Diabetes tipo 1 y Miastenia Gravis / Type-1 Diabetes and Myasthenia Gravis

Introducción: El desarrollo de la tolerancia inmunológica frente a los autoantígenos se denomina autotolerancia. La Diabetes Mellitus tipo 1A (1ADM) es un trastorno metabólico secundario a la destrucción autoinmune de las células beta pancreáticas e insulitis. La miastenia grave (MG) es una enfermedad autoinmune causada por el bloqueo postsináptico de la placa mioneural por AAcs contra los receptores de acetilcolina (ACRA) o contra moléculas de la membrana postsináptica. La asociación entre DM1A y MG se puede observar en el síndrome poliglandular tipo III, caracterizado por enfermedad autoinmune de la glándula tiroides asociada con otras entidades autoinmunes. Método: Reporte de Casos, cuatro pacientes entre 7-19 años, con asociación de MG y DM1A atendidos en el Hospital Garrahan. Conclusión: La Tiroiditis de Hashimoto y la Enfermedad Celíaca son las enfermedades autoinmunes relacionadas más frecuentemente con DM1A en nuestra población. La bibliografía describe la asociación de MG y Tiroiditis de Hashimoto y su coexistencia con DM1A se describe en el Síndrome Poliglandular III. En este trabajo presentamos 4 casos de DM1A asociado con MG fuera de dicho síndrome (AU)

Introduction: The development of immune tolerance to autoantibodies (AAbs) is referred to as self-tolerance. Type 1A Diabetes Mellitus (1ADM) is a metabolic disorder secondary to autoimmune destruction of pancreatic beta cells and insulitis. Myasthenia gravis (MG) is an autoimmune disease caused by postsynaptic blockade of the myoneural plate by AAbs against acetylcholine receptors (Acra) or against postsynaptic membrane molecules. The association between 1ADM and MG may be observed in polyglandular syndrome type III, characterized by autoimmune disease of the thyroid associated with other autoimmune conditions. Methods: Case report; four patients between 7-19 years old, with an association of MG and 1ADM seen at the Garrahan Hospital. Conclusion: Hashimoto's thyroiditis and celiac disease are autoimmune diseases most frequently related to 1ADM in our population. In the literature, the association of MG and Hashimoto's thyroiditis has been described and its coexistence with 1ADM is reported in polyglandular syndrome III. In this study we present 4 cases of 1ADM associated with MG unrelated to this syndrome. (AU)

Diabetes-related-distress and its relationship with glycaemic control among type 2 diabetes mellitus patients attending a specialty clinic in Lagos, Nigeria

Diabetes Mellitus (DM) is a chronic metabolic disease with various complications throughout its course. The presence of emotional burden in diabetes disease, which is referred to as diabetes-related distress (DRD) is common among such patients and may affect their response to treatment. Objectives: To assess the relationship of diabetes-related distress and glycaemic control among patients with Type 2 Diabetes mellitus. Methods: This hospital-based cross-sectional study was conducted at the Family Medicine Department of LASUTH, Ikeja, Lagos. A total of 317 patients with Type 2 Diabetes mellitus were systematically recruited. The data were collected over a four-month period. Important clinical information including clinical characteristics and diabetes-related distress using the diabetes distress scale (DDS-17) was collected. Glycosylated haemoglobin (HbA1c) was also assessed. Results: The degrees of DRD were as follows: 54.9% (None/little), 40.1% (moderate) and 5.0% (severe). The mean HbA1c estimate for all participants was 7.83±1.8%. Among the 317 study participants, 67.2% had poor glycaemic control while 32.8% had good glycaemic control. There was a statistically significant association between DRD and glycaemic control (p< 0.001). Likewise, the various domains of DRD had statistically significant associations with glycaemic control with the exception of physician-related domain. Participants with better glycaemic control reported lower levels of DRD than participants with poorer glycaemic control. Conclusion: There is a high level of diabetes-related distress patients with diabetes mellitus. Good glycaemic control is important in improving or preventing DRD. Therefore, T2DM patients should be screened for DRD during their treatment.

