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The history of assisted human conception with especial reference to endocrinology.

This review lecture is primarily concerned with the study of assisted human conception and especially in-vitro fertilization (IVF). It also places in perspective the role of endocrinology in history of IVF. A knowledge of the hypothalamic-pituitary control of ovulation, and of ovarian follicle dynamics is assumed. A detailed consideration of these topics, together with extensive references, are available in a recent textbook (Edwards and Brody, 1995). Many of the early pioneers studying animal reproduction combined reproductive physiology and endocrinology, especially Marshall, who analysed oestrous and menstrual cycles in many mammalian species. The clarification of the roles of pituitary gland and hypothalamus in the menstrual cycle and ovulation, and their regulation by steroidal feedbacks from the gonads gave an immense stimulus to studies on human reproduction (Smith and Engle, 1927; Lewis and Gregory, 1933; Harris, 1970). Three periods of research into assisted human conception are covered in this lecture including the initial work on the introduction of the endocrinology and embryology of human IVF, the rapid advances in technique as it expanded worldwide, and finally some of the recent remarkable advances in the field.

Animals↗

Subspecialty training in the ambulatory clinic: a preliminary investigation of an endocrinology curriculum.

PURPOSE: There is scant literature on education in the ambulatory subspecialty clinic. This preliminary study was conducted to investigate subspecialty education, using endocrinology as a model. METHOD: In 2002, a questionnaire was mailed to 90 former University of Virginia internal medicine (IM) residents who completed training between 1998 and 2001. The questionnaire asked how well residency prepared them to take care of patients with various endocrine disorders, and to state the best and worst parts of their endocrine training. In 2001-02, 11 fourth-year medical students and 26 senior IM residents rotating on the endocrinology service were asked to record their patient encounters in logbooks. This information was compared to the perceived strengths and weaknesses of endocrine training. RESULTS: Sixty-one residents (68%) completed questionnaires. Significant differences were found in perceived preparedness to care for patients with various endocrine disorders, with diabetes, hypothyroidism, and osteoporosis as strengths and reproductive disorders representing a significant weakness. Fifteen residents (58%) and ten students (91%) completed logs. The logbooks revealed that current learners were well exposed to patients with diabetes and thyroid disorders during the block rotation, but saw relatively few patients with other endocrine disorders. CONCLUSION: Former IM residents felt well prepared by residency to manage certain common endocrine problems, but felt significantly less prepared for other problems, most notably reproductive disorders. University of Virginia's curriculum was modified using information from this study to improve the educational experience in endocrinology. More studies are needed to define optimal strategies for teaching and learning in the subspecialty clinic.

Adult↗

Ten categories of statistical errors: a guide for research in endocrinology and metabolism.

A simple framework is introduced that defines ten categories of statistical errors on the basis of type of error, bias or imprecision, and source: sampling, measurement, estimation, hypothesis testing, and reporting. Each of these ten categories is illustrated with examples pertinent to research and publication in the disciplines of endocrinology and metabolism. Some suggested remedies are discussed, where appropriate. A review of recent issues of American Journal of Physiology: Endocrinology and Metabolism and of Endocrinology finds that very small sample sizes may be the most prevalent cause of statistical error in this literature.

Bias↗

11th International Congress of Endocrinology.

The Olympics of endocrinology, the 11th International Congress of Endocrinolgy was held rather appropriately in Sydney, four weeks after the summer games of the XXWIIth Modern Olympiad. Both occasions were a great success and whilst it may be tempting to extend the analogy to the pool or the track or heaven forbid, digress into 'drugs in sport', this review will focus on endocrinology. There were over 3000 participants with ten plenary lectures, 20 meet-the-expert sessions, 41 symposia, 128 oral free communications and 1500 posters. Sydney post-Olympics provided a vibrant, exciting and picturesque setting with outstanding convention facilities. The Congress Party was held at Campbells Cove in the lee of the Harbour Bridge looking toward the Opera House which provided an opportunity for delegates to view the two architectural icons that had become so familiar in the preceding months. Credit must be given both to the Local Organising Committee of Sydney endocrinologists who made it all happen and to the International Program Organising Committee who crafted a pageant of first rate endocrinology. It is self-evident that this report can only hope to give the reader a flavour of a Congress such as this with the choice of topics being largely idiosyncratic. With five concurrent symposia and two concurrent orals each morning and afternoon of the four days, any omissions reflect not on the topic or its importance but on this reviewer's inability to be in more than one place at once!

Animals↗

Structural genomics in endocrinology.

