Treatment-Resistant Hypophosphataemia After Ferric Carboxymaltose: Expanding the Spectrum of 6h Syndrome (Hypophosphataemia, Hyperphosphaturia, Hypovitaminosis D, Hypocalcaemia, Secondary Hyperparathyroidism, High Fibroblast Growth Factor-23)

铁羧基麦芽糖治疗后难治性低磷血症:6h 综合征谱的扩大(低磷血症、高磷尿症、维生素 D 缺乏症、低钙血症、继发性甲状旁腺功能亢进、成纤维细胞生长因子-23 高)

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Abstract

BACKGROUND: Ferric carboxymaltose (FCM) is widely used to treat iron deficiency anaemia (IDA), particularly in patients with gastrointestinal disease who are intolerant of oral iron. While generally well tolerated, FCM is increasingly recognised to cause hypophosphatemia. Most cases are mild and transient, but severe and prolonged episodes remain uncommon. CASE REPORT: A 40-year-old woman with newly diagnosed coeliac disease and severe IDA, received two intravenous FCM infusions (total 1.5 g). Within 1 week she developed profound symptomatic hypophosphatemia (0.34 mmol/l), presenting with escalating fatigue, exertional dyspnoea and arthralgia. Investigations revealed renal phosphate wasting (109.4 mmol/day) and secondary hyperparathyroidism, consistent with FCM-induced fibroblast growth factor-23 phosphaturia; also described as "6H syndrome". Coexistent coeliac-related malabsorption further compounded the condition and rendered oral phosphate supplementation ineffective. The patient required continuous intravenous phosphate infusions via a peripherally inserted central catheter for 5.5 weeks, in addition to dietary optimisation and calcitriol. Gradual recovery was achieved 8.5 weeks after onset, with stabilisation of serum phosphate at 0.9 mmol/l and resolution of symptoms. CONCLUSION: This case highlights an uncommon, severe and resource-intensive manifestation of FCM-associated hypophosphatemia. It reinforces the clinical utility of the 6H syndrome framework in recognising the biochemical pattern of FCM-induced phosphate wasting and underlines the importance of considering coexistent malabsorptive disorders, such as coeliac disease, which can magnify severity. Clinicians should remain vigilant, monitor phosphate in at-risk patients, and provide clear safety-netting to enable early detection and intervention. LEARNING POINTS: Ferric carboxymaltose can cause severe, prolonged hypophosphatemia that is treatment-resistant and may necessitate weeks of continuous intravenous phosphate and activated vitamin D therapy.The full constellation of 6H syndrome (hypophosphatemia, hypophosphaturia, hypovitaminosis D, hypocalcaemia, secondary hyperparathyroidism, high fibroblast growth factor-23) offers a practical diagnostic framework when evaluating post-iron infusion phosphate disturbances.Coexistent malabsorptive disorders can exacerbate renal phosphate wasting and complicate management, therefore at-risk patients need proactive phosphate monitoring and early specialist input, and consideration of fibroblast growth factor-23 directed management.

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