Hyperthyroid Mothers Research Articles

Hyperthyroidism and production of precocious involution in the mammary glands of lactating rats

This study investigated the influence of chronic hyperthyroidism on mammary function in lactating rats and the effects on their pups. Thyroxine-treated (10 microg per 100 g body weight per day; hyperthyroid (HT)) or vehicle-treated rats were mated 2 weeks after the start of treatment and killed with their litters on days 7, 14 and 21 of lactation. Serum concentrations of triiodothyronine (T(3)) and tetraiodothyronine (T(4)) increased in thyroxine-treated rats. In HT mothers, serum prolactin decreased on day 7 and day 14 of lactation, whereas insulin-like growth factor I (IGF-I) and progesterone concentrations decreased, and corticosterone increased on day 7 of lactation. In HT pups, T(4) concentration increased on day 7 and day 14 of lactation, whereas T(3) increased only on day 14 of lactation, and growth hormone increased on day 7 of lactation. Mammary prolactin binding sites did not vary, but there was an increase in the binding sites in the liver on day 14 of lactation in thyroxine-treated rats. In an acute suckling experiment, thyroxine-treated rats released less oxytocin, growth hormone and prolactin and excreted less milk than did control rats. Mammary casein, lactose and total lipid concentrations in thyroxine-treated rats were similar to those of control rats on day 14 of lactation. Histological studies of the mammary glands showed an increased proportion of alveoli showing reduced or no lumina and cells with condensed nuclei on day 14 and day 21 of lactation; the TdT-mediated dUTP nick-end labelling (TUNEL) test revealed an increase in apoptosis in alveolar cells on day 21 of lactation in thyroxine-treated rats. Expression of SGP-2, a gene expressed during mammary involution, increased in thyroxine-treated rats on day 14 and day 21 of lactation, whereas expression of insulin-like growth factor binding protein 5, a proapoptotic signal, was unchanged. Bcl-2, which promotes survival of mammary gland epithelial cells was unchanged, whereas expression of IGF-I, which also promotes survival of mammary gland epithelial cells, increased on day 21 of lactation in thyroxine-treated rats. These results indicate that thyroxine treatment produces some milk stasis as a result of impairments in suckling induced release of oxytocin that may initiate the first stage of mammary involution, increasing apoptosis in a gland that is otherwise actively producing and secreting milk.

The effect of abnormal intrauterine thyroid hormone economies on infant cognitive abilities.

To evaluate how intrauterine and neonatal thyroid hormone deficiencies affect infant cognitive abilities. 26 infants with intrauterine or neonatal thyroid hormone deficiency and 20 full-term infants with normal thyroid economies were studied at 6 months of age or corrected age. Reasons for thyroid hormone deficiency were maternal hypothyroidism, maternal hyperthyroidism treated with antithyroid medication, congenital hypothyroidism, and low-risk prematurity. A computer-generated task during which infants' eye-movements were videotaped was used to assess attention, memory, and learning abilities Data from transcribed videotapes showed the study group was significantly less attentive and had longer reaction times than controls but did not differ on indices of sustaining attention or learning. Within thyroid-deficient groups, offspring of treated hyperthyroid mothers showed an atypical profile suggestive of hypervigilance. A decreased fetal or maternal thyroid hormone supply in pregnancy is associated with infants' poorer attention and altered rates of information processing.

Altered maternal thyroid function: Effect of L-carnitine supplementation on fetal and neonatal myocardial free fatty acid oxidation,in vitro

Effect of L-carnitine supplementation on myocardial free fatty acid oxidation,in vitro, in offsprings born of hypothyroid and hyperthyroid mothers was studied in rats. L-carnitine supplementation stimulated myocardial fatty acid oxidation during gestational period in offspring born of control and hyperthyroid mothers. In contrast L-carnitine supplementation induced stimulation in myocardial fatty acid oxidation was very less in fetuses born of hypothyroid mothers. However, in neonates born of hypothyroid mothers L-carnitine stimulated myocardial fatty acid oxidation to a great extent. The results suggested that during maternal hypothyroidism low availability of thyroid hormones to fetuses through maternal circulation and availability of less carnitine to neonates due to hypolactation might be responsible for decreased myocardial free fatty acid utilization. In neonates born of hypothyroid mothers and with cardiac energy insufficiency parenteral carnitine supplementation might be of great help to prevent mortality and morbidity of such offsprings.

