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.

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.

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.

Pediatric endocrine diseases in pre-Hispanic Aztecs.

Aztec medical and religious knowledge derived from Olmecs (800 BC), Teotihuacans (100 BC) and Toltecs (1100-1521 AC); however, there is no unique source that accurately presents Aztec medicine. Sahagfin combines naturalism and religion but not magic ("First Memorials", "Matritense Codex", "Florentine Codex" and "General History of New Spain"); Hernández gives a naturalistic image but is full of mistakes ("Natural History of the New Spain"); Badiano tries to match Aztecs with contemporary Europeans and with the first century medicine of the Romans ("Badiano Codex"), and Ruiz de Alarcón contains plenty of magical concepts ("Book of Superstition"). For the Aztecs, surveillance of growth was very important and represented a balance between body and soul. They described the different steps of pubertal development. They had specific treatments for thyroid disease in children, mainly hypothyroidism and goiter. There are no references to rickets, nor to type 1 or 2 diabetes mellitus.

[Henry IV of Castilla (1454-1474). An exceptional urologic patient. An endocrinopathy causing the uro-andrological problems of the Monarch. Chronic renal lithiasis (II)]. / Enrique IV de Castilla (1454-1474). Un singular enfermo urológico. Una endocrinopatía causa de los problemas uro-andrológicos del monarca. La litiasis renal crónica (II).

OBJECTIVES: To review all known data about the endocrinopathy and renal disease suffered by Henry IV of Castile according to contemporary chronicles and manuscripts, comparing the clinical diagnosis made by Gregorio Marañon 70 years ago in his work "Biological essay about Henry IV and his time" (Madrid 1930) with present concepts, because we consider, as other medical authors, that his endocrinopathy is not well determined. Regarding his chronic renal lithiasis, it could have played an important role as negative factor in the Monarch's quality of life, and have been related to his endocrinopathy, so that it should also be reviewed. METHODS: We reviewed a total of 10 chronicles and 5 contemporary manuscripts treating the look and diseases of Henry IV to obtain the most important data about both diseases and be able to characterize the kind of endocrine disease suffered by the Monarch, and all aspects regarding his lithiasis, and compare them with our current knowledge. RESULTS: From the review of those chronicles and manuscripts, it is my opinion that Henry IV suffered acromegaly secondary to a GH and prolactine producing hypophyseal tumor from childhood, which might justify the impotence he suffered from his youth and other symptoms clearly referred in the chronicles. Chronic renal lithiasis (flank pain, lumbar illness, and hematuria) finally led to acute obstructive uropathy, main cause of his death. This fact has not been emphasized by historians. The renal lithiasis benign part of a multiple endocrine neoplasia syndrome (MEN I) can not be ruled out.