Abstract
INTRODUCTION: Familial hypocalciuric hypercalcemia (FHH) is a rare group of autosomal dominant disorders that result from genetic defects leading to reduced calcium-sensing receptor (CASR) activity. The gold standard for diagnosis of FHH is to detect a heterozygous mutation that causes a loss of function in CaSR gene activity by sequence analysis. Isolated cases have documented the rare coexistence of FHH and Primary hyperparathyroidism (PHPT). Herein, we would like to describe a patient with concurrent FHH and PHPT. CLINICAL CASE: A 59-year-old woman with no active complaints was referred for evaluation following the detection of hypercalcemia during routine examinations. Her laboratory results revealed serum calcium (Ca) of 11.1 mg/dl (8.4-10.2), phosphorus (P) of 2.57 mg/dl (2.5-4.5), parathormone (PTH) of 120 ng/dl (15-65), 25-Hydroxyvitamin D of 27 ng/ml (30-70), and 24-hour urine calcium of 128 mg (100-300 mg). Initial suspicion of primary hyperparathyroidism led to a neck ultrasound, which did not identify any mass lesions in the parathyroid origin. However, parathyroid scintigraphy indicated a suspicious area of hyperfunctioning parathyroid adenoma on the left. Additionally, neck ultrasonography revealed multinodular goiter. As a result, the patient underwent total thyroidectomy and parathyroidectomy, with a preoperative diagnosis of parathyroid adenoma and multinodular goiter. Pathological examination revealed a parathyroid lipoadenoma, 1 cm in diameter, with adipocyte and chief cell proliferation. papillary microcarcinoma was detected in the left lobe. Postoperatively, laboratory examination demonstrated serum Ca was 11 mg/dl (8.4-10.2), P was 2.63 mg/dl (2.5-4.5), PTH was 112 ng/dl (15-65), and 24-hour urine calcium was 56 mg/dL (100-300 mg). In the follow-op period, neck USG, sestamibi scan, neck and thorax CT did not reveal any parathyroid adenoma. Due to the suspicion of familial hypocalciuric hypercalcemia, a genetic test was performed. It revealed heterozygous CASR c.665G>A (p.Gly222Glu) and heterozygous c.2027 C>G (p.Thyr676Arg) potential pathogenic variants, leading to the diagnosis of familial hypocalciuric hypercalcemia. CONCLUSION: Although parathyroidectomy is generally not curative or advised for typical cases of FHH, it is crucial to acknowledge the potential link between PHPT and FHH, as well as the role of CASR mutations in the development of some PHPT cases. Since having FHH does not rule out the possibility of a parathyroid adenoma and there can be similarities in the clinical features of both conditions. It is important to consider the possibility of coexisting PHPT and FHH in patients presenting with hypercalcemia, hypophosphatemia, high PTH levels, and low urinary calcium excretion. After surgery, patients might still show mild to moderate hypercalcemia, and further invasive interventions should be avoided; it should not be presumed that the parathyroid exploration was unsuccessful.