Rebound Effect Following the Discontinuation of Palopegteriparatide.

A 62-year-old male with postsurgical hypoparathyroidism developed symptomatic hypocalcemia one month after discontinuing palopegteriparatide therapy.

• The patient had been on palopegteriparatide therapy for three years before discontinuation.
• One week post-discontinuation, calcium and phosphorus remained stable.
• One month post-discontinuation, albumin-adjusted serum calcium fell to 7.4 mg/dL and phosphorus rose to 5.1 mg/dL.
• The hypocalcemia was symptomatic and required increased oral calcium doses to restore calcium levels to target ranges.

Upon discontinuation of palopegteriparatide, calcium and calcitriol were restarted at modified doses compared to pre-palopegteriparatide regimens.

• Calcium was restarted at a 25% reduction compared to the dose used before starting palopegteriparatide.
• Calcitriol was restarted at double the dose compared to the dose used before starting palopegteriparatide.
• Despite these adjustments, symptomatic hypocalcemia still developed one month after discontinuation.
• Further dose adjustments after the hypocalcemic episode were required to restore calcium and phosphorus to therapeutic ranges.

After dose adjustments following the rebound hypocalcemia, calcium and phosphorus levels stabilized at six months with lower doses of calcium and calcitriol than were used before palopegteriparatide treatment.

• Six months after discontinuation, calcium and phosphorus levels remained stable.
• The doses of calcium and calcitriol required at six months were lower than the pre-palopegteriparatide doses.
• The patient reported symptom improvement after dose adjustments.
• The hypocalcemia was described as mild and managed in the outpatient setting.

Palopegteriparatide is a long-acting prodrug of PTH (1-34) approved as PTH replacement therapy for chronic hypoparathyroidism that offers improved biochemical control.

• Hypoparathyroidism results from deficient parathyroid hormone secretion or action, leading to hypocalcemia, hyperphosphatemia, and hypercalciuria.
• Traditional 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.
• There is limited information regarding the effects of discontinuing palopegteriparatide prior to this report.

This case highlights a potential rebound effect following discontinuation of palopegteriparatide, with hypocalcemia occurring despite reinstatement of conventional therapy.

• The authors describe the hypocalcemia following discontinuation as a 'potential rebound effect.'
• The case emphasizes the need for close monitoring and possible adjustments in therapy upon discontinuation of palopegteriparatide.
• The rebound hypocalcemia was delayed, emerging at one month rather than immediately after discontinuation.
• The case suggests that initial conventional therapy doses after palopegteriparatide discontinuation may need to be higher than anticipated to prevent rebound hypocalcemia.