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After administration of intravenous iron in its carboxymaltose form, hypophosphatemia is a possible side effect, with its incidence being widely variable according to the literature and possibly underestimated given the low measurement of serum phosphate in these patients.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">One of the main aetiological mechanisms is the transient increase in fibroblast growth factor 23 (FGF-23), which on the one hand inhibits phosphorus reabsorption in the proximal convoluted tubule and on the other decreases the production of 1,25-OH2 vitamin D from 25-OH vitamin D, increasing phosphaturia and causing hypocalcaemia, which triggers secondary hyperparathyroidism as a compensatory mechanism. Therefore, the first days after infusion and up to 5 weeks later, hyperphosphaturic hypophosphatemia can be observed together with elevated FGF-23 and parathyroid hormone (PTH), as well as decreased vitamin D.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> This set of biochemical alterations has recently been described as “<span class="elsevierStyleItalic">6H syndrome: hypophosphatemia, high FGF-23, high urinary phosphate excretion, hypocalcitriolemia, hypocalcaemia, and secondary hyperparathyroidism</span>”.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">We report the case of a 33-year-old male who came to the emergency department for a 15-day history of diarrhoea. He reported 4–6 loose stools with blood per day, tenesmus and faecal incontinence, with associated arthralgia in the knees and elbows. Blood tests showed a GPT of 80 µ/l (5–41 µ/l) and elevated acute phase reactants, so it was decided to admit the patient to hospital to complete the study.</p><p id="par0030" class="elsevierStylePara elsevierViewall">During admission, a colonoscopy showed lesions compatible with severe ulcerative pancolitis, and the diagnosis was confirmed histologically. During hospital follow-up, progressive anaemia was observed, with haemoglobin levels ranging from 13 g/dl (13.5−18 g/dl) on admission to 10.1 g/dl, iron 20 µg/dl (59−158 µg/dl), ferritin 1,818 ng/dl (30−400 ng/dl), transferrin 117 mg/dl (200−360 mg/dl) and transferrin saturation index of 14% (23%–63%).</p><p id="par0035" class="elsevierStylePara elsevierViewall">Two doses of 1 g intravenous iron carboxymaltose (Ferinject®, CSL Vifor, Switzerland) were administered, separated by one week. Subsequently, she started with severe hypophosphatemia (with phosphorus levels of 3.6 mg/dl [2.6–4.5 mg/dl] on admission and a gradual decrease after both infusions to 1.1 mg/dl), with PTH 43 pg/ml (10–65 pg/ml), 25-OH vitamin D 19 ng/dl (30−100 ng/dl), albumin-adjusted calcium 9.2 mg/dl (8.6–10.2 mg/dl), albumin 2.9 g/dl (3.5–5.20 g/dl) and normal renal function.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The patient was assessed by Endocrinology and Nutrition, and 40−50 mmol of intravenous phosphate was prescribed together with 1 or 2 sachets of oral phosphate (3.56 g each) per day for a week, with slow improvement, achieving a phosphorus level of 3.1 mg/dl (2.6–4.5 mg/dl) at discharge.</p><p id="par0045" class="elsevierStylePara elsevierViewall">He was diagnosed with new-onset severe ulcerative colitis and severe hypophosphatemia secondary to parenteral iron administration.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Finally, the patient was discharged with no symptoms, with good oral tolerance, afebrile and without the need for home oral phosphate replacement therapy.</p><p id="par0055" class="elsevierStylePara elsevierViewall">A randomised clinical trial was recently published comparing the rate of hypophosphatemia after administration of ferric carboxymaltose and derisomaltose for iron deficiency anaemia in inflammatory bowel disease, concluding a higher rate with the former.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Burosumab, a recombinant human monoclonal antibody that binds to FGF-23, has been described for iron-induced FGF-23-mediated severe osteomalacia with successful results, although it is currently only licensed for X-linked hypophosphatemia.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In conclusion, hypophosphatemia is a reported adverse effect to be considered after intravenous iron carboxymaltose administration, especially in patients with preserved renal function and the need for higher iron doses. Measurement of serum phosphate before and after administration is recommended. Treatment of hypophosphatemia after intravenous iron consists of oral or intravenous phosphate supplementation and cessation of iron infusion.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical considerations</span><p id="par0070" class="elsevierStylePara elsevierViewall">The patient was informed in detail about the publication of this case, accepting and signing the informed consent form.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0075" class="elsevierStylePara elsevierViewall">We have not received any funding for the publication of this case report.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">I declare that there is no conflict of interest in the publication of this case report.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical considerations" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypophosphatemia after ferric carboxymaltose is unrelated to symptoms, intestinal inflammation or vitamin D status" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "W. 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Letter to the Editor
Severe hypophospathemia secondary to intravenous iron
Hipofosfatemia grave secundaria a hierro intravenoso
Marina Jara Vidal
, Andrés Ruiz de Assín Valverde, Silvia Aznar Rodríguez
Corresponding author
Servicio de Endocrinología y Nutrición, Complejo Hospitalario Universitario de Albacete, Albacete, Spain