Hyperthyroidism-Induced Hypercalcemia: Timing of Response to Treatment in the Acute Setting

Hyperthyroidism is an uncommon cause of hypercalcemia (HYPERCA). There is little information to guide the clinician on calcium (CA) response in relation to thyroid hormone control. This knowledge may be important when HYPERCA needs to be quickly treated due to its severity or to underlying patient co-morbidities. We describe a patient with HYPERCA of moderate severity due to Graves’ disease (GD) hyperthyroidism in whom normalization of CA level was a priority. Changes in CA levels in response to improvement in thyroid function and the role of anti-resorptive agents in this setting are discussed.

Case Description:

A 27-year-old male, on no prior medications, presented to the hospital with symptomatic cholelithiasis. He also reported a 3-month history of dizziness, palpitations, anxiety, heat intolerance, tremors, and a 60 lb weight loss. Exam was significant for tachycardia, mild thyromegaly and a fine tremor; body mass index was 18.6 kg/m2. Laboratory results revealed a suppressed TSH ( <0.02 mIU/L; reference [ref]: 0.45-4.7), free T4: 6.82 ng/dL (ref: 0.78-2.2), and free T3: 19.9 pg/mL (ref: 2.77-5.27). Additionally, he was found to be hypercalcemic (corrected CA of 11.9 mg/dL; ref 8.6-10.6). PTH was appropriately low (1.9 pg/mL; ref: 12-88), PTHrP undetectable and serum protein electrophoresis was normal; hypercalciuria (619 mg/24 hrs; ref: 100-300) was present despite underlying vitamin D deficiency. A mildly enlarged thyroid gland with increased vascularity on imaging and positive TSH-receptor antibodies confirmed GD. He was started on propranolol and transiently, due to allergic reactions, on thionamides. Saturated solution of potassium iodide stabilized thyroid function in preparation for surgery. Despite intravenous fluids, antithyroid therapy and significant reduction of free T4 levels over the course of 7 days, HYPERCA persisted and was above 12.0 mg/dL. When given 60 mg of pamidronate, HYPERCA resolved within 2 days and the patient successfully underwent major surgery, including a total thyroidectomy. Four years later, he remains normocalcemic.

Discussion:

Hyperthyroidism-induced HYPERCA is associated with an increase in pro-inflammatory cytokines, including interleukin-6, which increase bone remodeling by stimulating osteoclastogenesis. Our case suggests that despite normalization of thyroid hormone levels, resolution of HYPERCA is delayed. Others have described parallel reductions in thyroid hormone and CA levels, but did not assess short-term changes as done in this report. In situations in which prompt resolution of hyperthyroid-induced HYPERCA is necessary, intravenous anti-resorptive agents, such as pamidronate, are effective.