EVIDENCE FOR HYPOTHALAMIC-PITUITARY DYSFUNCTION IN THE PRADER-WILLI SYNDROME

The etiology of the Prader-Willi Syndrome is obscure. Although the clinical characteristics (obesity, mental retardation, hypotonia and hypogonadism) suggest hypothalamic dysfunction, this has not been documented. We have studied two patients (15 and 22 yr.) with this disorder in whom clinico-pathologic correlation was possible. Both were severely obese (150 and 190 kg) with glucose intolerance. Cold exposure (4° C for 1 hr.) produced an abnormal decrease in body temperature in one child. Plasma growth hormone (GH) did not increase with arginine-insulin, or L-dopa stimulation. Plasma cortisol showed a diurnal variation but blunted response to hypoglycemia. Basal T4 and TSH were normal and the TSH, T4 and T3 responses to TRH were normal in both patients. Basal testosterone was low in both individuals and LH and FSH responses to LRH were blunted. Clomiphene stimulation failed to augment plasma gonadotropin levels. The pituitary glands were of decreased weight but neither the pituitary nor hypothalamus was abnormal on light microscopy. These studies indicate abnormal hypothalamic-pituitary function in both patients. Involvement of the temperature control center, absent clomiphene response, abnormal GH responsiveness and normal anatomical findings support the formulation of a functional hypothalamic abnormality.