SAT-519 - Post-Gastric Bypass Hypoglycemia (PGBH) Amplified by Palopegteriparatide Therapy.

Introduction: PGBH is a recognized complication of Roux-en-Y gastric bypass. We describe a case of worsening postprandial hypoglycemia following initiation of Palopegteriparatide for hypoparathyroidism.

Case Report: A 50-year-old woman with a history of papillary thyroid carcinoma, status post total thyroidectomy complicated by post-surgical hypoparathyroidism, and Roux-en-Y gastric bypass (RYGB) surgery presented with worsening hypocalcemia four years after bypass surgery. Over a three-month period, she required three hospital admissions for severe, symptomatic hypocalcemia (corrected calcium 5.9 mg/dL; phosphorus 7.9 mg/dL; PTH low-normal at 21.5 pg/mL) refractory to oral calcium supplementation. During this time, she also reported intermittent episodes of postprandial hypoglycemia. Blood glucose (BG) decreased to 60-69 mg/dL following meals, at which time the patient would experience symptoms of blurred vision and tremors.
After the third admission, treatment was initiated with the PTH analogue, Palopegteriparatide, which normalized her calcium and phosphorus levels. In the weeks following this pharmacotherapy, however, she experienced significant worsening of hypoglycemia. Symptomatic postprandial episodes averaged twice daily with BG frequently ranging from 40-50 mg/dL. Fasting hypoglycemia occurred as well with an associated twenty-pound weight gain in the succeeding months. Continuous glucose monitor revealed 20% of BG readings < 69 mg/dL. Palopegteriparatide was titrated to the lowest effective dose, and the patient was subsequently managed with dietary and lifestyle modifications.

Discussion: PGBH results from exaggerated postprandial insulin release because of rapid transit of food into the small intestine. Glucagon-like peptide from the L-cells and GIP from the K cells stimulate the β cells to release insulin. The final step of insulin release by β cells is calcium-dependent exocytosis of insulin caused by changes in the electrical activity in β cells. Change in anatomy of GI tract following RYGB cause mismatch between rapid glucose absorption and exaggerated insulin release which results in hypoglycemia.
After normalization of calcium levels in this patient on Palopegteriparatide therapy, there may have been more calcium available for influx across the pancreatic β cell membranes. Secretory granules respond to calcium entry across these voltage-gated ion channels with increased insulin release, illustrating a possible mechanism for intensified postprandial hypoglycemia.

Conclusion: Case highlights a potential interaction between PTH-analogues and insulin regulation, and it is suggestive that pharmacotherapy directed towards selective calcium channel inhibition may represent a future avenue to modulate postprandial glycemic control for these patients.

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