bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroendocrine tumour markers
Authors: Ramachandran R. , Dhillo W.
Published: July 2011

Neuroendocrine cells occur either singly or in small groups in a variety of tissues and organs. Although morphologically and embryologically diverse, they are characterized by a number of unifying features. They have dense core secretory vesicles in the cytoplasm and hormone receptors on the cell membranes. There is evidence of prohormone activity within the cells and they synthesize, store, and secrete hormones. In addition, neuroendocrine cells possess an ability to take up and decarboxylate amine precursors.

Components of this diffuse endocrine system are particularly prominent in the gastrointestinal tract, pancreas, C cells of the thyroid, adrenal medulla, parathyroid tissue, respiratory tract, skin, and genitourinary system. Neuroendocrine tumours (NETs) are known to occur in all these tissues.

Historically, the diagnosis of NET was made on the basis of characteristic histological findings. The significantly worse prognosis in advanced disease and the availability of multiple therapeutic options have highlighted the need for robust tumour markers that can be used both for diagnosis and follow-up. Currently, a number of normal and abnormal forms of peptides, biogenic amines, and hormones, secreted by NETs, are routinely measured as markers of disease.

An ideal tumour marker would be one that is secreted exclusively by the tumour cells and is useful (1) for screening and differential diagnosis of NETs; (2) as a prognostic indicator; (3) as an estimate of tumour burden; and (4) as a surveillance tool. Although none of the currently available markers completely fits the paradigm for an ideal tumour marker, when measured in conjunction with each other, they are useful not only for making a diagnosis but also for monitoring response to therapy and in surveillance post-remission.
Gastrinoma
Authors: Toumpanakis Christos , Caplin Martyn
Published: July 2011

Gastrin is a gastrointestinal hormone, produced predominantly by the G cells of the gastric antrum and duodenum, although small amounts of gastrin have been isolated in the pituitary and some vagal nerve fibres. The biologically active forms of gastrin include carboxy-amidated gastrin-17 and carboxy-amidated gastrin-34, which bind mainly to the cholecystokinin (CCK)-2 receptor. The main role of amidated gastrin is the stimulation of gastric acid secretion by regulation of histamine release from the gastric enterochromaffin-like (ECL) cells, while it may also have a trophic effect on gastric mucosa. There is evidence that the precursor forms of gastrin, such as progastrin and glycine-extended gastrin, are also of biological importance, binding to a separate CCK-C receptor. These precursor may induce cellular and tumour growth and they are implicated in several cancers, such as colon and pancreatic adenocarcinomas.

Gastrinomas represent a group of functional pancreatic neuroendocrine tumours, characterized by autonomous release of gastrin by the tumour cells, which results in symptoms not only due to the tumour growth per se, but also to gastric acid hypersecretion.

In 1955, at the annual meeting of American Surgical Association, Robert M. Zollinger and Edwin H. Ellison presented a study entitled Primary Peptic Ulcerations of the Jejunum Associated with Islet Cell Tumour of the Pancreas. They proposed a new clinical syndrome of: (1) ulceration in unusual locations in the upper gastrointestinal tract or recurrent ulcerations; (2) gastric acid hyperseretion; and (3) non-β‎ islet cell tumours of the pancreas. However, the potent gastric secretagogue for the Zollinger–Ellison syndrome was not identified until 1960, when Rodney Gregory and Hilda Tracy of the University of Liverpool discovered that the extract from the pancreas of a patient with Zollinger–Ellison syndrome was the hormone gastrin. Thus, these pancreatic tumours were termed ‘gastrinomas’.
Insulinoma and hypoglycaemia
Authors: Mehta Puja , Todd Jeannie F.
Published: July 2011

