Mini Review

Thyroid disorders in pregnancy

Menaka Ramprasad, Shaila Shamanur Bhattacharyya, Arpandev Bhattacharyya
ShivaJoyti, A Center for Paediatric and Adult Diabetes and Endocrine Disorders, Bangalore, India

A B S T R A C T

Thyroid disorders are common in pregnancy and the most common disorder is subclinical hypothyroidism. Due to the complex
hormonal changes during pregnancy, it is important to remember that thyroxine requirements are higher in pregnancy. According to
recent American Thyroid Association (ATA) guidelines, the recommended reference ranges for TSH are 0.1 to 2.5 mIU/L in the first
trimester, 0.2 to 3.0 mIU/L in the second trimester, and 0.3 to 3.0 mIU/L in the third trimester. Maternal hypothyroidism is an easily
treatable condition that has been associated with increased risk of low birth weight, fetal distress, and impaired neuropsychological
development. Hyperthyroidism in pregnancy is less common as conception is a problem. Majority of them are due to Graves’ disease,
though gestational hyperthyroidism is to be excluded. Preferred drug is propylthiouracil (PTU) with the target to maintain free T4 in
upper normal range. Doses can be reduced in third trimester due to the immune-suppressant effects of pregnancy. Early and effective
treatment of thyroid disorder ensures a safe pregnancy with minimal maternal and neonatal complications.

Key words: Thyroid disorders, pregnancy, hypothyroidism

Introduction receptor because of partial structural similarity[1,2] [Figure 1].

A large plasma volume and thus an altered distribution of
Thyroid disorders are encountered frequently during thyroid hormone, increased thyroid hormone metabolism,
pregnancy and the postpartum period. Thyroid disease is increased renal clearance of iodide, and higher levels of
the second most common endocrine condition encountered hepatic production of thyroxine-binding globulin (TBG)
in the hyperestrogenic state of pregnancy are responsible
in women of childbearing age after diabetes. Most of
for higher thyroxine requirements in pregnancy.[3] It is very
these conditions are treatable, and may affect mother and
important to remember that biochemical thyroid function
fetus adversely if they are not evaluated and managed
should be free thyroid hormone, as total hormone will
appropriately. mislead showing more than normal value when the patient
is euthyroid.
Pregnancy is a time of complex hormonal changes. In
women with normal thyroid function, there is an increase in Pregnancy and Hypothyroidism
thyroxine (T4) and triiodothyronine (T3) production, which Clinical or subclinical thyroid disorders are usually detected
results in inhibition of thyroid-stimulating hormone (TSH) during pre-conceptional counseling or in women who have
in the first trimester of pregnancy, due to a high human just conceived and have done tests for thyroid function.
chorionic gonadotropin (hCG) level that stimulates the TSH According to recent American Thyroid Association (ATA)
guidelines, if laboratory-dependent, trimester-specific
ranges for TSH are not available, the recommended
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reference ranges for TSH are 0.1 to 2.5 mIU/L in the first
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trimester, 0.2 to 3.0 mIU/L in the second trimester, and
Website:
www.ijem.in 0.3 to 3.0 mIU/L in the third trimester.[4]

DOI: The typical case is a women in the first trimester of

10.4103/2230-8210.104031 pregnancy who is referred with a high TSH value with
the free thyroid hormones in the low normal range or

Corresponding Author: Dr. A Bhattacharyya, ShivaJoyti, 3366, 13th Main, Indiranage, Bangalore – 560 008, India.
E-mail: [email protected]

Indian Journal of Endocrinology and Metabolism / Vol 16 / Supplement 2 S167

 Ramprasad, et al.: Thyroid disorders pregnancy

with frank hypothyroidism and in certain instances with should be taken on an empty stomach (45 minutes before
biochemical euthyroxinemia with TPO antibody positivity. consumption of food, beverages, or other medications). In
The presence of thyroid antibody, even in euthyroid addition, calcium, iron, and prenatal vitamin supplements
patients, has been shown to be associated with increased should be avoided within four hours of ingestion of LT4, as
number of miscarriage, perinatal death, and postpartum these can decrease the absorption of thyroxine. In a typical
dysfunction, low motor and intellectual development case, the dose requirement goes up as pregnancy advances,
in the offspring.[5] But, till now, biochemical normal as pregnancy is a hypermetabolic condition [Table 1]. Our
thyroid test with positive antibody do not make a case for aim is to keep the free thyroxine value in the upper normal
thyroxine supplement. We need more data before we start range.[7] We keep on counseling patients on this so that their
recommending therapy in such a situation. compliance remains perfect.

