Graves’ Disease and the Manifestations of Thyrotoxicosis
DeGroot LJ.
ncbi.nlm.nih.gov/books/NBK2...
FEMALE REPRODUCTIVE SYSTEM
Menstruation is characteristically decreased in volume. With severe thyrotoxicosis, the menstrual cycle may be either shortened or prolonged, and finally amenorrhea develops. The relative importance of a primary action of excess thyroid hormone on the ovary or uterus, and pituitary dysfunction, are unclear. In some cases, amenorrhea with a proliferative endometrium is found. This finding suggests failure of pituitary LH production and ovulation [384, 385].
Fertility is depressed, but pregnancy can develop. The incidence of miscarriage, premature delivery, pre-eclampsia and heart failure are increased by maternal hyperthyroidism [386, 387]. Evidence has been presented that high maternal thyroid hormone levels can lead to suppressed fetal TSH, lower fetal weight, and fetal death (388). Pregnancy, on the other hand, often ameliorates the symptoms of thyrotoxicosis due to Graves’ disease, but relapse is prone to occur in the 3-4 months following delivery (Figure 10-10). This topic is discussed in Chapter 14. Premature ovarian failure co-occurs with Graves' disease and thyroiditis in Multiple Endocrine Autoimmunity Type II [9]. Reduced fertility and increase miscarriage rates are associated with AITD and positive antibodies. Increased rates of thyroid dysfunction and positive antibody tests have been reported in infertile women (389). One study reports that treatment of euthyroid women with positive antibodies by administration of thyroxine reduced the incidence of miscarriage to the that found in anti body-negative women (390).
Infants born to thyrotoxic mothers usually show no evidence of hyperthyroidism at birth. Fetal and neonatal thyrotoxicosis, fortunately infrequent events, are discussed in Chapter 14. Maternal thyrotoxicosis is associated with increased fetal loss (391), generally attributed to effects on the maternal system. However a recent study shows that elevated maternal thyroid hormone levels lead to elevated thyroid hormone levels in the fetus, and induce fetal loss. Surviving fetuses have lower birth weight (388).
MALE REPRODUCTIVE SYSTEM
Gynecomastia, with ductal elongation and epithelial hyperplasia, occurs occasionally. [392] The circulating level of free estradiol may be elevated in these men [393-395]. Peripheral conversion of testosterone and androstenedione to estrone and estradiol is increased in both sexes during hyperthyroidism [261]. This elevation probably accounts in part for the abnormality. In addition, the slightly elevated LH in men with gynecomastia suggests hypothalamic insensitivity to feedback control and some peripheral unresponsiveness to LH [393]. An imbalance between testosterone and estrogen may be related to gynecomastia.
Kidd et al [397] found impotence in half of a small group of thyrotoxic men and sperm counts below 40 million in four of five tested. In these studies, the total testosterone level was elevated, but because the testosterone-estrogen binding globulin level was also high, the free testosterone level was reduced and the response to hCG was blunted. In thyrotoxicosis, mean sperm density is lower, and fewer sperm have normal morphology. Motility is lower in thyrotoxic males. The abnormalities normalize when the patients become euthyroid (398). Thus, both Leydig cell and spermatogenic abnormalities may be present. Abalovich et al (399) reported similar findings, and in addition noted a high incidence of sperm abnormalities. All of the abnormalities returned to normal after therapy of the thyrotoxicosis. Radioiodine therapy can cause transient reductions in both sperm count and motility but do not seem to cause permanent effects with ordinary doses used in treatment under 14 mCi, equivalent to around 500 MBq (398).
PRL probably plays no role in these reproductive abnormalities, since in hyperthyroidism, its release tends to be inhibited both at the hypothalamic and pituitary level [400]. Surprisingly, galactorrhea, in women with normo-prolactinemia, is reported to occur in increased frequency [264].
Any advice on finding a good reproductive endocrinologist in London?
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