Growth and Growth Hormone through the Ages: Art and Science.

BACKGROUND: People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in classical art, as well as the courts of European monarchs, and were exploited in "shows." Serious medical evaluation began in the late 19th century with the description of acromegaly and its association with pituitary tumors. In the early 20th century, multiple investigators attempted to extract a growth-promoting factor from the anterior pituitary and then, over the decades, to purify it and distinguish it from other anterior pituitary hormones. With relatively pure growth hormone (GH), its biological activity in growth promotion and as a metabolic hormone were studied, and species specificity became apparent: primate GH was the only GH active in man. Human GH was prepared from cadaveric pituitaries and distributed by the NIH to treat children with GH deficiency, but there was never enough pituitary hGH for all of the children who required it. When Creutzfeldt-Jakob disease was found in some patients who received pituitary GH, the production and FDA approval of biosynthetic hGH dramatically accelerated. With a large supply, one could treat those who were GH deficient and test its efficacy in other causes of short stature; longer acting versions of hGH have now been developed, tested, and in a few instances received FDA approval. SUMMARY: It has been a long journey from the description of over- and underproduction of GH in animals to the production and clinical use of the biosynthetic hormones. KEY MESSAGES: The efforts of basic scientists led to the extraction and purification of GH. Clinical scientists have expanded the appropriate use of hGH for short children with conditions in addition to GH deficiency.

El 'rejuvenecimiento' y los inicios de la endocrinología chilena en la década de 1920 / The 'rejuvenation' and beginnings of Chilean endocrinology in the 1920s

El rejuvenecimiento fue un capítulo de la máxima importancia en el desarrollo de la endocrinología a nivel mundial en la década de 1920. Este trabajo explora la recepción de estas técnicas en Chile. Desde finales del siglo XIX, la Revista Médica de Chile incorporó referencias a los experimentos con preparados de glándulas endocrinas que se estaban realizando en Europa en aquel momento. A partir de 1920 se inició una apropiación en Chile de los experimentos del austríaco Eugen Steinach, con figuras destacadas como el profesor italiano Juan Noé Crevani y el joven estudiante chileno Ottmar Wilhelm. Entre 1922 y 1924, Wilhelm desarrolló una serie de experimentos en los cuerpos de perros, toros, cerdos, ratas y pacientes de la Junta de Beneficencia, a través de la llamada operación Steinach, que consistía en la sección del canal eferente de uno de los testículos. La política de patronazgo científico del profesor Noé y la estrategia de sucesión en el campo de Wilhelm, llevaron a este último a ocupar una cátedra en la naciente Escuela de Medicina de la Universidad de Concepción, a la edad de 25 años. Desde esa posición, la figura de Wilhelm fue fundamental en el desarrollo de una línea de investigación endocrinológica que logró posicionar a la Universidad de Concepción como un polo de desarrollo científico, fortalecido con la llegada de otro discípulo de Steinach a Chile, el profesor letón Alejandro Lipschütz (AU)

Rejuvenation was a chapter of critical importance for the worldwide development of endocrinology in the 1920s. This work explores the acceptance of these techniques in Chile. Starting in the late 19th century, the Chilean Medical Journal (Revista Médica de Chile) incorporated references to experiments with endocrine gland preparations that were being conducted in Europe at the time. An appropriation of the experiments by the Austrian Eugen Steinach began in 1920, with prominent figures such as the Italian professor Juan Noe Crevani and the young Chilean student Ottmar Wilhelm. Between 1922 and 1924, Wilhelm developed a series of experiments on dogs, bulls, pigs, rats and Welfare Board patients through the so-called Steinach operation, which consisted of the sectioning of the efferent channel in one of the testicles. Professor Noe’s scientific patronage policy and Wilhelm’s strategy of succession in the field led the latter to hold a chair in the new School of Medicine of Universidad de Concepción at the age of 25. From this position, the figure of Wilhelm was fundamental for the development of a line of endocrinological research that was able to position Universidad de Concepción as a scientific development centre, which was strengthened by the arrival of another disciple of Steinach in Chile, the Latvian professor Alejandro Lipschütz (AU)

The Historical Development of Immunoendocrine Concepts of Psychiatric Disorders and Their Therapy.

Relationships between the central nervous, immune and endocrine systems are a focus of psychiatric research, particularly in depression and schizophrenia. The field has long antecedents. Observed phenomena attributable to these relationships date back to the Neolithic era. Immunoendocrine theories in the broadest sense are recorded in antiquity. In the 19th century, Kraepelin and Wagner-Jauregg reported pioneering clinical observations in psychiatric patients. Von Basedow, Addison and Cushing described psychiatric symptoms in patients suffering from endocrine diseases. The 20th century opened with the identification of hormones, the first, adrenaline, chemically isolated independently by Aldrich und Takamine in 1901. Berson and Yalow developed the radioimmunoassay (RIA) technique in 1959 making it possible to measure levels of hormones and cytokines. These developments have enabled great strides in psychoimmunoendocrinology. Contemporary research is investigating diagnostic and therapeutic applications of these concepts, for example by identifying biomarkers within the endocrine and immune systems and by synthesizing and testing drugs that modulate these systems and show antidepressant or antipsychotic properties.

