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Unlabelled: The effect of 5 to 9 days of metyrapone administration (400 mg/m2 every 4 h) on aldosterone, deoxycorticosterone, plasma renin activity, electrolyte balance, and blood pressure was investigated in 2 normotensive siblings (one of whom showed limited ACTH reserve), in 3 patients with hypertension and dexamethasone-suppressible hyperaldosteronism, and in a hypertensive patient with primary hyperaldosteronism due to bilateral adrenal hyperplasia., Results: 1. Plasma and urinary aldosterone levels were steadily suppressed by metyrapone in all cases, except in the oldest patient studied who had dexamethasone-suppressible hyperaldosteronism and in whom, after a few days, aldosterone gradually rose to normal levels. 2. Mild mineralocorticoid effect occurred only in the normal subject. In all other patients there was no apparent mineralocorticoid effect despite deoxycorticosterone hypersecretion. 3. There was no significant change in blood pressure with metyrapone administration in any patient.

A 9 year old Mexican boy presented with severe hypertension, hypokalaemia and features suggesting acute glomerulonephritis. Nephrosclerosis was present on renal biopsy. Aldosterone levels were unresponsive to variations in dietary salt intake and plasma renin activity was suppressed. Following oral dexamethasone therapy (2 mg/day), plasma aldosterone decreased to undetectable levels, serum potassium normalized and plasma renin activity gradually increased. Dexamethasone also restored the normal responsiveness of the renin-aldosterone system to postural stimuli. The patient exhibited a marked response to a single dose of ACTH with a rise in plasma aldosterone. Long-term blood pressure control and normal potassium levels have been achieved with oral prednisone therapy (5 mg/day) for a period of one year. This case of dexamethasone suppressible hyperaldosteronism (DSH) illustrates that the degree of hypertension in this syndrome may produce severe renal microvascular lesions. DSH should be considered in all children who present with low renin hypertension.

The effect of normalization of sodium balance was evaluated in children with aldosterone deficiency of several etiologies. In salt-losing congenital adrenal hyperplasia (CAH), treatment with a mineralocorticoid in doses that normalized plasma renin activity (PRA) induced a marked increase in linear growth. Serum 17-hydroxyprogesterone (17-OHP) and androgens fell further when adequate sodium balance was achieved, allowing in some cases a reduction in glucocorticoid replacement dose. Together with PRA measurement they were the most sensitive indicators of adequate mineralocorticoid and glucocorticoid replacement therapy. In 2 teenage children with aldosterone deficiency due to Addison's and autoimmune polyglandular disease similar improvement in growth as well as onset of puberty occurred when sodium balance was normalized by increased mineralocorticoid therapy. These studies show that adequate sodium balance is essential for normal growth and pubertal development.

In order to determine the source of androgens in precocious adrenarche, serum androgens were determined in 8 girls with precocious adrenarche and 5 agonadal children in adrenarche under conditions of adrenal and gonadal stimulation and suppression. All androgens increased with ACTH stimulation in both groups. Stimulability of serum androgens in girls with precocious adrenarche with ACTH was more consistent than in 13 prepubertal children. Human chorionic gonadotrophin administration increased serum delta4-androstenedione, testosterone and dihydrotestosterone in the girls with precocious adrenarche but not in the agonadal children, demonstrating the failure of HCG to stimulate adrenals. Dexamethasone suppression decreased levels of all androgens in both groups, whereas Norlutin or Ovral produced variable changes. These studies support the adrenal origin of androgens in precocious adrenarche and the lack of ovarian contributions in this condition.

Baseline somatomedin activity in seven of eight patients with Turner's syndrome was found to be within normal limits. Somatomedin activity readily suppressed with oestrogen administration. The overall mean serum somatomedin activity during oestrogen therapy (0.87 U/ml, SD 0.15) was significantly lower (P less than 0.005) than the mean of the control serum somatomedin activities (1.09 U/ml, SD 0.24). During oestrogen therapy, suggestive elevations of fasting growth hormone levels were noted in five of eight patients. The data indicate that oestrogenic suppression of serum somatomedin was not due to decreased growth hormone secretion and suggest the existence of a negative feedback link between somatomedin and growth hormone.

Unlabelled: A 12 year old child (46,XY) with 17-ketosteroid reductase deficiency was investigated. The patient, reared as a female, was first noted to have clitoromegaly at 10 years of age. Increased facial hair, deepening of the voice, acne, increased body hair and minimal breast development were noted at 12 years. delta4-Androstenedione (delta4) in peripheral blood was markedly elevated (1913 ng/100 ml) whereas testosterone (T) was in the male range of Tanner III puberty (240 ng/100 ml). Thus, delta4/T in this patient was 9.4, compared to a normal ration of 0.15 to 0.25. T/DHT was normal (10.5). Oestrone (Oe1) level was slightly elevated (6 ng/100 ml, normal: 2.5-4.5 ng/100 ml). Oestradiol (Oe2) was normal (1.7 ng/100 ml, normal: 1.5-3 ng/100 ml. Oe1/Oe2 was slightly elevated (3.6, normal: 1-2). At laparotomy, testes were found and spermatic vein blood was obtained prior to castration. Androgen determinations of spermatic vein blood demonstrated extremely high delta4 levels (283 microgram/100 ml) and low levels of T (16 microgram/100 ml). delta4/T in spermatic vein was 17, higher than in the peripheral blood, suggesting intact peripheral conversion of delta4 to T. Incubation of testes slices with delta4 demonstrated severely impaired conversion to T. Conversion of Oe1 to Oe2 was impaired to a lesser degree., Conclusion: 17-ketosteroid reductase deficiency was documented in vivo by impaired conversion of precursor hormones resulting in higher than normal delta4T and Oe1/Oe2 ratios in blood. In vitro studies with testes slices confirmed the enzymatic defect.

A primary intracranial HCG-producing tumour was studied in an 8 year old boy with congenital adrenal hyperplasia. The case provided a unique opportunity to study the sequential changes in serum and urinary androgens and HCG as measured by radioreceptor assay for HCG and by radioimmunoassay for HCG using antisera raised against the hormone specific for the beta subunit of HCG. Plasma concentrations of HCG, measured by the radioreceptor assay, closely correlated with the biologic activity of his tumour, as measured by serum testosterone concentration. This case demonstrates that precocious puberty in any child, including one with a known androgen disorder such as congenital adrenal hyperplasia, warrants through investigation.