Diagnosed with primary adrenal insufficiency? search adrenoleukodystrophy-two brothers presented with similar phenotype

X-linked adrenoleukodystrophy (X-ALD) is a genetic disease with a variety of phenotypic expression. This is the first case report of X-AMN/ALD in two brothers in Bangladesh confirmed by raised VLCFA. Our index patient of 19 years presented on 2014 with adrenal insufficiency, after one year developed progressive spastic paraparesis along with cognitive declination and behavioral abnormality. His only brother was clinically asymptomatic at presentation with Addison’s disease and extensor planter reflexes. After three years of follow up, index patient became bed bound with slurred speech, urinary urge incontinence and his brother developed spastic paraparesis with cognitive impairment. None had gonadal impairment. Follow up MRI after three years revealed lesion in brainstem in both along with atrophy of thoracic segment of spinal cord in index patient and cerebellum, internal capsule involvement in his brother. Both were of pure AMN variety but due to presence of cognitive impairment and behavioral abnormality they can be categorized as cerebral variety of AMN. On 2023, our index patient is still surviving with major functional disability and his brother died on 2019, 5 years of initial diagnosis.

Síndromes poliglandulares autoimunes: uma revisão geral em busca novas evidências / Autoimmune polyglandular syndromes: a general review in search of new evidence / Síndromes poliglandulares autoinmunes: una visión general de la búsqueda de nuevas evidencias

As Síndromes Poliglandulares Autoimunes (SPA) são consideradas endocrinopatias raras em que ocorrem alterações autoimunes nas glândulas endócrinas, acompanhadas de outras doenças não endócrinas. Tendo em vista a complexidade de associações em cada subtipo, suas particularidades e gênese dos mecanismos envolvidos, este artigo busca, através de uma meta-analise, equacionar seus aspectos descritivos mais atuais e importantes para a prática clínica. As SPA podem ser classificadas nos tipos I, II, III e IV de acordo com a idade de início e os órgãos afetados. Interações complexas entre fatores genéticos, epigenéticos e ambientais provavelmente contribuem para o desenvolvimento dessas síndromes, que idealmente devem ser diagnosticadas em estágios iniciais, dada a sua alta morbidade e mortalidade. O tratamento adequado de cada uma das alterações é essencial para preservar a qualidade de vida dos pacientes.

Autoimmune Polyglandular Syndromes (APS) are considered rare endocrinopathies characterized by autoimmune alterations in the endocrine glands, accompanied by other non-endocrine diseases. Bearing in mind the complexity of associations in each subtype, its particularities and the genesis of the mechanisms involved, this article seeks, through meta-analysis, to equate its most current and important descriptive aspects for clinical practice. APS can be classified into types I, II, III and IV according to age of onset and affected organs. Complex interactions between genetic, epigenetic, and environmental factors likely contribute to the development of these syndromes, which ideally should be diagnosed at an early stage, given their high morbidity and mortality. Appropriate treatment of each of the alterations is essential to preserve the quality of life of patients.

Los Síndromes Polilandulares Autoinmunes (SPA) se consideran endocrinopatías raras en las que se producen cambios autoinmunes en las glándulas endocrinas, acompañadas de otras enfermedades no endocrinas. En vista de la complejidad de las asociaciones en cada subtipo, sus particularidades y la génesis de los mecanismos involucrados, este artículo busca, a través de un metaanálisis, considerar sus aspectos descriptivos más actualizados e importantes para la práctica clínica. Las ZEPA podrán clasificarse en los tipos I, II, III y IV según la edad de inicio y los órganos afectados. Las complejas interacciones entre los factores genéticos, epigenéticos y ambientales probablemente contribuyan al desarrollo de estos síndromes, que idealmente deberían ser diagnosticados en etapas tempranas, dada su alta morbilidad y mortalidad. El tratamiento adecuado de cada cambio es esencial para preservar la calidad de vida de los pacientes.

Identificación de manifestaciones tempranas de enfermedad de addison en consulta odontológica. reporte de caso / Identification of early manifestations of Addison's disease in dental practice. Case report

La enfermedad de Addison es un trastorno raro que afecta progresivamente a las glándulas suprarrenales. La etiología es variada siendo su principal causa autoinmune, el diagnóstico se obtiene mediante valores de laboratorio y exploración clínica. Se expone el caso de paciente femenino que en consulta presentó un evento sincopal, en la revisión clínica se observó pigmentación de mucosas orales y uñas de manos y pies; los valores de laboratorio mostraron: ACTH elevada, cortisol disminuido y alteraciones de electrolitos, confirmándose Enfermedad de Addison. Un diagnóstico oportuno evita complicaciones mortales en quien la padece.

