Adrenocorticotropic hormone (ACTH) concentration levels are key in determining the cause of Cushing’s syndrome, however the assay is vulnerable to interference. This report discusses the case of a 40 year old woman with cortisol excess and unilateral adrenal lesion but elevated ACTH concentration suggestive of ACTH-dependent Cushing’s syndrome. Through close collaboration with the chemical pathology team, it was determined that assay interference was likely leading to a falsely elevated ACTH concentration. The patient underwent a successful unilateral adrenalectomy and avoided unnecessary testing.
Ms M is a 40 year old woman referred due to an adrenal mass found incidentally, and a raised serum cortisol level. She had two year history of lethargy, central adiposity and easy bruising, as well as three months of amenorrhea.
CT findings showed a 3cm left adrenal adenoma with heterogenous contrast enhancement. Random cortisol level was 656nmol/L (NR 145-619) and failed to suppress with 1mg dexamethasone suppression test. ACTH (using Siemens immulite assay throughout) was detectable throughout 4mg Dexamethasone suppression test, with a peak of 3.0 pmol/L at 4 hours.
This picture suggested ACTH-dependent hypercortisolaemia. However, this is discordant with clinical picture and known adrenal lesion. ACTH testing on two other platforms (Roche & Diasorin Liasion) showed undetectable and low levels, prompting a successful left adrenalectomy rather than invasive inferior petrosal sinus sampling. Histology showed a 35mm cortical benign adenoma. ACTH levels measured on the Roche assay rose in the 8 hours post surgery as would be expected with the removal of a cortisol secreting adenoma. The patient was subsequently placed on a weaning dose of hydocortisone with clinical improvement.
In addition to a review of the literature, we review the attributes of the three platforms used to measure ACTH in Australia, and techniques to manage potential assay interference.