Hypothyroidism in Pregnancy

Review Article
PHYSIOLOGY
Changes in pregnancy occur in thyroid gland due to
(a) Pregnancy induces a marked increase in circulating
levels of major thyroxine transport protein, thyroxine
binding globulin, in response to high estrogen levels,
(b) Several thyroidal stimulatory factors of placental
origin are produced in excess,
(c) Pregnancy is accompanied by a decreased availability
of iodide for the maternal thyroid. This occurs due to
increasedrenalclearanceandexcretionthatresultsina
relative iodine deficiency state (Table 1).
Moderate thyroid enlargements occur due to glandular
hyperplasia and increase in vascularity. Thyroid volume
determined ultrasonographically increases although its
echostructures and echogenecity remains unchanged [1].
These enlargements are not pathological and normal
pregnancydoesnottypicallycausesignificantthyromegaly,
thus,anygoitershouldbeinvestigated.Aclinicallyapparent
goiter suggests iodine deficiency or pathology [2].
In early pregnancy, thyrotropin activity decreases
because of thyroid stimulation from the weak crossover
activity of chorionic gonadotrophin (Fig.1) [3].
Fetal physiology
The pituitary thyroid system is functional by the end of
first trimester. The thyroid gland is able to synthesize
hormones by 10-12 weeks, and TSH, thyroxine and
thyroxine binding globulin (TBG) have been detected in
fetal serum as early as 11 weeks [4]. The placenta actively
concentrates iodide on the fetal side, and by 12 weeks and
throughout pregnancy, the fetal thyroid concentrates
iodide more avidly than does the maternal thyroid. Thus,
maternal administration of either radioiodide or
appreciable amounts of ordinary iodide is hazardous after
this time.
Immediately after birth, there are major changes in
thyroid function and metabolism. Atmospheric cooling
evokes sudden and marked increase in thyrotropin
secretion, which in term causes a progressive increase in
serumT4 levels that are maximal 24 to 36 hours after birth.
INCIDENCE
Theincidenceofhypothyroidismisapproximately1%.
Thyroid disease is the second most common cause of
endocrine dysfunction in women of childbearing age
(diabetes is the first).
In a study [5], the overall incidence of hypothyroidism
was 2.5 %; overt thyroid deficiency was 1.8 per 1000 and
subclinical cases 23 per 1000.
CLASSIFICATION
Clinical or overt hypothyroidism is diagnosed when an
abnormally high serum thyrotropin levels is accompanied
byanabnormallylowthyroxinelevels.
Subclinical hypothyroidism is defined by an elevated
serum thyrotropin level with normal serum thyroxine.
HYPOTHYROIDISM IN PREGNANCY
Geeta Chadha * and Mamta Goel **
*Senior Consultant,** Registrar, Department of Obstetrics & Gynaecology, Indraprastha Apollo Hospitals,
Sarita Vihar, New Delhi 110 076, India.
Correspondence to: Dr Geeta Chadha, Senior Consultant, Department of Obstetrics & Gynaecology,
Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India.
Due to pregnancy thyroid economy is affected with changes in iodine metabolism, TBG and development of
maternal goiter. The incidence of hypothyroidism in pregnancy is quite common with autoimmune
hypothyroidism being the most important cause. Overt as well as subclinical hypothyroidism has a varied
impact on maternal and neonatal outcome. After multiple studies also, routine screening in pregnancy for
hypothyroidism can still not be recommended. Management mainly comprises of dosage adjustments as soon
as pregnancy is diagnosed based on results of thyroid function tests. The aim should be to keep FT4 at the
upper end of normal range.
Key words: Hypothyroidism in pregnancy, Physiology, Pregnancy outcome, Screening, Management.
Apollo Medicine, Vol. 6, No. 4, December 2009 322

