INTRODUCTION:
The thyroid is a small endocrine gland
located in front of the trachea. It utilizes iodine to produce thyroid
hormones, which are essential for normal growth, development, maturation and
regulation of metabolism [1]. Thyroid disorders are prevalent in women of child
bearing age and for this reason are commonly present in pregnancy and
puerperium [2]. Thyroid diseases are known to affect the reproductive health of
women, who thus have trouble in conceiving [3]. It is known that the fetus is
totally dependent on maternal thyroid hormone supply during the first trimester
of pregnancy, which is the crucial time in organogenesis [4]. Pregnancy has an
appreciable effect on thyroid economy [5].
Pregnancy may affect the course of thyroid
disorders and, conversely, thyroid diseases may affect the course of pregnancy.
Moreover, thyroid disorders (and their management) may affect both the pregnant
woman and the developing fetus [6]. Maternal thyroid function changes during
pregnancy and inadequate adaptation to these changes results in thyroid
dysfunction [7].
MATERNAL THYROID HORMONES:
In pregnancy, the alterations in total
thyroid levels are the direct consequence of the marked increase in serum
thyroxine-binding globulin (TBG): total T4 and T3 levels increase significantly
during the first half of gestation. Levels of serum T4 rise sharply between 6
and 12 weeks, progress more slowly thereafter, and stabilize around
midgestation; for serum T3, the rise is more progressive [8]. Both total T4 and
T3 reach their plateau values by 20 weeks and are maintained until term.
Because of the 20-fold greater affinity of TBG for T4 compared with T3, changes
in T4 levels follow the changes in TBG more closely. It can be expected
therefore that the T3/T4 molar ratio should remain essentially unaltered during
pregnancy [9]. Sufficient supply of Thyroid hormones to fetal tissues is
important for proper fetal development [10]. This is illustrated by the harmful
effects of iodine deficiency during pregnancy, which can lead to insufficient
supply of Thyroid hormones to the developing fetal brain, resulting in mental
and motor retardation of the child [11]. A number of studies have analyzed the
effects of maternal thyroid status during pregnancy and mental and motor
development of the child [12].
IMPORTANCE OF
THYROID FUNCTION IN PREGNANT STATE:
During normal pregnancy, the maternal
thyroid produces up to 50% more thyroid hormones. The rise in thyroid hormones
results from physiological changes in pregnancy. Firstly, following conception,
estrogen concentrations increase markedly[13]. leading to increased synthesis
of TBG from the liver and increased binding of T4 to TBG [14]. Also, the
developing fetus utilizes the maternal thyroid hormone supply, maternal plasma
volume is increased and the distribution volume of T4 is higher during
pregnancy, contributing to the increased need of thyroid hormones [15]. It is
probable that the changes in thyroid hormone during gestation relate to the
necessity of delivering thyroxine to the foetal cells, particularly neuronal
cells. Adequate concentrations of T4 are essential for neural development and
this T4 can only be maternally derived from, at least during the first
trimester [16].
THYROID
DEVELOPMENT IN FETAL:
During early pregnancy, the fetus is
totally dependent on maternal thyroid hormone supply. Thyroid hormones are
needed for normal development of the fetus, especially brain, lung and bone
tissue, and thyroid hormone receptors can be found in fetuses in very early pregnancy.
The thyroid gland is derived from the endoderm of the alimentary canal during
the embryonic period. The Thyroid gland does not become metabolically active
during the fetal period until the 9th to 12th weeks of pregnancy. At the
4th week of pregnancy the fetal thyroid gland is able to produce TG,
the precursor of thyroid hormones and the concentration of iodine takes place
from 11th week onwards. The fetal hypothalamus-pituitary-thyroid axis is fully
developed and the thyroid gland has developed its typical follicular structure
and it can start producing thyroid hormones of its own at approximately 18
weeks of pregnancy [17]. In the first trimester, total T4 concentrations rise
in the fetal compartment and are directly related to the concentrations
observed in the mother. However, T3 concentrations tend to be lower in the
fetus than in the mother, but rT3 concentrations are higher in the fetus. This
is due to high activity of D3 (type III deiodinase) in the placenta, which acts as a barrier for the transfer
of maternal thyroid hormones to the fetus and protects the fetus from thyroid
hormone excess. Concentrations of fT4 are high in the fetus and similar to
those observed in adults. The fetus has lower amounts of binding proteins and
therefore has high free thyroid hormone levels. Fetal tissues have D2 and D3
activity, which ensures the them a supply of f T3 [4].
HYPERTHYROIDISM:
MATERNAL
HYPERTHYRODISM:
Hyperthyroidism, thyroid hormone
overproduction, has a prevalence of approximately 1% in the population.
Thyrotoxicosis refers to increased amounts of thyroid hormones in the
circulation, the cause of which can be also other than thyroid hormone
overproduction [18]. It is critical to interpret thyroid function tests
correctly so as not to miss the diagnosis as there are significant maternal
complications including miscarriage, placenta abruption and preterm delivery
and preclampsia. 1-5% of neonates of
mothers with Graves’ disease have hyperthyroidism due to the transplacental
passage of maternal stimulating thyrotropin receptor antibodies (TRabs) (even
though the mother may be euthyroid and has received previous treatment for
Graves’ disease). Ideally a woman who is known to have hyperthyroidism should
seek pre-pregnancy advice; appropriate education should allay fears that are
commonly present in these women [19].
NEONATAL
HYPERTHYROIDISM:
Neonatal hyperthyroidism may also be due
to an activating mutation of the TSH receptor dominantly inherited from the
mother. Transient neonatal central hypothyroidism is due to poorly controlled
Graves’ disease leading to suppression of the foetal pituitary thyroid axis due
to placental transfer of T4 [20].
TREATMENT:
Propylthiouracil is recommended as the
first-line drug for treatment of hyperthyroidism during pregnancy, because of
the probable association of methimazole with fetal developmental abnormalities [21].
HYPOTHYROIDISM:
MATERNAL AND NEONATAL
HYPOTHYROIDISM:
Hypothyroid women who become pregnant also
carry an increased risk for obstetrical complications such as intra- uterine
fetal demise, gestational hypertension, placental abruption, and poor perinatal
outcome. There are indications that thyroid hormone administration greatly
improves, although it does not entirely suppress, the frequency of these abnormalities
[22].
In general, infants of hypothyroid mothers
appear healthy without evidence of thyroid dysfunction. In infants born to
hypothyroid mothers, some studies have indicated the risk of a higher perinatal
mortality and congenital malformations, and there is also evidence for an
increased frequency of low birth weight [23] and a concern about potential
long-lasting psychoneurological impairment in the progeny [24]. Babies born with
healthy mothers can develop hypothyrodism after birth.This should be diagnosed
and treated as early as possible.
TREATMENT:
Systematic screening for congenital
hypothyroidism in the neonate constitutes a major progress in the prevention of
mental retardation, as the condition occurs in 1/4,000 newborns and necessarily
results in brain damage if not properly detected and treated during the first
days of life [25].
CONCLUSION:
There is agreement that pregnancy imposes
a stress on the thyroid which is greater in areas of iodine deficiency. Hyperthyroidism
in pregnancy, usually due to Graves’ disease, is uncommon but has deleterious
effects on mother and foetus and requires therapy. Thyroid dysfunction and/or
antibodies increase the maternal risk of subsequent thyroid disease. Their
detection of during pregnancy would help to identify women at future risk of
thyroid diseases. Also, in women with overt hypothyroidism the risk of
subsequent diabetes was increased.
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