Spironolactone interference in the immunoassay of androstenedione

Abstract

Background: In an evaluation of androstenedione results from patient serum samples using the Siemens Immulite 2500 analyser and manual Coat-A-Count (CAC) methods, three outliers were evident with grossly elevated results in the CAC assay. Methods: The clinic notes of three patients with apparently high serum androstenedione concentrations by the CAC assay were checked for medications. The samples were all from patients with polycystic ovary syndrome taking 100 -200 mg/d of a steroidal antiandrogen (spironolactone). Two other patients on 50 mg spironolactone per day had less markedly higher androstendione results with the CAC assay. In a further five patients who were selected since they were on spironolactone and had high androstenedione results by the CAC method, spironolactone was temporarily withdrawn and fresh blood samples obtained for analysis. Results: Spironolactone treatment was associated with higher androstenedione concentrations measured by the CAC assay that reverted to normal on treatment withdrawal. Based on a single test with spironolactone at 1000 ng/mL, the manufacturer reported only 0.109% interference in the CAC assay. Conclusions: Spironolactone (and/or its metabolites) may interfere in the Siemens CAC assay for androstenedione but not in the Immulite 2500 assay. This experience highlights the need for information from clinicians on drug treatment when laboratory investigations are requested. Drug interferences in immunoassay are common and need evaluation beyond tests performed to certify laboratory reagents.

Analytical Interference in Chemiluminescence Assay–Measured Angiotensin I, Angiotensin II, Aldosterone, and Renin

“…Similarly, Honour et al. [ 46 , 47 ] reported that spironolactone interfered with androstenedione and aldosterone immunoassays because spironolactone is an analog of aldosterone, which may lead to typical physical interference or cross‐reactivity.…”

Spironolactone interference in the immunoassay of androstenedione in a patient with a cortisol secreting adrenal adenoma

“…The authors speculated that the androstenedione antibodies in the assay could be reacting with the C/D ring or 7-modified thiol residue of spironolactone or its metabolites. 4 The patient was receiving a low dose of spironolactone, but it is apparent that the dose was sufficient to cause interference because serum androstenedione normalized after withdrawal. The manufacturer suggests that the cross-reaction of spironolactone with androstenedione in this assay is 0Á109%; this implies that our patient's blood spironolactone concentration would have to have been greater than 4000 ng/ml to give this androstenedione result through interference.…”

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