Gynecological Endocrinology

ISSN: 0951-3590 (Print) 1473-0766 (Online) Journal homepage: https://www.tandfonline.com/loi/igye20

2017 ATA guidelines on the management of

thyroid dysfunctions in pregnancy: what do OB/
GYNs need to know?

Mario Rotondi, Valentina Capelli, Luca Chiovato & Rossella E. Nappi

To cite this article: Mario Rotondi, Valentina Capelli, Luca Chiovato & Rossella E. Nappi (2019):
2017 ATA guidelines on the management of thyroid dysfunctions in pregnancy: what do OB/GYNs
need to know?, Gynecological Endocrinology, DOI: 10.1080/09513590.2018.1532496

To link to this article: https://doi.org/10.1080/09513590.2018.1532496

Published online: 05 Feb 2019.

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GYNECOLOGICAL ENDOCRINOLOGY
https://doi.org/10.1080/09513590.2018.1532496

REVIEW ARTICLE

2017 ATA guidelines on the management of thyroid dysfunctions in pregnancy:

what do OB/GYNs need to know?
Mario Rotondia, Valentina Capellia, Luca Chiovatoa and Rossella E. Nappib
a
Department of Endocrinology, IRCCS Maugeri Foundation, University of Pavia, Pavia, Italy; bResearch Center for Reproductive Medicine,
Gynecological Endocrinology and Menopause, IRCCS S. Matteo Hospital, University of Pavia, Italy

ABSTRACT ARTICLE HISTORY

In the past two decades, the issue of thyroid dysfunctions during pregnancy and the postpartum period Received 23 August 2018
received increasing attention by both endocrinologists and obstetrics/gynecologists (OB/GYNs), the latter Revised 2 September 2018
often became the first to diagnose an impaired thyroid function in pregnant women. In this setting, a ser- Accepted 2 October 2018
ies of different clinical guidelines have been published and reviewed, the latest ones being represented Published online 5 February
2019
by the 2017 ATA guidelines, which extensively address a wide variety of topics, including iodine supple-
mentation, thyroid autoimmunity, hyper- and hypo-thyroidism, thyroid nodules and cancer, post-partum KEYWORDS
management, as well as the need for pre-conception screening. Aim of this editorial is to offer a practical Thyroid; pregnancy;
guidance to the OB/GYN reader by focusing upon evidence-based changes introduced by the latest guidelines; screening;
guidelines, with particular regard to: (a) prescribing further endocrine testing before referral; (b) providing hypothyroidism
evidence-based answers to some of the frequently asked questions.