The fetus in maternal hyperthyroidism.

A recent article in the New England Journal of Medicine reported the successful diagnosis and treatment of fetal goitrous hypothyroidism in a mother with Graves' disease. The fetus is being recognized as an important patient in its own right in terms of thyroid disease. The fetal thyroid system develops independently of the normal maternal thyroid axis. Presence of feedback suppression of TSH by T4 has been demonstrated in a 35-week fetus. Information learned from congenital hypothyroidism suggests that lack of fetal thyroid hormones may have a negative impact on the developing fetal brain with lack of normal myelination. It is uncertain at what gestational age the fetus and the developing central nervous system become adversely affected by thyroid hormone deficiency. Since congenital hypothyroidism is sporadic and since there is no current method for easily screening all pregnancies for hypothyroidism, the thrust in fetal diagnosis and therapy has been in those pregnancies suspected of having a hypothyroid fetus when a fetal goiter is detected by ultrasonography or in a hyperthyroid mother who may be on antithyroid therapy. Intraamniotic injections of L-thyroxine have proven successful for fetal therapy. Amniotic fluid TSH may prove useful in the diagnosis and treatment of a hypothyroid fetus. Previous studies have suggested that the period of thyroxine dependency of the fetal central nervous system is limited predominantly to the last 4-8 weeks of gestation. Fetal hyperthyroidism due to transplacental transmission of thyroid-stimulating immunoglobulins may occur in a mother with a history of hyperthyroidism due to Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithyroid drug treatment of Graves' disease in pregnancy: Long-term effects on somatic growth, intellectual development and thyroid function of the offspring

With regard to their thyroid function, somatic and intellectual development, we compared 17 children of 13 hyperthyroid mothers (group I) receiving antithyroid drug treatment during their pregnancies with 25 children of 15 mothers who were euthyroid without any antithyroid treatment during their pregnancy (group II). Mean duration of maternal treatment was 3.5 months in group I, using carbimazole or thiamazole (N = 12) and propylthiouracil (N = 1). Age at examination in group I was 7.2 +/- 6.2 years, in group II 8.7 +/- 7.1 years (mean +/- SD). Both groups showed no significant differences in the results of the clinical examination and in the degree of their mental and psychomotoric development at the time of study. We found the mean birth weight of the infants in group I significantly lower than in group II (3165 +/- 339 vs 3666 +/- 670 g, p less than 0.03). The individual birth weights, however, were normal for gestational age. The body weight difference between groups disappeared during the further somatic development of the children. The serum concentration of free thyroxine in group I was significantly higher than in group II (17.2 +/- 2.4 vs 14.9 +/- 1.9 pmol/l, p less than 0.003), but fell in both groups within the normal range. The evaluation of the psychomotoric and intellectual capacity of the children at different developmental stages showed no abnormalities detectable by our tests. Thus, in the children of the two groups we found no adverse effects of a maternal antithyroid drug treatment during pregnancy or of inactive maternal Graves' disease alone, neither on thyroid gland size and function nor on the physical or intellectual development, after the neonatal period.

Altered Maternal Thyroid Function: Fetal and Neonatal Myocardial Metabolism

The influence of the maternal thyroid status on the fetal and neonatal myocardial protein, carbohydrate and lipid metabolism was studied in rats. The neonates born of hypothyroid mothers could not survive beyond 8 days after birth. The offsprings born of hypothyroid mothers showed growth retardation, decreased level of heart mitochondrial protein, reduced myocardial free fatty acid (FFA) oxidation at birth and afterwards, low glucose oxidation by the heart at later fetal stages, and afterwards, despite low heart glycogen reserve, glucose oxidation was high. The offsprings born of hyperthyroid mothers showed stimulation in overall growth, increased myocardial FFA oxidation and increased 14C-glucose incorporation into glycogen as well as increased myocardial glucose oxidation during fetal stages. Results indicate that maternal thyroid hormones play an important role in the metabolic control of fetuses and neonates.

Propylthiouracil disposition in pregnant and post-partum women.