Hypoglycaemia is a clinical syndrome with diverse aetiology. Insulinomas, although rare, are the most common functioning pancreatic islet cell tumour and may be part of the multiple endocrine neoplasia type 1 (MEN 1) syndrome. Patients present with symptoms of neuroglycopenia and a catecholamine response. Diagnosis is confirmed by evidence of endogenous hyperinsulinaemic hypoglycaemia. Tumours are localized by ultrasonography, CT and/or intra-arterial calcium stimulation with venous sampling. Most tumours are benign and solitary, making surgical cure possible with complete resection. Medical options, including diazoxide or octreotide, are available for multifocal tumours.
Glucagonoma
Authors: Nijher G.M.K. , Bloom S.R.
Published: July 2011

Glucagonomas are neuroendocrine tumours arising from the α‎ cells of the islets of Langerhans, which result in excessive secretion of glucagon and peptides derived from preproglucagon. Post-translational modification of proglucagon is tissue specific and results in various glucagon peptides (1). It is the ratio of insulin to glucagon that controls the balance of gluconeogenesis and glycogenolysis in the liver. Glucagon stimulates hepatic gluconeogenesis and inhibits both glycolysis and glycogen synthesis. It increases production of free fatty acids from triglyceride breakdown by activating hormone-sensitive lipase; these undergo fatty oxidation in the liver via acetyl CoA, forming ketone bodies. The increase in free fatty acids from lipolysis inhibits hepatic lipogenesis. Glucagon also increases muscle proteolysis, resulting in an increase in amino acid supply to the liver.
Neurofibromatosis
Authors: Tharakan George
Published: July 2011

Neurofibromatosis 1 and 2 have historically been grouped together. However they represent two distinct diseases separated both genetically and clinically. Both diseases are discussed in this chapter with the emphasis on neurofibromatosis 1 (NF 1), which has more endocrine manifestations.
Menstrual cycle and ovulation
Authors: Ledger William L.
Published: July 2011

The drive to reproduce is the most basic imperative followed by all animal and plant species. The human race has demonstrated great efficiency in increasing its numbers despite relatively low reproductive efficiency when compared with many other species. Humans are monotocous, and the coordinated ovarian and uterine cycles that are evidenced by monthly menstruation serve the purpose of preparing the uterus for implantation at the time when a single fertilized oocyte has completed its journey along the Fallopian tube and into the uterine cavity. Failure of the ovarian or uterine cycles at

any point can lead to infertility, and eventual depletion of the pool of primordial follicles within the ovaries results in menopause with cessation of menses and clinical symptoms of hypo-oestrogenism.

This chapter will describe the physiology of the ovarian and uterine cycles with particular reference to the various pathological consequences that can result when the complex mechanisms that regulate the processes fail to function.
Hyperprolactinaemic anovulation
Authors: Davis Julian R. E.
Published: July 2011

Prolactin is a polypeptide hormone, named from its well-known effects to promote lactation. It is essential for successful reproduction in man and mammals, although it is known to have a wide variety of nonreproductive effects whose clinical significance remains uncertain.

Hyperprolactinaemia, reflecting sustained overproduction of lactin by the pituitary, is relatively common in the population. The commonest cause is the use of drugs that have dopamine D2 receptor antagonist activity (e.g. antipsychotic agents such as phenothiazines), pregnancy and lactation are the commonest physiological causes, and short-term acute stress, such as the anxiety provoked by blood sampling, is also a frequent cause of transient rises in serum prolactin that may be misinterpreted and necessitate a second confirmatory blood sample. Pathological pituitary causes of hyperprolactinaemia may reflect a functioning pituitary prolactinoma, but in many cases no adenoma is detectable on scanning, in which case the condition is termed idiopathic or nontumoral hyperprolactinaemia.

The typical clinical features that suggest hyperprolactinaemia are those of galactorrhoea and oligo-/amenorrhoea. Weight gain has been reported in hyperprolactinaemic women, as has insulin resistance. Serum prolactin levels are readily measured by most clinical biochemistry laboratories, and prolactin levels should be measured on more than one occasion, with persistent unexplained hyperprolactinaemia requiring evaluation.