Addison's disease is a rare disorder that progressively affects the adrenal glands. The etiology is varied, being its main autoimmune cause, the diagnosis is obtained through laboratory values and clinical examination. The case of a female patient who presented a syncopal event in the consultation is exposed. In the clinical review, pigmentation of the oral mucosa and fingernails and toenails was observed; Laboratory values showed: elevated ACTH, decreased cortisol and electrolyte disturbances, confirming Addison's disease. A timely diagnosis prevents fatal complications in those who suffer from it.

Insuficiencia suprarrenal aguda secundaria a hemorragia adrenal espontánea por síndrome antifosfolipídico: serie de casos / Acute secondary adrenal insufficiency due to spontaneous adrenal hemorrhage in antiphospholipid syndrome: a case series

En la insuficiencia suprarrenal (ISR) la destrucción progresiva del tejido adrenal conduce a la disminución de la secreción de corticoides suprarrenales de forma tal que, una vez instalada, el cuadro clínico reviste gravedad y, sin tratamiento, una elevada mortalidad. El síndrome antifosfolipídico (SAF) es una rara causa de la ISR. En virtud de esto, y de la escasez de la literatura disponible, se presentan dos casos de ISR asociada a SAF en un sanatorio privado de la ciudad de Santa Fe. Ambos se caracterizaron por ser del sexo femenino, tener diagnóstico previo de SAF y no presentar otros sitios de trombosis al momento de la consulta. La presentación como hemorragia suprarrenal y estar previamente en tratamiento anticoagulante constituyeron un desafío diagnóstico. Si bien la ISR es una enfermedad infrecuente, y más aún los casos asociados al SAF, la gravedad de la patología, así como la rapidez de su instalación, ameritan tener una elevada sospecha clínica cuando el cuadro sindrómico es orientador.

In adrenal insufficiency (AI), the progressive destruction of adrenal tissue leads to a decrease in the secretion of adrenal corticoids, such that once established, the clinical picture becomes severe, and without treatment, there is a high mortality rate. Antiphospholipid syndrome (APS) is a rare cause of AI. Given this and the scarcity of available literature, two cases of AI due to APS are presented in a private clinic in the city of Santa Fe, Argentina. Both cases were characterized by being female, having a previous diagnosis of APS, and not having other sites of thrombosis at the time of consultation. The manifestation as adrenal hemorrhage and the fact of being previously on anticoagulant therapy posed a diagnostic challenge. Although AI is an uncommon condition, and even more so when linked to APS, the severity of the pathology, as well as the rapidity of its onset, warrant a high clinical suspicion when the syndromic picture is suggestive.

El cumpleaños de la endocrinología: una revisión histórica / The birthday of endocrinology: a historical review

En esta revisión histórica se establece que nuestra especialidad tiene una fecha fundacional precisa, ­el 1 de junio de 1889­ y que su padre fundador fue el excéntrico fisiólogo mauriciano Charles-Édouard Brown-Séquard, en quien se encuentran ancestros irlandeses, indios y franceses. El paradigma sustitutivo, pilar fundacional de la especialidad, fue enunciado esa noche por Brown-Séquard: los déficits de las secreciones internas de las glándulas desprovistas de conducto pueden remediarse administrando extractos de las glándulas homólogas de animales. Brown-Séquard es un reconocido padre de la neurología y el síndrome producido por la hemisección de la médula espinal lleva su nombre. Su aporte más genial, sin embargo, es la fundación de nuestra especialidad. Relatamos cómo un neurofisiólogo llegó a fundar nuestra especialidad, siguiendo una idea que nace de su demostración que las suprarrenales son esenciales para la vida (1856). Luego ­en Inglaterra-, adhirió erróneamente a un mito victoriano absurdo: los varones que se abstenían voluntariamente de eyacular reabsorbían principios testiculares desconocidos aún, que les proporcionaban grandes beneficios de salud. Finalmente, su experiencia personal con la andropausia lo lleva a inyectarse extractos acuosos de testículos de cuy y de perro, reportando una milagrosa mejoría frente a la comunidad científica francesa, que rechazó sus conclusiones y lo acusó de ser un "profesor senil". Dos años más tarde, en 1891 Murray en Inglaterra curó a una mujer mixedematosa con extractos acuosos de tiroides de oveja, validando así la órgano-terapia. Treinta años más tarde ­en 1921­, Banting y Best en Toronto, aislaron la insulina y se inició la era insulínica en la diabetes. En 1923 este trabajo fue premiado con el Premio Nobel de Medicina. Si bien es cierto que los extractos testiculares de Brown-Séquard parecen no haber tenido testosterona, la maravillosa intuición de Brown-Séquard le permitió la enunciación del paradigma fundacional de la especialidad.

