Impact of maternal hyperthyroidism on male minipuberty: a matched cohort pilot study

Background Minipuberty is a transient phase of activation of the reproductive axis that plays an important role in the growth of the genital organs during infancy and in the sex differences in body growth and fat distribution. Alterations in its course have been observed in certain maternal conditions during pregnancy, including poorly controlled hypothyroidism. To date, minipuberty has not been evaluated in the offspring of mothers with hyperthyroidism. Objective The aim of this study was to compare the course of minipuberty in sons of mothers with the two most common causes of hyperthyroidism during pregnancy. Methods The study was designed as a prospective matched cohort study covering the first 12 months of life. Participants included 64 apparently healthy male infants who were sons of women with gestational transient thyrotoxicosis or Graves’ disease during pregnancy and a control group consisting of 32 sons of women without thyroid pathology during pregnancy. Salivary concentrations of sex hormones [i.e., testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), estradiol, and progesterone] and urinary concentrations of gonadotropins were measured at monthly intervals during the first 6 months of life and at bimonthly intervals during the second 6 months. At each visit, the testicular volume and penile length were also assessed. Results Compared with the offspring of healthy women, the sons of mothers with Graves’ disease exhibited significantly higher concentrations and a longer period of detectability of both gonadotropins, testosterone, and estradiol. However, in this group, no peak in the testosterone and luteinizing hormone (LH) concentrations was observed, whereas in the control group, such a peak occurred in the second month of life. The gonadotropin levels correlated with both the free thyroxine concentrations and the thyroid receptor antibody titers. These changes were accompanied by greater testicular volume and increased penile length in the sons of mothers with Graves’ disease. No differences in the course of minipuberty—either in the hormone concentrations or the genital size—were observed between male offspring of women with gestational transient thyrotoxicosis and those of healthy women. Conclusions Maternal hyperthyroidism during pregnancy has an etiology-specific effect on male minipuberty, evident exclusively in offspring of mothers with Graves’ disease.