Clinical features and genetic analysis of a child with late-onset immune dysregulation, polyendocrinopathy, enteropathy, X-Linked syndrome / 中华医学遗传学杂志

OBJECTIVE@#To report on the clinical features and result of genetic testing for a child featuring immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.@*METHODS@#Clinical records, genetic testing, laboratory investigation and treatment of the child were summarized in addition with a comprehensive review of the literature.@*RESULTS@#The 3-year-old boy was administered due to intractable diarrhea, recurrent infections, liver dysfunction and failure to thrive, though no diabetes or skin disorder was observed. Laboratory testing showed elevated liver enzymes and total IgE, decreased albumin and electrolyte imbalance. Gastrointestinal endoscopy revealed erosion and granules in the duodenum, and edema in the terminal ileum and colon. Biopsies showed villous atrophy in the duodenum and terminal ileum. Genetic testing revealed that the patient has carried a missense c.1087A>G (p.I363V) variant in the exon 10 of the FOXP3 gene. He was treated with enteral and parenteral nutrition, anti infection and Sirolimus, and was waiting for hemopoietic stem cell transplantation.@*CONCLUSION@#Although IPEX syndrome usually occur during infancy, it should not be ruled out solely based on the age, and its presentation can be variable. For male children with refractory diarrhea, autoimmune disorder and growth retardation, the diagnosis should be suspected and confirmed by genetic testing.

Endocrinopatía múltiple autoinmune autoinmune / Autoimmune polyendocrinopathy

Los autoanticuerpos son proteínas producidas en el organismo por la inducción de un antígeno propio del individuo el cual no reconocen y rechazan. Su aparición en sangre puede iniciarse tiempo antes de la presentación de síntomas o signos. El deterioro funcional de dos o más glándulas es una afectación endocrinológica múltiple que puede asociarse con otras patologías autoinmunes no endocrinas, tales como vitiligo, alopecia areata, gastritis autoinmune y anemia perniciosa. Se clasifica en tres síndromes poliendocrinos autoinmunes (SPA). En Europa la incidencia del tipo I es menor a 1:100000 por año y los 2 y 3 varían entre 1­2:100000 por año. Colombia no cuenta con registros que permitan calcularla. Se reporta el caso de un hombre de 18 años diagnosticado con hipotiroidismo autoinmune, a los 15 años de edad debutó con cetoacidosis diabética y a los 17 con posterior aparición de vitiligo. El manejo inicial se realizó con levotiroxina sódica y análogos de insulina. Este caso corresponde a un SPA tipo IIIA, ya que cursa con hipotiroidismo autoinmune, diabetes mellitus y como último hallazgo cronológico la asociación con vitiligo. La detección de una endocrinopatía autoinmune en pacientes jóvenes debe alertar sobre la posible existencia de un SPA

Autoantibodies are blood proteins produced in response to and counteracting a specific antigen. Autoantibodies may be present before signs and symptoms occur. A polyendocrinopathy is characterized by the coexistence of at least two endocrine glands insufficiency and may be associated with another non-endocrine autoimmune illness including vitiligo, alopecia areata, autoimmune gastritis and pernicious anemia. It is classified into three types of autoimmune polyglandular syndromes (APS). In Europe the incidence of APS-1 is less than one new case per 100000 persons per year and the incidence of the other two APS types vary between1 to 2 new cases per 100000 persons per year. APS incidence in Colombia cannot be estimated due to lack of records on this subject. We report the case of an 18-year-old male with autoimmune hypothyroidism diagnosed at 15 years of age, with onset of diabetic ketoacidosis at 17 followed by vitiligo. Therapy with levothyroxine 100 mcg daily and insulin glargine 10 units daily did not yield successful correction of APS in the patient. This patient was affected by APS- IIIA, characterized by the association of autoimmune hypothyroidism, diabetes mellitus and vitiligo, as the last manifestation. Detecting an autoimmune polyendocrinopathy in young patients should raise the suspicion of APS.

