Primary hyperparathyroidism unmasking after dienogest-altered estrogen dynamics: implications for calcium homeostasis

Normocalcemic primary hyperparathyroidism (PHPT) is increasingly recognized as an early or indeterminate disease form. Although estrogen is believed to modulate calcium homeostasis, its role in progression to overt PHPT remains incompletely understood. A parathyroid adenoma was suspected in a 33-year-old woman despite normal calcium and parathyroid hormone (PTH) levels. At 37 years of age, approximately 6 months after starting dienogest 0.5 mg twice daily for menorrhagia, she developed prolonged amenorrhea and improved anemia. The PTH level subsequently increased from 38 to 57 pg/mL (SI: 4.0-6.0 pmol/L) (reference range 10-65 pg/mL [SI: 1.1-6.9 pmol/L]) with mild hypercalcemia (corrected calcium, 10.3 mg/dL [SI: 2.58 mmol/L]) (reference range, 8.8-10.1 mg/dL [SI: 2.20-2.53 mmol/L]). Despite the prolonged amenorrhea, her estradiol levels were not suppressed. The dienogest was discontinued preoperatively and menstruation resumed; however, the hypercalcemia and elevated PTH persisted. Imaging revealed the parathyroid adenoma. Upon its resection, the PTH level promptly normalized. Altered estrogen dynamics rather than an absolute estrogen deficiency may have contributed to the transition to overt PHPT noted herein. Manifested hypercalcemia is not readily reversible, suggesting a shift to a self-sustaining state. This case raises the possibility that altered hormonal dynamics may contribute to the manifestation of PHPT.