Endocrine Abstracts

This case shows the potential unreliability of a single ACTH assay in the context of Cushing’s syndrome and need for better ways of measuring ACTH and precursors. A 35 year-old lady presented with severe abdominal pain and cushingoid features. CT scan showed a 2.9 cm right adrenal nodule. Investigations: 24-hour UFC 446 nmol/l, post-dexamethasone cortisol level of 572 nmol/l. The referring hospital found a suppressed ACTH < 0.1ng/l consistent with ACTH-independent Cushing’s but repeat testing showed elevated ACTH 20ng/l (2.2 – 13.3 pmol/l), which were repeatedly mildly elevated. CRH stimulation showed flat ACTH response. Urine steroid profile showed an elevation in cortisol metabolites relative to other adrenocortical steroid metabolites. Androgen levels were normal apart from suppressed DHEA <0.8umol/l. Despite the non-suppressed ACTH, the lack of correlation of ACTH with clinical features suggested assay interference. Failure of appropriate serial dilution of ACTH at dilutions 1, 2 and 4 suggesting a problem measuring ACTH. Roche Elecys assay in two other laboratories revealed ACTH < 0.1ng/l confirming that this was ACTH-independent Cushing’s. The patient underwent an uneventful laparoscopic adrenalectomy with post-operative cortisol <25mol/l, good resolution of cushingoid features and the histology showed a benign adrenal cortical adenoma. Current diagnostic tests for Cushing’s syndrome measure ACTH (1-39) which is unstable and has a short half-life. High stakes decisions can be made on a single laboratory result. ACTH fragments can interfere at high concentrations by saturating the capture antibody, leading to erroneous interpretation. A two-site assay including measurement of Joining Peptide (JP) secreted concomitantly with ACTH has the advantage of being more stable and may be more reliable. The development of further improved assays of ACTH and other POMC-precursors will help improve set the patient on the right diagnostic pathway and reduce the possibility of making high stakes surgical decisions based on erroneous ACTH results.