Autoimmune Polyglandular Syndrome type 2

SUMMARY Autoimmune polyglandular syndrome type 2 (APS 2) is defined by the presence of Addison's disease (AD) associated with autoimmune thyroid disease and/or Type 1 diabetes mellitus (T1DM). It is a rare disease, affecting about 1.4-2 cases/100,000 inhabitants. Its less frequent clinical presentation is the combination of AD, Graves' disease, and T1DM. We present the case of a 42-year-old woman with a history of total thyroidectomy due to Graves' disease, type 2 diabetes mellitus, and hypertension, who sought the ED due to asthenia, dizziness, nausea, and vomiting. She reported having stopped antihypertensive therapy due to hypotension and presented a glycemic record with frequent hypoglycemia. On physical examination, she had cutaneous hyperpigmentation. She had no leukocytosis, anemia, hypoglycemia, hyponatremia or hyperkalemia, and a negative PCR. Serum cortisol <0.5 ug/dl (4,3-22,4), urine free cortisol 9 ug/24h (28-214), ACTH 1384 pg/mL (4,7-48,8), aldosterone and renin in erect position of 0 pg/ml (41-323) and 430.7 uUI/ml (4.4-46.1) respectively. Quantiferon TB was negative; computerized axial tomography of the adrenals showed no infiltrations, hemorrhage, or masses. The 21-hydroxylase antibody assay was positive. B12 vitamin was normal, anti-GAD antibodies were positive, anti-insulin, anti-IA2, and anti-transglutaminase antibodies were all negative. The patient started insulin therapy and treatment for AD with prednisolone and fludrocortisone with good clinical response. This case aims to alert to the need for high clinical suspicion in the diagnosis of AD. Since this is a rare autoimmune disease, it is important to screen for other autoimmune diseases in order to exclude APS.

RESUMO A síndrome poliglandular autoimune tipo 2 (SPGA2) é definida pela presença de doença de Addison (DA) associada à doença tiroideia autoimune e/ou diabetes mellitus tipo 1 (DMT1). Trata-se de uma doença rara, afetando cerca de 1,4-2 casos/100.000 habitantes. A apresentação clínica menos frequente é a combinação de DA, doença de Graves e DMT1. Apresenta-se mulher de 42 anos, com antecedentes de tiroidectomia total por doença de Graves, diabetes mellitus tipo 2 e hipertensão, que recorre ao SU por quadro arrastado de astenia, emagrecimento, tonturas, náuseas e vômitos. Referia ter suspendido terapêutica anti-hipertensora por hipotensão e apresentava registro glicêmico com hipoglicemias frequentes. Ao exame físico, salientava hiperpigmentação cutânea. Analiticamente sem leucocitose, anemia, hipoglicemia, hiponatremia ou hipercaliemia, PCR negativa. Cortisol sérico matinal <0,5 ug/dl (4,3-22,4), cortisol livre na urina 9 ug/24h (28-214), ACTH 1.384 pg/mL (4,7-48,8), aldosterona e renina em posição ereta de 0 pg/mL (41-323) e 430,7 uUI/mL (4,4-46,1), respectivamente. Realizado estudo complementar para averiguar causa de insuficiência suprarrenal primária. Quantiferon TB negativo, tomografia axial computadorizada das suprarrenais sem infiltrações, hemorragia ou massas. Anticorpos anti-21-hidroxilase positivos. Foi aprofundada a investigação com vitamina B12 normal, anti-GAD positivo, anti-insulina, anti-IA2, antitransglutaminase, negativos. Nesse contexto, a doente iniciou insulinoterapia e tratamento dirigido para a DA com prednisolona e fludrocortisona, com boa resposta clínica. Este caso tem como objetivo alertar para a necessidade de elevada suspeição clínica no diagnóstico de DA. Sendo esta uma doença autoimune rara, é importante rastrear outras doenças autoimunes no sentido de excluir SPGA.

A novel compound heterozygous mutation of the AIRE gene in a patient with autoimmune polyendocrine syndrome type 1

Autoimmune polyendocrine syndrome type 1 (APS-1), or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare, autosomal recessive autoimmune disease caused by a mutation of the autoimmune regulator (AIRE) gene. The main symptom triad in APS-1 comprises chronic mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism. Various autoimmune diseases and ectodermal abnormalities are also commonly associated with the syndrome. The treatment of APS-1 includes hormone replacement and symptom control. It is important to monitor such patients for clinical manifestations of their disease through regular follow-up. We report the case of a 10-year-old Korean girl with APS-1 due to a novel compound heterozygous mutation of the AIRE gene. This patient's main clinical manifestations were adrenal insufficiency and chronic mucocutaneous candidiasis. The patient had a previously known pathogenic variant of c.1513delG (p.Ala505ProfsTer16), and a newly discovered variant of c.1360dupC (p.His454ProfsTer50).

