Inappropriate adrenal androgen secretion with once-a-day corticosteroid therapy for congenital adrenal hyperplasia.

To determine whether cortisone acetate given as a single daily dose would be as effective as the same amount divided into three doses in suppressing adrenal androgen secretion in congenital adrenal hyperplasia, we studied three patients with the salt-losing variety, who were judged to have been adequately treated during the previous year. Each patient was receiving cortisone acetate, 20.6 to 22.6 mg/m2 body surface area per day, divided into three doses, and 9 alpha-fluorohydrocortisone, 0.05 to 0.1 mg/day. Their spontaneous and adrenocorticotropic hormone-stimulated blood concentrations of 17 alpha-hydroxyprogesterone, androstenedione, and testosterone were measured initially and were normal. Cortisone acetate was then given once a day in the same total daily dose. After 3 months, plasma adrenocorticotropic hormone concentration was increased in all three patients, and in two of them the plasma levels of 17 alpha-hydroxyprogesterone and androstenedione were also increased. In the third patient, after 7 months of once-daily therapy, plasma levels of 17 alpha-hydroxyprogesterone and androstenedione were increased. We conclude that a physiologic replacement dosage of cortisone acetate given once daily is not effective in controlling excessive adrenal androgen secretion in congenital adrenal hyperplasia.

Secretion of melanocyte-stimulating hormone and adrenocorticotropin from transplanted pituitary pars intermedia in stressed and nonstressed rats.

Rats bearing kidney grafts of the pituitary pars intermedia were divided into three groups: unstressed, acutely stressed, and chronically stressed. Corresponding sham-operated rats were used for comparisons. Twenty days after grafting, the rats were sacrificed and alpha-melanocyte-stimulating hormone (alpha-MSH), adrenocorticotropin (ACTH), and corticosterone were estimated in plasma. The adrenal/body weight ratio and DNA content of the glands were also investigated. The following results were obtained: MSH was found not to be increased in unstressed rats, but it was in grafted animals subjected to acute and chronic swimming stress. ACTH and corticosterone rose in all three groups. Adrenal/body weight ratio and DNA content increased only in grafted chronically stressed rats. Moreover, plasma corticosterone was found higher in grafted hypophysectomized rats than in non-grafted hypophysectomized animals. Administration of ergocryptine to nonstressed grafted rats induced a decrease in the blood content of ACTH and MSH, indicating that the grafts were the source of a part of the circulating ACTH. On the other hand, the fall in MSH levels could show the effect of the drug upon the pars intermedia. Comparison of the ratios of both hormones released in incubations showed that grafts secreted more ACTH than MSH; on the other hand, when intact neurointermediate lobes were incubated, MSH predominated over ACTH. For the first time it is demonstrated that the pars intermedia can secrete ACTH in vivo. Nevertheless, the ability to secrete this hormone is not a property of normal intact pars intermedia, but it manifests in the transplantations probably due to the overactivity of light cells induced by chronic stoppage of dopaminergic inhibition.

Changes in alpha-melanocyte-stimulating hormone content in discrete hypothalamic areas of the male rat during a twenty-four-hour period.

Circadian variations in alpha-melanocyte-stimulating hormone (alpha-MSH) content of discrete hypothalamic areas of the male rat were observed either with radioimmunoassay or bioassay. In the medial basal hypothalamus and preoptic area the alpha-MSH content increased sharply between 02.00 and 06.00 h, showing the highest concentration at 06.00 h. In contrast, no significant changes in alpha-MSH content were detected in the lateral hypothalamus during a 24-hour period. Pituitary alpha-MSH also showed a diurnal variation which was different from that in the two hypothalamic areas. The finding that alpha-MSH values in the brain are maximal during the activity period of the rat is in agreement with results demonstrating a role of alpha-MSH in behaviour and locomotor activity.

Treatment of persistent pubertal gynecomastia with dihydrotestosterone heptanoate.

Four boys with persistent pubertal gynecomastia were given intramuscular dihydrotestosterone heptanoate (DHT-hp) at 2 to 4-week intervals for 16 weeks. By the end of treatment, breast size in all four boys had decreased 67% to 78%. Initial plasma levels of gonadotropins, estradiol, testosterone, and dihydrotestosterone (DHT) were normal. Mean plasma DHT concentration rose with the injections of DHT-hp, and remained elevated throughout the treatment period. Estradiol, LH, FSH, and testosterone decreased during treatment, as did 24-hour urinary LH and FSH. No regrowth of breast tissue was observed 6 to 15 months after treatment, although hormone concentrations had returned to near pretreatment values by 2 months after the last injection. DHT-hp has potential to be an effective medical therapy for persistent pubertal gynecomastia.