These results suggest that the sensitivity of secretion to physiological doses of ACTH in descending order is aldosterone > DHEA = cortisol. When peak and incremental values are used, sufficient doses of ACTH are 0.1 microgram for plasma aldosterone and 0.5 microgram for plasma cortisol and DHEA in the rapid ACTH test.

We examined the possibility that AVP and V1a receptors were involved in regulating cortisol production in a 49 year old man with ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH), and investigated the effects of a V1a receptor antagonist. An i.v. injection of a small dose (0.1 or 0.3 U) of AVP, insulin-induced hypoglycaemia, upright posture tests, and oral administration of a V1a receptor antagonist (OPC-21268; 300 mg), and its repeated administration at a dose of 600 mg/day for 8 days were performed. An in vitro study of dispersed cells obtained from resected AIMAH tissue was also conducted. Plasma ACTH, AVP and cortisol levels and 24-h urinary free cortisol excretion were measured in the in vivo studies and cortisol concentrations in incubation media in the in vitro study. Injection of small doses of AVP stimulated cortisol secretion without any elevation of plasma ACTH. Insulin-induced hypoglycaemia caused a rise in plasma AVP followed by an increase in plasma cortisol. Although plasma cortisol levels were not affected by single or repeated administrations of OPC-21268, 24-h urinary free cortisol excretion was significantly decreased by the repeated treatment. In the in vitro study, more cortisol was stimulated by AVP from adrenal cells of the AIMAH tissue than from those of a normal adrenal gland, and this secretion was completely suppressed by OPC-21268. These results suggested that hypersensitivity to AVP may have contributed to overproduction of cortisol in this case of ACTH-independent bilateral macronodular adrenocortical hyperplasia, and may have contributed to its pathogenesis.

Chronic adrenocorticotropin (ACTH) treatment in rats leads to a fall in aldosterone secretion (aldosterone turn-off or "aldosterone escape" phenomenon) with a concomitant rise in corticosterone. To elucidate whether ACTH-induced aldosterone suppression is mediated by steroid type II receptor or related to a free-radical effect by over-synthesized corticosterone, we examined the effects of a glucocorticoid antagonist, RU486, and antioxidants dimethyl sulfoxide (DMSO) and vitamin E, on the aldosterone turn-off phenomenon in rats. Each rat received daily for 5 days a different dose of ACTH-Z (5, 10, 20 or 40 micrograms/100 g body weight) 1 mg RU486/100 g body weight, 100 microliters (1.3 mmol) DMSO/100 g body weight or 2 mg vitamin E/100 g body weight with subcutaneous injection. Plasma steroid levels and in vitro release of steroids from the adrenal capsule were measured. The ACTH-Z treatment caused a dose-dependent increase in corticosterone and a decrease in aldosterone in both plasma and adrenal capsule experiments, as well as an increase in adrenal weights. For the following study 5 micrograms/100 g body weight of ACTH-Z was used. Administration of RU486 alone caused no change in plasma aldosterone level compared to controls, even though the steroid type II receptor was blocked, as evidenced by significant increases in plasma ACTH and corticosterone levels. Concomitant administration of RU486 and ACTH-Z increased both plasma corticosterone and aldosterone levels (p < 0.01) but decreased adrenal capsule corticosterone production (p < 0.05) compared to the rats treated with ACTH-Z alone.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

Abstract. Since a heterozygous missense mutation of the RET proto-oncogene in the germline was found to cause multiple endocrine neoplasia type 2A (MEN 2A) in 1993, some 20 different mutations of this gene have been identified in MEN 2A kindreds.We report an MEN 2A family in which serine (AGC) substitutes for cysteine (TGC) at codon 618 in exon 10 of the RET proto-oncogene. The mutation was identified by sequencing PCR products of exons 10 and 11 in the proband. Since this mutation results in creation of a new cleavage site for Alu I restriction enzyme, most of the other members of the family were screened by digestion of the PCR product of exon 10 with this enzyme. Eleven of 20 subjects across four generations examined have the mutation of the RET proto-oncogene, and all of the adult gene carriers except one woman had MTC. Characteristics of this family are 1) pheochromocytoma has been found in only the proband, 2) no obvious hyperparathyroidism has been observed, and 3) the prognosis is favorable, with nobody dying of MEN 2A itself. Genetic analysis of MEN 2A is definitely useful and essential for screening of a MEN 2A family. It is very important to accumulate cases with MEN 2A and investigate the phenotype and the prognosis in each mutation.