Hipofisitis linfoplasmocitaria y fibrosis retroperitoneal asociadas a un síndrome poliglandular autoinmune: enfermedades relacionadas con IgG4. Caso clínico / Hypophysitis and retroperitoneal fibrosis associated with autoimmune polyglandular syndrome and IgG4-related disease: report of one case

We report a 23 year old woman presenting with a nephrotic syndrome due to minimal change disease, central diabetes insipidus, primary hypothyroidism, vitiligo and universal alopecia. Eleven years later, she presented secondary amenorrhea due to hypogonadotropic hypogonadism, with mild hyperprolactinemia and central adrenal insufficiency. A magnetic resonance imaging of the sella turcica showed a pituitary mass with suprasellar extension that was resected using a transsphenoidal approach. Pathology confirmed the presence of a lymphoplasmacytic hypophysitis. She needed a second surgical resection due to mass growth and neuro-ophthalmologic impairment. One year later, systemic lupus erythematosus, arterial hypertension and type 2 diabetes mellitus were diagnosed. Two years later, due to back pain, constipation and renal failure, retroperitoneal fibrosis was found, satisfactorily treated with glucocorticoids and colchicine. Hence, this clinical vignette shows the coexistence of autoimmune polyglandular syndrome with retroperitoneal fibrosis and lymphoplasmacytic hypophysitis. Tissue analysis showed the presence of IgG4 producing plasma cells in the pituitary and retroperitoneum, which constitute a basis for the diagnosis of IgG4 related disease.

Primary amenorrhea associated with hyperprolactinemia in polyglandular autoimmune syndrome type II: A case report / Amenorreia primária associada com hiperprolactinemia em síndrome poliglandular autoimune tipo 2: relato de caso

Abstract Polyglandular autoimmune syndrome type II (PGA-II) is a rare immunoendocrinopathy syndrome characterized by the occurrence of autoimmune Addison disease along with diabetes mellitus type 1 and/or autoimmune thyroid disease. Here, we report the case of a 23-year-old female with PGA-II who was followed up at the dermatology and endocrinology clinics of the Universidade Federal do Triângulo Mineiro, located in the state of Minas Gerais, Brazil. First, the patient presented diffuse skin hyperpigmentation, vitiligo; and in sequence, due to vomiting, appetite and weight loss, hypoglycemia, amenorrhea, and galactorrhea, the patient was then diagnosed with PGA-II. The patient also presented intense hyperprolactinemia due to primary hypothyroidism. The late diagnosis of PGA-II is frequent because the disorder is uncommon and has non-specific clinical manifestations. This report emphasizes the significance of a timely diagnosis and appropriate treatment to reduce morbidity and mortality associated with these diseases, especially Addison disease. The present study reports a rare case of a patient with PGA-II with primary amenorrhea associated with hyperprolactinemia.

Resumo A síndrome poliglandular autoimune tipo 2 (SPGA-2) é uma síndrome de imunoendocrinopatia rara caracterizada por doença de Addison autoimune associada à diabetes mellitus tipo 1 e/ou doenças tireoidianas autoimunes. Relatamos aqui o caso de uma paciente de 23 anos de idade com SPGA-2 que foi acompanhada nos ambulatórios de dermatologia e endocrinologia da Universidade Federal do Triângulo Mineiro, localizada no estado de Minas Gerais, Brasil. Primeiramente, a paciente apresentou hiperpigmentação cutânea difusa e vitiligo; posteriormente, por apresentar vômitos, hiporexia, perda ponderal, hipoglicemia, amenorreia e galactorreia, foi diagnosticada com SPGA-2. A paciente apresentou também intensa hiperprolactinemia secundária apenas ao hipotireoidismo primário. É comum o diagnóstico tardio da SPGA-2, pois a doença é rara e apresenta manifestações clínicas inespecíficas. Este relato de caso enfatiza a importância do diagnóstico e tratamento precoces como objetivo de reduzir a morbimortalidade associada a essas doenças, especialmente à doença de Addison. O presente estudo descreve um caso raro de uma paciente com SPGA-2 com amenorreia primária associada a hiperprolactinemia.

