Endocrine Abstracts

JOINT2242

Introduction: Primary hyperparathyroidism (PHPT) is a common cause of hypercalcemia, often linked to parathyroid adenomas, hyperplasia, or, in rare cases, genetic mutations. Lithium therapy, frequently used in bipolar disorder, has been associated with PHPT due to its effects on calcium metabolism. However, distinguishing lithium-induced hyperparathyroidism from primary forms remains challenging. We present a case of PHPT in a lithium-treated patient with an underlying genetic mutation.

Case Report: A 48-year-old woman was referred to our clinic due to an incidental finding of hypercalcemia. She had a medical history of bipolar disorder, treated with lithium for over 10 years. Laboratory tests revealed a corrected calcium level of 11.4 mg/dL (8.3-10.6), phosphorus at 3.7 mg/dL (2.7-4.5), vitamin D at 30.3 ng/mL (20-60), parathyroid hormone (PTH) at 109.5 pg/mL (18.5-88), and 24-hour urinary calcium at 45.9 mg/24h (100-300), with a calcium/creatinine clearance ratio of 0.01. Given the suspicion of PHPT, repeat tests confirmed similar findings. Parathyroid scintigraphy indicated hyperplasia of the left superior and inferior parathyroid glands. Additional tests, including bone densitometry and renal ultrasound, showed no pathological findings. Considering these results, the mental health team evaluated the feasibility of discontinuing lithium therapy, and genetic testing was performed for potential hereditary causes of PHPT. Despite lithium discontinuation, hypercalcemia persisted. Genetic analysis identified a heterozygous variant in the GCM2 gene, associated with familial PHPT. The patient underwent selective parathyroidectomy of the left superior and inferior glands, leading to normalization of calcium and PTH levels postoperatively.

Discussion: Between 10% and 20% of lithium-treated patients develop hypercalcemia with hypocalciuria and elevated PTH due to reduced parathyroid gland sensitivity to calcium. Typically, calcium levels normalize within months of discontinuing lithium. However, in this case, persistent hypercalcemia suggested an alternative etiology. The identification of a GCM2 gene mutation, a rare cause of familial PHPT, explained the continued hypercalcemia despite lithium cessation. This highlights the importance of genetic testing in cases where standard etiologies do not fully account for clinical findings. Few cases of GCM2-related familial PHPT have been documented, underscoring the need for further research into its pathophysiology and optimal management. This case emphasizes the necessity of a comprehensive approach in evaluating hypercalcemia, particularly in patients on long-term lithium therapy, to differentiate between drug-induced and primary hyperparathyroidism and to consider potential genetic contributions when the clinical course is atypical.