Introduction the first to diagnose thyroid abnormalities in pregnant women

and/or in those with reproductive wishes. As a result, they often
Thyroid dysfunctions during pregnancy and the post-partum
face the problem of answering questions of worried future moth-
period received increasing attention by endocrinologists, and even
ers about the potential repercussions of their thyroid condition.
obstetricians and gynecologists (OB/GYNs) became progressively
That being so, to save time and to allow an early detection and
more concerned about thyroid status in pregnant women. In the
last two decades, clinical guidelines on thyroid dysfunctions in treatment of thyroid dysfunctions in pregnancy: (a) OB/GYNs
pregnancy from the Endocrine-Society (ES) [1], American- potentially have to prescribe further endocrine testing before
Thyroid-Association (ATA) [2,3], and European-Thyroid- referral to endocrinologists; (b) OB/GYNs should be able to pro-
Association (ETA) [4] followed each other at regular intervals. vide evidence-based answers to some of the commonly
The latest 2017-ATA guidelines addressed a wide spectrum of asked questions.
topics, including iodine supplementation, hyper- and hypo-thy-
roidism, thyroid nodules and cancer, post-partum management,
and pre-conception screening [3]. The issue of thyroid disease in Raised serum TSH in a pregnant woman: back to
fertility care was also taken into account. Each recommendation is the past
followed by a detailed explanation of supporting literature evi-
The 2011-ATA guidelines established a cutoff for normal TSH of
dence, most of which was published after the previous 2011-ATA
Guidelines. This short commentary focuses on what actually <2.5 lU/ml, which implied initiation of L-thyroxine (LT4) substi-
changed in the 2017-ATA Guidelines, particularly with regard to tution therapy in pregnant women with a TSH ranging from
the underlined need for a multi-disciplinary (endocrinologists, 2.5 lU/ml to the upper limit of normal range [2].
OB/GYNs, neonatologists and paediatricians) management aimed The most relevant change introduced by the 2017-ATA
at ensuring adequate care of mothers and new-borns. It is import- Guidelines regarding a re-definition of the TSH normal range,
ant noting that, at least for some specific sections, the recommen- which in the absence of in-house established values (a still
dations of the panel were also discussed with the American- unrealistic goal), should be calculated by reducing by 0.5 mU the
College-of-Obstetricians-and-Gynaecologists’ Committee (ACOG) upper limit of the non-pregnant reference range. This indication
and the Society-for-Maternal-and-Foetal-Medicine. implies that, using the main commercial kits for the measure-
In this work, our aim is not to provide a comprehensive ment of TSH, the normal range would fall between 0.4 and
review of the topic, but rather to offer a practical guidance to 4.0 mU/L (3). The recommendation for this novel TSH range in
the OB/GYN reader by focusing on evidence-based changes pregnant women stems from data derived from four large series
introduced by the latest guidelines. In particular, we will specific- published after the 2011-ATA guidelines. These surveys included
ally address those clinical situations requiring the need to dis- nearly 20 times as much women as before [5–8], thus represent-
criminate when to refer women to an endocrinological setting. ing a more adequate population for drawing conclusions as to a
Indeed, it is becoming increasingly frequent that OB/GYNs are normal reference range.

CONTACT Rossella E. Nappi [email protected] Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause, IRCCS S. Matteo
Hospital, University of Pavia, Piazzale Golgi 2, 27100 Pavia, Italy
ß 2019 Informa UK Limited, trading as Taylor & Francis Group
2 M. ROTONDI ET AL.