Síndrome poliglandular autoinmune tipo iii c: reporte de caso / Autoimmune polyglandular syndrome type iiic: case report

El síndrome poliglandular autoinmune comprende un grupo de enfermedades autoinmunes de las glándulas endócrinas, y que afecta órganos no endócrinos, puede ser de tipo I, II y III. Paciente masculino de 26 años presenta palpitaciones, debilidad, y disnea de esfuerzos de 2 meses de evolución. Al examen físico, índice de masa corporal 29,6 kg/m², obesidad central, con acromía en cara, axilas y cuello. Los estudios muestran TSH 0,01 uUl/ml,T4 libre 3,67 ng/dl, antitiroperoxidasa 505,70 Ul/ml, insulina en ayunas 32,77 U/l, y a las 2 horas 77 U/l, glicemia en ayunas 101 mg/dl, curva tolerancia oral a la glucosa a las 2 horas de 140 mg/dl. La ecografía tiroidea revela bocio multinodular. Diagnósticos: tiroiditis autoinmune, vitíligo, prediabetes, sobrepeso. Manejo con metimazol 5 mg c/12 h, y metformina 850 mg en la noche. El paciente baja de peso y la glicemia mejora. El diagnóstico definitivo fue Tiroiditis autoinmune y vitíligo compatible con síndrome poliglandular tipo IIIC.

Autoimmune Polyglandular Syndrome comprises a group of autoimmune diseases of the endocrine glands, and affecting non-endocrine organs, there are type I, II and III. Male patient, aged 26 years old has palpitations, weakness, and exertional dyspnea for 2 months. The physical examination found body mass index 29,6 kg/m², central obesity, with acromia on face, armpits and neck. Studies show TSH 0,01 uUl/ml, freeT4 3,67 ng/dl, antithyroperoxidase 505,70 U/ml, fasting insulin 32,77 U/l, after 2 hours 77 U/l, fasting glycemia 101 mg/dl, glucose tolerance at 2 hours 140 mg/dl. Thyroid ultrasound reveals multinodular goiter. Diagnoses: autoimmune thyroiditis, vitiligo, prediabetes, overweight. It prescribed metimazole 5 mg every 12 hours, and metformin 850 mg at night. Patient with weight reduction and glucose improvement. Definitive diagnoses patient with autoimmune thyroiditis and vitiligo, compatible with polyglandular syndrome type IIIC.

Síndrome de desregulação imune, poliendocrinopatia e enteropatia ligada ao X (IPEX): a importância da história familiar para o diagnóstico precoce / Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: the importance of family history for early diagnosis

A síndrome de desregulação imune, poliendocrinopatia e enteropatia ligada ao X (IPEX) é uma síndrome de imunodeficiência primária rara, de herança recessiva, que afeta lactentes do sexo masculino. A doença cursa com enteropatia perdedora de proteínas, dermatite eczematosa e poliendocrinopatias, podendo ser fatal naqueles sem tratamento apropriado. O objetivo deste relato é descrever um caso de IPEX, enfatizando a importância da história familiar para o diagnóstico precoce. O caso descreve um lactente com tipo grave da síndrome, com apresentação clínica precoce e história familiar característica, com episódios de morte prematura em doze homens pertencentes à linhagem materna. O diagnóstico por mapeamento genético demostrando mutação no gene FOXP3 foi obtido após o óbito do paciente, decorrente de choque séptico. O transplante de células-tronco hematopoiéticas é o melhor tratamento disponível, e na sua ausência, a síndrome IPEX pode ser fatal nos primeiros dois anos de vida. Assim, assegurar um diagnóstico precoce é fundamental.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare recessive primary immunodeficiency syndrome that affects male infants. The disease course is characterized by protein-losing enteropathy, eczematous dermatitis, and polyendocrinopathies, and may be fatal if not appropriately treated. The aim of this report was to describe a case of IPEX, emphasizing the importance of family history for early diagnosis. The case describes an infant with a severe manifestation of the syndrome, with early clinical presentation and characteristic family history, with episodes of premature death affecting 12 men belonging to the mother's lineage. Diagnosis was established by genetic mapping after the patient's death due to septic shock; a mutation in the FOXP3 gene was found. Hematopoietic stem cell transplantation is the best treatment available; in its absence, the IPEX syndrome can be fatal in the first 2 years of life. Therefore, ensuring early diagnosis is critical.

