Cetoacidosis diabética como debut de diabetes mellitus inmunomediada en paciente en tratamiento con inhibidores de checkpoint / Diabetic ketoacidosis as debut of immune-mediated diabetes mellitus in a patient in treatment with immune checkpoint inhibitors

Los inhibidores de checkpoint (ICP) son anticuerpos usados en inmunoterapia contra el cáncer. Uno de sus blancos de acción es el receptor de muerte celular programada-1 (PD-1), el cual es importante para mantener la tolerancia inmunitaria. Sin embargo, este mecanismo se asocia a riesgo de eventos adversos relacionados a la inmunidad que pueden afectar a múltiples órganos incluyendo el sistema endocrino. Se describe el caso inhabitual de un paciente que a los 18 meses de terapia con ICP debutó con cetoacidosis diabética (CAD).

Immune checkpoint inhibitors consist in antibodies used in immunotherapy against cancer. One of their targets is the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, this mechanism is associated with a risk for immune-related adverse events potentially affecting multiple organs, including the endocrine system. We describe the unusual case of a patient who, after 18 months of treatment with an immune checkpoint inhibitor, debuted with diabetic ketoacidosis

Ultrasonographic aspects of the gallbladder mucocele in 30 dogs: retrospective study / Aspectos ultrassonográficos da mucocele biliar em 30 cães: estudo retrospectivo

Gallbladder mucocele is characterized by hyperplasia of the gallbladder epithelium, increased mucus production, accumulation, and densification of the bile content, which can lead to biliary obstruction, necrosis, and rupture of the gallbladder wall. Its finding may be accidental or related to symptoms. A retrospective study (2016-2019) was carried out based on abdominal ultrasound examinations in dogs, correlating aspects of the gallbladder and biliary system in the mucocele with existing comorbidities. Thirty dogs diagnosed with biliary mucocele were evaluated, of which 46.66% had the disease at an early stage, and 53.33% showed a more advanced stage. Of these, 66.66% were related to endocrinopathies and hyperadrenocorticism. Signs of extrahepatic bile duct obstruction and biliary peritonitis were observed in two animals. Due to their potential risk of complications, follow-up ultrasound assessments are indicated in cases that opt for clinical treatment, not excluding the need for surgical intervention.(AU)

A mucocele biliar caracteriza-se pela hiperplasia do epitélio da vesícula biliar, aumento da produção de muco, acúmulo e densificação do conteúdo biliar, podendo levar à obstrução, necrose e ruptura da parede da vesícula biliar. Seu achado pode ser acidental ou estar relacionado à sintomatologia. Foi realizado um estudo retrospectivo (2016-2019) a partir de exames ultrassonográficos abdominais em cães, correlacionando os aspectos da vesícula biliar na mucocele, com comorbidades existentes. Foram avaliados 30 cães com diagnóstico de mucocele biliar, dos quais 46,66% apresentaram a doença em estágio inicial e 53,33% demonstraram estágio mais avançado. Destes, 66,66% tinham endocrinopatias, principalmente hiperadrenocorticismo. Sinais de obstrução de vias biliares extra-hepáticas e peritonite biliar foram observados em dois animais. Por seu potencial risco de complicação, avaliações ultrassonográficas de seguimento são indicadas nos casos de tratamento clínico, não se descartando a necessidade de intervenção cirúrgica.(AU)