Clinical consequences of the new TSH reference range 20–24 weeks of gestation [2], the 2017 panel recommends that in
for pregnancy every patient with past or present history of Graves’ disease a
TRAb determination should be performed early during preg-
The first, and not negligible, consequence of raising the upper nancy [3]. In the case of low/undetectable results, no further
threshold for a normal TSH to 4.0mU/L is a reduction in the TRAb testing is necessary. Conversely, in patients with elevated
number of women with SH. The reduction in the prevalence of TRAb concentration and/or taking ATD treatment, testing
diagnosed SH is much greater than one could expect because the should be repeated at weeks 18–22 and in late pregnancy (weeks
distribution curve of normal TSH is skewed to the left [9]. Thus, 30–34) in order to assess the need for neonatal and postnatal
an 80% drop in the diagnosis of new cases of hypothyroidism is monitoring [3]. The indications for fetal surveillance remains
easily envisaged. This implies a much smaller number of preg- unchanged, and comprise uncontrolled hyperthyroidism in the
nant women requiring LT4 substitution treatment. second half of pregnancy or elevated TRAb levels at any time.
Fetal ultrasound should include the assessment of (1) fetal heart
rate, (2) fetal growth, (3) amniotic fluid volume, (4) presence of
Once a raised TSH is documented, which additional
fetal goiter [3]. OB/GYNs should be aware that a positive history
tests should be performed?
of GD, even when hyperthyroidism is in long-term remission
Measure TSH – do not measure FT4 – but measure TPOAb after medical treatment, implies that: (1) TRAb should be meas-
ured during pregnancy; (2) patients should be informed
At variance with the 2011-ATA guidelines, the 2017-ATA about the high risk of recurrence of hyperthyroidism in the post-
Guidelines do not recommend routinely assaying FT4 in preg- partum period.
nant women [3]. Thus, FT4 levels are no longer needed for clin-
ical decision making (treat or not treat with LT4), this decision
is based upon the circulating thyroid auto-antibodies Thyroid function and fertility care
status. Thus, the recommendation indicates to measure thyroid-
In 2011, the issue of women undergoing Assisted-Reproduction-
peroxidase-antibody (TPOAb) in pregnant women found to have
Technologies (ART) was specifically addressed for two aspects
an elevated serum TSH (from 4.0 to 10.0mU/L). LT4 treatment
only: (1) the routine screening for thyroid autoantibodies and (2)
should be always initiated when positive results for TPOAb are
the initiation of LT4 treatment in euthyroid women undergoing
obtained. The main reason for treating SH in TPOAb-positive
in vitro fertilization (IVF). In both cases, the panelists found no
women would be to prevent progression to overt hypothyroidism
sufficient evidence to recommend for or against those actions
during gestation. Indeed, overt hypothyroidism is a well-estab-
[2]. From 2011 to 2016, the attention to fertility care has rapidly
lished cause of maternal and fetal complications, which include
grown, with a concomitant raised attention on the role of thy-
anemia, pre-eclampsia, placental abruption, post-delivery hemor-
roid function in this context. In the 2017-ATA Guidelines, the
rhage, and other, less common, pathologic conditions [10,11]. authors performed an extensive revision of available data taking
The previously reported association between SH and impaired into consideration more than 50 papers, most of which were
neuropsychological development of the progeny [12,13], which published after 2011. The only strong recommendation relates to
largely influenced the 2011 recommendation for LT4 treatment the management of hypothyroid women (both overt and subclin-
in SH, was questioned by recently published prospective, ical) undergoing ART. At variance with what indicated in spon-
randomized intervention studies [14,15]. On the contrary, in taneous pregnancies, LT4 treatment is highly recommended in
women with negative tests for TPOAb and a TSH level between women undergoing ART if their TSH is higher than 2.5mU/L,
4 and 10 mU/L, as well as in those with positive tests for TPOAb which is actually the old cutoff for TSH [3].
and a TSH level between 2.5 and 4 mU/L, the recommendation All the other recommendations are weak, and supported by
is to consider treatment according to the case-specific clinician’s low- to moderate-quality evidence. These include the need for:
judgment [3]. However, this recommendation was recently ques- (1) TSH screening in women seeking pregnancy; (2) initiating
tioned by an Italian panel of experts proposing the treatment of LT4 therapy in TPOAb-positive euthyroid women (even if TSH
all pregnant women with a TSH level between 4 and 10 lU/ is <2.5mU/L). Finally, due to the influence of ovarian hyper-
ml [16]. stimulation on thyroid function [17], the panel recommends
that, in order to avoid interferences in the assay, TSH measure-
ment should be performed either before or 1–2 weeks after the
Low serum TSH in a pregnant woman: interpretation procedure [3].
and management
At difference with what seen for hypothyroidism, in the latest
2017-ATA guidelines, little has changed for what concerns thyro- What happens after delivery?
toxicosis. Gestational hyperthyroidism associated with hypereme- One of the few novelties of the 2017-ATA recommendations
sis gravidarum still represents the most common cause of newly regarding the post-partum period stems from both animal and
diagnosed thyrotoxicosis in early pregnancy, and the new human studies investigating the influence of thyroid dysfunction
Guidelines do not substantially differ from the previous ones. on breastfeeding. While it is not clear if maternal hyperthyroid-
There is an overall agreement that a strict cooperation with ism may negatively affect lactation, a clear role has been estab-
endocrinologists is necessary in pregnant patients with hyperthy- lished for maternal hypothyroidism [18]. Therefore, the panel
roidism [3]. advices to treat both subclinical and overt hypothyroidism in lac-
Interestingly enough, the 2017 panel gives more precise indi- tating women, as well as to screen for thyroid dysfunction in
cations regarding anti-thyroid drugs (ATD) treatment, thyroid those women experiencing poor lactation without other identi-
function testing, and particularly TSH-receptor antibody (TRAb) fied causes. When ATD initiation is required, the use of these
monitoring in Graves’ disease (GD). Indeed, while in 2011 drugs is confirmed to be safe during lactation, but the lowest
Guidelines TRAb measurement was only indicated at effective dose should be administered [3]. As breast-feeding is
 GYNECOLOGICAL ENDOCRINOLOGY 3