Traditionally, endocrine research evolved from the phenotypical characterisation of endocrine disorders to the identification of underlying molecular pathophysiology. This approach has been, and still is, extremely successful. The introduction of genomics and proteomics has resulted in a reversal of this sequence of endocrine research: reverse endocrinology. This approach has provided endocrinology with powerful tools to dissect novel molecular pathways involved in health and disease and to identify new drug targets, like the peroxisome-proliferator activated receptor (PPAR) nuclear receptor family. The reiterative combination of innovative genomics and proteomics, and classical endocrine approaches will enable maintenance of endocrinology as a front-runner in biological research and innovate therapeutical approaches in a continuing interaction between bed and bench.

Biomedical Research↗

Current concepts in aesthetic endocrinology.

The extragenital effects of ovarian steroids are relevant to the metabolism of skin and hair, the changes in body composition and the alterations of the subcutaneous fat distribution throughout life. When ovarian steroids become deficient or are produced in excess, different problems may arise in these tissues and some of these problems, i.e., obesity and cellulite, display gender-specific components. Therefore, a new field in endocrine research known as aesthetic endocrinology is gaining more interest. Because sex steroids are small molecules they can be transported into the skin by topical application when properly formulated. This possibility is used in aesthetic endocrinology in order to achieve local effects but to avoid systemic reactions. After reviewing the current data it collectively seems legitimate to recommend estrogens, either orally or topically, in order to counteract the aging of the skin after menopause. Although a reconstitution of juvenile skin cannot be achieved through this method, a slowing in the skin aging process seems a reasonable expectation. In contrast, the successful treatment of hair loss in women is only confirmed for the application of the non-hormonal compound minoxidil. Apart from the difficult problem of hirsutism, acne and changes in body composition offer promising therapeutical options for endocrinological methods.

Aging↗

The emergence of endocrinology.

Endocrinology was recognized as a new branch of biological science mainly as a result of events which took place between about 1890 and 1905, but ideas and discoveries dating from antiquity contributed to it also. Experiments supporting the concept of internal secretions by the testicles were described by Aristotle (4th c. B.C.) and by Hunter (18th c.) and Berthold (19th c.). In 1855 Bernard described glucose as an internal secretion of the liver and Addison reported the effects of adrenal disease in man. Adrenalectomy was fatal in animals. Goitre was known in antiquity and cretinism had been described by Paracelsus. Myxoedema was reported by Gull in 1873, and Kocher described cachexia strumipriva in 1883. In 1888 cretinism, myxoedema and cachexia strumipriva were attributed to thyroid insufficiency. In the 1890s Gley found that tetany after thyroidectomy was due to removal of the parathyroids. In 1884 Rehn proposed that toxic goitre was due to thyroid excess. In 1889 Brown-Séquard claimed that injections of testicular extract rejuvenated the elderly, and in 1893 he introduced organotherapy. In 1891 Murray treated myxoedema successfully with thyroid extract. In 1893 Oliver and Schäfer found that an adrenal extract raised the blood pressure, and soon adrenaline was extracted from the adrenal medulla. Adrenocortical deficiency was proposed as the cause of Addison's disease, and in 1896 Osler prepared an extract which relieved one patient. Diabetes mellitus, described in the first century, was usually fatal. Thirst and polyuria followed experimental pancreatectomy, and pancreatic lesions were found in some human diabetics. In the 19th century workers in France and Germany found that diabetes resulted from absence of an internal secretion by the islets of Langerhans and, in 1893, Laguesse described the function of the islets as "endocrine". In 1895 Beatson treated advanced breast cancer successfully by oöphorectomy. In 1895 Schäfer commended study of the internal secretions to physiologists. In 1902 Bayliss and Starling discovered secretin, a chemical messenger secreted by the intestinal mucosa. In 1905 Starling proposed the name "hormone" for this class of internal secretions. By then endocrinology had been launched as a new branch of science. The crucial events which led to the recognition of endocrinology as a new branch of biological science took place between about 1890 and 1905. Many ideas and discoveries dating from antiquity and apparently unrelated at first had, however, contributed to it. Most of the organs and tissues that form the endocrine system were recognized over 100 years ago.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Emergence of the concept of endocrine function and endocrinology.

