We report the case of a 35 yrs- old man, who was referred to our Department in 2012, for symptomatic nephrolithiasis and low bone mass. Biochemical evaluation showed moderate hypercalcemia [albumin-corrected calcium 13.1 mg/dl (8.610.2) and markedly elevated PTH levels [1391 pg/ml (1365)] consistent with the diagnosis of primary hyperparathyroidism (PHPT). Neck ultrasound revealed three enlarged parathyroid glands. The patient underwent right superior and inferior and left superior parathyroidectomy (PTx). Histology showed hyperplasia in two glands and atypical adenoma in the other. After surgery, a persistence of PHPT was evident with serum calcium of 11,4 mg/dl and PTH 724 pg/ml. Neck ultrasound revealed an hypoechoic lesion localized under the left lobe of the thyroid, that showed an uptake at 99mTc-MIBI scintigraphy. No other endocrine lesions were present. The patient underwent left inferior PTx. Histology revealed an atypical adenoma. Post surgical hypoparathyroidism was diagnosed and the patient started calcium and calcitriol treatment. The patient continued to have symptomatic nephrolithiasis with a reduction of kidney function. Taking into account the young age, histology and multigland parathyroid involvement, genetic analysis of the MEN1 and CDC73 gene was carried out. Genetic analysis revealed a germline mutation of the CDC73 gene, leading to the substitution of a guanine to a adenine in splicing donor site 3. The genetic screening was negative in the parents and siblings indicating that the mutation was de novo. CDC73 mutations are responsible for hyperparatyroidism-Jaw tumor syndrome (HPT-JT), a rare autosomic dominant disease characterized by multigland parathyroid involvement, increased prevalence of parathyroid carcinoma and atypical adenoma, benign ossifying fibromas of the jaw, benign and malignant renal lesions and uterine tumors. The patient did not have kidney lesions and ossifying fibroma of the jaw. During the follow up there was evidence of permanent postsurgical hypoparathyroidism with good control of serum calcium, phosphate and magnesium, but not of 24-h urinary calcium on treatment with calcium and calcitriol. Thus, the patient started thiazides diuretics leading to a reduction of 24-h urinary calcium and improvement of nephrolithiasis. In conclusion, we described a case of an apparently sporadic PHPT who carries a germline mutation of the CDC73 gene. It is of great importance to recognize this syndrome to confirm the diagnosis, screen the associated lesions, make a familial screening and plan the adequate surgery. Moreover, our patient need a careful treatment on standard therapy and monitoring of postsurgical hypoparathyroidism.
18 - 21 May 2019
European Society of Endocrinology