Review Article
323 Apollo Medicine, Vol. 6, No. 4, December 2009
subacute de Quervain’s thyroiditis or post partum
thyroiditis.
CLINICAL FEATURES
Many symptoms occur as in normal pregnancy;
discriminatory symptoms are cold intolerance, slow heart
rate and delayed relaxation of deep tendon reflexes,
particularly those of the ankle.
Pregnancy outcome with subclinical
hypothyroidism (Table 2)
Abnormalities in maternal thyroid function can
adversely affect the fetus directly by the way of the
transplacental passage of abnormal maternal hormone
concentration, thyroid stimulating hormone(TSH)
receptor antibodies, or prescribed antithyroid medication
and indirectly by way of the altered maternal gravid
physiology [6].
Studies show that hypothyroidism may impair fetal
neuropsychological development. Studies show that
children born to uncontrolled hypothyroid mothers are at
increasedriskofpsychomotordevelopmentanddiminished
school performance, reaching recognition and IQ scores.
Pregnancy with hypothyroidism is associated with
higher incidence of maternal complications like PIH and
GDM as seen in a study [7].
Pregnancy outcome with overt hypothyroidism
(Table 3)
The most serious consequence of hypothyroidism is
myxedema coma but it is extremely rare. Cretinism (deaf
mutism, spastic motor disorder, and hypothyroidism) is a
distinct and severe form, of brain damage caused by severe
maternal iodine deficiency.
Overt hypothyroidism causes subfertility,and the
presence of thyroid autoantibodies,even if the mother is
euthyroid,isassociatedwithanincreasedriskofmiscarriage
Severe hypothyroidism with pregnancy is uncommon,
probably because it is often associated with infertility and
increased miscarriage rates.
CAUSES
(i) Atrophic (autoimmune) hypothyroidism – Most
commoncauseisautoimmuneassociatedwiththyroid
peroxidase autoantibodies, leading to destruction of
the gland, lymphoid infiltration and eventual atrophy
and fibrosis. Antibodies blocking TSH receptor are
also present in some cases.
(ii) Hashimotos thyroiditis – It is differentiated form of
thyroiditis,alsowiththyroidperoxidase(microsomal)
autoantibodies, often at high titer. However, atrophic
changes occur with regeneration and result in goiter
formation.
(iii) Iatrogenic like after treatment with Lithium,
amiodarone or antithyroid drugs.
(iv) Transient occurring as a part of the disease course in
Table 1. Physiological changes in pregnancy
Physiological change TFT’s
Increased TBG Increased total T3, T4
First trimester increase in hCG Increased FT4 & decreased TSH
Increased plasma volume Increased T3, T4, pool size
Increased type III, 5- deiodinase due to increased placental mass Increased T4, T3, degradation
Increased iodine clearance Decreased hormone production in iodine deficient
areas.
Fig.1 TSH and hCG during gestation.

Review Article
that was quantified as having an odds ratio of 2.3% (95%
CI,1.8 – 2.95) in a recent meta analysis [9].According to
guidelines 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 decrease in the miscarriage in thyroid
antibody positive euthyroid women.
A study [10] reported a higher cesarean section rates in
thestudygroup(28.7%)comparedwiththeinstitutionalrate
(18%). In hypothyroidism there are placental hypoxic
changes. This may be responsible for thick meconium
stained liquor and/or fetal distress.
DIAGNOSIS
Normal values for Thyroid Function Tests during
pregnancy are given in Table 4 [11].
SCREENING IN PREGNANCY
Routine screening for hypothyroidism is still contro-
versial. One school of thought is that thyroid testing
during pregnancy should be performed on symptomatic
women or those with a personal history of thyroid disease.
ACOG [12] had recommended against implantation of
screening until further studies were done to validate or
refute the findings of association of adverse neuropsycho-
logical development with subclinical hypothyroidism.
However, many studies on delayed neurological
development in babies born to hypothyroid women have
been published in recent years, and have advocated
routine, prepregnancy, and early pregnancy screening [13].
Table 2. Pregnancy outcomes in women with untreated subclinical hypothyroidism
Outcome Euthyroid controls (n = 15,689) Subclinical hypothyroidism
(n = 404) P value
Hypertension (%) 9 11 0.39
Placental abruption (%) 0.3 1.0 0.026
Gestational age delivered (%)
36 weeks 6.0 7.0 0.390
34 weeks 2.5 4.0 0.011
32 weeks 1.0 2.5 0.068
Mean birth weight (g) 3367 ±567 3317 ±599 0.081
RDS – ventilator (%) 1.5 3.0 0.048
Neonatal intensive care (%) 2.0 4.0 0.019
RDS = Respiratory distress syndrome; Data from Casey and colleagues (2005) [5]
Table 3 Pregnancy complications in 112 women
with hypothyroidism
Complications Hypothyroidism (%)
Overt Subclinical
(n=49) (n=63)
Preeclampsia 31 16
Abruptio placentae 8 0
Cardiac dysfunction 3 2
Birthweight less than 2000 g 3 19
Stillbirths 8 2
Modified fromAbalovich (2002) [8] Davis (1988), and
Leung (1993), and all their associates.
Table 4. Normal values for thyroid function test
Test Non pregnant First trimester Second trimester Third trimester
Free T4 (pmol/L) 11-23 10-24 9-19 7-17
Free T3 (pmol/L) 4-9 4-8 4-7 3-5
TSH(mu/L) <4 0-1.6 1-1.8 7-7.3

