The effect of oral dexamethasone on the plasma content of cortisol and dexamethasone was investigated in 175 patients suspected of having Cushing's syndrome. Plasma concentrations of cortisol and dexamethasone were measured by specific radioimmunoassays at 08.00 h following administration of either a low-low (0.5 mg), low (1.0 mg), high (4.0 mg) or high-high (8.0 or more mg) dose of dexamethasone at midnight. All seventeen patients with documented Cushing's syndrome exhibited resistance to the action of low-low and/or low dose dexamethasone on suppression of 08.00 h plasma cortisol content. Nine of twelve patients with pituitary dependent Cushing's syndrome had plasma cortisol values of less than 166 nmol/l following high-high dose testing. In 157 patients with suspected Cushing's syndrome, standard dexamethasone testing was considered unsatisfactory in at least 20%. After low-low or low dose tests 11% had supranormal cortisol values, but plasma cortisol content overlapped with values observed in patients with Cushing's syndrome only when plasma dexamethasone content was less than 5.6 nmol/l. Twelve per cent of patients suspected of having Cushing's syndrome had sufficient elevation of plasma dexamethasone values after low dose testing so that marked reduction of plasma cortisol might be expected even in patients with pituitary dependent Cushing's syndrome. Four patients receiving anticonvulsants had subnormal plasma levels of dexamethasone for the dose administered, but all exhibited normal suppression when plasma levels of dexamethasone and cortisol were correlated simultaneously. In summary, there is considerable variation in the plasma content of dexamethasone following oral doses. Simultaneous measurement of both plasma levels of dexamethasone and cortisol has proved most useful in identifying patients with unsatisfactory dexamethasone suppression tests.

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Both hereditary and nonhereditary factors have a decided influence on plasma sex steroid concentrations in men. We studied the relative contributions of genetic and nongenetic factors on the production rate (PR) and MCR of testosterone and dihydrotestosterone (DHT) and their conversion ratios to other metabolites in monozygotic (MZ; n = 22) and dizygotic (DZ; n = 24) male twins. Zygosity was determined by measurement of 10 blood proteins and enzymes. The kinetic studies were conducted with isotope dilution techniques. The genetic effect was determined from the equation: 2[rMZ - rDZ], where r is intraclass correlation. A heritability of over 40% was found for the PRs of DHT/body surface area and of testosterone/body surface area. Nongenetic factors accounted for 50% or more of the variation of the conversion ratios for testosterone/3 alpha-androstanediol and DHT/3 alpha-androstanediol. The results suggest that genetic factors markedly influence the PRs of testosterone and DHT, suggesting that the PR of these potent androgens is under genetic control despite the decided influence of environmental factors on their clearance.

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