Primary hypothyroidism of childhood: evaluation of the hypothalamic-pituitary gonadal axis before and during L-thyroxine replacement.
Hypothyroidism is frequently associated with abnormal sexual development. To determine the longitudinal influence of thyroxine replacement on the hypothalamic pituitary gonadal axis, we studied five prepubertal hypothyroid girls and two boys before, and all the girls six weeks and one year after, thyroxine replacement. All girls showed significantly elevated basal gonadotrophin concentrations before treatment. Following one year of therapy, despite all girls having begun puberty, basal gonadotrophin concentrations were significantly decreased in the four euthyroid girls as compared with our normal pubertal girls. The fifth girl studied at one year was hypothyroid at the time of testing and her gonadotrophin values were increased even above previous basal values. Pretreatment serum TSH values inversely correlated with maximum pretreatment incremental LH (r = -0.54) and FSH (r = -0.52) responses to LHRH. Serum TSH values directly correlated with PRL concentrations (r = +0.82). Of the two hypothyroid boys evaluated, Patient 1 was mildly hypothyroid and showed normal prepubertal basal LH, FSH, testosterone and low normal LHRH responsiveness. Patient 2, who was more severely hypothyroid, had elevated basal gonadotrophin secretion and responsiveness to LHRH but prepubertal testosterone concentrations. These data indirectly show that thyroxine may increase the biological/immunological potency of gonadotrophins. The elevated gonadotrophin values in the hypothyroid state suggest that the metabolic clearance rate of gonadotrophins is prolonged. The more severe the elevation in TSH secretion, the more marked was the alteration in the hypothalamic pituitary axis in respect to PRL secretion and delta max LH and FSH response to LHRH. Replacement with thyroxine was followed by normal pubertal development, and normal pubertal oestradiol and PRL concentrations, despite low immunoreactive gonadotrophin secretion.
D000293:Adolescent; D002648:Child; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology*; D007037:Hypothyroidism / Q000188:drug therapy / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D010053:Ovary / Q000503:physiopathology*; D010902:Pituitary Gland / Q000503:physiopathology*; D013737:Testis / Q000503:physiopathology*; D013974:Thyroxine / Q000627:therapeutic use*
D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013974:Thyroxine