Review Article
325 Apollo Medicine, Vol. 6, No. 4, December 2009
One major concern is that it seems unlikely that treatment
given after the period of early cerebral development would
be totally efficacious to prevent neurological damage [14].
This is further strengthened by the January 2005 statement
of The American Thyroid Association and The American
Association of Clinical Endocrinologists recommending
routine TSH measurement during prepregnancy evaluation
or as soon as pregnancy is diagnosed [15].
IODINE DEFICIENCY
Adequate iodine is requisite for normal fetal
neurological development beginning soon after
conception. The WHO estimated in 1990 that 20 million
people worldwide have varying degree of preventable
brain damage due to fetal iodide deficiency [16].
Iodide supplementation before pregnancy prevents
neurological morbidity from severe deficiency.Addition of
supplemental iodine to pre-natal vitamins has been
proposed.
CONGENITAL HYPOTHYROIDISM
Because the clinical diagnosis of hypothyroidism in
neonates is usually missed, newborn mass screening was
introduced in 1974 and is now required by law.
Early and aggressive thyroxine replacement is
critical for these infants. Except in those with severe
congenital hypothyroidism, sequalae including intellectual
impairment are typically preventable [17].
Preterm Infants
Transient hypothyroxinemia is common in preterm
infants, and it has been assumed that treatment with
thyroxine is not necessary.
MANAGEMENT
Pre-pregnancy
Consider diagnosis of hypothyroidism in patients with
infertility or menstrual disorders and medical therapy
should be optimized and pregnancy to be delayed until
good control is achieved.
Pre-natal
In a newly diagnosed hypothyroid patient, a full
replacement thyroxine dose should be instituted
immediately, assuming there are no abnormalities in
cardiac function. Treatment should be initiated with a dose
of 100 – 150 microgm/day or titrated according to body
weight (2.0 – 2.4 micrograms/kg body weight/day).
In diagnosed cases, as thyroxine requirements increase,
dosage adjustments are required. Suggested mechanisms
for this increased requirement include an elevated
extrathyroidal pool of T4; the need to saturate large
quantities of thyroid-binding globulin; increased
degradation of T4; reduced absorption of T4, especially if
taken with iron supplements; and increased transfer of T4
from mother to fetus. Because a similar increased
requirement is seen in post menopausal women, with
hypothyroidism who are given estrogen replacement, this
increased demand in pregnancy may be caused by
increased estrogen production [18]. A study shows that
thyroxine requirement increases in majority of patients as
early as fifth week of pregnancy and the authors propose
that the hypothyroid women should increase their
levothyroxine dose by approximately 30% as soon as
pregnancy is diagnosed [19].
However it was also generally believed that
hypothyroid women on maintenance dose rarely require an
increase in dosage during pregnancy.Arecent study shows
that none of the women who had stable doses of thyroxine
during pregnancy had required recent pre-pregnancy
changes in dose or needed postnatal changes [20].
Baseline thyroid function test should be performed as
soon as possible. They should be performed every 3
months and more frequently if dosage adjustments are
made. The adjustment should be made based on results of
thyroid function tests. Thyroxine replacement should be
done to a dose that insures that thyroid function test are
normal with FT4 at the upper end of normal range for each
trimester of pregnancy and serum TSH should be < 2.5 m
U/L. Exception is women who have had a thyroidectomy
for thyroid cancer as it is necessary to suppress TSH
secretion.
Thyroxine absorption is decreased by certain drugs
including iron and calcium supplement. Thyroxine is best
taken on an empty stomach and four hours apart from iron
or other supplements or soy products.
Some studies show that the etiology of hypothyroidism
plays a pivotal role in determining the timing and
magnitude of thyroid hormone adjustments during
pregnancy. For example patients with primary
hypothyroidism required smaller cumulative dose
increases whereas patients with treated Graves disease
required largest cumulative increases in LT [4] dosage.
Labour and delivery
When adequate control is achieved, no specific
measures are needed for labour and delivery. However,
when large goiter causes respiratory compromise,
anaesthetic or surgical advice may be required.

Review Article
Post-Natal
Women should resume their prepregnancy
levothyroxine dosage immediately after delivery and have
their serum TSH level re-evaluated after 6 weeks. Thyroid
peroxidase auto antibodies are significantly associated with
postpartum thyroiditis and postpartum depression.
Post Partum thyroiditis
Transient autoimmune thyroiditis has consistently been
found in 5 to 10 percent of women during the first year after
childbirth [21].Yet there are insufficient data to recommend
screening of all women for postpartum thyroiditis.The
propensity for thyroiditis antedates pregnancy and is
directly related to increasing serum levels of thyroid
autoantibodies.Women with high antibody titers in early
pregnancy commonly are affected [22].Women known to
be thyroid peroxidase antibody positive should have a TSH
performed at 3 and 6 months postpartum.Upto 25% of
women with type 1 diabetes develop postpartum thyroid
dysfunction [23].Women who experience postpartum
thryoiditis have about 30% risk of developing permanent
hypothyroidism [24]. Asymptomatic women with PPTwho
have aTSH above the reference range but below 10 U/mL
and who are not planning a subsequent pregnancy do not
necessarily require intervention, but should, if untreated, be
re-monitored in 4-8 weeks. Symptomatic women and
women with a TSH above normal and who are attempting
pregnancy should be treated with levothyroxine.
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8. Abalovich M, Gutierrez S, Alcaraz G, et al. Overt and
subclinical hypothyroidism complicating pregnancy.
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9. Prummel MF, Wiersinga WM. Thyroid autoimmunity and
miscarriage. Eur J Endocrinol 2004; 150(6),751-755.
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hypothyroidism in early and late gestation: effects on
neonatal and obstetric outcome. Clin Endocrinol (Oxf)
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