In this historical review, the precise birthdate of our specialty is remembered (June 1, 1889) and the figure of its founding father, the eccentric Mauritian physiologist, Dr. Charles-Édouard Brown-Séquard ­who had Irish, Indian, and French ancestors­, is highlighted. The substitutive paradigm, the foundational pillar of our specialty, was enunciated that night by Brown-Séquard: deficits in internal secretions from the ductless glands may be remediated by administering extracts from homologous animal glands. Brown-Séquard is one of the acknowledged fathers in the field of Neurology, and the syndrome produced by the hemisection of the spinalcord bears his name. However, his most genial achievement is the foundation of Endocrinology. We disclose how a neurophysiologist became the founding father of our specialty. Firstly, he demonstrated that the adrenal glands are essential to sustain life (1856). Later on, while working in London, he mistakenly accepted an absurd Victorian myth: disciplinary men who voluntarily refrained from ejaculation in any form resorbed testicular principles ­unknown by then­, endowing them with great health benefits. As he aged, he had a personal encounter with andropause and decided to inject himself with testicular aqueous extracts from animals. On June 1, 1889, Brown-Séquard reported his miraculous health improvements to the French Biology Society. The audience rejected his conclusions and accused him of being a "senile Professor". However, just two years after this episode, G. Murray in England reported the cure of a myxedematous woman with injections of aqueous extracts from sheep thyroids. Thirty years later, in1921, Banting and Best in Toronto isolated insulin and started the insulin era in diabetes therapy. In 1923 their work was awarded the Nobel Prize in Medicine. Even though the testicular aqueous extracts used by Brown-Séquard were probably devoid of testosterone, his marvelous imagination allowed him to enunciate the foundational paradigm of our specialty.

Diagnostico tomografico de tuberculosis adrenal primaria en enfermedad de Addison en la altitud. Reporte de caso / Diagnosis tomograph of primary adrenal tuberculosis in Addison's disease in high altitude. Case report

RESUMEN Reportamos el caso de un varón de 23 años, natural y residente de altitud, con hiperpigmentación. astenia, fatiga, náuseas, vómitos, pérdida de peso, dolor abdominal, hiporexia e hipotensión, con dosaje de cortisol disminuido y ACTH elevado. Radiografía de tórax normal, baciloscopia en esputo y en orina negativo, antígeno TB LAM negativo. En la tomografía computarizada de abdomen con contraste se visualiza incremento de dimensiones y pequeñas calcificaciones en ambas adrenales sugerentes de infiltración granulomatosa de tipo específico. En zonas endémicas de tuberculosis como en el Perú; ante la ausencia de la biopsia adrenal, se puede recurrir en forma precoz, como alternativa diagnóstica a la tomografía para descartar el compromiso adrenal. En conclusión, el presente reporte a descrito como la tomografía puede ser usado como un método diagnostico alternativo en hospitales donde no es factible realizar la biopsia en forma rápida.

ABSTRACT We report the case of a 23-year-old male, natural and resident of height, with hyperpigmentation. Asthenia, fatigue, nausea, vomiting, weight loss, abdominal pain, hiporexia and hypotension, with decreased cortisol dosage and elevated ACTH. Normal chest X-Ray, smear in sputum and negative urine. Negative TB-LAM Antigen. In contrasted abdomen computed tomography, an increase in dimensions and small calcifications is shown in both adrenals suggestive of specific type granulomatous infiltration. In endemic areas of tuberculosis as in Peru, in the absence of the adrenal biopsy, it can be used early, as a diagnostic alternative to the tomography to rule out the adrenal commitment. In conclusion, this report described as the tomography can be used as an alternative diagnostic method in hospitals where it is not feasible to perform the biopsy in a rapid manner.

Diagnóstico tomográfico tuberculosis adrenal y addison - altura / Tomographic Diagnosis Of Adrenal Tuberculosis And Addison - Height

Reportamos el caso de un varón de 23 años, natural y residente de la altura, con hiperpigmentación. astenia, fatiga, náuseas, vómitos, pérdida de peso, dolor abdominal, hiporexia e hipotensión, con dosaje de cortisol disminuido y ACTH elevado. Radiografía de tórax normal, baciloscopia en esputo y en orina negativo. Antígeno TB LAM negativo. En la tomografía computarizada de abdomen con contraste se visualiza incremento de dimensiones y pequeñas calcificaciones en ambas adrenales sugerentes de infiltración granulomatosa de tipo específico. En zonas endémicas de tuberculosis como en el Perú, ante la ausencia de la biopsia adrenal, se puede recurrir en forma precoz, como alternativa diagnóstica a la tomografía para descartar el compromiso adrenal. En conclusión, el presente reporte a descrito como la tomografía puede ser usado como un método diagnostico alternativo en hospitales donde no es factible realizar la biopsia en forma rápida.

