Letter to the Editor
Resistance to Vitamin D Treatment as an Indication of Celiac Disease in a Patient with Primary Hypoparathyroidism
José Antonio Miguel Marcondes, Pedro Seferian Junior, Cristina Aparecida Proques da Silveira Mitteldorf
Hospital Sírio Libanês - São Paulo/SP, Brazil
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A: abductor pollicis longus (APL); extensor carpi radialis brevis (ECRB); extensor carpi radialis longus (ECRL); extensor carpi ulnaris (ECU); extensor digitorum tendons (ED); extensor indicis (EI); extensor pollicis brevis (EPB); extensor pollicis longus (EPL); <elsevierMultimedia ident="202212060814030661"></elsevierMultimedia>indicates the anomalous muscle. B: The extensor carpi radialis brevis and the extensor carpi radialis longus tendons were cut to show the insertion site of the anomalous muscle. APL; dorsal tubercle of Lister (d); extensor carpi radialis brevis tendon reflected (ECRB); extensor carpi radialis longus tendon reflected (ECRL); extensor carpi ulnaris (ECU); extensor digitorum tendons (ED); extensor pollicis brevis (EPB); extensor pollicis longus (EPL); insertion of brachioradialis tendon (IBRT); styloid process of radius (S); <elsevierMultimedia ident="202212060814030662"></elsevierMultimedia>indicates the anomalous muscle. The white arrows indicate the insertion site of the anomalous muscle.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Soubhagya R. Nayak, Rajanigandha Vadgaonkar, Ashwin Krishnamurthy, Latha V. Prabhu" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Soubhagya R." "apellidos" => "Nayak" ] 1 => array:2 [ "nombre" => "Rajanigandha" "apellidos" => "Vadgaonkar" ] 2 => array:2 [ "nombre" => "Ashwin" "apellidos" => "Krishnamurthy" ] 3 => array:2 [ "nombre" => "Latha V." "apellidos" => "Prabhu" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222026801?idApp=UINPBA00004N" "url" => "/18075932/0000006400000003/v1_202212060813/S1807593222026801/v1_202212060813/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1807593222026783" "issn" => "18075932" "doi" => "10.1590/S1807-59322009000300017" "estado" => "S300" "fechaPublicacion" => "2009-03-01" "aid" => "2678" "copyright" => "CLINICS" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/" "subdocumento" => "rev" "cita" => "Clinics. 2009;64:253-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "A Brief Review of Chronic Exercise Intervention to Prevent Autonomic Nervous System Changes During the Aging Process" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "253" "paginaFinal" => "258" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 553 "Ancho" => 993 "Tamanyo" => 52023 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">A</span>: Graphs showing no differences in sympathetic (ST) and vagal (VT) tone between young and old rats. The intrinsic HR (IHR) was lower in old rats. <span class="elsevierStyleItalic">B</span>: The increase in HR (from 347 ± 9 to 527 ± 11 beats/min) after methylatropine injection [vagal effect (VE)] was higher in young rates than in older specimens. * Significant difference between young and old rats (<span class="elsevierStyleItalic">P</span>< 0.05).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rogério Brandão Wichi, Kátia De Angelis, Lia Jones, Maria Claudia Irigoyen" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Rogério Brandão" "apellidos" => "Wichi" ] 1 => array:2 [ "nombre" => "Kátia" "apellidos" => "De Angelis" ] 2 => array:2 [ "nombre" => "Lia" "apellidos" => "Jones" ] 3 => array:2 [ "nombre" => "Maria Claudia" "apellidos" => "Irigoyen" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222026783?idApp=UINPBA00004N" "url" => "/18075932/0000006400000003/v1_202212060813/S1807593222026783/v1_202212060813/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Resistance to Vitamin D Treatment as an Indication of Celiac Disease in a Patient with Primary Hypoparathyroidism" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "259" "paginaFinal" => "261" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "José Antonio Miguel Marcondes, Pedro Seferian, Cristina Aparecida Proques da Silveira Mitteldorf" "autores" => array:3 [ 0 => array:3 [ "nombre" => "José Antonio Miguel" "apellidos" => "Marcondes" "email" => array:1 [ 0 => "marcondesmd@uol.com.br" ] ] 1 => array:3 [ "nombre" => "Pedro" "apellidos" => "Seferian" "sufijo" => "Junior" ] 