SUN-767 Therapeutic Management of ADH1 in a 16-year Old Boy Using Palopegteriparatide.

Abstract Disclosure: A. Zygmunt: I am the PI in the Calypso study and I have lectured and trained for Er-Kim, the representative of Amolyt Pharma in Poland.. L. Krotowski: None. A. Lupinska: None. A. Gach: None. R. Stawerska: None. A. Lewinski: None. A 16-year-old boy (b.m. 61 kg, h. 1.75 cm) with congenital hypoparathyroidism caused by an activating mutation of the calcium-sensing receptor [ADH1 - NM_001178065.2(CASR):c.2534C>A (p.Ala845Asp)] was started on treatment with a long-acting PTHR1 analog—palopegteriparatide, at an initial dose of 9 mcg/day. Previously, the patient was receiving alfacalcidol (1.25 mcg/day), CaCO3 (600 mg Ca/day), hydrochlorothiazide (12.5-6.25 mg), MgSO4 (260 mg Mg/day), and KCl (782 mg K/day). Interestingly, despite having a total calcium level of 6.5-7.5 mg/dL, the patient felt relatively well, with tetany occurring only sporadically (e.g., during viral infections or after significant physical activity). However, the patient presented with phosphate retention (TmP/GFR > 3.0), leading to hyperphosphatemia (8-11 mg/dL) and an elevated calcium-phosphate product of 55-65 mg2/dL2. In addition to a low-phosphate diet (<800 mg/day), the patient had previously received sevelamer periodically; however, the pharmacotherapy was ineffective and caused abdominal pain and diarrhea. The patient also presented with hypercalciuria (FeCa > 2.0%), nephrocalcinosis, cataracts, and in the basal ganglia calcifications. After 4 months of treatment, the patient feels well, with no episodes of tetany. The calcium level increased to 8.68 mg/dL (nadir), phosphate levels decreased to 5.46 mg/dL (nadir), and the calcium-phosphate product dropped to 44-55 mg2/dL2. The palopegteriparatide dose was reduced to 6 mcg/day, alfacalcidol to 0.25 mcg/day, and hydrochlorothiazide to 6.25-6.25 mg/day. Magnesium (260 mg/day) and potassium (782 mg/day) supplementation was maintained, while calcium supplements were discontinued. Notably, the palopegteriparatide dose is relatively low (the recommended starting dose is 18 mcg/day). Calcilytics (e.g., encaleret) should be the drugs of choice in the treatment of ADH1, but they are currently still the subject of/ under investigation (CALIBRATE trial). In cases where calcilytic therapy is unavailable, PTH administration can be considered, although there are currently limited reports on this approach. Given the lack of access to calcilytics, palopegteriparatide may be a therapeutic option for patients with ADH1. The treatment improved calcium-phosphate homeostasis parameters but did not normalize them (phosphate levels remain elevated). The long-term effects of using long-acting PTHR1 analogs are currently unknown. However, this treatment should be considered in cases of severe abnormalities in calcium and phosphate levels that lead to calcium salt precipitation and subsequent organ dysfunction. Presentation: Sunday, July 13, 2025