We report the case of a 23-year-old male, natural and resident of height, with hyperpigmentation. Asthenia, fatigue, nausea, vomiting, weight loss, abdominal pain, hiporexia and hypotension, with decreased cortisol dosage and elevated ACTH. Normal chest X-Ray, smear in sputum and negative urine. Negative TB-LAM Antigen. In contrasted abdomen computed tomography, an increase in dimensions and small calcifications is shown in both adrenals suggestive of specific type granulomatous infiltration. In endemic areas of tuberculosis as in Peru, in the absence of the adrenal biopsy, it can be used early, as a diagnostic alternative to the tomography to rule out the adrenal commitment. In conclusion, this report described as the tomography can be used as an alternative diagnostic method in hospitals where it is not feasible to perform the biopsy in a rapid manner.

Infecção de trato urinário inferior por Citrobacter sp em cadela com hipoadrenocorticismo / Citrobacter sp lower urinary tract infection in a bitch with hypoadrenocorticism

Citrobacter sp. é um microrganismo frequentemente encontrado em vagina de cadelas, mas corresponde a menos de 3% do total de microrganismos isolados em urocultura. O hipoadrenocorticismo (HA) é uma doença endócrina incomum e que leva a poliúria e hipostenúria. O objetivo deste trabalho é relatar o caso de uma fêmea da espécie canina, da raça Teckel, 11 anos, atendida com queixa de urina de odor alterado há vários dias, além de vômito, diarreia e inapetência há três dias, e poliúria e polidipsia há 2 meses, com histórico de tratamento anterior com mitotano para hiperadrenocorticismo. O diagnóstico foi de ITU por Citrobacter sp., além de HA iatrogênico. Como destaques nos exames, relação sódio:potássio de 22,6 foi observada, sugestiva de HA, que foi confirmado por teste de estimulação com ACTH, além de urina inicialmente hipostenúrica (densidade 1,006), o que pode ser atribuído ao washout medular renal devido à hiponatremia causada pelo hipoadrenocorticismo. O tratamento foi feito com amoxicilina associada a ácido clavulânico por 20 dias, além da terapia específica para HA com prednisona e fludrocortisona, que foi continuado. A paciente recuperou-se bem, a densidade urinária aumentou após início do tratamento para HA e não houve recidiva da ITU em período de acompanhamento de 8 meses. Acredita-se que a baixa densidade urinária causada pelo HA tenha sido fator essencial para a oco

Citrobacter sp. is a normal constituent of bitches’ vagina, but it is related to less than 3% of total isolated microorganism in uroculture. Hypoadrenocorticism (HA) is an endocrine disease uncommonly diagnosed that leads to polyuria and hypostenuria. The aim of this work is report the case of a Teckel bitch, 11 years old, attended with complaint of altered urinary smell for several days, besides vomiting, diarrhea and inappetence for three days, and polyuria and polydispsia for two months, with previous mitotane treatment for hyperadrenocorticism. The diagnosis was Citrobacter UTI, besides iatrogenic HA. The most important exam results include sodium:potassium ratio of 22.6, suggestive of HA, that was confirmed by ACTH stimulation test. Besides, hypostenuria (urinary specific gravity – USG - of 1.006) was noted, attributed to renal medular washout due to hyponatremia seen in HA. Therapy comprised amoxicillin associated with clavulanic acid for 20 days, in addition to specific therapy for AH with prednisone and fludrocortisone. The patient recovery well, USG increased after the beginning of the treatment for HA and there was no UTI reinfection for a 8 month period. It is believed that low USG due to HA was essential for the occurrence of Citrobacter UTI.

Infecção de trato urinário inferior por Citrobacter sp em cadela com hipoadrenocorticismo / Citrobacter sp lower urinary tract infection in a bitch with hypoadrenocorticism

Citrobacter sp. é um microrganismo frequentemente encontrado em vagina de cadelas, mas corresponde a menos de 3% do total de microrganismos isolados em urocultura. O hipoadrenocorticismo (HA) é uma doença endócrina incomum e que leva a poliúria e hipostenúria. O objetivo deste trabalho é relatar o caso de uma fêmea da espécie canina, da raça Teckel, 11 anos, atendida com queixa de urina de odor alterado há vários dias, além de vômito, diarreia e inapetência há três dias, e poliúria e polidipsia há 2 meses, com histórico de tratamento anterior com mitotano para hiperadrenocorticismo. O diagnóstico foi de ITU por Citrobactersp., além de HA iatrogênico. Como destaques nos exames, relação sódio:potássio de 22,6 foi observada, sugestiva de HA, que foi confirmado por teste de estimulação com ACTH, além de urina inicialmente hipostenúrica (densidade 1,006), o que pode ser atribuído ao washout medular renal devido à hiponatremia causada pelo hipoadrenocorticismo. O tratamento foi feito com amoxicilina associada a ácido clavulânico por 20 dias, além da terapia específica para HA com prednisona e fludrocortisona, que foi continuado. A paciente recuperou-se bem, a densidade urinária aumentou após início do tratamento para HA e não houve recidiva da ITU em período de acompanhamento de 8 meses. Acredita-se que a baixa densidade urinária causada pelo HA tenha sido fator essencial para a ocorrência da ITU por Citrobacter.