Endocrinology as a scientific discipline is relatively new. The term "hormone" was introduced in 1905, and "endocrinology" was introduced in 1909. However, its origins are ancient and rooted in the millennia-old practice of organotherapy, from its archaic religious beginnings, through early attempts to explain the integrated functions of the body by the philosophically sound but scientifically mysterious humors of Greek medicine, to its incorporation into the pharmacopoeias of the eighteenth century. The concept of internal secretions germinated in the anatomical discoveries of the Renaissance, which described ductless glands, and after the discovery of the circulation, came the suggestion of "internal secretions" into blood as organ "emanations which are useful to the body." The principal events that led to the emergence of endocrinology occurred in the latter half of the nineteenth century, from the experimental studies of Claude Bernard (1813-1878), the clinical observations of Thomas Addison (1793-1860), and the combined experimental and clinical studies of Brow-Sequard (1817-1894). The first decades of the twentieth century saw in sequence the isolation of crude organ extracts, their preparation as hormones in pure crystalline form, and their ultimate use in the cure of diseases that had haunted mankind thereto.

Endocrine Glands↗

Two endocrinological anniversaries.

In 2004, the First Faculty of Medicine will commemorate two significant anniversaries related to the small, yet important field of endocrinology. On January 31, 2004 it has been twenty years since the death of the founder of the discipline in this country, professor Josef Charvát (6.8.1897 - 31.1.1984). The occasion was marked by the Dean of the First Faculty of Medicine, by the Prorector of Charles University and by the President of the Czech Academy of Science who jointly unveiled a memorial plaque dedicated to the founder-of Czech endocrinology placed on at the house in Ostrovní Street, where professor Charvát lived and died. During the brief ceremony, short quotes were read from the works of professor Charvát by the famous Czech actor Radovan Lukavský and a speech was delivered by professor Vratislav Schreiber, the most notable of professor Charvat's students. On June 29, 2004, professor Schreiber himself, still full of vigour celebrated his 80th birthday. That day, too, is a significant anniversary in the history of Czech endocrinology.

Czech Republic↗

[Future of endocrinology].

With regards to the future of endocrinology, the author displays a spectrum formed by the following "hot" subjects: A) From a research point of view: 1) Membrane and cytosomal molecular receptors. 2) Prohormones, with regards to: a) paraneoplastic and tumoral syndromes; and b) "messenger" or transitory hormones. 3) Metabolic clearings: a) Normal; b) in endocrine pathology and c) in pathology of transformation and elimination: liver and kidney. B) From a practical-empirical point of view: 1) Tests of fetoplacental function. 2) Clinical perspectives of the use of hormonal factors and provoked endocrinological clinics (iatrogenic endocrinology). 3) Growth factors and somatostatine. 4) Thymus hormones. 5) Gastrointestinal hormones. 6) The renine-angiotensine-aldrosterone system, the problems of hypertension and preservation of the hydric compartments. Natriuretic hormones.

Aldosterone↗

[Present state and perspectives of endocrinology in Czechoslovakia].

The contemporary state of the sub-discipline of endocrinology within the framework of internal medicine is generally considered rather desolate, but so far actual data were lacking. Based on an analysis of data provided by regional specialists in the Czech Republic and by regional (district) specialists in internal medicine in Slovak republic it may be said that in the majority of health institutions the number of endocrinologists does not reach even the unsatisfactory standard (i. e. 1 endocrinologist per 150 to 250,000 population), that specialized training of endocrinologists, specialists in internal medicine and other specialist is not ensured, that there are not adequate numbers of community doctors and factory medical officers, that there are not adequate capacities of specialized laboratory examinations and that adequate collaboration with other disciplines is not ensured (the position is in particular alarming as regards immunological methods and cytological processing of specimens obtained by aspiration biopsy from the thyroid gland. With regard to these data the authors recommend to raise the numbers of endocrinologists so that in institutions corresponding to hospitals with policlinics type II there will be one endocrinologist per 50-100,000 population, to improve the standard and availability of auxiliary examinations, to ensure endocrinological in-patient care at the level of hospitals with policlinics type III and to create specialized centres within the framework of the research base or university hospitals. It is important to resolve the link between endocrinology and other disciplines (paediatrics, gynaecology etc). It is also essential to coordinate closely therapy, education and research, Federal coordination is essential.

Czechoslovakia↗

Advances in field-based studies of primate behavioral endocrinology.

The papers in this issue were inspired by a symposium we organized for the 27th Annual Meeting of the American Society of Primatologists, held in June 2004. The purpose of the symposium was to highlight some of the new ways in which noninvasive techniques for measuring steroids are being employed to investigate the relationships between hormones and behavior in wild primates. Endocrinological data from the field provide new insights and more precise interpretations of behavioral data on topics ranging from social and reproductive strategies to seasonality, reproductive suppression, concealed ovulation, and development. Advances in the development of methods for extracting steroids from urine and feces have increased the options available to field workers, who can now select the most appropriate methodology for their study subjects, field conditions, and specific research questions. Field-based studies of behavioral endocrinology have spread to include a wide diversity of primate species. As the scope of these studies continues to grow, we anticipate the emergence of a dynamic new field in which comparative models of primate behavioral endocrinology contribute new perspectives on primates.