Personajes históricos en la consulta de Endocrinología / Historical figures at the office of Endocrinology

Algunos personajes históricos han sufrido enfermedades endocrinológicas. Esta revisión relaciona aquellos cuyas enfermedades han sido publicadas en la literatura científica. Se realiza un breve apunte biográfico y se describe el proceso patológico en aquellos considerados más relevantes por la naturaleza de la enfermedad o la importancia del personaje en el ámbito español e iberoamericano: el faraón Akhenatón, Maximino I, Bodhidharma, Sancho I de León, Guillermo el Conquistador, Enrique IV de Castilla, Enrique VIII de Inglaterra, María Tudor, Carlos II de España, Pío Pico, Pedro II de Brasil, Eisenhower y J. F. Kennedy

Some historical figures have suffered endocrine diseases. This review relates those whose diseases have been published in the scientific literature. It takes a biographical summary and describes the disease process in those considered most relevant by the nature of the disease or the importance of the figure in the Spanish and Latin American context: the Pharaoh Akhenaten, Maximinus I, Bodhidharma, Sancho I of Leon, William the Conqueror, Enrique IV of Castile, Henry VIII, Mary Tudor, Carlos II of Spain, Pio Pico, Pedro II of Brazil, Eisenhower and J. F. Kennedy

La cuestión sociosanitaria en la obra de Marañón en el contexto de la lucha contra las enfermedades infecciosas / Social-sanitary situation in Marañon’s work in the context of the fight against infectious diseases

Como es conocido, Gregorio Marañón y Posadillo (1887-1960), jugó un papel fundamental enel nacimiento de la Endocrinología en España. Sin embargo, su trabajo médico también se centróen otros importantes campos. Fue, sobre todo, en la década de 1910 y 1920, cuando Marañón centrósu atención en la situación sociosanitaria de Madrid, probablemente relacionada con su vinculaciónprofesional al tratamiento de las enfermedades infecciosas puesto que desde 1911 se hizocargo de la Sala de Enfermedades Infecciosas del Hospital General del Madrid, donde tuvo laoportunidad de tratar a este tipo de enfermos. Como consecuencia de su preocupación por la etiologíasocial de enfermedades de prevalencia excesiva o de los brotes epidémicos, en los años siguientes,publicó diversos artículos especializados y presentó comunicaciones en la Real AcademiaNacional de Medicina acerca de estas cuestiones vinculadas a la situación sociosanitaria del país.Este trabajo trata de estudiar este aspecto menos conocido de la obra de Gregorio Marañón(AU)

Gregorio Marañón y Posadillo (1887-1960), played a leading role in the birth of Endocrinologyin Spain as is well known. However, his medical work included other important and significant fields.Thus, it was specially in the 1910s and 1920s, when Marañón dealt with the social-sanitary situationin Madrid probably due to his professional attachement to the treatment of several infectious diseasesand epidemic outbreaks. Actually, since 1911 onwards, he was in charge of the wards of infectiousdiseases in the Hospital General de Madrid where he had the opportunity of treating an importantnumber of patients suffering from this type of pathology and, as a consequence, in the following yearshe published several articles in medical journals and presented, in the Royal Academy of Medicine inSpain, some reports on infectious diseases and the Spanish health and social conditions at the time.This paper try to analyze this field of Marañón’s social and scientific activity(AU)

Critical appraisal of growth retardation and pubertal disturbances in thalassemia.

Growth and pubertal disturbances are the commonest endocrinopathies in homozygous thalassemia, accounting for significant morbidity in 70-80% children and adolescents globally. This review focuses on the pathophysiology of the endocrinopathy from a historical perspective and altered natural history induced by better care due to transfusion and chelation therapy. We have also discussed clinical features, diagnosis, and management strategies of growth retardation, sexual infantilism, pubertal aberrations, and scope of growth hormone, sex steroids, and other endocrine therapies. The article also emphasizes current and future strategies for screening, monitoring of growth and pubertal disturbances, and early intervention for the restoration of fertility potential and bone mass in the affected individuals.

Mechanisms of sex difference: a historical perspective.

OBJECTIVE: The history of the discovery of mechanisms contributing to sex difference helps to better appreciate gender factors in a variety of disease states. The objective of this article is to illustrate four mechanisms of sex differences in disease incidence: X-linkage (including inactivation, escape from inactivating, skewed inactivation), sex-specific exposure to disease-producing pathogens, fetal microchimerism, and iron depletion. METHODS: This is a historic review. RESULTS: An emphasis on sex difference led to the uncovering of four different mechanisms by which illness rates differ in men and women. CONCLUSIONS: Research into many disease states can benefit from a focus on potential mechanisms that yield sex differences in illness susceptibility, progression, and outcome.

Neuroendocrine basis of human disease.

This paper is a short review of the traditionally obvious diseases of neuroendocrine origin (diabetes insipidus, Kallman syndrome, etc.), but also of the newly recognized participation of several peptides originally characterized in the hypothalamus and of their receptors, in a series of diseases, both in internal medicine and in psychiatry (rheumatoid arthritis, inflammation, carcinoids, anxiety, depression, etc.). The concept of neuropeptides is now vastly expanded, as these molecules and their several receptors are now known to be widely distributed throughout the brain and the periphery with increasing evidence of paracrine and autocrine modes of action.