Letter to the Editor – Brief Case Reports
Response to acetazolamide in a patient with tumoural calcinosis
Respuesta a acetazolamida en paciente con calcinosis tumoral
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(a) Areas with a cystic appearance with calcium deposits and epithelioid cells. (b) Presence of multinucleate giant cells.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Tumoural calcinosis (TC) is a rare disorder of phosphorus metabolism, characterised by the formation of periarticular deposits of calcium phosphate.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> The disease is the result of a defect in renal phosphorus excretion, due to mutations in the genes for fibroblast growth factor 23 (<span class="elsevierStyleItalic">FGF23</span>), Klotho (<span class="elsevierStyleItalic">KL</span>), and N-acetylgalactosaminyltransferase-3 (<span class="elsevierStyleItalic">GALNT3</span>). The loss of FGF23 function results in increased tubular phosphorus reabsorption, and subsequent deposition in subcutaneous tisses.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 23-year-old man with no significant past medical history, whose symptoms began at the age of 18 years, with the appearance of a mass in the right dorsal region, lateral buttock, and thigh. The patient reported a progressive increase in size of the mass, related with physical activity, and pain in the affected limb as a functional limitation. Six months before his admission to our hospital, the tumour had been excised, measuring 18<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>cm from the right thigh, and 20<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>cm from the right buttock, with amorphous characteristics.</p><p id="par0015" class="elsevierStylePara elsevierViewall">On admission, he had a solid painless mass in the area of excision on the superficial lateral right thigh, measuring 10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>cm. Laboratory analysis reported normal serum levels of calcium, phosphate, creatinine, albumin, and PTH. X-ray revealed a multinodular calcified mass around the right hip joint.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Biopsy of the lesion reported amorphous calcified nodules, some surrounded by a proliferation of macrophages and osteoclast-like giant cells, separated by dense fibrous tissue, consistent with TC (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). He was followed up for 2 years while receiving acetazolamide (August 2008 to October 2011) and showed clinical improvement and cessation of growth of the lesions. There were no reported acid–base disturbances during treatment. A follow-up X-ray was taken 7 years after starting treatment, with no increase in the size of the lesions (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The pathophysiology of TC is based on abnormal phosphorus metabolism.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Serum phosphate concentration is regulated by endocrine communication between bone, kidney, and the intestine.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> The endocrine factors involved in phosphate metabolism are 1,25-hydroxyvitamin D3, parathyroid hormone (PTH) and FGF23. FGF23 and PTH act synergistically to reduce the expression of the cotransporters NaPi-IIa and NaPi-IIc in the brush border of the proximal renal tubule, increasing renal phosphorus excretion.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">FGF 23 is a glycoprotein, formed by 251 amino acids, and has an N-terminal and a C-terminal made of 71 amino acids.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> It promotes phosphorus excretion by reducing the expression of NaP(i) cotransporters in the proximal tubular cell brush border.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> For FGF23 to bind to its receptor, FGFR1c, Klotho is essential to form a functional heterodimer.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> FGF23 is glycosylated by GALNT3.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Only the complete FGF23 protein is biologically active. Therefore, an abnormality at any of these points can lead to increased tubular phosphorus reabsorption, which is what happens in TC.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The disease manifests as hyperphosphatemia and massive calcium deposition in the subcutaneous tissue, which are the main causes of patient symptoms.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> This disease is more frequent in women and in patients of African origin, with initial presentation in childhood or early adolescence.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The treatment of TC can be divided into surgical excision and medical treatment. Surgical excision of the lesion is a well-documented treatment, but recurrence is common. Furthermore, this patient had shown recurrence after surgical excision, probably due to the tumour being poorly-circumscribed.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Medical treatment is preferable because of the metabolic nature of the disease. Described treatments include dietary phosphate restriction, antacids, phosphaturic drugs, and phosphate binders. However, the most effective demonstrated treatment is the combination of surgical excision with phosphate restriction and acetazolamide.