Animals↗

Endocrinology of breast cancer.

Oestrogen predominance over progesterone may cause hyperproliferation of mammary epithelium and thus promote breast carcinogenesis. In patients with a hormone-dependent tumour, oestrogens may also accelerate cancer growth. Conversely, they may inhibit tumour growth in patients with an oestrogen receptor-negative carcinoma which has grown in an oestrogen-poor environment. Progesterone opposes oestrogen-induced epithelial proliferation and causes cellular differentiation with decreased mitosis, thus reducing the risk of breast cancer. Prolactin brings about mammary epithelial differentiation for secretory function; in the lactation state, epithelial proliferation is minimal. The role of androgens, melatonin, thymosin, metabolic hormones (growth hormone, thyroid hormone(s), insulin, glucocorticosteroids) and prostaglandins in the pathobiology of breast cancer is poorly understood. A breast cancer population consists of individuals in whom more than 20 different tumour subsets may be present, i.e. patients with different individual tumour pathobiology and endocrinology patterns and therefore different prognoses. Progress in the endocrinology of breast cancer seems possible through prospective studies in which hormones are determined in normal breast tissue (ductal fluid, cyst fluid) and then related to the corresponding concentrations in the plasma and urine of patients who develop breast cancer and those who do not. In addition, genetic and nonhormonal risk factors for breast cancer must be taken into consideration to define the endocrinological aspects involved.

Aged↗

The clinical, neuroradiographic, and endocrinologic profile of patients with bilateral optic nerve hypoplasia.

PURPOSE: The purpose of the study was to expand on ophthalmologic and endocrinologic data and report the neuroimaging findings of 35 patients with bilateral optic nerve hypoplasia (BONH). METHODS: A retrospective chart review of 35 children with BONH was conducted. Data on visual acuity, refractive error, and presence of nystagmus and strabismus were collected. Twenty-six children underwent full-endocrinologic evaluation and magnetic resonance imaging or computed tomography scanning. RESULTS: The male:female ratio was 2:1. Ten percent of eyes had visual acuity of 20/60 or better, whereas 34% had no light perception. Eighty-six percent of eyes had acuity less than 20/200, and 80% of patients were legally blind. Most patients (86%) had nystagmus or strabismus or both. Forty-six percent had absence of the septum pellucidum and corpus callosum on neuroimaging. Twenty-seven percent of patients had endocrinologic abnormalities, with growth hormone deficiency being the most common. Panhypopituitarism occurred in 11.5% of children. CONCLUSIONS: Although the visual prognosis of children with BONH generally is poor, 10% of such patients have excellent acuity. In contrast to previous reports, endocrine abnormalities were seen in only one quarter of patients, and the full-blown deMorsier syndrome (septo-optic dysplasia with panhypopituitarism) was seen in only 11.5% of patients with BONH.

Abnormalities, Multiple↗

Effects of subchronic paroxetine administration on night-time endocrinological profiles in healthy male volunteers.

To evaluate the subchronic effects of paroxetine, a selective serotonin reuptake inhibitor, on nocturnal endocrinological profiles, eight healthy male volunteers with no personal or family history of a psychiatric or neurological disease were administered paroxetine (30 mg/day) or placebo in a double-blind cross-over design. Drugs were given as a single dose at 10:00 h for a period of 4 weeks each. Between days 21 and 28 of each treatment period, sleep EEG was registered for four consecutive nights from 23:00 to 07:00 h. During the last night, hormonal profiles for prolactin, growth hormone (GH), cortisol, corticotropin (ACTH), luteinizing hormone (LH), testosterone and melatonin were determined, and area-under-the-curve values were calculated. None of the endocrinological parameters revealed any statistically significant changes. A trend could be found for an increased cortisol production under paroxetine (P = 0.069). ACTH, LH, and melatonin showed slight and non-significant decreases. Prolactin release was only marginally elevated (+7%). The mean sleep onset GH release (as measured for a time period of 180 min after sleep onset) was decreased by about 30% under paroxetine. However, statistical significance could not be reached. For hGH, there was a delayed mean GH-peak under paroxetine. Nocturnal testosterone secretion remained almost unaltered. The lack of significant endocrinological alterations might be partially explained by both adaptational phenomena under subchronic treatment conditions and the extended time span between the single morning dose and the registration period, respectively.

