Endocrine Function in the Prader‐willi Syndrome

Abstract

Hypothalamic, pituitary and gonadal function was studied in five male and three female patients with the Prader-Willi syndrome. All were clinically hypogonadal: all males had low circulating testosterone levels, although in two females basal plasma oestradiol was within the normal range for the early follicular phase of the menstrual cycle. Basal gonadotrophin levels were low and the response to the intravenous ater 10 days and 6 weeks treatment with oral clomiphene (200 mg daily) was followed by a normal rise in luteinizing hormone (LH) and follicle stimulating hormone (FSH) in four out of five patients tested. All five males were tested with human chorionic gonadotrophin (hCG) and the rise in plasma testosterone was subnormonal in four. Treatment with hCG was continued for 6 weeks in these four patients, but in only one did testosterone levels rise (transiently) to the normal adult male range. In one female patient studied no rise in plasma oestradiol was detected in response to human menopausal gonadotrophin (hMG). These results suggest that the hypogonadism in the Prader-Willi syndrome is due to combined hypothalamic and primary gonadal abnormalities.

Hypogonadism in females with Prader–Willi syndrome from infancy to adulthood: variable combinations of a primary gonadal defect and hypothalamic dysfunction

“…Hypogonadotropic hypogonadism was found in more than 25% of the participants in our study, while in males with PWS, severe gonadotropin deficiency is a rare cause of hypogonadism (6,(8)(9)(10). The dissimilarity in hypothalamic-pituitary function between males and females with PWS might be explained by the divergence in the regulation of FSH secretion between normal males and females.…”

“…Clinical features, attributed mainly to hypothalamic dysfunction (2, 5-7), include severe hypotonia and feeding difficulties in infancy, an insatiable appetite leading to severe obesity in childhood, short stature, and hypogonadism as well as dysmorphic features and variable degrees of mental retardation (2)(3)(4). Although hypogonadism has often been attributed to hypothalamic dysfunction, some studies show that a primary testicular defect contributes to the hypogonadism in PWS males (8)(9)(10).…”

Immunohistochemical and hybridocytochemical study on ghrelin signalling in the rat seminiferous epithelium.

“…In turn, experimental hyperghrelinemia in prepubertal male rats decreased serum LH and testosterone concentration and delayed timing of puberty [64]. Moreover, an overexpression of ghrelin gene resulting in high level of ghrelin was reported for Willi-Prader syndrome with combined impairment of LH secretion, LH stimulated testosterone production and local, presumably, primary defects in Sertoli and gametogenic cell line maturation [65][66][67].…”

Fatal Outcome of Sleep Apnoea in PWS during the Initial Phase of Growth Hormone Treatment

“…Hypothalamic dysfunction, as already originally presumed by Prader et al, appears to underlie many of the features of PWS, including hypogonadism [10, 11], abnormal appetite control, high pain threshold and sleep disorders, but no overt structural abnormalities of the hypothalamus have been found yet. In recent years, it was shown that growth hormone (GH) deficiency due to hypothalamic dysregulation contributes not only to the abnormal growth pattern and osteopenia, but also to the excess of body fat and to the deficit of lean body mass, with consequently reduced energy expenditure.…”