Bernard Kliman

PROTON-BEAM THERAPY IN ACROMEGALY.

Abstract Bragg-peak proton hypophysectomy was used in 22 acromegalic patients. Of 14 followed for two to 36 months, size of hands, feet or face decreased in nine. Variable improvement took place in...

The biologic activity of a potent analogue of gonadotropin-releasing hormone in normal and hypogonadotropic men.

We studied the biologic activity of a long-acting analogue of luteinizing hormone-releasing hormone, D-Trp6-Pro9-NEt-LHRH (LHRHa), in five normal men and four hypogonadotropic men previously unresponsive to natural LHRH. All subjects responded to LHRAa, but there were quantitative and qualitative differences between the normal and hypogonadotropic men. Normal men showed a linear dose-response relation, endogenous gonadal steroid secretion, and an adult pattern of gonadotropin secretion characterized by a high ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH). Hypogonadotropic men had improving pituitary responses to each dose of LHRHa (priming response), no demonstrable gonadal steroid secretion, and a prepubertal pattern of gonadotropin release characterized by reversal of the normal ratio of LH to FSH. When compared with native LHRH, LHRHa had an augmented ability to discharge gonadotropins acutely and to sustain their release in normal and hypogonadotropic men.

High Incidence of Cortical Atrophy of the Cerebral and Cerebellar Hemispheres in Cushing's Disease

Abstract One of the most striking generalized metabolic changes in Cushings disease is catabolism of protein, which results in protein depletion. The resultant osteoporosis, muscle wasting, skin atrophy, and fragility of the blood vessels have been recognized. The present study of 31 cases also shows a high degree of cerebral and cerebellar cortical atrophy in this disease.

Percutaneous absorption of corticosteroids: systemic effects.

SINCE 19521 the corticosteroids have held an unrivaled position among medications used for the topical treatment of various skin diseases and have come to be employed extensively for clinical purpo...

Familial hyperthecosis: Comparison of endocrinologic and histologic findings with polycystic ovarian disease

Abstract Two siblings and their mother were found to have ovarian hyperthecosis as defined by the presence of luteinized cells within the ovarian stroma. In the daughters, plasma testosterone and androstenedione levels were high-normal or elevated. The production rates of both hormones were increased, while the metabolic clearance rates per square meter were elevated for testosterone and were normal for androstenedione. Plasma FSH levels were low or low-normal and LH levels were normal; both were unaffected by ovarian wedge resection. Following operation, plasma testosterone and androstenedione levels fell during the first week but rose to preoperative levels or higher within three months. The relation of stromal hyperthecosis and polycystic ovarian disease is discussed.

Hypogonadotropinism in Prader-Willi syndrome: Induction of puberty and spermatogenesis by clomiphene citrate

Abstract Prader-Willi syndrome is characterized by infantile hypotonia, mental retardation, hyperphagia with obesity, and hypogonadism. Three affected male patients, ages nineteen, twenty and twenty-three, were found to have hypogonadotropic hypogonadism. Pituitary function was otherwise normal. Testicular biopsy revealed prepubertal tubules with abnormalities of interstitial tissue in one patient and arrest of tubular development in another. One patient was treated with clomiphene citrate for forty days and plasma luteinizing hormone (LH), testosterone and urinary gonadotropin levels rose to the normal range for males. These hormonal levels remained normal for at least eighty days after treatment was stopped. Normal Spermatogenesis was present on repeat testicular biopsy, and physical signs of puberty were evident. Hypogonadism in Prader-Willi syndrome appears to be the result of hypothalamic dysfunction. Clomiphene citrate may be effective treatment for male hypogonadism in this syndrome.

Familial Syndrome of Primary Testicular Insufficiency with Normal Virilization, Blindness, Deafness and Metabolic Abnormalities

Abstract In spite of the presence of small testes and elevated urinary gonadotropin levels, two brothers with a new syndrome of familial hypogonadism had normal secondary sex characteristics. Assoc...

Changes in fluid compartments, renal hemodynamics, plasma renin and aldosterone secretion induced by low sodium intake.

Renin plasma level, aldosterone secretion rate, extracellular and blood volumes, glomerular filtration rate, renal plasma flow, serum sodium and potassium were measured in 6 subjects before and during a 6-day period of low sodium diet. Urine volume and excretion of Na and K, arterial pressure, and body weight were measured daily. Restriction of sodium decreased extracellular fluid and blood volumes and produced a clear rise in plasma renin activity and in the secretion rate of aldosterone, whereas renal plasma flow and glomerular filtration rate fell below the control values. Calculated renal vascular resistance increased 15 per cent above control values. Changes in serum sodium and potassium were not statistically significant, and arterial pressure decreased slightly during the period of diet. These findings suggest the participation of renal vascular constriction as one of the factors involved in renin release.

Pure Gonadal Dysgenesis with Progressive Hirsutism

Abstract A 24-year-old woman with pure gonadal dysgenesis was evaluated to determine the cause of progressive hirsutism. Plasma testosterone levels (0.06 to 0.15 μg per 100 ml) ranged from the upper limit of normal (for adult females) to elevated. The plasma androstenedione level (0.18 μg per 100 ml) was normal. Plasma testosterone fell to 0.03 μg per 100 ml in response to gonadotropin suppression with estrogen but did not respond to ACTH suppression or stimulation. A threefold gradient of testosterone concentration between the gonadal and peripheral vein blood confirmed the streaks as the source of excess androgen. Cytogenetic studies of leukocytes and both gonadal streaks showed 46 chromosomes with an XX sex-chromosome constitution. Histologic studies of the streaks revealed the presence of hilus cells and luteinized gonadal stromal cells. Estrogen deficiency apparently caused elevation of endogenous gonadotropin, which in turn stimulated excess androgen production by gonadal-streak tissue.

Derivative ratio analysis: A new method for measurement of steroids and other compounds with specific functional groups using radioassay by gas-liquid chromatography

Abstract A new isotope method of microassay, derivative ratio analysis, has been developed. To the substance to be measured, e.g., testosterone, an unlabeled internal standard with a similar functional group is added. The mixture is acetylated with acetic anhydride-C14 following which the derivatives are separated by gas-liquid chromatography. Detection and measurement of C14 in the effluent of the chromatography is performed either continuously during the analysis or by fractionating the effluent and then assaying each fraction individually. The quantity of unknown is related to the quantity of standard in the same ratio as the radioactivity of the unknown is related to the radioactivity in the standard. This method may be used with a variety of compounds, and may be extended to measurement of nanogram quantities.