BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder and the most frequent benign cause of hypercalcemia. PHPT is characterized by autonomous hypersecretion of parathyroid hormone (PTH), regardless of serum calcium levels. Familial hypocalciuric hypercalcemia (FHH) is a rare, benign syndrome only affecting the regulation of calcium metabolism. FHH is an autosomal-dominant genetic disease with high penetrance, caused by an inactivating variant in the CASR gene encoding the calcium-sensing receptor (CaSR). We present a unique case of concomitant PHPT and FHH without clinically actionable variants in MEN1.
CASE PRESENTATION: A 47-year-old Caucasian man with severe hypercalcemia, genetic FHH, and initially normal parathyroid scintigraphy was referred for endocrine evaluation due to nonspecific symptoms. Biochemical evaluation showed elevated serum ionized calcium and PTH. The calcium-creatinine clearance ratio was low. All other biochemical measures were normal, including kidney function. Genetic evaluation was redone and confirmed FHH. A new parathyroid scintigraphy showed a significant single adenoma corresponding to the lower left gland. The patient underwent parathyroidectomy, and a parathyroid adenoma was removed. A reduced level of hypercalcemia persisted due to FHH.
CONCLUSIONS: The correct diagnosis of the underlying cause of hypercalcemia is important to ensure the right treatment. Patients with FHH should avoid operative treatment, and PHPT should be differentiated from MEN1 to determine whether surgery should include parathyroidectomy with removal of one adenoma or 3.5 hyperplastic parathyroid glands.