Developing Sex: From Recremental Semen to Developmental Endocrinology.

During the 1890s, animal development became associated with glandular activity, with profound implications for pediatric nosology and treatment. The significance of this endocrinological turn of developmental physiology and pathophysiology in part hinges on an often-overlooked continuity with ubiquitous early modern medical thought concerning semen as a recrementitious (reabsorbed) nutrient or stimulant. Mid-19th-century interests in adult sexual physiology were increasingly nerve-centered and antihumoral. Scattered empirical, particularly veterinarian, interests in gonadal developmental functions failed to moderate these explanatory trends. While Brown-Séquard's rejuvenation experiments still offered no clear starting point for a developmental endocrinology, in 1892 Gaston Variot and Paul Bezançon more explicitly deduced a testicular developmental endocrinological function from various observations on testicular ectopy and a local form of animal "demi-castration." Ensuing interest in the thyroid, the thymus and in the testicles led to various working conceptions of their respective and putatively reciprocal developmental properties, including the idea of a thyroid-testis axis. From 1896, the pubertal affliction of chlorosis became the subject of multiple opotherapeutic approaches, providing an experimental basis for theories of ovarian internal secretion. Polyglandular therapy, piloted for divergent developmental conditions, remained routine until the 1930s despite the biological inefficacy of many endocrine products.

Endocrinology's early historians (1889-1914) and the forgotten prehistory of testosterone.

INTRODUCTION: An often-retold historical outline of endocrinology was established over a century ago. An exhaustive history of sexual physiology remains forthcoming, however. OBJECTIVES: To explore and contextualize the remarkable medical-historical and medical-anthropologic frenzy triggered by Brown-Séquard's 1889 self-injections with testicular juice, which ultimately settled down into an early history of endocrinology. METHODS: Pertinent primary sources were selected from a broader study, primarily between 1889 and 1914, as well as selected older texts identified and unidentified by these sources. RESULTS: Endocrinology's early historians in a short space of time moved from the history of testicular opotherapy to that of glandular typology and physiology and to increasingly encompassing medical-historical accounts of internal secretion as an epochal idea. Early historians nominated "precursors" to Brown-Séquard but underestimated physiologic continuities-specifically, early modern protoendocrinologic notions concerning semen as a "recrement," notions still recited by Brown-Séquard and early Brown-Séquardists as well their detractors. Brown-Séquard himself worked through this old (recremental) concept of semen between 1889 and 1892 but was later identified with it, by among others Ancel and Bouin. CONCLUSION: Western sexual physiology is a medical palimpsest, the undertexts of which remain to be studied in detail.

Gastrointestinal hormones: History, biology, and measurement.

This chapter attempts to provide an all-round picture of a dynamic and major branch of modern endocrinology, i.e. the gastrointestinal endocrinology. The advances during the last half century in our understanding of the dimensions and diversity of gut hormone biology - inside as well as outside the digestive tract - are astounding. Among major milestones are the dual brain-gut relationship, i.e. the comprehensive expression of gastrointestinal hormones as potent transmitters in central and peripheral neurons; the hormonal signaling from the enteroendocrine cells to the brain and other extraintestinal targets; the role of gut hormones as growth and fertility factors; and the new era of gut hormone-derived drugs. Accordingly, gastrointestinal hormones have pathogenetic roles in major metabolic disorders (diabetes mellitus and obesity); in tumor development (common cancers, sarcomas, and neuroendocrine tumors); and in cerebral diseases (anxiety, panic attacks, and probably eating disorders). Such clinical aspects require accurate pathogenetic and diagnostic measurements of gastrointestinal hormones - an obvious responsibility for clinical chemistry/biochemistry. In order to obtain a necessary insight into today's gastrointestinal endocrinology, the chapter will first describe the advances in gastrointestinal endocrinology in a historical context. The history provides a background for the subsequent description of the present biology of gastrointestinal hormones, and its biomedical consequences - not least for clinical chemistry/biochemistry with its specific responsibility for selection of appropriate assays and reliable measurements.

