The functioning of thyroid
gland is significantly altered by pregnancy. The production of thyroxine (T4)
and triiodothyronine (T3), increase almost one and half times in pregnancy. In
healthy women these changes take place seamlessly but many women with
borderline thyroid status develop abnormalities in functioning of thyroid gland
during pregnancy. Thyroid dysfunction during pregnancy is widely prevalent and
undetected hypothyroidism can adversely affect perinatal and fetal outcome. That
is why assessment of thyroid function in pregnancy is of immense importance.
The symptoms of hypothyroidism during pregnancy and in non-pregnant
state are similar. The manifestations can range from fatigue, hair fall, dry
skin, intolerance to cold, gain in weight, constipation, etc. Many of these
symptoms occur commonly in pregnancy and identification of hypothyroidism on
the basis of symptoms can be misleading. Pregnant women with hypothyroidism
often do not manifest any symptoms. Subclinical hypothyroidism (SCH) in usually
asymptomatic and detected only on laboratory testing.
To meet the metabolic demands during pregnancy, the thyroid
physiology is altered. These changes are also reflected in alteration in
thyroid function tests. The T4-binding globulin (TBG) is elevated, that in turn
raises the total T4 and T3 levels by 1.5 times higher than in non-pregnant
state. Besides, high serum human chorionic gonadotropin (hCG) levels, particularly
in early pregnancy, result in a reduction in serum thyroid stimulating hormone
(TSH) levels in first trimester.
If population and trimester-specific reference ranges for TSH
are not available, an upper reference cut off of approximately 4 mU/L can be
used. Trimester specific reference values for free T4 (FT4) should be provided
with the assay kits. High levels of bound T4 in pregnancy can make assessment
of FT4 challenging. Assays based on methods of separation like equilibrium
dialysis or ultrafiltration are laborious, time-consuming, expensive, and not
widely available. FT4 measurement is performed by indirect analog immunoassays
by the majority of clinical laboratories, largely because of its ability to be
quickly performed on automated platforms. Measurement of total T4 may be superior to immunoassay
measurement of FT4 in pregnant women. However, reference ranges should take into
account the 50% increase in TBG occurring in pregnancy. Thyroid peroxidase
(TPO) antibodies are elevated in 30-60% of pregnant women with an elevated TSH.
The risk of complications is higher in women with SCH and positive TPO
antibodies compared to those with negative TPO antibodies. If the serum TSH is >2.5 mU/L, estimation
of TPO antibodies should be done.
The diagnosis of primary hypothyroidism during pregnancy is
based upon the finding of an elevated serum TSH level, calculated using
population and trimester-specific TSH ranges for women with pregnancy. Any
women with symptoms suggestive of hypothyroidism should undergo a TSH
estimation. There is inadequate evidence to recommend for or against routine screening
for thyroid dysfunction of asymptomatic pregnant women but estimation of TSH is
commonly done in first trimester of pregnancy in clinical practice.
As per the recommendation of the American Thyroid Association
(ATA) 2017 guidelines the following trimester-specific ranges and cutoffs can
be considered when local assessments are not available. In the first trimester,
the lower reference value of TSH can be decreased by 0.4 mU/L, while the upper
reference range is reduced by 0.5mU/L. This usually corresponds to a TSH upper
reference limit of 4.0mU/L. Women with central hypothyroidism from pituitary or
hypothalamic disease will not have elevated TSH concentrations during
pregnancy. For women in the first trimester of pregnancy with a TSH above 4.0
mU/L, FT4 or total T4 value should be estimated to differentiate between SCH
and overt hypothyroidism.
Hypothyroidism can have adverse effects on pregnancy
outcomes, depending upon the severity of the biochemical abnormalities:
?Maternal hypothyroxinemia (isolated low maternal FT4)
hypothyroidism — Uncorrected overt hypothyroidism in pregnancy is unusual
(0.3-0.5% of screened women). Anovulation in hypothyroid women and increased
rate of first trimester spontaneous abortion (often undetected) are responsible
for this finding.
In continuing pregnancies, hypothyroidism has been
associated with an increased risk of several complications, including:
?Preeclampsia and gestational hypertension
?Nonreassuring fetal heart rate tracing