An Unusually Prolonged Case of FGF23-mediated Hypophosphatemia Secondary to Ferric Carboxymaltose Use.

Ferric carboxymaltose (FCM)-induced hypophosphatemia is seen in up to 75% of patients receiving this therapy for iron deficiency anemia. Hypophosphatemia has been attributed to increased circulating levels of fibroblast growth factor-23 (FGF23), the transcription of which is upregulated in an iron-deficient state. However, hypophosphatemia typically resolves within 12 weeks of FCM administration. Here, we present a case of unusually prolonged hypophosphatemia that developed after treatment with FCM in a 39-year-old female with autosomal dominant polycystic kidney disease (ADPKD) but normal renal function. Workup was significant for low tubular reabsorption of phosphate and inappropriately normal FGF23. Genetic disorders of hypophosphatemia and a FGF23-secreting tumor were ruled out. Treatment with calcitriol was required for nearly 3.5 years. The prolonged hypophosphatemia was attributed to underlying ADPKD because these patients demonstrate inappropriately elevated FGF23 levels for the degree of severity of reduced glomerular filtration rate. However, the stimulus driving FGF23 secretion in these patients is incompletely understood. Elevated FGF23 in the kidney suppresses renal tubular phosphate reabsorption and 1α-hydroxylase activity ultimately leading to hypophosphatemia. We conclude that our patient was at a high risk of developing hypophosphatemia because of underlying ADPKD, and FCM was the likely precipitant to identify this underlying process.

A Randomized, Placebo-Controlled Double-Blind Trial of a Closed-Loop Glucagon System for Postbariatric Hypoglycemia.

BACKGROUND: Postbariatric hypoglycemia (PBH) can threaten safety and reduce quality of life. Current therapies are incompletely effective. METHODS: Patients with PBH were enrolled in a double-blind, placebo-controlled, crossover trial to evaluate a closed-loop glucose-responsive automated glucagon delivery system designed to reduce severe hypoglycemia. A hypoglycemia detection and mitigation algorithm was embedded in the artificial pancreas system connected to a continuous glucose monitor (CGM, Dexcom) driving a patch infusion pump (Insulet) filled with liquid investigational glucagon (Xeris) or placebo (vehicle). Sensor/plasma glucose responses to mixed meal were assessed during 2 study visits. The system delivered up to 2 doses of study drug (300/150 µg glucagon or equal-volume vehicle) if triggered by the algorithm. Rescue dextrose was given for plasma glucose <55 mg/dL or neuroglycopenia. RESULTS: Twelve participants (11 females/1 male, age 52 ± 2, 8 ± 1 years postsurgery, mean ± SEM) completed all visits. Predictive hypoglycemia alerts prompted automated drug delivery postmeal, when sensor glucose was 114 ± 7 vs 121 ± 5 mg/dL (P = .39). Seven participants required rescue glucose after vehicle but not glucagon (P = .008). Five participants had severe hypoglycemia (<55 mg/dL) after vehicle but not glucagon (P = .03). Nadir plasma glucose was higher with glucagon vs vehicle (67 ± 3 vs 59 ± 2 mg/dL, P = .004). Plasma glucagon rose after glucagon delivery (1231 ± 187 vs 16 ± 1 pg/mL at 30 minutes, P = .001). No rebound hyperglycemia occurred. Transient infusion site discomfort was reported with both glucagon (n = 11/12) and vehicle (n = 10/12). No other adverse events were observed. CONCLUSION: A CGM-guided closed-loop rescue system can detect imminent hypoglycemia and deliver glucagon, reducing severe hypoglycemia in PBH. CLINICAL TRIALS REGISTRATION: NCT03255629.