Patients with hyperprolactinaemia may require treatment for various reasons, including restoration of ovulatory function, maintenance of adequate oestrogenization, suppression of galactorrhoea, or reduction in size of a mass lesion. Depending on the presentation and underlying cause, there are several treatment options; the main current treatment option is dopamine agonist therapy, surgery and (rarely) radiotherapy are also used in the treatment of prolactinomas.
Hirsutism
Authors: Yildiz Bulent O. , Azziz Ricardo
Published: July 2011

Hirsutism is defined as excess growth of body or facial terminal (coarse) hair in females, in a male-like pattern. The condition has a significant negative impact on a woman’s self-esteem and on her quality of life. Hirsutism affects 5–15% of the women, and is the most commonly used clinical diagnostic criterion of androgen excess or hyperandrogenism (1). Depending on age and race/ethnicity, 80–90% of women with hirsutism will have an androgen excess disorder, most often polycystic ovary syndrome (PCOS), and including idiopathic hirsutism, and non-classic congenital adrenal hyperplasia (NCAH), among the others.

This chapter outlines androgen metabolism in women, physiology and pathophysiology of hair growth, epidemiology of and differential diagnosis of hirsutism, other signs of androgen excess including acne, androgenetic alopecia, and virilization, and the clinical investigation, and treatment of the hirsute patient.
Nutrition and reproduction
Authors: Lim Siew S. , Norman Robert J.
Published: July 2011

Reproductive function is closely related to nutritional status. In the animal kingdom reproduction often takes place when food and climatic conditions are favourable towards optimal nutrition to maximize the survival of the offspring. This is sensible considering

pregnancy and lactation are times of greatest nutritional needs in the life of female mammals. In humans, under- and over-nutrition as reflected in body weight and body composition significantly impact fertility. Aside from the mother’s energy status, her micronutrient adequacy throughout the pregnancy and lactation period also influences the development of the offspring.
Prevention in endocrinology
Authors: Laurberg Peter , Andersen Stig
Published: July 2011

The basis of health care is that it is much better for the individual member of society to be healthy and well than to be ill or deceased (1). To assist the individual in staying alive and well the health care system provides a broad range of services aimed at cure or control of disease. These services are available when someone becomes ill.

A different approach to preservation of good health and longevity is the prevention of disease. Prevention may take many forms. This may vary from legislation on food declaration via public campaigns on the importance of physical exercise to neonatal screening programmes. The intervention may be directed at decreasing the risk for disease in healthy subjects (primary prevention). A common variation is prevention of the severe consequences of disease by early detection of subclinical disease by screening or case-finding (secondary prevention). Other variants are prevention of complications of disease (tertiary prevention) or prevention of recurrence of disease by secondary intervention.

Often the costs of classic clinical care and prevention are compared in a way suggesting that the primary advantage of prevention is that it saves money. This conclusion may be correct in some areas of prevention such as in iodine deficiency disorders. It is, however, far too simple when it comes to many other areas such as prevention of complications in elderly patients with diabetes mellitus (1). The major appeal of prevention is that it is a most effective and often also a cost-effective way of reducing the burden of disease.
Molecular aspects of hormonal regulation
Authors: Chew Shern L.
Published: July 2011

The wide molecular effects of hormones have complicated the understanding of how hormones work on a cell. The old view was of a linear signalling pathway from the receptor to the nucleus, thereby stimulating gene transcription. This view is probably an oversimplification. Hormones can not only regulate most of the molecular machines of the cell, certainly the transcription machinery, but also others. These machines perform and coordinate functions such as RNA and protein biosynthesis, macromolecular transport, cell division or death, and intracellular signalling. Physiological studies have shown that hormonal regulation is specific, yet flexible, and has the ability to generate feedback loops. Advances in genetics, cellular, and molecular biology, and biochemistry have allowed much new, and sometimes confusing, data on the mechanisms underlying hormonal regulation. Many advances have been due to methods of identifying and verifying networks of interactions between proteins. One example is the yeast two-hybrid system, an in vivo genetic screening method for such interactions. Another example is the use of protein tagging (e.g. with histidine residues) which can allow rapid and high-yield protein purification for biochemical studies. This chapter will briefly review some of the mechanisms of hormonal regulation.
Endocrine autoimmunity
Authors: Simmonds Matthew J. , Gough Stephen C. L.
Published: July 2011