Table 1. Proposed risk factors to select patients to be screened for serum TSH, according to the 2017 ATA guide-
lines (1).
1. A history of hypothyroidism/hyperthyroidism or current symptoms/signs of thyroid dysfunction
2. Known thyroid antibody positivity or presence of a goiter
3. History of head or neck radiation or prior thyroid surgery
4. Age >30 years
5. Type 1 diabetes or other autoimmune disorders
6. History of pregnancy loss, preterm delivery, or infertility
7. Multiple prior pregnancies (‡2)
8. Family history of autoimmune thyroid disease or thyroid dysfunction
9. Morbid obesity (BMI ‡40 kg/m2)
10. Use of amiodarone or lithium, or recent administration of iodinated radiologic contrast
11. Residing in an area of known moderate to severe iodine insufficiency

TSH screening in a pregnant woman (mU/L)

Low Normal range High

<0.4 0.4-4 >4

Spontaneous pregnancy

ART pregnancy
(opmal <2,5)

<2,5 >2,5

FT4, FT3
Further tesng No need TPOAb
TRAb*§

Refer to Endo? Yes No need May be considered Yes

* Should also be measured in all paent with history of Graves’ disease (GD)
§ If posive, repeat at 18-22 wk and 30-34 wk
Figure 1. Algorithm for thyroid diseases in pregnancy.

important both from a physiological as well as from a psycho- optimally be started at least 3 months in advance [3]. A likely
logical standpoint, mothers should not be discouraged but should good strategy could be to advise iodine supplementation together
be instructed to take their ATD dose just after breast-feeding, with a folic acid prescription. On the other hand, no clear indi-
which should provide a 3–4 h interval before subse- cation is provided by the 2017-ATA guidelines on whether or
quent lactation. not to start iodine supplementation in women who are being
treated for hyper- or hypothyroidism.
Focus on iodine supply: when, how much, how long
Maternal and fetal iodine deficiency still represents the major Pre-conception/antenatal screening for thyroid
cause of preventable intellectual deficits worldwide. Several stud- dysfunction: to whom and why
ies published from 2011 to 2016 did not substantially modify the The most relevant novel indication present in the 2017-ATA
previous recommendations, but rather strengthened their level of guidelines (3) is the recommendation that women planning
evidence. In fact, even if the iodine status is still not considered assisted reproduction should have TSH measurement as part of
adequate worldwide [19,20], an initial benefit from the adopted
their work-up. In addition, the categories of patients considered
prevention strategies was registered. The indications can be sum-
to be at high risk for thyroid dysfunction throughout gestation
marized as follows: (1) the adequate iodine intake for pregnancy
(and in whom TSH measurement should be performed) was fur-
and lactation is approximately 250 lg/day, (2) this amount
ther increased (Table 1).
should be reached through country-related specific strategies
(e.g. in the US a daily supplementation of 150 lg/day is consid-
ered enough), (3) excess supplementation (>500 lg/day) should Final remarks
be avoided [3].
The most relevant new recommendation regards women plan- This article pointed to underline the most recent ATA-clinical-
ning pregnancy, in whom iodine supplementation should guidelines on thyroid disease in pregnancy (Figure 1) and should
4 M. ROTONDI ET AL.

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