Metabolic Bone Disease in Children With Transfusion-Dependent Thalassemia

Objective: This study aimed to detect metabolic bone disease and endocrinopathies in a cohort of patients with transfusion-dependent thalassemia (TDT). Methods: This prospective study was conducted between March 2020 - August 2021. Children with TDT older than 5 years, receiving regular blood transfusion, underwent comprehensive endocrine and metabolic bone disease evaluation, which included screening for short stature, delayed puberty, diabetes mellitus, hypothyroidism, adrenal insufficiency and hypoparathyroidism. Children older than 10 years also underwent. X-ray of thoracolumbar spine, and dual energy X-ray absorptiometry (DXA) scanning. Results: Out of 37 patients (19 males), with mean (SD) age 15 (6) years, hypogonadism was the commonest endocrine deficiency seen in 15 (62%), followed by short stature, abnormal glucose metabolism, subclinical adrenal insufficiency, hypothyroidism, and hypoparathyroidism. Vitamin D insufficiency/deficiency was seen in 12 (60%) and hypocalcemia in 2 patients. Low bone mass was seen in 8, and osteoporosis, as evidenced by vertebral fractures, in 4 patients. Of the four patients with vertebral fracture, three were aged ?18 years, one was symptomatic, two each had grade 1 and grade 2 fractures, one had multiple vertebral fractures, and all four had hypogonadism and multiple endocrine deficiencies. Conclusion: Vertebral fractures occur even in the second decade among patients with TDT, and are often associated with endocrinopathies, most commonly hypogonadism. Early screening and prevention of vertebral fractures is necessary.

Endocrinopatías por inmunoterapia oncológica / Endocrinopathies by oncological immunotherapy

La relación entre inmunidad y cáncer es compleja. Las células tumorales desarrollan mecanismos de evasión a las respuestas del sistema inmunitario. Esta capacidad permite su supervivencia y crecimiento. La inmunoterapia ha transformado el tratamiento oncológico mejorando la respuesta inmunitaria contra la célula tumoral. Esta se basa en el bloqueo de los puntos de control inmunitario mediante anticuerpos monoclonales contra la molécula inhibidora CTLA-4 (antígeno 4 del linfocito T citotóxico [CTLA-4]) y la proteína 1 de muerte celular programada y su ligando (PD-1/PD-L1). Aunque los inhibidores de los puntos de control inmunitario (ICIs) son fármacos bien tolerados, tienen un perfil de efectos adversos conocido como eventos adversos inmunorrelacionados (EAI). Estos afectan varios sistemas, incluyendo las glándulas endocrinas. Los eventos adversos endocrinos más frecuentes son la disfunción tiroidea, la insuficiencia hipofisaria, la diabetes mellitus autoinmune y la insuficiencia suprarrenal primaria. El creciente conocimiento de estos efectos adversos endocrinos ha llevado a estrategias de tratamiento efectivo con el reemplazo hormonal correspondiente. El objetivo de esta revisión es reconocer la incidencia de estas nuevas endocrinopatías, la fisiopatología, su valoración clínica y el manejo terapéutico. (AU)

The relationship between immunity and cancer is complex. Tumor cells develop evasion mechanisms to the immune system responses. This ability allows their survival and progression. Immunotherapy has transformed cancer treatment by improving the immune response against tumor cells. This is achieved by blocking immune checkpoints with monoclonal antibodies against cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 and its ligand (PD-1 / PD-L1). Although the immune checkpoint inhibitors (ICIs) are well tolerated drugs, they have a profile of adverse effects known as immune-related adverse events (irAES). These involve diverse systems, including the endocrine glands. The most frequent endocrine immune-related adverse events are thyroid and pituitary dysfunction, autoimmune diabetes mellitus and primary adrenal insufficiency. The increasing knowledge of these irAES has led to effective treatment strategies with the corresponding hormonal replacement. The objective of this review is to recognize the incidence of these new endocrinopathies, the physiopathology, their clinical evaluation, and therapeutic management. (AU)

Patologías endocrinas más frecuentes en el adulto mayor / Most frequent endocrine pathologies in the elderly

Resumen El sistema endócrino es el encargado del metabolismo interno, en forma tal que su regulación tanto intracelular como en tejidos, órganos y sistemas es responsable de un adecuado funcionamiento. El envejecimiento afecta los diferentes ejes de forma diversa y en velocidades cambiantes, volviendo susceptible al organismo de tener una falla en su control. Factores ambientales, como la nutrición, la falta de actividad física o el tabaquismo favorecen la aparición de patologías; en este caso, nos interesa la aparición de diabetes mellitus tipo 2, el hipotiroidismo y el hipogonadismo, que no solo alteran la función de nuestro organismo, sino que también tienen una repercusión muy importante en la calidad de vida de las personas. La gran prevalencia de estas enfermedades, en especial en el adulto mayor, hace necesario revisar algunos puntos importantes, como es el manejo farmacológico de la diabetes, la oportuna identificación del hipotirodismo, el conocimiento del hipotiroidismo subclínico así como cuando debe tratarse el hipogonadismo masculino a pesar de los riesgos inherentes al uso de testosterona en edades avanzadas.