Citrobacter sp. is a normal constituent of bitches' vagina, but it is related to less than 3% of total isolated microorganism in uroculture. Hypoadrenocorticism (HA) is an endocrine disease uncommonly diagnosed that leads to polyuria and hypostenuria. The aim of this work is report the case of a Teckel bitch, 11 years old, attended with complaint of altered urinary smell for several days, besides vomiting, diarrhea and inappetence for three days, and polyuria and polydispsia for two months, with previous mitotane treatment for hyperadrenocorticism. The diagnosis was Citrobacter UTI, besides iatrogenic HA. The most important exam results include sodium:potassium ratio of 22.6, suggestive of HA, that was confirmed by ACTH stimulation test. Besides, hypostenuria (urinary specific gravity ­ USG - of 1.006) was noted, attributed to renal medular washout due to hyponatremia seen in HA. Therapy comprised amoxicillin associated with clavulanic acid for 20 days, in addition to specific therapy for AH with prednisone and fludrocortisone. The patient recovery well, USG increased after the beginning of the treatment for HA and there was no UTI reinfection for a 8 month period. It is believed that low USG due to HA was essential for the occurrence of Citrobacter UTI.

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.

Insuficiencia suprarrenal en paciente con dificultad respiratoria y úlceras en miembros inferiores Suprarrenal / insufficiency in patient with respiratory difficulty and ulcers in lower members

La Insuficiencia Suprarrenal es un cuadro grave que presenta numerosas manifestaciones clínicas secundarias a la depresión de la producción hormonal de dicha glándula. Las causas son varias e incluso depende de las regiones y épocas. En América Latina se debe considerar al Paracoccidioides como probable causa. Presentamos el caso de un hombre campesino, ingresado al Hospital por Insuficiencia Suprarrenal, con dificultad respiratoria y lesiones ulcerosas en piernas debidas a paracoccidioidomicosis, que también fue la causa del trastorno respiratorio y posiblemente suprarrenal.

Adrenal insufficiency is a serious condition that presents numerous clinical manifestations secondary to the depression of the hormonal production of said gland. The causes are several and even depends on the regions and times. In Latin America, Paracoccidioides must be considered as a probable cause. We present the case of a peasant man, admitted to the Hospital for Adrenal Insufficiency, with respiratory distress and ulcerous leg injuries due to paracoccidioidomycosis, which was also the cause of the respiratory and possibly adrenal disorder.

Doença de Addison e esclerose múltipla: relato de caso / Addison's disease and multiple sclerosis: case report

A doença de Addison é uma endocrinopatia rara, de etiologia autoimune. É caracterizada por défice na secreção de glicocorticoides e mineralocorticoides. A esclerose múltipla consiste em patologia neurológica, de origem autoimune, que resulta na desmielinização da bainha de mielina. O objetivo deste relato foi demonstrar a associação rara entre essas duas patologias e suas possíveis relações imunológicas. A paciente analisada é do sexo feminino, 41 anos, portadora de esclerose múltipla, que posteriormente foi diagnosticada com insuficiência adrenal primária. (AU)

Addison's disease is a rare endocrinopathy of autoimmune etiology. It is characterized by a secretion's deficit of glucocorticoids and mineralocorticoids. Multiple sclerosis is a neurological pathology of autoimmune origin, which results in demyelination of the myelin sheath. The purpose of this report is to demonstrate the uncommon association between these two pathologies and their possible immunological relationships. The analyzed patient is a woman, 41 years old, with multiple sclerosis, who was later diagnosed with primary adrenal insufficiency. (AU)

One case of adrenoleukodystrophy with initial Addison disease and identification of a novel ABCD1 gene mutation / 中华内分泌代谢杂志

Objective To identify the clinical manifestations, imaging findings, and genetic mutation characteristics in an uncommon case of adrenoleukodystrophy ( ALD) with adrenocortical dysfunction ( Addison's disease) as the first manifestation. Methods The clinical data of the proband and his family members were comprehensively collected, and ABCDl gene sequencing was meticulously performed for the proband and his mother using high-throughput sequencing method. Results The patient presented with systematical skin pigmentation accompanied by fatigue in early stage, arose stroke-like episodes manifested as a sudden loss of consciousness and incontinence induced by high fever, and followed by progressive unclear speech, unstable walking and worsening vision. Serum very long-chain fatty acid (VLCFA) concentration increased over normal range. The brain MRI showed an abnormal signal of the symmetric distribution of the bilateral corpus callosum. A new c. 874 876del GAG hemizygous variation in the patient's ABCD1 gene was detected, while his mother had a nucleotide heterozygous variation to this site . Conclusion The diagnosis of ALD requires a combination of clinical manifestations, imaging examination, and serum VLCFA levels, while the detection of ABCD1 gene mutations is considered to be the most reliable approach.

