MON-443 POEMS Syndrome: A Complex Multisystemic Disorder with Diagnostic Challenges

Abstract Disclosure: A. Dharia: None. M. Grimes: None. Introduction: POEMS syndrome is a rare paraneoplastic disorder linked to plasma cell dyscrasia, characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell proliferation, and skin changes, often with additional clinical features. Clinical Case A 76 year old male presented with progressive lower extremity weakness over three months, eventually requiring a wheelchair. His symptoms developed gradually and included chest pain radiating to his back, vomiting, bilateral tingling and numbness in his hands and feet, visual changes, primarily decreased acuity, lower extremity edema, fatigue, and erectile dysfunction. Physical examination revealed hypertrichosis, white nails, hyperpigmentation, and a previously excised glomeruloid angioma. He was found to have an IgG lambda M protein, lambda serum free light chain of 177 mg/L (5.71 -26.3 mg/L) and VEGF 10,999 pg/mL (62-707 pg/mL). CT imaging revealed multiple sclerotic lesions in pelvis and T12 of the spine, and splenomegaly. EMG showed motor and sensory polyneuropathy with axonal and demyelinating features. Bone marrow biopsy confirmed a plasma cell clone and megakaryocytic hyperplasia. Endocrine was consulted for abnormal TFTs and a diagnosis of POEMS was considered. Labs revealed sodium 134 mmol/L (136-145 mmol/L), potassium 5.6 mmol/L (3.5-5.2 mmol/L) creatinine 2.28 mg/dL (0.7-1.2 mg/dL), platelet 561 k/mcL (145-445 k/mcL), TSH 12.3 mIU/L (0.4-4.5mIU/L), FT4 0.65ng/dl(0.7-1.9 ng/dl), ACTH 70 pg/ml (10-48 pg/ml), cosyntropin stimulation test showed a peak cortisol of 13 mcg/dL, total testosterone 40 ng/dL( 300-1,000 ng/dL), LH <1 mIU/mL(2-9 mIU/mL), FSH <1 mIU/mL( 1-12 mIU/mL), prolactin 35.9 ng/mL(4-15.2 ng/mL) and IGF-1 24 ng/mL (50-185 ng/mL). His prior brain MRI showed a normal sella/pituitary, and a dedicated pituitary MRI was deferred until renal function improved. His symptoms met major POEMS criteria (polyneuropathy, sclerotic bone lesions, M-protein spike) and minor criteria (splenomegaly, endocrinopathy, hyperpigmentation, hypertrichosis, glomeruloid angioma, and thrombocytosis). Treatment included initiation of physiologic hydrocortisone, weight-based levothyroxine and chemotherapy (daratumumab, dexamethasone, lenalidomide), which improved renal function and strength, with the patient transitioning to leg braces for ambulation. Despite clinical improvement, his hypogonadal symptoms, including erectile dysfunction persisted, so topical testosterone was initiated for secondary hypogonadism. Discussion POEMS syndrome demands high clinical suspicion due to its nonspecific presentation. Early diagnosis and a multidisciplinary approach are key to improving outcomes. Endocrinopathies like hypothyroidism, adrenal insufficiency, and hypogonadism complicate management, making prompt detection and hormone replacement crucial for optimal care. Presentation: Monday, July 14, 2025