Familial hypocalciuric hypercalcemia and primary hyperparathyroidism: a case report of an unusual association and literature review

Abstract Background Familial Hypocalciuric Hypercalcemia (FHH) is a group of rare inherited diseases caused by loss-of-function mutations in the calcium-sensing receptor (CaSR) gene or related proteins. A significant link has not been discovered between germline inactivating CaSR mutations and parathyroid tumors in sporadic PHPT. However, it has been observed that most adenomatous and hyperplastic tumors have decreased CaSR expression. Case presentation A 59-year-old woman was referred to our clinic for evaluation of hypercalcemia despite having no active complaints. She underwent total thyroidectomy and parathyroidectomy due to parathyroid adenoma and multinodular goiter. Pathology revealed a parathyroid lipoadenoma. Postoperatively, calcium levels did not return to physiological ranges, raising suspicion of FHH. Genetic analysis identified compound heterozygosity for CASR c.665G > A (p.Gly222Glu) and CASR c.2027 C > G (p.Tyr676Arg) variants, confirming the diagnosis of FHH. Conclusion Co-existence of PHPT due to a parathyroid lipoadenoma and FHH is rare. Patients may still exhibit mild to moderate hypercalcemia following surgery, thus more invasive procedures should be avoided; failure of parathyroid exploration should not be assumed.