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)

Rol de la osteocalcina más allá del hueso / Role of osteocalcin beyond bone

Los hallazgos osteológicos se intensi!caron en los últimos años. Se demostró que el esqueleto se comporta, además de sus funciones clásicas, como un órgano de secreción endocrina que sintetiza al menos dos hormonas: el factor de crecimiento de !broblastos 23 (FGF-23) y la osteocalcina (Ocn). La Ocn es un péptido pequeño que contiene 3 residuos de ácido glutámico. Estos residuos se carboxilan postraduccionalmente, quedando retenida en la matriz ósea. La forma decarboxilada en el primer residuo de ácido glutámico (GluOcn) fue reportada por poseer efectos biológicos; la resorción ósea es el mecanismo clave para su bioactivación. La presente revisión se centra en los conocimientos actuales sobre la función hormonal de la Ocn. A la fecha se reporta que la Ocn regularía el metabolismo energético aumentando la proliferación de células ` pancreáticas, y la secreción de insulina y de adiponectina. Sobre el músculo esquelético actuaría favoreciendo la absorción y el catabolismo de nutrientes. La función reproductiva masculina estaría regulada mediante el estímulo a las células de Leydig para sintetizar testosterona; en el desarrollo cerebral y la cognición, la Ocn aumentaría la síntesis de neurotransmisores monoaminados y disminuiría el neurotransmisor inhibidor GABA. Si bien son indispensables mayores evidencias para dilucidar los mecanismos reguladores por medio de los cuales actuaría la Ocn, los resultados enumerados en los distintos estudios experimentales establecen la importancia de este novedoso integrante molecular. Dilucidar su rol dentro de estos procesos interrelacionados en seres humanos abriría la posibilidad de utilizar a la Ocn en el tratamiento de enfermedades endocrino-metabólicas. (AU)

Osteological !ndings have intensi!ed in recent years. The skeleton behaves as an endocrine secretion organ that synthesizes at least two hormones: osteocalcin (Ocn) and !broblast growth factor 23 (FGF-23). Ocn is a small peptide that contains 3 glutamic acid residues. After translation, these residues are carboxylated to make possible its retention into the bone matrix. Decarboxylation on the !rst glutamic acid residue (GluOcn) has been reported to have biological effects. Bone resorption is the key mechanism for its bioactivation. This review focuses on current knowledge on Ocn hormonal function. It has been reported that Ocn regulates energy metabolism by increasing the proliferation of pancreatic ` cells, and the secretion of insulin and adiponectin. On the skeletal muscle, it may act by favoring the absorption and catabolism of nutrients. Male reproductive function might be regulated by stimulating Leydig cells to synthesize testosterone. Regarding brain development and cognition, Ocn would increase monoamine neurotransmitters synthesis and decrease inhibitory neurotransmitter GABA. Although more evidence is needed to elucidate the regulatory mechanisms of Ocn, different experimental studies establish the importance of this novel molecular mediator. Clarifying its role within interrelated processes in humans, might open the possibility of using Ocn in different treatments of endocrine-metabolic diseases. (AU)

Hypogonadotropic Hypogonadism Revisited

Impaired testicular function, i.e., hypogonadism, can result from a primary testicular disorder (hypergonadotropic) or occur secondary to hypothalamic-pituitary dysfunction (hypogonadotropic). Hypogonadotropic hypogonadism can be congenital or acquired. Congenital hypogonadotropic hypogonadism is divided into anosmic hypogonadotropic hypogonadism (Kallmann syndrome) and congenital normosmic isolated hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism). The incidence of congenital hypogonadotropic hypogonadism is approximately 1-10:100,000 live births, and approximately 2/3 and 1/3 of cases are caused by Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism, respectively. Acquired hypogonadotropic hypogonadism can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X. The clinical characteristics of hypogonadotropic hypogonadism are androgen deficiency and a lack/delay/stop of pubertal sexual maturation. Low blood testosterone levels and low pituitary hormone levels confirm the hypogonadotropic hypogonadism diagnosis. A prolonged stimulated intravenous GnRH test can be useful. In Kallmann syndrome, cerebral MRI can show an anomalous morphology or even absence of the olfactory bulb. Therapy for hypogonadotropic hypogonadism depends on the patient's desire for future fertility. Hormone replacement with testosterone is the classic treatment for hypogonadism. Androgen replacement is indicated for men who already have children or have no desire to induce pregnancy, and testosterone therapy is used to reverse the symptoms and signs of hypogonadism. Conversely, GnRH or gonadotropin therapies are the best options for men wishing to have children. Hypogonadotropic hypogonadism is one of the rare conditions in which specific medical treatment can reverse infertility. When an unassisted pregnancy is not achieved, assisted reproductive techniques ranging from intrauterine insemination to in vitro fertilization to the acquisition of viable sperm from the ejaculate or directly from the testes through testicular sperm extraction or testicular microdissection can also be used, depending on the woman's potential for pregnancy and the quality and quantity of the sperm.

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.