The History of Obesity Research.

Perhaps the most unexpected development in pediatric endocrinology in the past 50 years has been the recognition of obesity as an endocrine/metabolic disorder rather than a life choice or moral failing. The history of obesity research is disjointed, having followed two separate paths in the 20th century, based on two independent yet overlapping paradigms. Proponents of the "Energy Storage" hypothesis point to data implicating monogenetic disorders, the ventromedial hypothalamus, insulin, cortisol, and the adipocyte itself in the pathogenesis of obesity. Alternatively, proponents of the "Energy Balance" hypothesis point to data implicating increased caloric intake, decreased caloric expenditure, gastrointestinal hormones, and microbiome changes as being critical for obesity. These two separate lines of research merged somewhat with the discovery of leptin in 1994, as leptin established a major hormonal role in weight control. Leptin has explained some of the dichotomy and has proved essential in understanding the importance of developmental programming and epigenetics. However, the mystery of leptin resistance remains unsolved. Despite all our collective knowledge, we appear no closer in solving the obesity puzzle today than we were 50 years ago.

100 YEARS OF INSULIN: Pancreas pathology in type 1 diabetes: an evolving story.

We review the current knowledge of pancreas pathology in type 1 diabetes. During the last two decades, dedicated efforts toward the recovery of pancreas from deceased patients with type 1 diabetes have promoted significant advances in the characterization of the pathological changes associated with this condition. The implementation of autoantibody screening among organ donors has also allowed examining pancreas pathology in the absence of clinical disease, but in the presence of serological markers of autoimmunity. The assessment of key features of pancreas pathology across various disease stages allows driving parallels with clinical disease stages. The main pathological abnormalities observed in the pancreas with type 1 diabetes are beta-cell loss and insulitis; more recently, hyperexpression of HLA class I and class II molecules have been reproduced and validated. Additionally, there are changes affecting extracellular matrix components, evidence of viral infections, inflammation, and ER stress, which could contribute to beta-cell dysfunction and the stimulation of apoptosis and autoimmunity. The increasing appreciation that beta-cell loss can be less severe at diagnosis than previously estimated, the coexistence of beta-cell dysfunction, and the persistence of key features of pancreas pathology for years after diagnosis impact the perception of the dynamics of this chronic process. The emerging information is helping the identification of novel therapeutic targets and has implications for the design of clinical trials.

Apuntes para la historia de la Endocrinología en Camagüey / Notes for the history of Endocrinology in Camagüey

Introducción: En la década del 60 del pasado siglo, se inicia la atención especializada de Endocrinología en la provincia de Camagüey, Cuba. No existen evidencias documentales sobre esta temática en el territorio, por lo que puede afirmarse que es este un tema pendiente y necesario para la formación integral de los futuros especialistas. Objetivo: Describir la historia de la Endocrinología en la provincia de Camagüey, a partir de la labor de sus principales exponentes y los momentos más importantes de su desarrollo. Método: Investigación histórica basada en la investigación documental. Se utilizó el submétodo cronológico para establecer el orden de los hechos que se describen. Se hicieron entrevistas a personalidades que laboraron en la especialidad y se revisaron algunos artículos históricos publicados, así como documentos de la Biblioteca Provincial "Julio Antonio Mella." Resultados: Se pudo comprobar que antes de 1967 no existía atención endocrinológica especializada en la provincia y los pacientes con este tipo de afecciones eran atendidos fundamentalmente por especialistas en Medicina Interna. A inicios de 1967 llega a la provincia el primer especialista en Endocrinología, el Dr. Sergio Amaro Méndez. Este último, establece un servicio en esta especialidad y se inicia a partir de este momento un desarrollo acelerado en los aspectos docente, asistencial y científico. Conclusiones: La historia de la Endocrinología en Camagüey se inicia en 1967 y tiene su mayor esplendor durante el período de 1979-1990 con el inicio de las determinaciones hormonales por radioinmunoanálisis en la provincia y el inicio de la docencia médica de posgrado. El Grupo Provincial de Endocrinología se ha consolidado hasta alcanzar el prestigio nacional(AU)