Dysfunction within the endocrine system can lead to a variety of diseases with autoimmune attack against individual components being some of the most common. Endocrine autoimmunity encompasses a spectrum of disorders including, e.g., common disorders such as type 1 diabetes, Graves’ disease, Hashimoto’s thyroiditis, and rarer disorders including Addison’s disease and the autoimmune polyendocrine syndromes type 1 (APS 1) and type 2 (APS 2) (see Table 1.6.1). Autoimmune attack within each of these diseases although aimed at different endocrine organs is caused by a breakdown in the immune system’s ability to distinguish between self and nonself antigens, leading to an immune response targeted at self tissues. Investigating the mechanisms behind this breakdown is vital to understand what has gone wrong and to determine the pathways against which therapeutics can be targeted. Before discussing how self-tolerance fails, we first have to understand how the immune system achieves self-tolerance.
Endocrine disruptors
Authors: Creatsas George , Mastorakos George
Published: July 2011

During the past 50 years, there has been a huge increase in the number of chemical substances used worldwide as plasticizers, pesticides, detergents, paints, metal food cans, flame retardants, cosmetics, and chemical wastes, which exhibit the potential to interfere with the endocrine system of humans and animals. In addition, it has been found that many natural plant products have the same features (i.e. phyto-oestrogens). The public health risks related to these substances have raised reasonable concerns. Thus, the so-called endocrine disruptors have become the target of major scientific research.
Lipoprotein metabolism
Authors: Angelin Bo , Parini Paolo
Published: July 2011

The realization that raised concentrations of plasma lipids, particularly cholesterol, are associated with an increased risk of coronary heart disease has stimulated the study of factors regulating plasma lipid metabolism. With the use of increasingly refined methodology, our understanding of normal plasma lipoprotein metabolism and its derangements due to the influence of genetic and environmental factors is continuously expanding. This chapter summarizes some current concepts regarding plasma lipoprotein transport in normal humans, forming a basis for the discussion of the development of various dyslipidaemias in the following chapters.

Lipids represent a heterogeneous group of substances with several biological functions. Phospholipids and cholesterol are essential components of cell membranes, and cholesterol is also the precursor of steroid hormones and bile acids. Some fatty acids form the origin of bioactive compounds such as prostaglandins, thromboxanes, and leukotrienes; phospholipids, fatty acids, and cholesterol may also serve as signalling molecules in their own right. Furthermore, lipid complexes are necessary for the transport of lipid-soluble vitamins, and may have a protective role in the defence against toxins and infectious agents. From an overall physiological perspective, however, the major function of plasma lipid metabolism is the exchange of fat as energy substrates.
Genetic defects in sterol synthesis, absorption, and degradation into bile acids
Authors: Romeo Stefano
Published: July 2011

Cholesterol is the most abundant steroid in animals. Not only is it a vital constituent of cell membranes, where it establishes proper membrane permeability and fluidity, but it is also the immediate metabolic precursor of all known steroid hormones and bile acids. Synthesized de novo in cells or absorbed from the diet, cholesterol circulates in the body in association with lipoproteins and is ultimately degraded into bile acids by the liver. Every perturbation of the numerous enzymes involved in cholesterol metabolism leads to impairment in the development and function of the gastrointestinal, cardiovascular, skeletal, and nervous systems.
The porphyrias
Authors: Badminton Michael N. , Elder George H.
Published: July 2011

The porphyrias are metabolic diseases resulting from deficiency, or in one disease, an increase in the activity, of specific enzymes in the haem biosynthetic pathway (1, 2). Each of the eight main types of porphyria is defined by the association of characteristic clinical features with a specific pattern of excess production of pathway intermediates. Each pattern indicates the site of the underlying enzymatic abnormality (Fig. 12.3.3.1).