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Previous studies have demonstrated positive results with the use of acetazolamide as a phosphaturic treatment for TC, causing mild metabolic acidosis in these patients as an adverse effect. Acetazolamide, a sulphonamide-derivative, acts as a carbonic anhydrase inhibitor in the apical and basolateral membrane of the proximal tubule lumen. It induces natriuresis, kaliuresis, phosphaturia and bicarbonaturia. This causes a reduction in these ions in the body, leading to clinical and biochemical improvement in patients with hyperphosphataemia.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Our patient improved clinically after starting therapy with acetazolamide, with reduced pain and cessation of tumour formation with no tumour recurrence, as had occurred after the previous surgical excision of the lesion. Phosphorus levels decreased but did not reach normal levels.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Landini-Enríquez V, Escamilla MA, Soto-Vega E, Chamizo-Aguilar K. Respuesta a acetazolamida en paciente con calcinosis tumoral. Nefrologia. 2015;35:504–506.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 716 "Ancho" => 1808 "Tamanyo" => 174353 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Histological sections of the lesions in the right buttock and thigh, in a 23-year-old patient. (a) Areas with a cystic appearance with calcium deposits and epithelioid cells. (b) Presence of multinucleate giant cells.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1003 "Ancho" => 1506 "Tamanyo" => 76525 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Comparative radiographic imaging of a patient with TC after 7 years of acetazolamide treatment: (a) Start of treatment (August 2008). 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 9 | 15 |
| 2024 October | 43 | 40 | 83 |
| 2024 September | 47 | 35 | 82 |
| 2024 August | 50 | 71 | 121 |
| 2024 July | 44 | 25 | 69 |
| 2024 June | 55 | 59 | 114 |
| 2024 May | 66 | 27 | 93 |
| 2024 April | 67 | 27 | 94 |
| 2024 March | 53 | 32 | 85 |
| 2024 February | 65 | 38 | 103 |
| 2024 January | 51 | 26 | 77 |
| 2023 December | 39 | 39 | 78 |
| 2023 November | 52 | 52 | 104 |
| 2023 October | 56 | 21 | 77 |
| 2023 September | 35 | 18 | 53 |
| 2023 August | 55 | 32 | 87 |
| 2023 July | 40 | 28 | 68 |
| 2023 June | 68 | 21 | 89 |
| 2023 May | 98 | 36 | 134 |
| 2023 April | 67 | 12 | 79 |
| 2023 March | 99 | 20 | 119 |
| 2023 February | 64 | 15 | 79 |
| 2023 January | 59 | 26 | 85 |
| 2022 December | 94 | 31 | 125 |
| 2022 November | 65 | 22 | 87 |
| 2022 October | 66 | 39 | 105 |
| 2022 September | 65 | 26 | 91 |
| 2022 August | 75 | 41 | 116 |
| 2022 July | 62 | 38 | 100 |
| 2022 June | 58 | 30 | 88 |
| 2022 May | 58 | 35 | 93 |
| 2022 April | 100 | 54 | 154 |
| 2022 March | 74 | 44 | 118 |
| 2022 February | 64 | 49 | 113 |
| 2022 January | 51 | 34 | 85 |
| 2021 December | 63 | 50 | 113 |
| 2021 November | 58 | 34 | 92 |
| 2021 October | 44 | 46 | 90 |
| 2021 September | 38 | 24 | 62 |
| 2021 August | 43 | 40 | 83 |
| 2021 July | 60 | 33 | 93 |
| 2021 June | 39 | 15 | 54 |
| 2021 May | 64 | 30 | 94 |
| 2021 April | 118 | 41 | 159 |
| 2021 March | 51 | 42 | 93 |
| 2021 February | 44 | 14 | 58 |
| 2021 January | 38 | 19 | 57 |
| 2020 December | 35 | 15 | 50 |
| 2020 November | 31 | 13 | 44 |
| 2020 October | 24 | 16 | 40 |
| 2020 September | 23 | 15 | 38 |
| 2020 August | 37 | 11 | 48 |
| 2020 July | 42 | 18 | 60 |
| 2020 June | 30 | 11 | 41 |
| 2020 May | 45 | 12 | 57 |
| 2020 April | 27 | 17 | 44 |
| 2020 March | 29 | 15 | 44 |
| 2020 February | 42 | 19 | 61 |
| 2020 January | 50 | 20 | 70 |
| 2019 December | 50 | 22 | 72 |
| 2019 November | 37 | 22 | 59 |
| 2019 October | 18 | 11 | 29 |
| 2019 September | 29 | 11 | 40 |
| 2019 August | 30 | 22 | 52 |
| 2019 July | 30 | 18 | 48 |
| 2019 June | 29 | 18 | 47 |
| 2019 May | 34 | 21 | 55 |
| 2019 April | 56 | 25 | 81 |
| 2019 March | 22 | 13 | 35 |
| 2019 February | 21 | 17 | 38 |
| 2019 January | 46 | 14 | 60 |
| 2018 December | 161 | 34 | 195 |
| 2018 November | 279 | 24 | 303 |
| 2018 October | 161 | 17 | 178 |
| 2018 September | 124 | 25 | 149 |
| 2018 August | 77 | 27 | 104 |
| 2018 July | 74 | 22 | 96 |
| 2018 June | 80 | 15 | 95 |
| 2018 May | 60 | 12 | 72 |
| 2018 April | 77 | 6 | 83 |
| 2018 March | 82 | 10 | 92 |
| 2018 February | 104 | 5 | 109 |
| 2018 January | 63 | 5 | 68 |
| 2017 December | 106 | 11 | 117 |
| 2017 November | 44 | 13 | 57 |
| 2017 October | 28 | 4 | 32 |
| 2017 September | 34 | 12 | 46 |
| 2017 August | 29 | 14 | 43 |
| 2017 July | 29 | 14 | 43 |
| 2017 June | 48 | 8 | 56 |
| 2017 May | 49 | 6 | 55 |
| 2017 April | 35 | 10 | 45 |
| 2017 March | 36 | 19 | 55 |
| 2017 February | 24 | 6 | 30 |
| 2017 January | 22 | 17 | 39 |
| 2016 December | 52 | 14 | 66 |
| 2016 November | 51 | 19 | 70 |
| 2016 October | 84 | 14 | 98 |
| 2016 September | 95 | 3 | 98 |
| 2016 August | 107 | 3 | 110 |
| 2016 July | 127 | 9 | 136 |
| 2016 June | 80 | 0 | 80 |
| 2016 May | 126 | 0 | 126 |
| 2016 April | 76 | 0 | 76 |
| 2016 March | 77 | 0 | 77 |
| 2016 February | 101 | 0 | 101 |
| 2016 January | 97 | 0 | 97 |
| 2015 December | 65 | 0 | 65 |
| 2015 November | 15 | 0 | 15 |
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