Falsely Increased Serum Estradiol Results Reported in Direct Estradiol Assays

Direct, or nonextraction, assays of male sex hormones occasionally yield artefactually increased results (1)(2). Here, we report a patient who was determined by three direct assays to have an increased female sex hormone, estradiol, in serum. An 82-year-old man had a history of enlargement of the breast. Blood pressure was 110/86 mmHg. Erythrocyte and leukocyte counts were within the range of normal values. Results of thyroid-function tests were normal, and urea and creatinine concentrations in serum were within reference limits. Urinalysis results were also normal. Biopsy of breast tissue indicated gynecomastia. Computed tomographic scan showed normal adrenal glands, no extraneous mass, and no hypertrophy. Ultrasound of the testes also showed normal features except for a small left hydrocele. There was no obvious tumor in other organs. Serum estradiol by Coat-A-Count direct RIA [Diagnostic Product Corp. (DPC), Los Angeles, CA] was markedly increased at 536 ng/L (upper reference limit for an 82-year-old man <50 ng/L). In two other direct chemiluminescence immunoassays (Immulite by DPC, and ACS-180 Estradiol-6 from Chiron, Medfield, MA) performed with automated equipment, the results were also high: 216 and 165 ng/L, respectively. These results decreased some but were still high, 186 and 148 ng/L, respectively, after ultracentrifugation to remove lipemia and reassay. However, after extraction with ethyl acetate:hexane (3:2 by vol) before RIA (by an unextraction kit from Pantex, Santa Monica, CA), the estradiol result was normal (42 ng/L and, on repeat, 40 ng/L). Apparently, the falsely increased serum estradiol by direct assay was caused by some water-soluble interferant that could be removed by a simple organic solvent extraction. All laboratory tests were ordered by the patient’s treating physicians. The procedures followed were in accordance with ethical standards of our institutions’ responsible committees and with the Helsinki Declaration.