Factitious Cushing's syndrome: discovery with use of a sensitive immunoradiometric assay for corticotropin

Factitious Cushing's syndrome is an unusual problem that may be clinically and biochemically indistinguishable from endogenous hypercortisolism. Results of biochemical studies may be misleading because of cross-reactivity of synthetic corticosteroids or their metabolites with plasma or urine cortisol. Because of its lack of specificity, radioimmunoassay (RIA) for corticotropin (adrenocorticotropic hormone or ACTH) may not show completely suppressed results in patients with surreptitious use of glucocorticoids. A new sensitive and specific immunoradiometric assay (IRMA) for ACTH demonstrates reliably suppressed levels after administration of glucocorticoids. In this report, we describe a 37-year-old woman with typical clinical and biochemical features of ACTH-dependent hypercortisolism. Metabolic evaluation had shown urinary free cortisol excretion of 7,499 nmol/day and plasma ACTH-RIA levels of 13.2 and 33.0 pmol/L on two separate occasions. The use of IRMA for the measurement of ACTH during inferior petrosal sinus sampling revealed a very low peripheral ACTH concentration (=0.4 pmol/L) and a considerably blunted response to ovine corticotropin-releasing hormone, findings that suggested ACTH-independent Cushing's syndrome. Plasma samples obtained during inferior petrosal sinus sampling were assayed for prednisolone and showed a concentration of 360 nmol/L; thus, the presence of factitious Cushing's syndrome was confirmed. Some commercial ACTH-RIA measurements may be unreliable in distinguishing ACTH-dependent from ACTH-independent hypercortisolism. ACTH-IRMA levels are low in patients with ACTH-independent Cushing's syndrome and will be helpful in identifying factitious Cushing's syndrome.