MON-779 Mild Primary Hyperparathyroidism Masquerading as Severely Overactive Parathyroid Function Behind PTH Assay Abnormalities

Abstract Disclosure: R.S. MacLeod: None. A. Ramirez: None. J.J. Wysolmerski: None. Introduction: Patients with primary hyperparathyroidism (PHPT) can exhibit hypercalcemia, kidney stones, and osteoporosis. Biochemical evidence or clinical signs of PHPT should be established before proceeding with further evaluation such as imaging modalities. Case: A 69-year-old woman with history of high-grade serous carcinoma of the ovary with extensive spread to the omentum, peritoneum, and bowel with tumor debulking surgery followed by multiple courses of chemotherapy on different protocols presents to endocrine surgery for new finding of suspected primary hyperparathyroidism. Chart review of her calcium values revealed in the 3 years following her surgery, she had intermittent hypercalcemia with a maximum total calcium (Ca) measurement of 11.0 (8.8-10.2) mg/dL. In the month prior to her endocrine surgery referral, she was noted to have elevated Ca to 10.5 mg/dL with first PTH measurement of 2006 (15-65) pg/mL on the Yale intact PTH assay. Repeat labs and further workup showed PTH of 1999 pg/mL, iCa of 5.47 mg/dL, magnesium 1.9 (1.7-2.4) mg/dL, 24-hour urine calcium of 123 (100-300) mg, and vitamin D25-hydroxy of 30 (20-50) ng/mL. A 4D CT scan of the neck showed suspicious parathyroid adenomas measuring 6 and 9mm. Bone mineral density evaluation of the axial and appendicular skeleton with DXA showed normal bone density of the lumbar spine and total hip and osteopenia of the femoral neck and distal radius. She was taken to surgery and had 3.5 parathyroid glands removed plus thymectomy yet her intraoperative PTH levels did not decline. Pathology revealed parathyroid hyperplasia with glands 324 mg/1.9 cm, 76 mg/0.9cm, and 59 mg/1 cm and no ectopic parathyroid tissue identified in the thymus. She was re-admitted 3 days later with symptoms of hypocalcemia with Ca of 7.0 mg/dL, iCa of 3.75 mg/dL, phosphorous of 5.7 (2.2-4.5) mg/dL, and PTH of 1984 pg/mL despite her symptoms and labs suggesting hypoparathyroidism. She was treated with calcium supplementation and calcitriol, and her symptoms improved. She had a clear mismatch in her immunoreactive PTH levels and serum calcium. Staining of her archived ovarian tumor samples was negative for PTH immunoreactivity. Single gene analysis of her PTH gene showed no abnormalities, and hypoparathyroid and hyperparathyroid genetic screens were negative for pathogenic variants, mutations, or variants of unknown significance. Simultaneous labs sent to Yale and Quest Diagnostics facilities revealed the following: Yale PTH 2112 pg/mL, Yale Ca 9.4 mg/dL, Quest intact PTH 47 (16-77) pg/mL, Quest Ca 9.4 (8.6-10.4) mg/dL. This indicated that she has a circulating factor that interferes with the Yale PTH immunoassay. Conclusion: Highly abnormal PTH values associated with relatively minor signs of PHPT should raise suspicion for immunoactivity mismatch and possible mutation or assay abnormality. Presentation: Monday, July 14, 2025