SUN-821 - Coexisting Primary Hyperparathyroidism and Familial Hypocalciuric Hypercalcemia: A Diagnostic and Therapeutic Challenge

Introduction
Familial hypocalciuric hypercalcemia (FHH) is a rare genetic disorder caused by inactivating mutations in the calcium-sensing receptor (CASR) gene, resulting in mild hypercalcemia and relative hypocalciuria. Primary hyperparathyroidism (PHPT) is typically distinguished from FHH by increased urinary calcium excretion and localizing parathyroid imaging. The coexistence of both entities is rare and can complicate diagnosis and management.

Case
A 65-year-old woman with a past medical history of gastroesophageal reflux disease, empty sella syndrome, hypothyroidism, and osteopenia of the hips was referred for the evaluation of longstanding hypercalcemia. Blood work revealed calcium 10.6 mg/dL (8.8–10.2), ionized calcium 5.6 mg/dL (4.64–5.28) with inappropriately normal parathyroid hormone (PTH) 47 pg/mL (18.5–88.0). Additional laboratory results showed creatinine 0.65 mg/dL (0.60 - 1.00), GFR >60 ml/min/1.73m2 (>59), TSH 1.05 u[IU]/mL (0.270 - 4.200), 25-hydroxyvitamin D 40 ng/mL (>30), phosphorus 2.2 mg/dL (2.5–4.5) and 24-hour urine calcium excretion 144 mg/day (35–250). Sestamibi scan was negative for parathyroid adenoma. The patient was asymptomatic, without nephrolithiasis, and denied any family history of calcium, parathyroid, or thyroid disorders.

One year later, she was diagnosed with ovarian cancer treated with chemotherapy and maintenance therapy with olaparib. During treatment, serum calcium increased to 11mg/dL and bone mineral density showed progression of osteopenia. She developed constipation requiring treatment with lactulose. Repeat laboratory testing showed phosphorus 3.4 mg/dL, PTH 53.8 pg/mL, ionized calcium 5.92 mg/dL, and 25-hydroxyvitamin D 28.1 ng/mL. The calcium-to-creatinine clearance ratio was >0.02, consistent with PHPT. Genetic testing revealed a pathogenic CASR exon 7 frameshift mutation consistent with FHH and a heterozygous MEN1 variant of uncertain significance. A 4D CT scan localized a 7.5 mm left paraesophageal parathyroid adenoma, with a possible smaller right-sided lesion. Parathyroidectomy was deferred due to thrombocytopenia and the need to continue olaparib therapy.

Discussion/Conclusion
This case illustrates the rare coexistence of FHH and PHPT, emphasizing that a diagnosis of FHH does not preclude the development of parathyroid adenoma. The key to identifying dual pathology was a multidimensional diagnostic approach incorporating repeat laboratory testing, alternative imaging modalities, and genetic testing. This case underscores the need for individualized management strategies and close longitudinal monitoring in patients with complex hypercalcemia.
Clinicians should maintain suspicion for concomitant PHPT in patients with FHH especially in the presence of discordant findings. Recognition of overlapping disorders is essential to guide appropriate management.

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