C
entral hypothyroidism is
characterized by impaired secretion of thyroid hormone due to a defect in
the hypothalamic-
pituitary-thyroid (HPT) regulatory system. Exposure of fetal HPT system to
a higher thyroid hormone concentration might impair its physiologic
maturation leading to central hypothyroidism in neonates born to
thyrotoxic mothers(1). It is usually detected during first week of life.
We report delayed recognition of central hypothyroidism in a neonate born
to a mother with uncontrolled thyrotoxicosis during pregnancy.
Case Report
A male infant was born at 38 weeks of gestation (birth
weight, 2084 grams) to a 25 years old primigravida mother, who had been on
irregular treatment for Graves’ disease. Mother was diagnosed to have
Graves’ disease during her tenth week of gestation and advised 30 mg/day
of carbimazole. Although she was compliant to the medications initially,
took medicines irregularly during third trimester. She was hospitalized at
37 weeks of gestation with pregnancy induced hypertension and congestive
cardiac failure. On admission her total triiodothyronine (TT3), total
thyroxine (TT4) and TSH were 3.80 nmol/L, 308.88 nmol/L and 0.01 mIU/mL,
respectively. After ensuring drug compliance and stabilization of general
condition, baby was delivered by cesarean section.
Infant cried immediately after birth and was
asymptomatic till third day of life, when he developed jaundice; peak
serum bilirubin was 22.4 mg/dL on seventh day of life. Infant’s T4 and TSH
were 123.55 nmol/L (9.6 mg/dL) and 0.014 mIU/mL, respectively on fifth day
of life. Hyperbilirubinemia was managed by phototherapy and baby
discharged home on tenth day of life with the advice to follow up in
Endocrinology out patient department after a week with repeat thyroid
hormone evaluation. The infant was followed at sixtieth day of life. The
diagnosis of central hypothyroidism was confirmed with free thyroid
hormone profile which showed low FT3 and FT4 [FT3: 2.7 pmol/L and FT4:
6.435 pmol/L]. Infant was started on 50 µg of thyroxine. Follow up after
two months of therapy showed the infant to be euthyroid (T3- 2.1 nmol/L,
T4-114.07 nmol/L) with 50 µg of thyroxine.
Discussion
First reported in 1988(2), incidence of neonatal
central hypothyroidism in infants of mothers with Graves’ disease is at
least 1 per 35,000 neonates, but the exact mechanism has not been fully
elucidated(3). It is usually seen with uncontrolled maternal
thyrotoxicosis, though rarely associated with well controlled disease
also.
Mitsuura, et al.(4) showed higher
thyroxine (T4) levels at birth than on fifth day of life in infants born
to mothers with uncontrolled Graves’ disease. Higuchi, et al.(5)
also reported a phase of transient hyperthyroxinemia before settling
down to a hypothyroid phase in infants born to mothers with Graves’
disease. There are case reports of neonates with low TSH, low
normal/normal FT4 levels in cord blood which subsequently declined to
subnormal levels, on serial monitoring (at days four and seven of
life)(6). The above studies suggest that fetal thyroxine may be elevated
due to passive transfer of maternal thyroxine during the last trimester
leading to suppression of fetal pituitary-thyroid axis.
The minimum duration of passive hyperthyroidism during
fetal life that can lead to central hypothyroidism is unknown. In a
previous review of case reports was suggested that the possibility of
central hypothyroidism can not be excluded in term infants who are born to
euthyroid mothers with Graves’ disease, but exposed to maternal
thyrotoxicosis before 32 weeks’ gestation(5). They also proposed that
maternal thyrotoxicosis before 32 weeks of gestation may be critical for
development of central hypothyroidism in the offspring(5). Tamaki, et
al.(7) showed that neonates born to mothers with Graves’
disease with cord TSH levels below the normal range have a high
predilection to develop thyrotoxicosis or central hypothyroidism. In this
infant, TSH on fifth day of life was below normal range, which suggested
the need for serial monitoring.
In most of these infants, recovery of the HPT axis
varies from months to years(5). It is prudent to continue L-thyroxine
replacement therapy until 2–3 years of age, to prevent possible delay in
mental and motor faculties. We planned to continue thyroxine till three
years of age in our patient.
It is recommended that all infants born to mothers with
Graves’ disease should not only have both fT4 and TSH measured in the cord
blood, but also be monitored serially (such as at days 4 and 7), even if
either of the cord measurements appear normal(8). There are no specific
guidelines on the frequency and timing for further monitoring of these
infants. We suggest monitoring once in a week till TSH normalizes to watch
for delayed development of central hypothyroidism.
Contributors: All authors contributed to the
diagnosis and management, and writing the report.
Funding: None.
Competing interests: None stated.
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