ODP128 Unusually High Serum Calcium in a Patient with Familial Hypocalciuric Hypercalcemia
Authors: Spiro Andrew J , Leimbach Robert D , Hoang Thanh D , Shakir Mohamed K M 
Published: November 2022

Background

Familial hypocalciuric hypercalcemia (FHH) causes hypercalcemia via inactivating genetic mutations in the calcium-sensing receptors of parathyroid cells. FHH generally presents as a chronic, mild, asymptomatic hypercalcemia (&lt;12mg/dL) with normal to moderately-elevated serum PTH levels. Low renal calcium/creatinine clearance ratio (CCCR) is the primary biochemical method of distinguishing FHH from primary hyperparathyroidism (PHPT). Most patients do not require treatment. Surgery is generally inappropriate as hypercalcemia persists after subtotal parathyroidectomy.

Clinical Cases

A 19-year-old male was admitted to the psychiatry service due to suicidal ideation. He denied taking any medications or supplements. Initial labs noted a corrected calcium of 11.6 mg/dL (ref. 8.6-10.2 mg/dL) and repeat labs verified hypercalcemia. Intact PTH level was 118.8 pg/mL (ref. 15-65 pg/mL). He denied muscle weakness, fatigue, joint pain, constipation, kidney stones, or increased thirst. After IV-fluid repletion, his calcium remained elevated. Serum calcium was measured as high as 13.1mg/dL, corrected calcium was as high as 12.5 mg/dL, and ionized calcium was 6.9 mg/dL (ref. 4.5-5.6 mg/dL). 24-hour urine calcium was 93.6 mg/24-hr and CCCR was 0.29%. A presumptive diagnosis of FHH was made, based on the elevated calcium and PTH, with CCCR &lt; 1%. His mood improved and he was discharged by psychiatry without starting any medications. Initiation of cinacalcet was discussed, but the patient preferred not to start medication. During outpatient follow-up, he did not endorse depression or suicidal ideation. He was referred for genetic analysis to confirm FHH. Due to his significant hypercalcemia, PHPT remained in consideration. Evaluation for MEN syndromes was also performed, since these are associated with early onset PHPT. He knew limited family history. His mother had hypercalcemia and hyperparathyroidism, requiring surgery. He was uncertain of her age at diagnosis or whether she had genetic testing. He also reported a maternal half-brother with hypercalcemia and renal disease, requiring dialysis in his 30s. Repeat labs a few months after his admission showed corrected calcium of 12. 0 mg/dL, ionized calcium of 6.8 mg/dL, and CCCR of 0.30%. Thyroid ultrasound and Tc-99m Sestamibi scan did not show evidence of parathyroid adenoma(s). Genetic analysis showed a known heterozygous pathogenic variant in the CASR gene, consistent with FHH, type 1. The patient continued to deny any symptoms, including psychiatric, and did not start cinacalcet.

Conclusion

FHH can occasionally present with corrected calcium &gt; 12 mg/dL and PTH &gt;100. CCCR is essential to distinguish FHH from PHPT. Genetic analysis should be pursued in patients with a questionable diagnosis. PHPT is primarily managed with surgery, while FHH is generally not managed with surgery, so correct diagnosis is essential. Rarely, FHH patients may present with pancreatitis, chondrocalcinosis, muscle cramps, poor memory and psychosis. Calcimimetic therapy may be considered in select, symptomatic patients.

Presentation: No date and time listed