MON-102 - Multiple Endocrine Syndrome 1 masquerading as Hypercalcemia and Virilization

Background -
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome involving the parathyroid glands, anterior pituitary, and gastro-entero-pancreatic system. Advanced skeletal disease is now rarely encountered, and virilization is an atypical presenting feature seldom described in this context.

Case Presentation -
A 62-year-old postmenopausal woman presented with altered sensorium, generalized weakness, and shortness of breath. Examination revealed acromegaloid facies, virilization comprising hirsutism, bitemporal recession, voice deepening, and increased muscle bulk without clitoromegaly, and bilateral basal crackles requiring respiratory support. Investigations showed hypercalcemia (11.7 mg/dL), elevated PTH (160 pg/mL), markedly elevated prolactin (5200 mIU/L), and IGF-1 of 288 ng/mL against an age-adjusted upper limit of 155 ng/mL. Androgen profile demonstrated marginally elevated total testosterone (0.52 ng/mL) with profoundly suppressed SHBG (7 nmol/L) and low DHEAS (11.6 µg/dL). Cortisol and ACTH were within normal limits. Sestamibi scintigraphy localized a right inferior parathyroid adenoma. MRI sella revealed a mammosomatotroph macroadenoma (14×17×15 mm) with preserved optic chiasm. Skeletal radiographs demonstrated osteitis fibrosa cystica with subperiosteal resorption, punched-out lytic lesions, and salt-and-pepper skull, indicating longstanding uncontrolled hyperparathyroidism. Coexistence of primary hyperparathyroidism and a functioning mammosomatotroph adenoma fulfilled MEN1 diagnostic criteria.

Clinical Lessons -
First, MEN1 can present late with florid skeletal complications rarely seen in contemporary practice, underscoring the consequences of delayed diagnosis. Second, virilization in a postmenopausal woman with a complex endocrine background requires systematic evaluation. In this patient, suppressed DHEAS and normal cortisol argued against adrenal and glucocorticoid excess, while the absence of clitoromegaly and markedly elevated total testosterone made a discrete androgen-secreting tumor unlikely. The profoundly suppressed SHBG in the context of GH excess provides the most plausible explanation, illustrating that virilization can occur without overt biochemical androgen excess when SHBG is severely suppressed. Third, the absence of clitoromegaly or markedly elevated total testosterone should not exclude clinically significant androgen excess when SHBG is profoundly suppressed, and a structured hyperandrogenism evaluation remains essential in this setting.

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