Evaluation of the hypothalamic-pituitary-gonadal function in the Bardet-Biedl syndrome

Abstract

The hypothalamic-pituitary-gonadal system was evaluated in three siblings with the Bardet-Biedl syndrome. All patients had mental retardation, pigmentary retinopathy, obesity, polydactyly, and hypogonadism. Serum levels of luteinizing hormone (LH) were above the upper limit of normality in the elder brothers (101.6 and 62.6 ng/ml, respectively) but were within normal limits in the younger patient. Serum follicle-stimulating hormone (FSH) was within the normal range for all three patients. After 100 μg of intravenous gonadotropin-releasing hormone (LH-RH), the LH and FSH serum levels showed a response that correlated well with the respective pubertal stages of the patients. Chronic stimulation with synthetic LH-RH (500 μg for 3 days) was also followed by a marked rise in both LH and FSH. Clomiphene administration induced a marked rise in serum LH, while FSH values did not show a clear elevation. Although plasma testosterone was found to be normal for each individual patient, repeated stimulation with human chorionic gonadotrophin failed to further increase plasma testosterone in the two elder brothers. Basal levels of serum prolactin and growth hormone were within the normal range and stimulatory and supressive tests for these pituitary hormones were also normal in these patients. An oral glucose tolerance test revealed high basal levels and an exaggerated rise in plasma insulin values. Testicular biopsy performed in the three patients showed a nonuniform degenerative lesion of the seminiferous tubules with marked reduction of spermatogenic activity. Only scant groups of Leydig cells were seen in the interstitium with a clear decrease of the total number of these cells. These findings indicated a trend to an evolutive gonadal disorder possibly beginning near the onset of puberty and progressing throughout the adult life.