The porphyrias can therefore be defined clinically as either an acute porphyria, characterized by acute neurovisceral attacks that are associated with the overproduction of the porphyrin precursor, 5-aminolaevulinic acid (ALA, OMIM 125270), usually accompanied by porphobilinogen, or a nonacute porphyria in which these attacks are absent and photocutaneous symptoms due to excess formation of porphyrins are the main clinical manifestation. Other classifications include division into erythropoietic or hepatic, depending on the principal site of expression of the specific enzymatic defect.
Genetics of type 1 diabetes mellitus
Authors: Savage David A. , Bain Stephen C.
Published: July 2011

Type 1 diabetes, previously known as insulin-dependent diabetes mellitus, is a common chronic T-cell-mediated disease in which there is selective autoimmune destruction of the insulin-producing β‎ cells of the pancreas. Although the mechanisms underlying this process are not fully understood, type 1 diabetes occurs as a result of complex interactions between multiple genes (reviewed in references 1–3) and environmental influences, which may both promote and protect against disease. Type 1 diabetes clusters in some families, but with no distinct pattern of inheritance. The concordance rates in monozygotic twins for type 1 diabetes can reach 50%, compared to 6% for dizygotic twins. The sibling recurrence risk ratio (λ‎s) (risk to siblings ÷ risk to general population) value for type 1 diabetes is 15 (6.0 ÷ 0.4 or 6% ÷ 0.4%), and twin studies suggest that 80% to 85% of familial aggregation is accounted for by genes. Type 1 diabetes has been noted to coexist with other autoimmune diseases—notably, Graves’ disease and coeliac disease—in certain families, implying the involvement of common autoimmune pathways.

Improved understanding of the so-called ‘allelic architecture’ (the identity of disease-associated gene variants, their frequencies, and size of the risk conferred by each variant) and biological pathways involved in type 1 diabetes is expected to facilitate the identification of new therapeutic targets for the development of new treatments. DNA biomarkers could also assist risk prediction at a population level. This is clinically relevant since individuals can survive with only 20% intact β‎-cell mass, and the time to reach this level of destruction can be considerably delayed in some individuals, offering a window of opportunity for intervention therapy. Furthermore, clinical trials should be improved by only focusing on those patients at highest risk of developing type 1 diabetes.

Early prediction, improved treatments, and, ultimately, prevention of type 1 diabetes are major goals because incidence rates are increasing. A recent study by the EURODIAB Study Group, involving 20 population-based registries across 17 European countries, has assessed incidence trends in children diagnosed with type 1 diabetes under the age of 15 between 1989 and 2003: an overall increase of 3.9% per year was reported, and, in the under 5 age group, an increase of 5.4% per year was observed (4).
Immunology of type 1 diabetes mellitus
Authors: Peakman Mark
Published: July 2011

The concept that the pathological hallmark of type 1 diabetes—namely, irreparable damage to β‎ cells—is the result of an autoimmune process has gained sustained credence since it was first intimated in the 1970s. Forty years on, a robust set of criteria can be applied to settle this important question. As a result of numerous, reproducible research findings (Table 13.2.3.1), there is now an overwhelming case to support the assertion that type 1 diabetes is an autoimmune disease.

Perhaps the most persuasive evidence is provided by the case reports of diabetes arising in recipients of bone marrow from patients with type 1 diabetes (1, 2). In these cases, the recipients underwent bone marrow ablation as part of the treatment for their underlying condition (e.g. relapsed haematological cancers) that effectively removed all autologous innate and adaptive immune cells. To reconstitute their immune system, they then received bone marrow from a sibling with type 1 diabetes. They developed the disease themselves some years later. It is hard to argue against the proposal that immune cells transferred in the bone marrow inoculum were responsible for β‎ cell destruction. Indeed, current practice in these circumstances is to ensure immune depletion of any mature T lymphocytes that may be present in the transplanted bone marrow using specific monoclonal antibodies. This successfully circumvents the problem—and also provides clear evidence for the pivotal role for T lymphocytes in causing β‎ cell damage.