Aplicação de programa educativo multidisciplinar em gestações de alto risco devido a doenças endócrinas / Application of multidisciplinary educational program in high-risk pregnancies due to endocrine diseases

OBJETIVO: avaliar a aplicação de um programa de intervenção multidisciplinar educativo em mulheres com gestação de alto risco devido a doenças endócrinas. MÉTODOS: avaliamos retrospectivamente a aplicação de um programa educativo multidisciplinar em 185 gestantes com doenças endócrinas referenciadas para uma maternidade especializada em gestação de alto risco. As gestantes receberam atenção pré-natal multidisciplinar por times compostos por endocrinologistas, obstetras, ultrassonografistas, enfermeiras e nutricionistas. Informações orais e escritas sobre hábitos saudáveis, cuidados com diabetes, uso de adoçantes artificiais e exercícios na gestação foram passadas na primeira consulta endocrinológica. Plano nutricional individualizado foi feito em primeira visita à nutricionista. Nas reavaliações mensais com nutricionista e quinzenais com endocrinologista, as informações sobre mudanças saudáveis no estilo de vida eram reforçadas e o peso registrado. O grau de aderência à dieta e atividade física foi autorreferido. Comparou-se o peso semanal antes e após a intervenção multidisciplinar, peso fetal ao nascimento, taxa de macrossomia e baixo peso, e a frequência de parto cesário nas quatro categorias de índice de massa corpórea (IMC) pré-gestacional (<18,5; 18,5 a 24,9; 25 a 29,9 e >30 kg/m²). RESULTADOS: a principal patologia de encaminhamento foi o diabetes (84,9 por cento). Um terço das gestantes (31,2 por cento) era composto por portadoras de sobrepeso e 42,5 por cento tinham obesidade pré-gestacional. A maior parte das gestantes foi vista pela primeira vez pela equipe multidisciplinar no terceiro trimestre (64,1 por cento), e 50,5 por cento delas excederam o ganho de peso recomendado para toda a gestação à primeira avaliação. Gestantes obesas excederam o ganho de peso recomendado em 62,5 por cento dos casos. Após a intervenção multidisciplinar, o percentual de gestantes que excedeu o ganho de peso semanal recomendado reduziu em todas ...

PURPOSE: to investigate the application of a multidisciplinary educational program to high-risk pregnancies due to endocrine diseases. METHODS: we retrospectively evaluated the application of a multidisciplinary educational program to 185 pregnant women with endocrine diseases referred to a maternity specialized in high-risk pregnancy. All pregnant women received multidisciplinary prenatal care from a team consisting of endocrinologists, obstetricians, sonographers, nurses and dietitians. Oral and written information about healthy habits, diabetes care, use of artificial sweeteners and exercise during pregnancy was given to all patients at the first endocrine consultation. An individualized nutrition plan was prepared on the occasion of the first visit to the nutritionist. In bi-weekly and monthly endocrine and nutritional visits, respectively, information about healthy changes in lifestyle was emphasized and the weight was recorded. Adherence to physical activity and nutritional counseling was self-reported. We compared the weekly weight before and after the intervention, fetal weight at birth, rate of macrosomia and low birth weight, and frequency of cesarean delivery among the four categories of body mass index (BMI) before pregnancy (<18.5, from 18.5 to 24.9, from 25 to 29.9 and >30 kg/m²). RESULTS: the main disease of referral was diabetes (84.9 percent). One third of the pregnant women (31.2 percent) were overweight and 42.5 percent were obese before pregnancy. Most women was first seen by the multidisciplinary team in the third trimester of pregnancy (64.1 percent) and 50.5 percent exceeded the recommended weight gain at first evaluation. Obese women exceeded the recommended weight gain in 62.5 percent of cases. After the intervention, the percentage of women who exceeded the recommended weekly weight gain was reduced in all categories of pre-pregnancy BMI, although a statistically significant difference was found only in the ...

Endocrinopatía autoinmune múltiple / Multiple autoimmune endocrinopathy

Se presenta una niña de tres años y ocho meses, con antecedentes familiares de endocrinopatía autoinmune que consulta por síndrome malabsortivo y candidiasis mucocutánea con onicomicosis crónica. Evoluciona presentando una crisis de tetania generalizada secundaria a hipoparatiroidismo y luego un hipertiroidismo clínico. Con pruebas de laboratorio positivas para enfermedades autoinmune.

El proceso diagnóstico en las alteraciones endocrinológicas

Las alteraciones endocrinológicas, tanto diagnosticadas como no diagnosticadas, representan una gran parte de la practica médica. El presente artículo, dirigido al diagnostico y tratamiento de las alteraciones mas comunes y tambien de las menos comunes que afectan la glándula tiroides, las glándulas suprarenales y el metabolismo del calcio, constituyen una excelente guía para el médico sobre cuándo evaluar la función de una glándula, cuándo descartar la posibilidad de una enfermedad maligna y cuándo referir al paciente

Hyperprolactinaemia, diagnosis and treatment: a study of 150 cases

We reviewed the management of 150 patients with hyperprolactinaemia, who presented with infertility, amenorrhoea, menstrual irregularities and/or galactorrhoea during a 4 year period to evaluate the efficacy of treatment of the condition with bromocriptine. Radiographic evidence of pituitary microadenoma was seen in 23 patients and 7 had macroadenoma. The majority of our patients [53%] had no obvious cause for elevated prolactin levels. Seven patients were taking antidepressants, five had antihypertensive drugs and twelve had taken oral contraceptives for a period of six months or more. Patients with pituitary adenoma had a significantly higher baseline serum prolactin level than those with no adenoma. All patients in the study were treated with bromocriptine to normalise serum prolactin or to achieve pregnancy. The patients without an adenoma required a significantly smaller dose of bromocriptine than those with an adenoma. There was no significant difference in the pregnancy rate between the patients with and those without pituitary adenoma. Similarly, presence of galactorrhoea or a high level of prolactin did not influence the pregnancy rate. No lethal congenital foetal abnormalities were observed. The results obtained from this study indicate the efficacy and safety of bromocriptine therapy in the treatment of hyperprolactinaemia with and without pituitary adenoma