Gastritis autoinmunitaria. Abordaje diagnóstico y su relación con los síndromes poliglandulares autoinmunitarios / Autoimmune gastritis. Diagnostic approach and its relationship with autoimmune polyglandular syndromes

La gastritis autoinmunitaria (GAI) es una entidad subdiagnosticada; la mayoría de veces pasa inadvertida con graves consecuencias para la calidad de vida de la persona por sus complicaciones asociadas. Forma, además, parte de un grupo de trastornos autoinmunitarios conocidos como síndromes poliglandulares autoinmunitarios. Hace muchos años la GAI era un trastorno solitario; sin embargo, la reciente asociación con el Helicobacter pylori (HP) ha generado nuevo interés diagnóstico, manejo e incluso prevención de su desarrollo si se sospecha oportunamente. (AU)

Autoimmune gastritis (GAI) is an underdiagnosed entity, most often goes unnoticed with serious consequences on quality of life of the person by their associated complications. It is also part of disorders known as autoimmune polyglandular syndromes. Many years ago the GAI was a lonely disorder, however, the recent association with Helicobacter pylori (HP) has generated new interest in the diagnosis, management and even prevention when clinical suspicion exist. (AU)

Hipoparatiroidismo primario de presentación tardía asociado a patologías autoinmunes / Late onset primary hypoparathyroidism associated with autoimmune disorders

Se presenta una paciente que, en la sexta década de su vida, debuta con episodios de espasmo carpopedal espontáneo. Los valores bajos de calcemia (6,1 mg/dl) y de PTH (8 pg/ml) confirmaron el diagnóstico de hipoparatiroidismo. No había sido sometida a cirugías de cuello ni radioterapia. No existían antecedentes familiares vinculantes. Durante 11 años de seguimiento, la paciente presenta asociación con otras patologías que permiten sospechar la etiología autoinmune del hipoparatiroidismo: candidiasis de piel y uñas, hipotiroidismo por tiroiditis de Hashimoto, penfigoide y psoriasis. Finalmente fallece por una neumonía adquirida en la comunidad, complicada. (AU)

A patient who develops hypoparathyroidism during her sixth decade of life is reported. It was detected due to spontaneous carpopedal spasms. Low calcium (6.1 mg/dl) and PTH (8 pg/ml) levels confirmed the diagnosis. She had not undergone neck surgery or irradiation. There was no relevant family history. Throughout the 11 years follow up she presented association of other pathologies that allow the suspicion of autoimmune etiology of hypoparathyroidism: candidiasis of skin and nails, autoimmune thyroiditis, pemphigoid and psoriasis. She eventually died of complicated community-acquired pneumonia. (AU)

Clinical analysis and autoimmune regulator gene mutation of autoimmune polyendocrinopathy syndrome type I in a family: a report of one case / 中国当代儿科杂志

The clinical data of one patient with autoimmune polyendocrinopathy syndrome type I were collected. PCR-DNA direct bidirectional sequencing was applied for mutation screening of 14 exons in autoimmune regulator (AIRE) gene in the patient and her parents. A total of 50 unrelated healthy controls were selected and tested. The bioinformatic methods were used to predict the possible impact of the mutations on the structure and function of the AIRE protein. The results of sequencing showed that heterozygous mutation c.622G>T (p.G208W) in exon 5 of the AIRE gene was detected in the patient and was a novel mutation, which had not been reported in the HGMD database and latest articles. This mutation was not detected in the 50 unrelated normal controls. The novel mutation of c.622G>T (p.G208W) in AIRE gene might play an important role in the pathogenesis of this case of autoimmune polyendocrinopathy syndrome type I.

Enfermedades autoinmunitarias asociadas a diabetes mellitus tipo 1A / Autoimmune diseases in type 1A diabetes mellitus

Type 1A diabetes (DM1A) is an autoimmune disease that comprises 10% of patients with diabetes mellitus. Its frequency is gradually increasing in countries like Mexico. Patients with DM1A commonly have hypothyroidism, Addison disease, celiac disease and less common diseases such as polyglandular syndrome. These diseases are related to susceptibility genes such as HLA, CTLA-4 and PTPN22, which induce central and peripheral immunologic tolerance. This review article emphasizes the importance of searching other autoimmune diseases in patients with DM1A, to improve their prognosis and quality of life.