2 => array:2 [ "nombre" => "Cristina Aparecida Proques" "apellidos" => "da Silveira Mitteldorf" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Hospital Sírio Libanês - São Paulo/SP, Brazil" "identificador" => "af1" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 985 "Ancho" => 968 "Tamanyo" => 44529 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">The effect of a gluten-free diet on the ionized calcium levels in a patient with primary hypoparathyroidism associated with celiac disease</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Hypocalcemia may present as an asymptomatic laboratory finding or as a severe, life-threatening condition. Upon the diagnosis of acute hypocalcemia, a rapid treatment regimen may be necessary. In contrast, chronic hypocalcemia may be well tolerated by the patient, but treatment nonetheless remains necessary in order to prevent long-term complications.</p><p id="para20" class="elsevierStylePara elsevierViewall">The hallmark of acute hypocalcemia is neuromuscular irritability, although paresthesias of the extremities may also occur, along with fatigue and anxiety. In addition, very painful muscle cramps may develop and can progress into carpal spasms or tetany.<a class="elsevierStyleCrossRef" href="#bib1">1</a> From a clinical perspective, neuromuscular irritability can be demonstrated by testing for Chevostek or Trousseau signs. However, all of these symptoms can be corrected by the administration of calcium replacement treatments.</p><p id="para30" class="elsevierStylePara elsevierViewall">The observation of an inappropriately normal PTH coupled with hypocalcemia should promptly warrant the diagnosis of hypoparathyroidism, which may be transient, genetically inherited, or acquired due to an autoimmune process. It may also follow surgery or neck irradiation treatment.<a class="elsevierStyleCrossRef" href="#bib1">1</a></p><p id="para40" class="elsevierStylePara elsevierViewall">In this paper, we present a case study of a patient with primary hypoparathyroidism who is surprisingly resistant to the usual treatment consisting of calcium and vitamin D supplementation. The coincident observation of chronic diarrhea prompted us to consider the possibility of a malabsorption syndrome with steatorrhea, since vitamin D absorption is fat-dependent.</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">CASE REPORT</span><p id="para50" class="elsevierStylePara elsevierViewall">A 39-year-old woman was admitted to the emergency room at our facility with tetany that was resolved by the intravenous administration of calcium gluconate in high doses. The patient’s recent medical history revealed recurrent episodes of diarrhea, asthenia, paresthesias and weight loss (7.0 kg) over a one-month period. Approximately one year prior to this emergency room admission, the patient underwent a quadrantectomy for breast cancer. Overall, the patient’s family history was unremarkable. At the time of admission, the patient was being treated with tamoxifen.</p><p id="para60" class="elsevierStylePara elsevierViewall">Subsequent physical examination revealed a lean woman (body mass index of 22.7 kg/m<span class="elsevierStyleSup">2</span>) with a blood pressure of 120 over 60 mmHg and a heart rate of 100 beats per minute. In addition, the patient had a +/3 bilateral maleolar edema and no vitiligo was observed. The thyroid and the abdomen of the patient appeared normal.</p><p id="para70" class="elsevierStylePara elsevierViewall">Initial laboratory analyses revealed that the patient was hypocalcemic (total calcium of 5.4 mg/dL and ionized calcium of 0.74 mM/L), hypoalbuminemic (2.4 g/dL) and presented microcytic hypochromic anemia (9.4 g/dL). The PTH (30 nM/L), phosphorus (4.4 mg/dL) and magnesium concentrations (2.1 mg/dL) were normal. A liver functional test revealed a high prothrombin time (25 seconds) with normal transaminases and bilirubin levels. In addition, renal and thyroid function tests were normal.