Abstract The endocrine system is in charge of the internal metabolism in such a way that its regulation of the intracellular activity and tissues, organs and systems is responsible for an adequate functioning. Aging affects the different axes in many ways and at variable speeds, making the organism prone to having a control failure. Environmental factors such as nutrition, exercise, or smoking favor the appearance of pathologies. In this case we are interested in the appearance of Type 2 Diabetes Mellitus, hypothyroidism and hypogonadism that not only alter the functions of our body, but also have a very important impact on people's quality of life. The high prevalence of these diseases, especially in the elderly, makes it necessary to review some important points such as the pharmacological management of diabetes, timely identification of hypothyroidism, the knowledge of subclinical hypothyroidism as well as when hypogonadism should be treated in spite of the risks inherent to the use of testosterone in advanced ages.

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.

Endocrine diseases, perspectives and care in Turner syndrome / Doenças endócrinas, perspectivas e cuidados na síndrome de Turner

Turner syndrome is a frequent chromosome disorder in clinical practice. It is characterized by short stature, gonadal dysgenesia and multisystemic involvement, responsible for a high morbidity and reduced life expectancy. The aim of the present paper is to describe the endocrinopathies and major problems at different ages, and to present suggestion for follow-up care in these patients.

A síndrome de Turner é uma doença cromossômica frequente na prática clínica. É caracterizada pela baixa estatura, disgenesia gonadal e alterações em diversos sistemas, o que leva a uma alta morbidade e diminuição da expectativa de vida. O objetivo do presente estudo é descrever as endocrinopatias e outros problemas em cada idade e apresentar uma sugestão de cuidados e segmentos dessas pacientes.

Fibrous dysplasia & McCune-Albright syndrome: An experience from a tertiary care centre in north India.

Background & objectives Fibrous dysplasia (FD) is a rare metabolic bone disease and information available from India is limited to only anecdotal case reports. We describe the clinical profile and therapeutic outcome of 25 patients with FD observed over a period of 14 yr in a tertiary care centre from north India. Methods In this retrospective study patients (n = 25) with diagnosis of fibrous dysplasia based on either classical radiological features and/or histological evidence on bone biopsy, were analyzed. Associated endocrinopathies if any, were evaluated. The diagnosis of McCune Albright syndrome (MAS) was considered when fibrous dysplasia was accompanied by either café-au-lait macules and/or endocrinopathies. The clinical presentation, biochemical parameters and imaging were analysed. Seven patients received bisphosphonate therapy. The final outcome and side effects were noted. Results Age of the patients ranged from 7 to 48 yr (mean ± SD, 24.2 ± 11.4 yr) with a lag time between onset of symptoms and presentation ranging from 1 to 20 yr (mean ± SD, 6.6 ± 6.2 yr). The mean duration of follow up was 3.5 ± 2.1 yr. Eighteen (72%) patients had polyostotic disease while the remaining had monostotic FD. Eight patients had endocrinopathies: five had acromegaly, one each had gonadotropin independent precocious puberty (GIPP), hyperthyroidism and hypophosphatemic rickets. One child with GIPP later developed hyperthyroidism. McCune Albright syndrome was observed in 10 (40%) patients. A majority of the patients underwent various minor or major surgical procedures and seven patients received bisphosphonates for recurrent pathological fractures. Bone pain was reduced in all bisphosphonate treated patients with a decrease in subsequent fractures. Interpretation & conclusions This series of FD patients from north India shows the varying presentations of this rare disease. Medical treatment with bisphosphonates appears to be potentially rewarding.