THU472 Novel And Multifactorial Case Of Severe Hypercalcemia Due To Primary Hyperparathyroidism And Heterozygous Mutation Of CYP24A1
Authors: Liu Jannel , Angelos Peter , Barhoum Maan , Jain Rajesh 
Published: October 2023

Disclosure: J. Liu: None. P. Angelos: None. M. Barhoum: None. R. Jain: None.

Background: Mutations of CYP24A1 are known to be associated with hypercalcemia due to disruptions in 24-hydroxylase’s ability to break down 1,25-OH Vitamin D. A case involving heterozygous mutation of CYP24A1 and primary hyperparathyroidism leading to severe hypercalcemia has not been reported. Clinical Case: A 23-year-old female presented with severe fatigue and was found to be newly hypercalcemic to 13.2 mg/dL. There was no clear family history or exogenous source. Her PTH was 62 pg/mL and 1,25-OH vitamin D was elevated to 242.7 pg/mL. Her other laboratory work-up demonstrated: albumin 4.0 g/dL, magnesium 2.2 mg/dL, Phosphate 2.1 mg/dL, creatinine 0.72 mg/dL, 25OH Vitamin D 28.2ng/mL, 24hr urine calcium 150 mg/24hr, BSALP 32 ug/L, and within normal limits SPEP, PTHrP, TSH, Free T4, ACE, metanephrines, calcitonin, and ferritin. She required multiple administrations of pamidronate or zoledronic acid every 4-6 weeks. She was started on cinacalcet without substantial effect on hypercalcemia or need for bisphosphonate. She was also started on Vitamin D supplements, while further workup was pursued due to concern of non-PTH mediated causes of hypercalcemia. She had a bone scan, CT scan of the whole body, thyroid ultrasound, and Sestimibi scan that were read as normal. She was referred to an academic metabolic bone disease center. Vitamin D supplements were stopped and a 25-OH Vitamin D to 24,25-OH Vitamin D ratio was found to be elevated at 25.18 (Normal &lt;25). She was referred to an endocrine surgeon, who felt there was localization on Sestimibi and performed a parathyroidectomy with removal of a 3.5g parathyroid adenoma. Pathology showed a parafibromin deficient parathyroid neoplasm. Genetic testing was sent for CYP24A1 and CDC73. The patient’s CYP24A1 was positive for heterozygous pathogenic mutation with normal CDC73. Post-operatively, she had a low PTH level of 14 pg/mL but normal calcium level 9.6 mg/dL. 1,25-OH Vitamin D levels decreased to normal value 58 pg/mL (reference 18-72 pg/mL). She was weaned off calcium supplements and advised to be cautious with Vitamin D supplements. Genetic counseling was recommended. Conclusion: We report a case where a young woman with severe symptomatic hypercalcemia was found to have primary hyperparathyroidism that was exacerbated by an underlying heterozygous mutation in CYP24A1. Our case suggests that patients with mild PTH elevation and severe hypercalcemia should be screened with 1,25-OH Vitamin D levels and 25-OH to 24,25OH Vitamin D ratio for CYP24A1 mutations. While gentle Vitamin D supplementation is often recommended in primary hyperparathyroidism, in patients with mild PTH elevations but severe hypercalcemia, CYP24A1 mutations should be considered, and Vitamin D supplements should be avoided. Finally, our case suggests that primary hyperparathyroidism with underlying CYP24A1 mutation may be poorly responsive to cinacalcet.

Presentation: Thursday, June 15, 2023