Propylthiouracil (PTU) disposition was investigated in hyperthyroid women during pregnancy and post partum. The plasma half-life after the first dose averaged 0.66 h and became greater than 1 h with chronic drug therapy. The apparent volume of distribution after the first dose averaged 0.26 liter/kg, similar to nonpregnant hyperthyroid patients. There was a tendency to increased apparent volume of distribution with chronic drug ingestion. Plasma clearance of PTU showed no change related to disease or to pregnancy. Our data suggest that pregnancy does not have a major effect on the pharmacokinetic disposition of PTU in the hyperthyroid mother. Observation of a prolonged plasma half-life for PTU in 1 patient post partum deserves further investigation to determine if this change is associated with clinically significant therapeutic or toxic effects.

Acute hyperthyroidism during pregnancy: A case report and critical analysis

A rare case of acute hyperthyroidism during pregnancy is described and the management is discussed. Prompt subtotal thyroidectomy may be superior to the use of antithyroid drugs in particular circumstances. Fetal outcome of hyperthyroid mothers is discussed in the light of recent long-term follow-up studies and immunogenetic data. Women considered to be hyperthyroid are at high-risk for obstetrical and neonatal problems: early diagnosis of this condition is of paramount importance.

The possible relation between postpartum exacerbation of hyperthyroidism and neonatal thyrotoxicosis.

Hyperthyroidism is generally considered to be ameliorated during pregnancy, and there appears to be a high incidence of postpartum exacerbation. These phenomena have to our knowledge not been related to neonatal thyrotoxicosis, a transient hyperthyroidism seen only in newborns of previous or current hyperthyroid mothers. The first of two siblings of a previously thyrotoxic mother had marked symptoms of neonatal thyrotoxicosis and high levels of thyroid hormones. The mother had not received antithyroid treatment during her first pregnancy. During her next pregnancy she was treated with propylthiouracil from the second trimester. This infant had only minimal thyrotoxic signs but almost as high levels of thyroid hormones during the neonatal period as the elder. The mother had no signs of postpartum exacerbation but her thyroid hormones were significantly elevated in the postpartum period analogous to the infants. Neither the mother nor the infants presented any increase in thyroid-stimulation hormone and long-acting thyroid stimulator during the hyperthyroid periods. The possibility is discussed, that postpartum exacerbation of hyperthyroidism and neonatal thyrotoxicosis may be related. They could be the result of a changed balance between a thyroid stimulator and an inhibitor after birth.

IODIDE GOITER IN THE NEWBORN

A hyperthyroid mother, treated with potassium iodide, gave birth to a baby with an enormous goiter. The infant, although hypothyroid, had massive cardiomegaly and high output failure due to a shunt across the vessels of the goiter. Administration of thyroid caused shrinkage of the gland and concomitantly the heart became smaller. The infant then developed hyperthyroidism which persisted for several months. The late stage of onset of hyperthyroidism in the infant, the inability to demonstrate LATS in mother or child, and the resemblance to other reported cases of iodide goiter in infancy together indicate that the hyperthyroidism may have been a consequence of the iodide goiter rather than a result of the transmission of LATS from the hyperthyroid mother.

THE GOITROGENS IN THYROTOXICOSIS COMPLICATING PREGNANCY: A CASE REPORT

THE administration of an antithyroid drug such as thiouracil or propylthiouracil during pregnancy must be undertaken with caution because of the potential hazards to the fetus. From theoretical considerations the danger is twofold: a) the drug may interfere with the embryonic development of the thyroid gland, altering its postnatal function permanently, or b) it may merely block synthesis of the thyroid hormone in-utero, leaving a gland capable of normal function after birth. The thiourea derivatives pass the placental membrane in rats (1) and undoubtedly do so in humans. Davis and Forbes (2) found an enlarged, hyperplastic, thyroid in a 21-year-old mother who suddenly died during the sixth month of pregnancy while taking thiouracil. A normal-appearing child at birth does not necessarily mean a normally functioning thyroid. Normal in-utero development occurs because of the maternal thyroid hormone which appears to diffuse across the placenta (1). Thus, the fetus does not suffer, even though its thyroid function is depressed by the goitrogen. The problem as to whether or not the embryonic development of the fetal thyroid has been altered so as to interfere with the postnatal function of the gland can only be answered by the observation of a sufficient number of children born of hyperthyroid mothers treated with goitrogens during pregnancy.