoidedinthefirstandthirdtrimester.Duringthefirsttrimester,
there is concern over the possible teratogenic effects on the fetus, and surgery of any type is associated with
increased early fetal loss. Surgery of any type in the third trimester is associated with a higher incidence of preterm
labor. For cancer found early in pregnancy, surgery during the second trimester before fetal viability (<22 weeks)
appears safe for the patient and the fetus. Fetal loss has been reported only in association with extensive neck
exploration.
l Excessivelevelsofiodineintakemaypotentiallycausemoredisease.Furthermore,individualsmustbeidentified
who may have side effects from excessive iodine intake, such as patients with known or underlying autoimmune
thyroid disorders or autonomous thyroid tissue.

Contraindications
Contraindications
l Becausetheexperiencewithiodidesismorelimited,iodidesshouldnotbeusedasafirst-line therapy for women
with Graves' disease, but they could be used transiently if needed in preparation for thyroidectomy.
l Radioactiveiodine(RAI)diagnostictestsandtherapyarecontraindicatedduringpregnancy,andallwomenwho
could potentially become pregnant should have a pregnancy test before 131-I administration.
l Inaddition,131-I is contraindicated in breast-feeding mothers, and breast-feeding should cease if the exposure is
unavoidable.
Contraindications
Contraindications
l Becausetheexperiencewithiodidesismorelimited,iodidesshouldnotbeusedasafirst-line therapy for women
with Graves' disease, but they could be used transiently if needed in preparation for thyroidectomy.
l Radioactiveiodine(RAI)diagnostictestsandtherapyarecontraindicatedduringpregnancy,andallwomenwho
could potentially become pregnant should have a pregnancy test before 131-I administration.
l Inaddition,131-I is contraindicated in breast-feeding mothers, and breast-feeding should cease if the exposure is
unavoidable.

Qualifying Statements
Qualifying Statements
l ClinicalPracticeGuidelinesaredevelopedtobeofassistancetoendocrinologistsbyprovidingguidanceand
recommendations for particular areas of practice. The Guidelines should not be considered inclusive of all proper
approaches or methods, or exclusive of others. The Guidelines cannot guarantee any specific outcome, nor do they
establish a standard of care. The Guidelines are not intended to dictate the treatment of a particular patient.
Treatment decisions must be made based on the independent judgment of healthcare providers and each patient's
individual circumstances.
l TheEndocrineSocietymakesnowarranty,expressorimplied,regardingtheGuidelinesandspecificallyexcludes
any warranties of merchantability and fitness for a particular use or purpose. The Society shall not be liable for direct,
indirect, special, incidental, or consequential damages related to the use of the information contained herein.

Implementation of the Guideline


Description of Implementation Strategy
An implementation strategy was not provided.

Implementation Tools
Chart Documentation/Checklists/Forms

Foreign Language Translations

Patient Resources

Quick Reference Guides/Physician Guides


For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories


IOM Care Need
Getting Better

Living with Illness

IOM Domain
Effectiveness

Safety

Identifying Information and Availability


Bibliographic Source(s)
The Endocrine Society. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society
clinical practice guideline. Chevy Chase (MD): The Endocrine Society; 2007. 79 p. [281 references]

Adaptation
Not applicable: The guideline was not adapted from another source.

Date Released
2007

Guideline Developer(s)
The Endocrine Society - Disease Specific Society

Source(s) of Funding
The Endocrine Society

Guideline Committee
Thyroid Dysfunction during Pregnancy and Postpartum Guideline Task Force

Composition of Group That Authored the Guideline


Task Force Members: Marcos Abalovich; Nobuyuki Amino; Linda A. Barbour; Rhoda H. Cobin; Leslie J. De Groot; Daniel
Glinoer; Susan J. Mandel; Alex Stagnaro-Green

Financial Disclosures/Conflicts of Interest


Leslie J. DeGroot, MD( chair) Significant Financial Interests: None Declared; Governance: None Declared;
Consultation or Advisement: Occasional consultant with Abbott Laboratories; Grant or Other Research Support: None
Thyroid Dysfunction during Pregnancy and Postpartum Guideline Task Force

Composition of Group That Authored the Guideline


Task Force Members: Marcos Abalovich; Nobuyuki Amino; Linda A. Barbour; Rhoda H. Cobin; Leslie J. De Groot; Daniel
Glinoer; Susan J. Mandel; Alex Stagnaro-Green

