Interference in the Siemens Immulite ACTH Immunoassay Leading to Misdiagnosis of Primary Adrenal Insufficiency

Presentation Number: SAT-0749
Date of Presentation: June 21st, 2014

Alicia Algeciras-Schimnich*, Hemamalini Ketha, J Paul Theobald and Alice Y Chang
Mayo Clinic, Rochester, MN


Background: Interference in immunoassays is a rare event but a potentially clinically significant problem when it leads to additional diagnostic tests and inappropriate treatments. Previous reports identified falsely elevated ACTH concentrations due to heterophile antibodies and misdiagnosis of Cushing’s disease. We describe a case of misdiagnosed primary adrenal insufficiency that required evaluation beyond commercially available heterophile antibody blocking reagents.

Case: An 18 year old male, presented to the Endocrinology department for evaluation of primary adrenal insufficiency. Prior clinical history included growth hormone deficiency and delayed puberty in the context of secondary hypogonadism. During routine annual evaluation with his local endocrinologist, he was diagnosed with primary adrenal insufficiency based on a noon ACTH concentration of 156 pg/mL and a cortisol concentration of 3.9 μg/dL. The patient was treated with hydrocortisone (20 mg am, 10 mg pm). Patient presented for a second opinion because he was asymptomatic at the time of diagnosis. He denied any weight loss, nausea, fatigue and had no evidence of hyperpigmentation on exam. Baseline 8am cortisol (more than 24 hours from the last hydrocortisone dose) was 8.6 μg/dL (reference interval 7-25 μg/dL) and ACTH was 89 pg/mL (reference interval 10-60 pg/mL). Cortisol concentrations after cosyntropin stimulation were 19 and 22 μg/dL at 30 and 60 minutes, respectively. To investigate possible interference in the Siemens Immulite ACTH immunoassay, ACTH measurements were performed after serial dilutions. ACTH concentration was 83 pg/mL (non-diluted), 200 pg/mL (1:5), 280 pg/mL (1:10) and 420 pg/mL (1:20). This nonlinear response indicated an analytical interference affecting the Siemens Immulite ACTH immunoassay. The analytical interference could not be resolved using heterophile antibodies blocking reagents (Scantibodies Laboratories, Inc.).  ACTH concentration measured using the Roche Elecsys immunoassay was 8.9 pg/mL. With the clinical assessment otherwise arguing against adrenal insufficiency and evidence for a falsely-elevated ACTH, the patient was tapered off the hydrocortisone successfully without any difficulty.

Conclusion: In cases where the clinical presentation is inconsistent with the diagnosis of primary adrenal insufficiency, an analytical interference in the ACTH immunoassay should be considered and may need to be evaluated beyond standard heterophile antibody assessment.


Nothing to Disclose: AA, HK, JPT, AYC