Evaluation for primary hyperparathyroidism after radioactive iodine treatment in patients with Graves' disease

Background: Retrospective studies are conflicting regarding the risk of primary hyperparathyroidism after radioactive iodine treatment. We hypothesized that primary hyperparathyroidism rates are greater after radioactive iodine than after thyroidectomy and that patients with hypercalcemia after treatment for Graves' disease are not adequately evaluated for primary hyperparathyroidism, contributing to underdiagnosis of radioactive iodine-associated primary hyperparathyroidism. Methods: This retrospective review considers patients undergoing radioactive iodine or thyroidectomy for Graves' disease at a tertiary referral center between January 1, 2000, and January 31, 2022. Patients were identified using a hospital-based cohort discovery tool; exclusions included history of head/neck radiation, primary hyperparathyroidism/parathyroidectomy, renal dysfunction diagnoses, or treatment with both radioactive iodine and thyroidectomy. Patients with an elevated calcium (>10.2 mg/dL) level measured after treatment were classified as "incomplete workup" (no parathyroid hormone), "likely primary hyperparathyroidism" (parathyroid hormone > 40 pg/dL), or "unlikely primary hyperparathyroidism" (parathyroid hormone < 40 pg/dL). Results: Of 900 patients, 468 (52%) had been treated with radioactive iodine and 432 (48%) with thyroidectomy. At a median follow-up of 9.39 years (interquartile range, 5.12-13.25), 25% (n = 224) of patients did not have a serum calcium measured and 52 (8%, n = 676) patients had an elevated calcium level. Hypercalcemia was more common after radioactive iodine (10%) than thyroidectomy (6%, P = .061). Of patients with hypercalcemia, 33 (63%) were "incomplete workup," 5 (10%) were "likely primary hyperparathyroidism," and 14 (27%) were "unlikely primary hyperparathyroidism." There was no difference in primary hyperparathyroidism workup rates between patients treated with radioactive iodine (n = 23) and thyroidectomy (n = 10, P = .389). Conclusions: Patients treated with radioactive iodine for Graves' disease may experience an elevated rate of hypercalcemia, but the majority are not adequately evaluated for primary hyperparathyroidism. Patients with a history of radioactive iodine should undergo regular calcium screening and, if elevated, appropriate workup for primary hyperparathyroidism.