Adrenocorticotropic Hormone↗

Divergent reproductive endocrinology of the estrous cycle and pregnancy in dwarf hamsters (phodopus).

Progesterone (P4) and prolactin (PRL) in peripheral circulation of Siberian hamsters (Phodopus sungorus) throughout an estrous cycle and pregnancy were determined by repeated, small volume sampling from individuals housed in modified home cages. As predicted, the endocrinology of P. sungorus reproduction is similar to the rat, mouse and golden hamster and shows none of the eight distinctive features known for Djungarian hamsters (Phodopus campbelli). Specifically, in P. sungorus there is no evidence for resumption of pituitary PRL surges in late pregnancy, P4 concentrations during the differentiation of the corpus luteum on day 2 of pregnancy are higher (as opposed to lower) than concentrations on the comparable day of an unmated estrous cycle (diestrus 1), P4 concentrations increase throughout pregnancy, PRL surges are common during the estrous cycle, including a reliable surge on proestrus, and P4 plays an important role in facilitating the expression of behavioral receptivity. We conclude that 'novel' P. campbelli reproductive endocrinology has evolved since a common ancestor was shared with P. sungorus. With a time frame (the available time since the divergence of the two species) and an ecological context (known niches and behavior in the wild) these species offer the opportunity to study endocrinological evolution in progress.

Animals↗

Endocrinology in cancer of the breast. Status and prospects.

Breast cancer is the result of a multistage carcinogenic process. Initiation, promotion, dependency and autonomy make up a sequence of experimentally distinguishable phases of this process. Progression--the transition from dependency on hormonal support to autonomy--is demonstrable clinically. High-affinity saturatable estrogen binding by breast cancer cytosols distinguishes endocrine-responsive mammary neoplasms from autonomous breast cancers. Approximately 70% of neoplasms containing estrogen-recepor protein at a level of 2.5 femtomoles per mg. protein or higher regress after endocrine ablation (ovariectomy in premenopausal women; adrenalectomy or hypophysectomy in postmenopausal women). Only about 5% of neoplasms lacking the receptor will respond to these maneuvers. Estrogen-receptor content also predicts clinically for estrogen and androgen responsiveness, and experimentally for prolactin dependency. Fifty per cent of primary breast cancers in women are receptor-positive. Normal breast tissue and benign breast lesions characteristically lack receptor protein. The receptor proteins appear to be induced in neoplastic cells during mammary carcinogenesis in endocrinologic settings where non-cancerous breast cells do not contain free receptor in large amounts and fail to manifest endocrinologic growth stimulation. Implications of these findings for endocrinologic management of disseminated mammary cancer, adjuvant therapy, and breast cancer prevention are discussed.

9,10-Dimethyl-1,2-benzanthracene↗

Endocrinological outcome of different treatment options in children with craniopharyngioma: a retrospective analysis of 66 cases.

Craniopharyngioma is one of the leading causes of hypothalamic-pituitary dysfunction in childhood, caused either by the tumor itself or the consequences of treatment. Tumor management in terms of recurrence rate, quality of life and complications is still controversial. Sixty-six patients with craniopharyngioma at pediatric age were reviewed for symptoms, signs, types of treatment, recurrence rates, complications, and endocrinological outcome. The majority of symptoms was related to the neurological system. Complaints only affecting the endocrinological system were seen in 6% of patients. The most frequent complaints were headache and vomiting (74.2%). The main endocrinological complaints were polyuria and polydipsia (15%), and lassitude (10.6%). Although short stature was a symptom in 9.1% of patients, it was a finding in 39.7% of patients. Plain skull X-rays raised the suspicion of intracranial tumor in more than 90% of children with craniopharyngioma. Recurrence rates were independent of the extent of tumor removal (total or subtotal). The frequency of endocrine dysfunction increased significantly after treatment. The most frequent hypothalamic-pituitary dysfunction was growth hormone deficiency (100%) and gonadotropin deficiency (80%). Hypothyroidism was diagnosed in 74% of patients. The frequency of hypothalamic-pituitary dysfunction was not affected by the extent of tumor removal. Radiotherapy did not increase the frequency of endocrine dysfunctions further. In conclusion, growth follow-up in childhood seems to be an important indicator of craniopharyngioma in early diagnosis. Radiotherapy and extent of tumor removal - either total or subtotal - did not influence endocrine outcome.

Adolescent↗