Addison disease as presenting manifestation of one patient with adrenoleukodystrophy and identification of a novel ABCD1 gene mutation / 中华内分泌代谢杂志

Objective@#To identify the clinical manifestations, imaging findings, and genetic mutation characteristics in a rare case of adrenoleukodystrophy(ALD)with adrenocortical dysfunction(Addison′s disease)as the first manifestation.@*Methods@#The clinical data of the proband and his family members were comprehensively collected, and ABCDl gene sequencing was meticulously performed for the proband and his mother using high-throughput sequencing method.@*Results@#The patient presented with systematical skin pigmentation accompanied by fatigue in early stage, arose stroke-like episodes manifested as a sudden loss of consciousness and incontinence induced by high fever, and followed by progressive unclear speech, unstable walking and worsening vision. Serum very long-chain fatty acid(VLCFA)concentration increased over normal range. The brain MRI showed an abnormal signal of the symmetric distribution of the bilateral corpus callosum. A new c. 874_876del GAG hemizygous variation in the patient′s ABCD1 gene was detected, while his mother had a nucleotide heterozygous variation to this site .@*Conclusion@#The diagnosis of ALD requires a combination of clinical manifestations, imaging examination, and serum VLCFA level measurement, while the detection of ABCD1 gene mutations is considered to be the most reliable approach.

Approach to the patient with POEMS syndrome first manifested as Addison's disease / 中华内分泌代谢杂志

A middle aged male presented with darkened skin and edema of lower extremities was reported. He was diagnosed as primary adrenocortical insufficiency ( Addison' s disease ) accompanied with hypergonadotropic hypogonadism, hypoparathyroidism, and subclinical hypothyroidism after endocrinological workup. In addition, the patient also had thickened skin, hirsutism, and polyserositis. The diagnosis of POEMS syndrome was confirmed by elevated M protein and VEGF level. The image of CT showed normal adrenals. Besides the autoimmune polyglandular syndrome ( APS), the possibility of POEMS syndrome in an adult patient with multiple endocrine dysfunction should be considered.

Síndrome poliglandular autoinmunitario tipo II (síndrome de Schmidt): enfermedad de Addison y tiroiditis de Hashimoto asociado con vitíligo / Polyglandular autoimmune syndrome type II (Schmidt syndrome): Addison's disease and Hashimoto's thyroiditis associated to vitiligo

Resumen Los síndromes poliglandulares autoinmunitarios son afecciones poco frecuentes que se distinguen por la coexistencia de al menos dos enfermedades glandulares autoinmunitarias. Se clasifican en tipo I (o juvenil) y tipos II y III (o del adulto). El tipo II o síndrome de Schmidt se caracteriza por enfermedad de Addison, enfermedad tiroidea autoinmunitaria o diabetes mellitus tipo 1 que pueden vincularse con otras alteraciones de naturaleza autoinmunitaria, como vitíli go, hepatitis autoinmunitaria, miastenia gravis, anemia perniciosa, enfermedad celiaca y alopecia areata, entre otras. Se comunica el caso de una paciente de 61 años de edad con vitíligo a quien se le diagnosticó enfermedad de Addison y tiroiditis de Hashimoto (síndrome de Schmidt).

Abstract Autoimmune polyglandular syndromes are rare conditions characterized by the coexistence of at least two autoimmune glandular diseases. They can be classified in type I (or juvenile) and type II and III (or adult). Type 2 or Schmidt's syndrome is characterized by Addison's disease, autoimmune thyroid disease and/or type 1 diabetes mellitus and may be associated with other disorders of autoimmune nature, such as vitiligo, autoimmune hepatitis, myasthenia gravis, pernicious anemia, celiac disease or alopecia areata, among others. We communicate the case of a 61 year-old woman with vitiligo diagnosed with Addison's disease and Hashimoto's thyroiditis (Schmidt's syndrome).

Characteristics of Korean Patients with Primary Adrenal Insufficiency: A Registry-Based Nationwide Survey in Korea

BACKGROUND: Primary adrenal insufficiency (PAI) is a rare, potentially life-threatening condition. There are few Korean studies on PAI, and most have had small sample sizes. We aimed to examine the etiology, clinical characteristics, treatment, and mortality of PAI in Korean patients. METHODS: A nationwide, multicenter, registry-based survey was conducted to identify adults diagnosed with or treated for PAI at 30 secondary or tertiary care institutions in Korea between 2000 and 2014. RESULTS: A total of 269 patients with PAI were identified. The prevalence of PAI was 4.17 per million. The estimated incidence was 0.45 per million per year. The mean age at diagnosis was 49.0 years, and PAI was more prevalent in men. Adrenal tuberculosis was the most common cause of PAI in patients diagnosed before 2000; for those diagnosed thereafter, adrenal metastasis and tuberculosis were comparable leading causes. The etiology of PAI was not identified in 34.9% of cases. Of the patients receiving glucocorticoid replacement therapy, prednisolone was more frequently administered than hydrocortisone (69.4% vs. 26.5%, respectively), and only 27.1% of all patients received fludrocortisone. We observed an increased prevalence of metabolic disease and osteoporosis during the follow-up period (median, 60.2 months). The observed overall mortality and disease-specific mortality rates were 11.9% and 3.1%, respectively. CONCLUSION: The prevalence of PAI is significantly lower in Koreans than in reports from Western countries. The high frequency undetermined etiology in patients with PAI suggests the need to reveal accurate etiology of PAI in Korea.

