The impact of the synthetic glucocorticoid prednisone on adrenal steroid hormone production was examined using 24-hour urinary steroid hormone profiling. Five women, who were chronically taking low-dose prednisone, were tested, and the relevant literature was reviewed. As expected, adrenal glucocorticoid production, measured by urinary terminal cortisol and cortisone metabolites, was markedly suppressed compared to reference range values (p=0.03). Urinary cortisol and cortisone, reflecting

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... lating glucocorticoids, were decreased to a lesser extent than their terminal metabolites. Urinary dehydroepiandrosterone (DHEA) excretion was dramatically suppressed (p=0.03), while the downstream androgen metabolites androsterone and etiocholanolone were suppressed to a lesser extent. Aldosterone and tetrahydrocorticosterone production demonstrated modest suppression after prednisone administration, but allo-tetrahydrocorticosterone, which is highly sensitive to adrenocorticotropic hormone (ACTH) secretion, was suppressed to a greater extent. Prednisone administration results in a decrease in ACTH secretion by the anterior pituitary, suppressing synthesis of glucocorticoids, DHEA, and DHEA metabolites. Decreased glucocorticoid synthesis is adaptive, because prednisone is active at the glucocorticoid receptor, but suppression of DHEA synthesis is not mitigated by prednisone. DHEA is an important sex hormone precursor, neurosteroid, and endocrine and immune modulator; therefore, DHEA depletion may have significant adverse consequences in terms of sex hormone production, bone health, endocrine and immune system function, and neuropsychiatric status. Studies of DHEA replacement in patients taking prednisone for lupus demonstrate amelioration of some of these adverse effects.