A single sleeping midnight cortisol has 100% sensitivity for the diagnosis of Cushing's syndrome

Author(s): Trainer, P., Perry, L., Wass, J., Grossman, A., Besser, M.

Journal/Book: Clin Endocrinol. 1995; 43: Osney Mead, Oxford, Oxon, England OX2 0EL. Blackwell Science Ltd. 545-550.

Abstract: OBJECTIVE The diagnosis of Gushing's syndrome remains a major challenge in clinical endocrinology. Various screening tests are commonly used to support a biochemical diagnosis in the context of clinical suspicion. The aim of this study was to compare the sensitivity in the diagnosis of Gushing's syndrome of a single inpatient sleeping midnight cortisol to a standard 48-hour in-patient low-dose dexamethasone suppression test (LDDST) during the same admission. DESIGN A retrospective analysis was performed on 150 patients investigated in our department between the years 1970 and 1994 with a confirmed diagnosis of Gushing's syndrome. PATIENTS One hundred and fifty patients with a diagnosis of Gushing's syndrome were analysed: 110 with Gushing's disease; 12 with tumours with ectopic ACTH secretion; 8 with ACTH dependent Gushing's syndrome of so far undetermined origin; 17 with cortisol secreting adrenal tumours; 3 with adrenocortical nodular hyperplasia. Twenty normal volunteers and nine patients with non-endocrine conditions were also investigated as controls. MEASUREMENTS Plasma cortisol was measured by radioimmunoassay (RIA) in the 122 patients presenting after 1980, and by fluorimetry prior to this date. RESULTS In all the control subjects the sleeping midnight cortisol was < 50 nmol/l, below the lowest standard of the routine in-house RIA. In every patient with Cushing's syndrome the sleeping midnight cortisol was detectable with a value greater than 50 nmol/l, with a range of 70-2000 nmol/l. In contrast, in three cases, all of whom had proven Gushing's disease on histology, there was uncharacteristic complete suppression of plasma cortisol to < 50 nmol/l following the LDDST. CONCLUSION In this series of 150 cases, a single inpatient sleeping midnight cortisol above 50 nmol/l had a 100% sensitivity for the diagnosis of Gushing's syndrome, clearly different from normal subjects. In contrast, the low-dose dexamethasone suppression test had a sensitivity of 98% even when the drug was administered as an in-patient. We recommend that a low-dose dexamethasone suppression test should not be used alone for confirmation of Gushing's syndrome since it may miss 2% of cases.

Note: Article A Grossman, St Bartholomews Hosp, Dept Endocrinol, London EC1A 7BE, England

Keyword(s): CORTICOTROPIN-RELEASING HORMONE; DEXAMETHASONE SUPPRESSION TEST; DIFFERENTIAL-DIAGNOSIS; SERUM CORTISOL; DISEASE; RHYTHM; STATES

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