Financial Disclosures/Conflicts of Interest


Leslie J. DeGroot, MD( chair) Significant Financial Interests: None Declared; Governance: None Declared;
Consultation or Advisement: Occasional consultant with Abbott Laboratories; Grant or Other Research Support: None
Declared; Other: Grant support to Thyroidmanager.org Web site by Abbott Laboratories.
Marcos S. Abalovich, MD Significant Financial Interests: None Declared; Governance: None Declared; Consultation or
Advisement: None Declared; Grant or Other Research Support: None Declared.
Nobuyuki Amino, MD, PhD Significant Financial Interests: None Declared; Governance: None Declared; Consultation
or Advisement: None Declared; Grant or Other Research Support: None Declared.
Linda A. Barbour, MSPH, MD Significant Financial Interests: None Declared; Governance: None Declared;
Consultation or Advisement: None Declared; Grant or Other Research Support: None Declared.
Rhoda H. Cobin, MD Significant Financial Interests: None Declared; Governance: None Declared; Consultation or
Advisement: None Declared; Grant or Other Research Support: None Declared.
Daniel Glinoer, MD, PhD Significant Financial Interests: None Declared; Governance: None Declared; Consultation or
Advisement:NoneDeclaredGrantorOtherResearchSupport:MinistredelaCommunautFranaise(Administration
Gnraledel'EnseignementetdelaRechercheScientifique)withintheframeworkofA.R.C.(ActionsdeRecherche
ConcerteconventionN04/09-314).
Susan J. Mandel, MD, MPH Significant Financial Interests: None Declared; Governance: None Declared; Consultation
or Advisement: King Pharmaceuticals; Grant or Other Research Support: None Declared.
Alex Stagnaro-Green, MD Significant Financial Interests: None Declared; Governance: None Declared; Consultation
or Advisement: None Declared; Grant or Other Research Support: None Declared.

Guideline Endorser(s)
American Association of Clinical Endocrinologists - Medical Specialty Society

American Thyroid Association - Professional Association

Asian & Oceania Thyroid Association - Disease Specific Society

European Thyroid Association - Disease Specific Society

Latin AmericanThyroid Association - Disease Specific Society

Guideline Status
This is the current release of the guideline.

Guideline Availability

Electronic copies: Available in Portable Document Format (PDF) from The Endocrine Society .
Print copies: Available from The Endocrine Society, c/o Bank of America, P.O. Box 630721, Baltimore, MD 21263-0736;
Phone: (301) 941.0210; Email: Societyservices@endo-society.org

Availability of Companion Documents


The following is available:
l Managementofthyroiddysfunctionduringpregnancyandpostpartum:anEndocrineSocietyclinicalpractice
guideline. Executive summary. 2007. 14 p. Electronic copies: Available in Portable Document Format (PDF) from The

Endocrine Society .
Print copies: Available from The Endocrine Society, c/o Bank of America, P.O. Box 630721, Baltimore, MD 21263-0736;
Phone: (301) 941.0210; Email: Societyservices@endo-society.org

Patient Resources
The following are available:
l Patientguideonmaternalthyroidnodulesandcancerbefore,during,andafterpregnancy.Electroniccopies:

Available in Portable Document Format (PDF) from The Hormone Foundation Web site . See the related

QualityTool summary on the Health Care Innovations Exchange Web site .


l Patientguidetothemanagementofmaternalhyperthyroidismbefore,duringandafterpregnancy.Electronic

copies: Available in Portable Document Format (PDF) from The Hormone Foundation Web site . See the related

QualityTool summary on the Health Care Innovations Exchange Web site .


l Patientguidetothemanagementofmaternalhypothyroidismbefore,duringandafterpregnancy.Electronic

copies: Available in Portable Document Format (PDF) from The Hormone Foundation Web site . See the related

QualityTool summary on the Health Care Innovations Exchange Web site .


l Postpartumthyroiditisfactsheet.Electroniccopies:AvailableinSpanishandEnglishinPortableDocumentFormat

(PDF) from The Hormone Foundation Web site . See the related QualityTool summary on the Health Care
copies: Available in Portable Document Format (PDF) from The Hormone Foundation Web site . See the related

QualityTool summary on the Health Care Innovations Exchange Web site .


l Patientguidetothemanagementofmaternalhypothyroidismbefore,duringandafterpregnancy.Electronic

copies: Available in Portable Document Format (PDF) from The Hormone Foundation Web site . See the related

QualityTool summary on the Health Care Innovations Exchange Web site .


l Postpartumthyroiditisfactsheet.Electroniccopies:AvailableinSpanishandEnglishinPortableDocumentFormat

(PDF) from The Hormone Foundation Web site . See the related QualityTool summary on the Health Care

Innovations Exchange Web site .


Please note: This patient information is intended to provide health professionals with information to share with their patients to help them
better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC
to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then
to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to
their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals
included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether
or not it accurately reflects the original guideline's content.

NGC Status
This NGC summary was completed by ECRI Institute on November 1, 2007. The information was verified by the
guideline developer on December 10, 2007. This summary was updated by ECRI Institute on June 15, 2009 following
the FDA advisory on Propylthiouracil (PTU). This summary was updated by ECRI Institute on May 27, 2010 following the
revised FDA advisory on Propylthiouracil (PTU).

Copyright Statement
This is an author manuscript copyrighted by The Endocrine Society. This may not be duplicated or reproduced, other
than for personal use or within the rule of "Fair Use of Copyrighted Materials" (section 107, Title 17, U.S. Code) without
permission of the copyright owner, The Endocrine Society. From the time of acceptance following peer review, the full
text of this manuscript is made freely available by The Endocrine Society at http://www.endo-

society.org/guidelines/Current-Clinical-Practice-Guidelines.cfm .

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