ACTH Immunoassay Interference Leading to Diagnostic Pitfalls in Hypercortisolism

Presentation Number: MON 406
Date of Presentation: April 3rd, 2017

Serkan Yener1, Leyla Demir2, Muhammed Mustafa Demirpence3, Mustafa Mahmut Baris1, Secil Ozisik1 and Abdurrahman Comlekci*1
1Dokuz Eylul University Medical School, Izmir, Turkey, 2Ataturk Training Hospital, Izmir, Turkey, 3Tepecik Education and Research Hospital, Izmir, Turkey



Measuring plasma ACTH is important for the management of hypercortisolism. However, immunoassays are vulnerable to interference from endogenous antibodies.

Case Report

A 27 years-old female with typical features of Cushing’s syndrome was referred for further investigation. DSTs revealed non-suppressed cortisol levels. UFC was significantly elevated and diurnal variation of cortisol production was not preserved. Initial ACTH measurements showed ACTH dependent hypercortisolism (48, 56.2, 55 pg/ml (5-46); Immulite 2000Xpi; Siemens Healthcare Diagnostics). We did not observe significant cortisol suppression in high dose DST. IPSS with CRH administration indicated an ectopic production of ACTH. Ga-68 DOTA-TATE PET/CT showed somatostatin receptor expression in the left adrenal gland. Computed tomography showed a 33 mm left adrenal mass with benign features. At this point, further investigation to exclude falsely elevated ACTH levels was initiated. Plasma ACTH assayed on an alternative method was significantly suppressed (< 1 pg/ml (7.2-63.3); Elecsys E170, Roche Diagnostics). Then, patient’s plasma sample was subjected to precipitation with polyethylene glycol (PEG) 6000 to remove interfering antibodies. After the precipitation, plasma ACTH level was suppressed (< 10 pg/ml; Immulite 2000Xpi; Siemens Healthcare Diagnostics). The patient had an uneventful laparoscopic left adrenalectomy. Serum cortisol level significantly decreased from 19.3µg/dl to 6.3µg/dl (3.7-19.4); Immulite 2000Xpi; Siemens Healthcare Diagnostics) 3 hours after adrenalectomy. Clinical features significantly resolved and the patient became pregnant after 3 months. Pregnancy period was uneventful.


Analytical interference in ACTH immunoassay could lead to misjudgment of hypercortisolism. Ensuring communication between clinical and laboratory staff is mandatory to prevent unnecessary interventions.


Nothing to Disclose: SY, LD, MMD, MMB, SO, AC