Physician - Endocrinology PARKVIEW HOSPITAL Fort Wayne, IN, United States
Disclosure(s):
Sowjanya Naha, MD: No financial relationships to disclose
Case presentation: A 63-year-old postmenopausal woman was referred for evaluation of persistently elevated estrogen levels. Her history was notable for remote breast cancer, BRCA mutation, and prophylactic hysterectomy with bilateral salpingo-oophorectomy. Following surgery, she developed menopausal symptoms including persistent hot flashes, irritability, and bloating, and was briefly treated with estrogen replacement without symptomatic improvement. Estrogen therapy was discontinued due to concern for cancer recurrence. Despite cessation of hormone therapy, estrogen levels measured by electrochemiluminescence immunoassay (ECLIA) were markedly elevated and rising (782 pg/mL four months prior and 898 pg/mL two months prior; reference < 214 pg/mL for postmenopausal women). Notably, menopausal symptoms persisted. The patient denied use of supplements (including biotin or DHEA), topical or vaginal estrogen, or medications known to affect estrogen metabolism. Abdominal and pelvic CT imaging showed no adrenal hyperplasia, tumors, or pelvic masses. Given the discordance between biochemical results and clinical findings, assay interference was suspected. Fractionated estrogen levels measured by liquid chromatography–mass spectrometry (LC-MS) demonstrated estradiol < 5 pg/mL, consistent with a postmenopausal state. Gonadotropins were appropriately elevated (FSH 76 mIU/mL; LH 32.5 mIU/mL), confirming estrogen deficiency.
Conclusion: Unexplained elevation of estrogen levels in postmenopausal women, particularly when clinical features suggest estrogen deficiency, should raise suspicion for immunoassay interference. Confirmation with an alternate method such as LC-MS is essential before pursuing extensive diagnostic evaluations or altering management. Hormone levels must always be interpreted in clinical context.
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