Conduct protocol in emergency: Acute adrenal insufficiency / Protocolo de condutas em emergência: insuficiência adrenal aguda

Summary Introduction: Acute adrenal insufficiency or addisonian crisis is a rare comorbidity in emergency; however, if not properly diagnosed and treated, it may progress unfavorably. Objective: To alert all health professionals about the diagnosis and correct treatment of this complication. Method: We performed an extensive search of the medical literature using specific search tools, retrieving 20 articles on the topic. Results: Addisonian crisis is a difficult diagnosis due to the unspecificity of its signs and symptoms. Nevertheless, it can be suspected in patients who enter the emergency room with complaints of abdominal pain, hypotension unresponsive to volume or vasopressor agents, clouding, and torpor. This situation may be associated with symptoms suggestive of chronic adrenal insufficiency such as hyperpigmentation, salt craving, and association with autoimmune diseases such as vitiligo and Hashimoto's thyroiditis. Hemodynamically stable patients may undergo more accurate diagnostic methods to confirm or rule out addisonian crisis. Delay to perform diagnostic tests should be avoided, in any circumstances, and unstable patients should be immediately medicated with intravenous glucocorticoid, even before confirmatory tests. Conclusion: Acute adrenal insufficiency is a severe disease that is difficult to diagnose. It should be part of the differential diagnosis in cases of hypotensive patient who is unresponsive to vasoactive agents. Therefore, whenever this complication is considered, health professionals should aim specifically at this pathology.

Resumo Introdução: a insuficiência adrenal aguda ou crise addisoniana é uma comorbidade rara na emergência; porém, se não diagnosticada e tratada de forma correta, pode evoluir de maneira desfavorável. Objetivo: alertar a todos os profissionais da saúde sobre o diagnóstico e tratamento corretos dessa complicação. Método: foi realizada uma ampla pesquisa na literatura médica, por meio de ferramentas específicas, sendo selecionados 20 artigos sobre o tema. Resultados: a crise addisoniana é de difícil diagnóstico pela inespecificidade de seus sinais e sintomas. No entanto, pode ser suspeitada em pacientes que chegam à emergência com queixa de dor abdominal, hipotensão não responsiva a volume ou a agentes vasopressores, obnubilação e torpor. Esse quadro pode vir associado a sintomas sugestivos de insuficiência adrenal crônica, como hiperpigmentação e avidez por sal, bem como a doenças autoimunes, como vitiligo e tireoidite de Hashimoto. Pacientes estáveis hemodinamicamente podem passar por métodos diagnósticos mais apurados para se confirmar ou descartar a crise addisoniana. Os exames diagnósticos não podem retardar, em hipótese alguma, o tratamento de pacientes instáveis, que deve ser iniciado imediatamente com glicocorticoide endovenoso, inclusive antes das provas confirmatórias. Conclusão: a insuficiência adrenal aguda é uma patologia grave e de difícil diagnóstico, que deve fazer parte do diagnóstico diferencial do médico ao atender um paciente hipotenso sem reposta à infusão de drogas vasoativas. Logo, na suspeita dessa complicação, o profissional não deve tardar a agir especificamente nessa patologia.

Addison Disease Due to Adrenal Tuberculosis Presenting as an Abscess in a Nearby Psoas Muscle with a Duodenal Fistula / 대한내과학회지

An 80-year-old male with nausea and poor oral intake was referred for evaluation of hyponatremia. Primary adrenal insufficiency was diagnosed by a rapid adrenocorticotropic hormone (ACTH) stimulation test. The cause of the adrenal insufficiency was revealed to be adrenal tuberculosis presenting as a bilateral adrenal mass on computed tomography imaging. During the first few months of treatment, the size of the tuberculous mass increased and spread to an adjacent area, and further adrenal hormone replacement was needed. In addition, there was a newly developed tuberculous abscess in a nearby psoas muscle with a duodenal fistula. Thus, we report a case of a long-term clinical course of Addison's disease with changes in hormone replacement as a result of active adrenal tuberculosis, together with a review of the literature.