Seasonal variation of haemoglobin A1c in a Portuguese adult population

Objective Haemoglobin A1c (Hb A1c) is routinely used for monitoring glycemic control in patients with diabetes. Hb A1c seasonal fluctuations can be directly related to different biological, geographical and cultural influences. Our purpose was to evaluate seasonal variation of Hb A1c in a hospital-based adult population over a period of 5 years.Materials and methods We analyzed retrospectively monthly Hb A1c mean values (DCCT, %) based on all the assays performed to adult patients at a tertiary care university Portuguese hospital between 2008-2012.Results We obtained 62,384 Hb A1c valid measurements, with a peak level found in January-February (7.1%), a trough in August-October (6.8%) and an average peak-to-trough amplitude value of 0.3%. This trend was observed in both genders and age subgroups evaluated.Conclusions There is a Hb A1c circannual seasonal pattern with peak levels occurring in winter months in this Portuguese population. This finding should be recognized in daily clinical practice to warrant better clinical and epidemiological interpretation of Hb A1c values. Arch Endocrinol Metab. 2015;59(3):231-5.

Psoriasis in autoimmune polyendocrine syndrome type I: A possible complication or a non-endocrine minor component.

Introduction: Autoimmune polyendocrine syndrome type I (APS I) is an autosomal recessive systemic autoimmune disorder, affecting primarily endocrine glands, in which chronic mucocutaneous candidiasis is an early and prominent manifestation. We describe the rare occurrence of unstable psoriasis (with onset of pustular lesions) in a case of APS I without mucocutaneous candidiasis. A patient presenting with unstable psoriasis (with onset of pustular lesions) was detected to have persistent hypocalcemia which led to the diagnosis of hypoparathyroidism. Subsequently he was found to have hypergonadotrophic hypogonadism, primary adrenal insuffi ciency (compensated), and coeliac disease, thus confi rming the diagnosis of APS I. Psoriasis is very rarely reported in APS I, possibly due to the protective effect of antibodies to Th17 cytokines, which are responsible for the occurrence of candidiasis in this syndrome. However, psoriasis could occur in APS I patients without mucocutaneous candidiasis, who lack these antibodies. In our patient, possible factors aggravating psoriasis include hypocalcemia due to hypoparathyroidism as well as coeliac disease via anti-tissue transglutaminase antibodies. However, defi ning psoriasis as a possible minor component of APS I would require further studies of the autoimmune regulator (AIRE) gene functions.

Adult-onset generalized autoimmune enteropathy involving small intestine and colon: report of a case and review of literature / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features of adult-onset autoimmune enteropathy (AIE).</p><p><b>METHODS</b>A case of adult-onset AIE was described along with a literature review.</p><p><b>RESULTS</b>A 41-year-old male patient was admitted for intractable diarrhea for more than three months despite of any dietary restriction or anti-inflammatory therapy. Fat globule was observed by stool examination and Sudan III staining of the stool was positive. Enteroclysis showed weak movement and few plica of small intestine, while colonoscopy appeared normal. Small bowel biopsies revealed villus atrophy and increased crypt apoptotic bodies and lymphocytic infiltration in deep crypt. Although without significant surface intro-epithelial lymphocytosis, there were a large number of monocytes, lymphocytes, plasmacytes and neutrophilic granulocytes infiltrating in the lamina propria. Morphologically, the colonic mucous was similar to the small intestine although cryptitis and crypt abscess were significant in the former. Serum IgG anti-goblet cell antibody was demonstrated by indirect immunofluorescence. Other causes of diarrhea were excluded on the base of medical history, histopathology and other accessory examinations before the diagnosis of AIE was made. The patient had a complete remission after steroid treatment without recurrence for eight months during the follow-up even after steroid withdrawal for five months.</p><p><b>CONCLUSIONS</b>AIE is exceedingly rare and timely diagnosis is important for successful therapy. Histological differential diagnoses should include ulcerative colitis, celiac disease, lymphocytic colitis, etc. The final diagnosis should be based on histological examination combined with the patient history, clinical manifestation, endoscopy finding and serological testing.</p>

Polineuropatia hipotireóidea em um paciente com síndrome poliglandular autoimune tipo 2: relato de caso / Hypothyroid polyneuropathy in a patient with autoimmune polyglandular syndrome type 2: case report

