OR30-6 Parathyroid Carcinoma as a Complication of Inadequately Treated Pseudohypoparathyroidism

Abstract

Introduction Pseudohypoparathyroidism (PHP) is characterized by renal resistance to the effects of parathyroid hormone (PTH) resulting in hypocalcemia, hyperphosphatemia and elevated parathyroid hormone (PTH). Hypercalcemia in PHP has previously been reported to occur due to the development of tertiary hyperparathyroidism or due to over-replacement of calcitriol. This is the first reported case of parathyroid carcinoma in a patient with PHP. The presenting features were hypercalcemia and marked elevation of PTH over the course of 3 years. Clinical case A 47 year old woman with PHP type 1B presented for evaluation of hypercalcemia for the past 3 years. She was diagnosed with PHP at the age of 5 after a hypocalcemia seizure. At that time, she had hypocalcemia (5.5-6 mg/dl), hyperphosphatemia (9.3-9.7 mg/dl) and elevated PTH (2442 pg/ml, normal 160-360 pg/ml). Renal function was normal. Tubular reabsorption of phosphate was unchanged at 98% after an injection of PTH leading to the diagnosis of PHP. She had a long history of non-adherence to medication and multiple hypocalcemic seizures. She developed hypercalcemia (10.9 mg/dl), elevated PTH (1064.7 pg/ml, normal 12-88 pg/ml) and normalization of serum phosphate (2.8 mg/dl) at the age of 44 while on calcitriol 0.25 mcg daily. She remained hypercalcemic when calcitriol was stopped. Neck ultrasound revealed a 2.2 x 1.6 x 1.3 cm exophytic, hypoechoic nodule at the inferior pole of the left thyroid lobe with increased vascularity. It was irregularly marginated along the thyroid and had no clear border anteriorly along the strap muscles. Parathyroid exploration and total thyroidectomy was performed. Pathology revealed parathyroid carcinoma with multiple foci of vascular invasion and one focus of soft tissue extension. Post-operative PTH declined to 2.6 pg/ml and patient had recurrence of hypocalcemia (total calcium 6.5 mg/dl) due to which calcitriol was restarted. She developed hungry bone syndrome necessitating IV calcium for 2 days. Conclusion The initial presentation with spontaneous hypercalcemia and history of non-adherence with medication prompted concern for tertiary hyperparathyroidism but the PTH elevation was higher than in prior cases of tertiary hyperparathyroidism and had doubled over 3 years despite medical therapy with calcitriol raising concern for a neoplastic process. Rapid development of hypercalcemia in a patient with PHP should raise the suspicion for parathyroid carcinoma. PHP type 1B is associated with defects in the regulatory elements of GNAS1 whereas PHP type 1A is due to loss of function mutations in GNAS1. All cases of hypercalcemic hyperparathyroidism in PHP have been noted in PHP type 1B which indicates that the resistance to PTH in PHP type 1B is only relative and can be overcome when the PTH becomes markedly elevated. The PTH elevation was sufficient to excrete urinary phosphate and normalize the serum phosphate level.