Lithium-induced parathyroid dysfunction: A new case
A 28-year-old lady reported to the endocrinology department for evaluation of hypercalcemia detected at a local hospital. She was receiving 600 mg of lithium carbonate for bipolar mood disorder for last 2 years. She had a history of weight gain, polyarthralgia, and generalized weakness since 6 months. Clinical examination revealed an obese [body mass index (BMI) 36.30Kg], depressed lady with proximal girdle muscle weakness and generalized bone tenderness. Investigations revealed altered thyroid function: FT4 0.77 ng/dl (0.94-1.71 ng/dl) and thyroid stimulating hormone (TSH) 1.45 μIU/ml (0.45-4.5 μIU/ml). Serum corrected calcium levels were 11 mg/dl (8.5-10.2 mg/dl) on repeated assessment and serum phosphate was 2.4 mg/dl (2.7-4.5 mg/dl). Serum intact parathyroid hormone (PTH) was 489.6 pg/ml (16-62 pg/ml). Serum alkaline phosphatase was 1073 IU/l (39-117 IU/l) and Bone Mineral Density (BMD) studies showed Z scores of −2.5 and −2.9 on hip bones and lumbar spines, respectively. Serum albumin and creatinine remained in the normal ranges (4.1 g/dl and 0.8 mg/dl, respectively). 24-h urinary calcium was reduced to 75 mg (normal 100-300 mg), phosphorus was reduced to 288 mg (400-1300 mg), and creatinine was 408 mg (urine volume 1750 ml). The calcium creatinine clearance ratio was 0.013. Serum magnesium was 2.4 ng/dl (1.7-2.55 ng/dl). Serum 25-OH vitamin D estimation showed a normal level of 69 nmol/l (25-125 nmol/l). The serum prolactin (pooled and diluted) was 14.90 ng/ml (1.67-16.11 ng/ml), and serum insulin (total) was 5.80 μIU/ml (4-30 μIU/ml).\nSince the clinical and biochemical features were suggestive of lithium-induced hyperparathyroidism, lithium was discontinued. The clinical features and biochemical parameters did not normalize after 3 months of cessation of lithium treatment (serum calcium was 11.4 mg/dl and PTH 882.5 pg/ml). So, the patient was prepared for surgical treatment after localization studies. 99 mTc-sestamibi dual phase scintigraphy showed significant tracer retention in delayed images, suggestive of hyperfunctioning left inferior parathyroid gland. The patient was subjected to routine total neck exploration since lithium-induced parathyroid hyperplasia was still a possibility. The left inferior parathyroid gland was enlarged and hard in consistency. This was removed en bloc with neighboring soft tissue since parathyroid carcinoma was suspected. The other parathyroid glands appeared normal Rapid intraoperative PTH assay showed a fall from 1063 to 89.84 pg/ml after 10 min of the excision, ensuring completeness of resection.\nThe excised tissue showed a well-encapsulated tumor measuring 2 cm in size and weighing 3.9 g. Microscopy revealed diffuse sheets of cells separated by thin fibrovascular septa. Cells were round or oval with eosinophilic cytoplasm and focal areas of necrosis. Capsular infiltration and vascular invasion were seen. Immunostaining for Ki 67 showed less than 3% positive staining and so was diagnosed as atypical adenoma.\nThe patient received oral calcium supplementation for 12 months since the BMD studies showed osteopenia 6 months after the operation. The patient has been reviewed periodically for the last 31 months and the serum corrected calcium level remains within normal ranges. She is on thyroxine supplementation even though lithium was discontinued.