Introduction: In the 1960s, specialized endocrinology care began in the province of Camagüey, Cuba. There is no documentary evidence on this topic in the territory, so it can be stated that this is a pending and necessary issue for the comprehensive training of future specialists. Objective: Describe the history of Endocrinology in the province and the most important moments of its development. Method: Historical research based on documentary research. The chronological sub-method was used to establish the order of the events that are described. Interviews were conducted to important people who worked in the specialty and some published historical articles were reviewed, as well as documents from ´´Julio Antonio Mella´´ Provincial Library. Results: It was found that before 1967 there was no specialized endocrinological care in the province and patients with these types of conditions were cared primarily by specialists in Internal Medicine. At the beginning of 1967, the first specialist in Endocrinology, Dr. Sergio Amaro Méndez, arrived to the province. He established a service in this specialty and from this moment on, an accelerated development in the teaching, healthcare and scientific aspects begins. Conclusions: The history of Endocrinology in Camagüey province begins in 1967 and has its greatest splendor during the period 1979-1990 with the beginning of hormonal determinations by radioimmunoassay in the province and the beginning of postgraduate medical teaching. The Provincial Group of Endocrinology has established itself as a group of national prestige(AU)

ENDOCRINOLOGY IN THE TIME OF COVID-19-2021 UPDATES: The management of diabetes insipidus and hyponatraemia.

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counselling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of postoperative SIAD. They should know hyponatraemia symptoms. Hyponatraemia in COVID-19 is common with a prevalence of 20-30% and is mostly due to SIAD or hypovolaemia. It mirrors disease severity and is an early predictor of mortality. Hypernatraemia may also develop in COVID-19 patients, with a prevalence of 3-5%, especially in ICU, and derives from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.

One year of the pandemic - how European endocrinologists responded to the crisis: a statement from the European Society of Endocrinology.

Changes that COVID-19 induced in endocrine daily practice as well as the role of endocrine and metabolic comorbidities in COVID-19 outcomes were among the striking features of this last year. The aim of this statement is to illustrate the major characteristics of the response of European endocrinologists to the pandemic including the disclosure of the endocrine phenotype of COVID-19 with diabetes, obesity and hypovitaminosis D playing a key role in this clinical setting with its huge implication for the prevention and management of the disease. The role of the European Society of Endocrinology (ESE) as a reference point of the endocrine community during the pandemic will also be highlighted, including the refocusing of its educational and advocacy activities.

Extracellular Vesicles-The Next Frontier in Endocrinology.

Extracellular vesicles (EVs), including exosomes, are emerging as important carriers of signals in normal and pathological physiology. As EVs are a long-range communication or signaling modality-just like hormones are-the field of endocrinology is uniquely poised to offer insight into their functional biology and regulation. EVs are membrane-bound particles secreted by many different cell types and can have local or systemic effects, being transported in body fluids. They express transmembrane proteins, some of which are shared between EVs and some being specific to the tissue of origin, that can interact with target cells directly (much like hormones can). They also contain cargo within them that includes DNA, RNA, miRNA, and various metabolites. They can fuse with target cells to empty their cargo and alter their target cell physiology in this way also. Similar to the endocrine system, the EV system is likely to be under homeostatic control, making the regulation of their biogenesis and secretion important aspects to study. In this review, we briefly highlight select examples of how EVs are implicated in normal physiology and disease states. We also discuss what is known about their biogenesis and regulation of secretion. We hope that this paper inspires the endocrinology field to use our collective expertise to explore these new multimodal "hormones."