Rebound Effect Following the Discontinuation of Palopegteriparatide

Hypoparathyroidism (HypoPT) results from deficient parathyroid hormone (PTH) secretion or action, leading to hypocalcemia, hyperphosphatemia, and hypercalciuria. Traditionally, treatment involves oral calcium and active vitamin D supplementation. Recombinant PTH therapies, such as rh-PTH (1-84) and PTH (1-34), offer a more physiological alternative, improving calcium homeostasis and reducing associated complications. Recently, palopegteriparatide, a long-acting prodrug of PTH (1-34), was approved as PTH replacement therapy for chronic HypoPT, offering improved biochemical control. However, there is limited information regarding the effects of discontinuing palopegteriparatide. We present the case of a 62-year-old male with postsurgical HypoPT who discontinued palopegteriparatide therapy after three years of treatment, and restarted calcium and calcitriol therapy at different regimens (25% reduction in calcium and double dose of calcitriol compared to the respective doses before starting palopegteriparatide). One week post-discontinuation, his calcium and phosphorus remained stable. However, one month later, he developed symptomatic hypocalcemia (albumin-adjusted serum calcium 7.4 mg/dL and phosphorus 5.1 mg/dL), requiring increased oral calcium doses to restore calcium levels to target ranges. After dose adjustments, calcium and phosphorus levels returned to therapeutic ranges, with the patient reporting symptom improvement. Six months later, his calcium and phosphorus levels remained stable, and the dose of calcium and calcitriol therapy was lower than pre-treatment with palopegteriparatide. This case highlights a potential rebound effect following the discontinuation of palopegteriparatide. While the hypocalcemia was mild and managed at the outpatient setting, this case emphasizes the need for close monitoring and possible adjustments in therapy upon discontinuation of palopegteriparatide.