A incidência de polineuropatia em indivíduos com hipotireoidismo não é precisamente conhecida, mas alguns estudos relatam que cerca de 25% a 42% dos pacientes podem apresentar sinais clínicos neuropáticos. A seguir, relataremos um caso de síndrome poliglandular autoimune tipo 2 (SPA-2), cuja apresentação inicial foi uma polineuropatia hipotireóidea. Homem de 41 anos com queixas de parestesias e fraqueza lentamente progressiva acometendo os quatro membros associadas a sonolência frequente, astenia, intolerância ao frio, vertigens, náuseas e avidez por sal. O exame físico geral evidenciava hiperpigmentação de pele e mucosas, além de hipotensão. O exame neurológico demonstrou apenas hiporreflexia profunda global e simétrica com discretos sinais de hipoestesia superficial em extremidades dos membros. O estudo eletroneuromiográfico (ENMG), juntamente com a avaliação laboratorial, confirmou a suspeita de tireoidite de Hashimoto associada à doença de Addison, caracterizando o quadro de SPA-2. O paciente foi tratado com fludrocortisona 0,05 mg/dia e levotiroxina 100 mcg/dia e apresentou resolução gradual e completa das queixas e das alterações encontradas nos exames físico geral e neurológico. O ENMG, repetido após seis meses, evidenciou resolução completa do quadro neuropático. Este relato mostra um caso raro de SPA-2 apresentando-se como uma polineuropatia hipotireóidea e reforça a relevância da dosagem de hormônios tireoideanos em síndromes polineuropáticas. A reposição de levotiroxina mostrou-se efetiva em reverter o quadro clínico e eletrofisiológico da neuropatia. .

The incidence of polyneuropathy in patients with hypothyroidism is not precisely known, but some studies report that about 25% to 42% of patients may show neuropathic clinical signs. We report a case of autoimmune poliglandular syndrome type 2 (APS-2), whose initial presentation was hypothyroid polyneuropathy. A 41-year-old man complained of slowly progressive paresthesias and weakness affecting all four limbs, and associated with frequent drowsiness, weakness, cold intolerance, dizziness, nausea, and craving for salt. General physical examination showed hyperpigmentation of skin and mucous membranes, and hypotension. Neurological examination showed global, deep, and symmetrical hyporeflexia with slight signs of superficial hypoesthesia in the limbs. Electrodiagnostic studies (ENMG) together with laboratory tests, confirmed the suspicion of Hashimoto’s thyroiditis associated with Addison’s disease featuring the picture of APS-2. The patient was treated with fludrocortisone 0.05 mg/day and levothyroxine 100 mcg/day, and showed gradual and complete resolution of complaints. Changes were found in general physical and neurological examinations. ENMG repeated six months later showed complete resolution of neuropathy. This report shows a rare case of APS-2 presented as polyneuropathy hypothyroidism, and reinforces the importance of dosing thyroid hormone in polyneuropathy syndromes. Levothyroxine replacement was shown to be effective in reversing clinical and electrophysiologic neuropathy.

Glutamine-Supplemented Parenteral Nutrition and Probiotics in Four Adult Autoimmune Enteropathy Patients

To evaluate the effects of glutamine-supplemented parenteral nutrition (PN) and probiotics in adult autoimmune enteropathy (AIE) patients. Four adult AIE patients were identified from April 2006 to January 2012. Clinical and nutritional data were obtained from the patients' medical records. Glutamine-supplemented PN started immediately when the AIE diagnosis was confirmed. The total PN duration was 351 days. According to the PN prescription, the average caloric intake ranged from 20 to 25 kcal/kg/day, and the protein intake ranged from 1.2 to 1.5 g/kg/day. Alanyl-glutamine (20 g/day) was administered to AIE patients for 4 weeks followed by a 2-week break, and this treatment schedule was repeated when PN lasted for more than 6 weeks. Body weight gain and an increased serum albumin level were achieved after PN, and defecation frequency and quality also improved. Each patient received oral supplements, 250 mL of Ensure and two probiotics capsules (each capsule containing 0.5x10(8) colonies) three times a day when enteral nutrition started. Three AIE patients were successfully weaned off PN, and one patient died of pneumonia. Glutamine-supplemented PN and probiotics show promise in managing patients with AIE and related malnutrition.