A B S T R A C T The demonstration that luteinizing hormone (LH) release from the pituitary is episodic rather than constant raises fundamental questions regarding the physiologic control of pulsatile LH secretion and its possible alteration in patients with gonadal disorders. To evaluate this mode of LH secretion, quantitative means of analyzing LH pulse amplitude, frequency, shape, and area were established and utilized to study normal subjects and patients with disorders of gonadotropin secretion. Similar patterns of LH secretion were observed in normal men, in women during the follicular phase of the menstrual cycle, and in patients with hyperand hypogonadotropism, hirsuitism, and amenorrhea (mean pulse amplitude 39-179% from nadir to peak, frequency 2.7-3.9 secretory spikes/6 h). These observations suggested that the pattern of LH secretion is similar in both normal individuals and in those with a variety of pathologic conditions. By contrast, the pattern of pulsatile secretion appeared to differ in the following conditions. LH pulses of higher amplitude (333±170%) and lower frequency (1.6±0.24 SEM/6 h) characterized the secretory patterns of women during the luteal phase of the menstrual cycle, suggesting that gonadal steroids may modulate LH pulses. LH pulses of low amplitude (26±2.1%) and frequency (1.3±0.36/6 h) were observed in women with anorexia nervosa.Either integrated LH levels or a mean LH level determined from multiple samples provided a more accurate reflection of gonadotropin secretion than the use of
A patient with Cushing's syndrome due to ectopic ACTH secretion was treated successfully with the new glucocorticoid antagonist RU 486 [17 beta-hydroxy-11 beta-(4-dimethylamino phenyl) 17 alpha-(1-propynyl)estra-4,9-dien-3-one]. This compound is a 19-nor steroid with substitutions at positions C11 and C17 which antagonizes cortisol action competitively at the receptor level. Oral RU 486 was given in increasing doses of 5, 10, 15, and 20 mg/kg . day for a 9-week period. Treatment efficacy was monitored by assessment of clinical status and by measuring several glucocorticoid-sensitive variables, including fasting blood sugar, blood sugar 120 min after oral glucose administration, and plasma concentrations of TSH, corticosteroid-binding globulin, LH, testosterone-estradiol-binding globulin, and total and free testosterone. With therapy, the somatic features of Cushing's syndrome (buffalo hump, central obesity, and moon facies) ameliorated, mean arterial blood pressure normalized, suicidal depression resolved, and libido returned. All biochemical glucocorticoid-sensitive parameters normalized. No side-effects of drug toxicity were observed. We conclude that RU 486 may provide a safe, well tolerated, and effective medical treatment for hypercortisolism.
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