Maternal hypothyroidism has been associated with Immediately after delivery, the requirement of the thyroxine
increased risk of low birth weight, fetal distress, and drops and women who were taking thyroixine prior to
impaired neuropsychological development. Haddow and pregnancy will shift to their pre-pregnancy dose and those
colleagues described a 7-point IQ deficit in 7- to 9-year- who started their thyroxine in pregnancy will require
half the dose they were taking just before delivery. In
old children born to untreated hypothyroid women when
women who had started their thyroxine in pregnancy for
compared with age-matched children born to euthyroid
subclinical hypothyroidism, the medication can be stopped
women of less than 85, compared with 5% of controls.[6]
after delivery and thyroid balance re-assessed again after
six weeks and decision taken regarding continuation of
All women with overt and subclinical hypothyroidism
treatment. Obviously, some of these women goes through
should be treated irrespective of thyroid peroxidase (TPO)
post-partum thyroiditis and requires thyroxine replacement
antibody positivity with LT4 during pregnancy to maintain
for a longer time.
serum TSH in the trimester-specific goal range. It has
been recommended to check serum TSH every four weeks Pregnancy and Hyperthyroidism
during pregnancy so that appropriate dose adjustments can Conception is usually more of a problem in untreated
be made,[4] but our routine practice is to check every six hyperthoidism. Majority of the disorders are due to Graves’
weeks. The recommended therapy is with oral LT4, which disease. In the first trimester, there may be deterioration
in control due to reduced absorption of medication
secondary to vomiting or to hCG-driven stimulation of
TSH receptors. In the third trimesters, typically, treatment
doses can be reduced due to the immune-suppressant
effects of pregnancy as is seen in other autoimmune
conditions like rheumatoid arthritis, systemic lupus etc. The
typical ill-effects in pregnancy are accelerated hyperemesis
of pregnancy requiring repeated hospital admission for
intravenous fluid therapy, repeated miscarriage, poor
growth of fetus, premature delivery, pregnancy-induced
hypertension, etc. Untreated mother can also develop
thyrotoxic crisis, fortunately rare now with an early
diagnosis and effective treatment. Other uncommon effects
rarely seen now-a-days are stillbirth. Fetal Graves’ disease
is very rare and happens due to transplacental transfer of
Figure 1: Thyroid hormone profile in the mother and fetus during pregnancy TSH-receptor stimulating antibody.

Table 1: Showing the biochemistry and requirement of thyroxine in pregnancy in a patient with Primary
Hypothyroidism, Bhattacharyya A et al.[7]
Normal value Unit Pre-pregnancy First Trimester Second Third Trimester Post-partum
Trimester
TSH 0.5-4.5 mu/L 1.6 4.1 7.4 0.9 1.4
Free T3 1.5-4.5 pmol/L 4.1 4.7 3.1 3.9 4.2
Free T4 10-23 pmol/L 12.9 17.5 15 21.9 15
Thyroxine dose mcg 100 100 200 200 100

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 Ramprasad, et al.: Thyroid disorders pregnancy

