Cushing's disease with intermittent hypercortisolism

Abstract

In a patient with proved pituitary-dependent Cushing's syndrome (Cushing's disease), 24-hour urinary excretion of free cortisol fluctuated between normal (69 percent of the time, often in the low range and for several days in sequence) and high values. Increased urinary free cortisol excretion occurred unpredictably within the context of a persistent, progressive clinical picture. This case stands in contrast with previous reports of urinary steroid levels varying in a periodic infradiem pattern. Even with normal baseline cortisol indexes, control of the hypothalamic-pituitary axis (as indicated by the suppression test and by the circadian cortisol pattern in plasma) remained abnormal. This patient emphasizes the fact that abnormal control regulation, more than cortisol hypersecretion, is at times indicative of Cushing's disease. Hence, sensitive accurate screening requires not only urinary free cortisol measurement (the usefulness of which may be improved by assay of more than one, possibly nonsequential, 24-hour urine sample), but also dexamethasone suppression testing and late-evening plasma cortisol determination, even if baseline indexes are within the range of normal.