Primary hypoadrenocorticism in a dog / Hipoadrenocorticismo primário em um cão / Hipoadrenocorticismo primario en un perro

This report describes the clinical and laboratorial findings as well as the therapeutic protocol performed in a three-year-old mongrel female intact dog, referred to the Veterinary Hospital of FAMEZ/UFMS. The animal had a previous history of recurrent gastrointestinal signs (such as lethargy, vomiting, loss of appetite, melena and abdominal pain), acute crisis episodes, bradycardia, hypotension, hypothermia and increase of capillary refill time, recognized as addisonian crisis due to primary hypoadrenocorticism. Laboratorial findings included anemia, eosinophilia, neutrophilia, lymphocytosis, sodium-potassium ratio of 14,02 mEq/L and prerenal azotemia. Based on that, it was confirmed the diagnosis of primary hypoadrenocorcitism. Thus, it was recommended supplementation therapy with mineralocorticoid (aldosterone) and glucocorticoid (cortisol) corresponding respectively, fludrocortisone acetate of 0.2 mg per kg of BW, by mouth, once daily and prednisone 0.2 mg per kg of BW, by mouth, twice daily until further recommendations. The prognostic was excellent, since the animal significantly improved body condition, andclinical signs disappeared after therapy which lead the sodium-potassium ratio to 35.11 mEq/L. Thus, the clinician must always suspect of primary hypoadrenocorticism in dogs with intermittent nonspecific signs that get better with support therapy. Presumably, hypoarenocorticism must be under diagnosed in veterinary medicine, reinforcing the need to require specific exams in patients that show this wax and wane feature of clinical signs.

O presente relato descreve os achados clínicos, laboratoriais e conduta terapêutica de um animal da espécie canina, fêmea, com três anos de idade, inteiro, sem raça definida, diagnosticado com hipoadrenocorticismo primário atendido no Hospital Veterinário da FAMEZ/UFMS. O animal apresentou histórico de recidivas de sinais gastrintestinais (letargia, vômitos, perda de apetite, melena e dor abdominal), crise adrenal aguda, bradicardia, hipotensão, hipotermia e aumento do tempo de preenchimento capilar. As alterações laboratoriais compreenderam linfocitose, anemia, eosinofilia, neutrofilia, densidade urinária < 1.030, relação sódio: potássio 14,02 mEq/L e azotemia pré-renal. Baseado nos achados clínicos-laboratoriais confirmou-se o hipoadrenocorticismo primário. Em seguida, foi instituído terapia de suplementação de mineralocorticoide (aldosterona) e glicocorticoide (cortisol), correspondendo respectivamente ao acetato de fludrocortisona na dose de 0,2 mg/kg por via oral uma vez ao dia e prednisona 0,2 mg/kg por via oral duas vezes por dia até novas recomendações. O prognóstico foi excelente para este caso, já que houve melhora significativa do animal, com o desaparecimento dos sinais clínicos e com nova relação sódio: potássio de 35,11 mEq/L. Assim, deve-se sempre suspeitar de hipoadrenocorticismo primário canino em pacientes com o curso de aparecimento e desaparecimento com sinais inespecíficos que melhorem com terapia de suporte. Presume-se que o hipoadrenocorticismo primário em cães seja subdiagnosticado na medicina veterinária, por isso a importância dos clínicos em suspeitar e solicitar exames específicos em pacientes que apresentam esse curso da doença.

El informe describe los hallazgos clínicos, de laboratorio y manejo terapéutico de un perro, hembra, con tres años de edad, entera, mestizo, con diagnóstico de hipoadrenocorticismo primario atendido en el Hospital Veterinario de la FAMEZ/UFMS. El animal tuvo un historial de signos gastrointestinales recurrentes (letargia, vómitos, pérdida de apetito, melena y dolor abdominal), crisis renal aguda, bradicardia, hipotensión, hipotermia y un aumento del tiempo de llenado capilar. Las alteraciones de laboratorio presentaron linfocitosis, anemia, eosinofilia, neutrofilia, densidad de la orina < 1,030, relación sodio: potasio 14,02 mEq/L y azotemia prerrenal. Con base en los hallazgos clínicos y de laboratorio, se confirmó el hipoadrenocorticismo primario. A continuación, se introdujo terapia con administración de mineralocorticoide (aldosterona) y glucocorticoide (cortisol), que correspondieron respectivamente al acetato de fludrocortisona a una dosis de 0,2mg/kg por vía oral una vez al día y prednisona 0,2 mg/kg por vía oral dos veces al día hasta nuevas recomendaciones. El pronóstico fue excelente para este caso, ya que hubo mejora significativa del animal, desapareciendo los signos clínicos y con una nueva relación sodio: potasio de 35,11 mEq/L. Por lo tanto, siempre se debe sospechar del hipoadrenocorticismo primario canino en pacientes con el curso de aparecimiento y desaparecimiento con signos inespecíficos que mejoran con terapia de soporte. Es posible que el hipoadrenocorticismo primario en perros sea diagnosticado en la medicina veterinaria, así la importancia de los clínicos en sospechar y solicitar exámenes específicos en pacientes que presentan ese curso de la enfermedad.