Hyperthyroidism if diagnosed before conception is best authors can remember a single case they referred to surgeons
treated before conception in case radioactive iodine for uncontrolled hyperthyroidism in pregnancy.
is given; current recommendation is not to conceive
for at least four months. Neonatal outcome is better Breast feeding while on anti-thyroid medication remains a
with fewer anomalies and there is lower chance of sensitive issue; PTU is the preferred medicine as it is more
delivering prematurely if euthyroidism is achieved prior protein-bound and is secreted least in breast milk. Up to 600 mg
to conception, when compared with those women in a day PTU is considered safe; it is recommended to keep
whom either control is achieved in early pregnancy or an eye on growth of the baby clinically with biochemical
later pregnancy, in a stepwise manner. There is chance test for thyroid function if suspected for growth problem.
that they will develop hypothyroidism; we can tackle that
with thyroxine replacement as has been detailed earlier. For Gestational hyperthyroidism or gestational thyrotoxicosis
people diagnosed in the current pregnancy, we straightway is used when there are symptoms of hyperthyroidism
start with anti-thyroid medication. due to the high levels of HCG, which causes thyroid
hyperfunction. This condition needs to be differentiated
The preferred regimen is titration regimen; preferred from Graves’ disease, as most of the symptoms are similar
medicine is propylthiouracil (PTU). Our aim is to keep to those in pregnancy. Up to 15% of normal pregnancy
free T4 in the upper normal range, sometime TSH can be TSH can be suppressed due to hCG effect; they do not
require extra treatment; careful observation is good enough.
little lower than normal range, but we concentrate more
There is another entity in pregnancy called transient
of free T4 as we know TSH takes time to get settled.
gestational thyroticosis, where free thyroid hormone can
Block and replace regimen is not followed in pregnancy
be increased, and they require a short course of anti-thyroid
as thyroxine does not cross placenta freely but anti-thyroid
medication. Gestational thyrotoxicosis is usually transient
medications do. The dose of PTU depends on the control,
and recovers over a period of few weeks. This is essentially
sometime goes even up to 400-800 mg/day. It is to be
a retrospective diagnosis.[9]
given every 8th hourly. Liver function tests should be
monitored with PTU, as there is a risk of hepatotoxicity. Thyroid cancer and pregnancy
Methimazole is not preferred in the first trimester due to Thyroid cancer is the most common endocrine malignancy
the risk of aplasia cutis and the spectrum of birth defects affecting about 14 of 100000 pregnant women. The types
in pregnancy. Methimazole can be given in the second and of cancers seen in pregnant women are the same as in
third trimesters.[8] non-pregnant women. If the cancer is well-differentiated,
surgery can be done in the immediate postpartum period;
As the pregnancy advances, dose requirement comes down in however, in not well-differentiated cancers, surgery can be
most of the cases; one-third of pregnant women can actually done in the second trimester. Post-surgery, radioiodine scan
stop anti-thyroid medication in the third trimester [Table 2]. and ablation is absolutely contraindicated during pregnancy
A significant percentage of these women need to start after and lactation. In women who have been operated and are
delivery for relapse. Our routine practice is to check the on suppressive treatment with levothyroxine, dose should
thyroid function two weeks after delivery as opposed to six be adjusted so as to prevent thyrotoxicosis.[10]
to eight weeks in cases of hypothyroidism. Beta-blockers, if
necessary, can be given for a short duration for controlling Conclusion
symptoms. When thyroidectomy is needed for the control of
hyperthyroidism, it should be planned in the second trimester Thyroid disorders are common in pregnancy, and the
of pregnancy; fortunately, this is very rare, and none of the most common disorder is subclinical hypothyroidism.

Table 2: Showing the thyroid function and treatment of a patient with Graves’ disease in pregnancy treated by the
authors (unpublished)
Six months Three 6 wks* 8 wks 12 wks 17 wks 22 wks 27 wks 30 wks 36 wks 2 wks 6 wks
before months pp pp
conception before
TSH < 0.05 < 0.05 < 0.05 0.4 0.4 1.1 2.3 1.7 2.1 2.9 0.05 0.05
free T3 7.8 5.1 4.8 4.2 3.5 2.7 3.5 3.9 2.1 2.7 4.9 5.0
Free T4 38 27.1 26.9 27.6 19 15 18 16 17 19 28 31
PTU mg/day x x 100 200 200 150 100 50 x x 100 200
NMZ mg/d 40 30 stopped x x x x x x x x x
Normal value and units are same as table 1, *seen first by us.

Indian Journal of Endocrinology and Metabolism / Vol 16 / Supplement 2 S169

 Ramprasad, et al.: Thyroid disorders pregnancy

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a safe pregnancy with minimal maternal and neonatal Gagnon J, et al. Maternal thyroid deficiency during pregnancy and
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7. Bhattacharyya A, Wright JD, Vice PA. Obstetric difficulties due to
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Cite this article as: Ramprasad M, Bhattacharyya SS, Bhattacharyya A.
5. Matalon ST, Blank M, Ornoy A, Shoenfeld Y. The association between
Thyroid disorders in pregnancy. Indian J Endocr Metab 2012;16:S167-70.
anti-thyroid antibodies andpregnancy loss. Am J Reprod Immunol
2001;45:72-7. Source(s) of Support: None, Presentation at a meeting: None

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