</p><p id="para80" class="elsevierStylePara elsevierViewall">The patient was placed on a high protein diet and treated with oral calcium gluconate and calcitriol with a stepwise increase in the dosage of up to 1.0 mg/day, with persistence of the paresthesia, Chevostek and Trousseau signs, and maleolar edema and without significant changes in metabolic and nutritional parameters (<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>). The patient’s serum analysis indicated the presence of immunoglobulin A isotype antibodies against endomysium (1/640). Diagnosis of gluten-sensitive enteropathy or celiac disease was suggested at endoscopy, due to flat mucosa, and confirmed by histological findings in duodenal biopsy, including absent villi, crypt hyperplasia and T-cell lymphocytic infiltration in the epithelium. Eleven days after admitting the patient, she was placed on a gluten-free diet, which rapidly lead to the normalization of her bowel habits and improved her metabolic and nutritional parameters.</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><p id="para90" class="elsevierStylePara elsevierViewall">The patient was discharged from the hospital after 7 days on a gluten-free diet supplemented with daily doses of calcitriol (1.0 mg/day) and calcium carbonate (4.5 g/day). Her body mass index was 25.5 kg/m<span class="elsevierStyleSup">2</span> and blood pressure and heart rate were 120 over 80 mmHg and 80 bets per minute, respectively. Maleolar edema was no longer observed and the Chevostek and Trousseau signs were negative. In addition, the levels of total calcium, ionized calcium, albumin and hemoglobin increased to 8.3 mg/dL, 1.1 mM/L, 4.2 g/dL and 11.3 g/dL, respectively, while the prothrombin time decreased from 25 seconds to 11 seconds.</p><p id="para100" class="elsevierStylePara elsevierViewall">Six months thereafter, although the patient still reported occasional episodes of diarrhea, assays for the endomysial antibody were negative.</p></span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">DISCUSSION</span><p id="para110" class="elsevierStylePara elsevierViewall">This patient had a history of chronic diarrhea and weight loss. Upon admission, laboratory analyses indicated that the patient had low levels of total calcium and ionized calcium that were initially observed under conditions of inappropriately normal levels of PTH and magnesium. We diagnosed the patient with primary hypoparathyroidism and she was treated with intravenous calcium gluconate and vitamin D<span class="elsevierStyleInf">3</span> (calciferol) supplements that were administered via a stepwise increase of up to 0.25 mg four times a day. This is considered the maximum daily recommended dose.</p><p id="para120" class="elsevierStylePara elsevierViewall">Because the hypocalcemia persisted in the patient, we considered changing the diagnosis to malabsorption syndrome due to the presence of chronic diarrhea, since vitamin D absorption is fat-dependent. Assays for the presence of the endomysial antibody were positive and a subsequent biopsy of duodenal mucosa revealed results that were consistent with gluten-sensitive enteropathy or celiac disease. We then administered the patient a gluten-free diet in combination with vitamin D supplementation. This was followed by an encouraging increase in the levels of serum calcium over a period of several days until the patient’s bowel habits normalized and the symptoms of hypocalcemia reappeared.</p><p id="para130" class="elsevierStylePara elsevierViewall">Celiac disease is an immune disorder triggered by an environmental agent (the gliadin component of gluten) in genetically predisposed individuals.<a class="elsevierStyleCrossRef" href="#bib3">3</a> Epidemiological studies using IgA antibodies to gliadin and endomysium had a positive predictive value of 100%, with a prevalence of 1:22 in first degree relatives of patients with celiac disease and a prevalence of 1:133 in the not-at-risk groups.<a class="elsevierStyleCrossRef" href="#bib4">4</a></p><p id="para140" class="elsevierStylePara elsevierViewall">Hypocalcemia in celiac disease may arise from the impaired absorption of vitamin D or the loss of calcium through the binding of intraluminal calcium to unabsorbed fatty acids. Both secondary hypoparathyroidism due to hypomagnesemia<a class="elsevierStyleCrossRef" href="#bib5">5</a> and compensatory secondary hyperparathyroidism have been described elsewhere.<a class="elsevierStyleCrossRef" href="#bib6">6</a></p><p id="para150" class="elsevierStylePara elsevierViewall">On the other hand, only a few reports have been published on the coexistence of primary hypoparathyroidism and celiac disease.<a class="elsevierStyleCrossRef" href="#bib7">7</a>–<a class="elsevierStyleCrossRef" href="#bib14">14</a> The age of the disease onset ranged from early childhood<a class="elsevierStyleCrossRef" href="#bib14">14</a> to old age.<a class="elsevierStyleCrossRef" href="#bib12">12</a> In some reports, such as one describing a 62-year-old woman, hypoparathyroidism was diagnosed 33 years prior to the diagnosis of celiac disease,<a class="elsevierStyleCrossRef" href="#bib12">12</a> while in other reports, such as a report characterizing a 60 year-old man,<a class="elsevierStyleCrossRef" href="#bib7">7</a> the diagnosis of hypoparathyroidism was made concomitantly with the diagnosis of celiac disease. In a separate report, a patient with idiopathic autoimmune hypoparathyroidism who developed autoimmune hyperthyroidism (Graves’ disease) was subsequently diagnosed with celiac disease.<a class="elsevierStyleCrossRef" href="#bib13">13</a> The malabsorption of <span class="elsevierStyleItalic">l</span>-thyroxine was the only indication of the presence of celiac disease. In fact, a common immunological basis that associated the idiopathic hypothyroidism with the celiac disease was hypothesized in this instance.<a class="elsevierStyleCrossRef" href="#bib9">9</a> In yet another report, celiac disease was diagnosed in a patient with hypoparathyroidism in the absence of gastrointestinal symptoms.<a class="elsevierStyleCrossRef" href="#bib11">11</a></p><p id="para160" class="elsevierStylePara elsevierViewall">In conclusion, the possibility of celiac disease should be considered in patients with hypoparathyroidism that seems unduly difficult to treat. This should be evaluated even in the absence of gastrointestinal symptoms.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 1 => array:2 [ "identificador" => "cesec20" "titulo" => "CASE REPORT" ] 2 => array:2 [ "identificador" => "cesec30" "titulo" => "DISCUSSION" ] 3 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 985 "Ancho" => 968 "Tamanyo" => 44529 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">The effect of a gluten-free diet on the ionized calcium levels in a patient with primary hypoparathyroidism associated with celiac disease</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:14 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypoparathyroidism and pseudohypoparathyroidism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ SS Maeda \n \t\t\t\t\t\t\t\t """ 1 => """ EM Fortes \n \t\t\t\t\t\t\t\t """ 2 => """ UM Oliveira \n \t\t\t\t\t\t\t\t """ 3 => """ VC Borba \n \t\t\t\t\t\t\t\t """ 4 => """ M Lazaretti-Castro \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1590/s0004-27302006000400012" "Revista" => array:6 [ "tituloSerie" => "Arq Bras Endocrinol Metabol" "fecha" => "2006" "volumen" => "50" "paginaInicial" => "664" "paginaFinal" => "673" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17117292" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Celiac disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ RJ Presutti \n \t\t\t\t\t\t\t\t """ 1 => """ JR Cangemi \n \t\t\t\t\t\t\t\t """ 2 => """ HD Cassidy \n \t\t\t\t\t\t\t\t """ 3 => """ DA Hill \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am Fam Physician" "fecha" => "2007" "volumen" => "76" "paginaInicial" => "1795" "paginaFinal" => "1802" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18217518" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Celiac disease: screened by a new strategy" "autores" => array:1 [ 0 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 0 | 3 |
| 2024 October | 24 | 18 | 42 |
| 2024 September | 26 | 14 | 40 |
| 2024 August | 23 | 12 | 35 |
| 2024 July | 30 | 20 | 50 |
| 2024 June | 14 | 14 | 28 |
| 2024 May | 16 | 11 | 27 |
| 2024 April | 15 | 10 | 25 |
| 2024 March | 12 | 12 | 24 |
| 2024 February | 21 | 12 | 33 |
| 2024 January | 14 | 8 | 22 |
| 2023 December | 15 | 20 | 35 |
| 2023 November | 8 | 22 | 30 |
| 2023 October | 12 | 17 | 29 |
| 2023 September | 12 | 7 | 19 |
| 2023 August | 23 | 1 | 24 |
| 2023 July | 23 | 13 | 36 |
| 2023 June | 24 | 1 | 25 |
| 2023 May | 42 | 5 | 47 |
| 2023 April | 41 | 12 | 53 |
| 2023 March | 39 | 15 | 54 |
| 2023 February | 18 | 4 | 22 |
| 2023 January | 7 | 3 | 10 |
| 2022 December | 3 | 0 | 3 |
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