It should be noted that the overwhelming majority of patients with type 1 diabetes—especially those inhabiting the Western, developed world—have evidence of the underlying autoimmune processes, as discussed in this chapter. However, there is a recognition that type 1 diabetes may be heterogeneous, as, in some patients, evidence of autoimmunity is lacking (WHO diabetes classification type 1B). In Japan, a fulminant form of diabetes has been described as representing 15–20% of type 1 disease (15). Presentation is characterized by a high prevalence of preceding common cold-like and gastrointestinal symptoms, a near-normal level of HbA1c (despite very high plasma glucose levels and ketoacidosis), raised serum

pancreatic enzyme levels, and absent C-peptide—but only rarely any evidence of autoantibodies against islet cell autoantigens (16). Some cases of type 1 diabetes arising in sub-Saharan Africa have also been described as lacking evidence of autoimmunity against islet cells (see Chapter 13.4.3.4); however, these data require clarification, since it is known that the autoantibodies decline and may disappear from the circulation soon after diagnosis, making retrospective classification of cohorts with established disease highly problematic (17). Future studies in these locations will need to establish evidence of autoimmunity at diagnosis in currently equivocal situations, using the most comprehensive, up-to-date range of serological markers (see Table 13.2.3.2, below), as well as to establish the clinical and immunogenetic features of the disease.
Genetics of type 2 diabetes mellitus
Authors: Grarup Niels , Hansen Torben , Pedersen Oluf
Published: July 2011

For years, it has been well known that genetic factors are crucially important for the development of type 2 diabetes. Despite major efforts in seeking to understand the molecular genetic basis, until a few years ago, only a handful of genes responsible for relatively rare monogenic and syndromic subsets of diabetes were detected, and progress in finding genetic predispositions to common type 2 diabetes was lacking. Even though the unravelling of the molecular pathogenesis of type 2 diabetes is still in its infancy, the last few years have, nevertheless, brought some interesting developments. Box 13.3.1.1 provides a glossary of terms used currently in genetics.
Genetics of severe insulin resistance
Authors: Semple Robert K. , Savage David B. , O’Rahilly Stephen
Published: July 2011

As the prevalence of obesity burgeons, so the prevalence of insulin resistance follows. A small minority of patients have severe insulin resistance without obesity. These patients, while not contributing

significantly to the general prevalence of diabetes, often harbour pathogenic single gene defects affecting insulin signalling or adipose tissue function. Clinical history and examination may offer strong clues to the presence of severe insulin resistance, but laboratory confirmation should usually be sought. Biochemical diagnostic thresholds for severe insulin resistance are arbitrary, and should, ideally, be defined relative to BMI-adjusted population normal ranges (Fig. 13.3.5.1). However, one set of approximate diagnostic criteria is as follows:

◆ non-diabetic and BMI under 30 kg/m2—fasting insulin above 150 pmol/l OR peak insulin on oral glucose tolerance testing above 1500 pmol/l

◆ absolute insulin deficiency and BMI under 30 kg/m2—exogenous insulin requirement above 3 U/kg/day

◆ partial β‎ cell decompensation and/or BMI over 30 kg/m2—insulin levels are difficult to interpret in the context of obesity, while, in diabetes, glucotoxicity, impaired islet function, and a combination of endogenous and exogenous insulin in the circulation confuse the biochemical picture. In this setting, the clinical history and features such as acanthosis nigricans assume particular importance in making a diagnosis of likely monogenic severe insulin resistance, with subjective clinical judgement often required.
Metabolic syndrome
Authors: Lebovitz Harold E.
Published: July 2011

The metabolic syndrome (MetS) has been recognized as a clinical entity for more than 50 years. In 1947, Vague described upper body obesity as a predisposing factor in the development of diabetes mellitus, atherosclerosis, and gout. Reaven, in his 1988 Banting lecture, focused on the importance of insulin resistance and a related cluster of metabolic abnormalities that were associated with an

increase in coronary artery disease (1). This cluster included resistance to insulin-stimulated glucose uptake, glucose intolerance, hyperinsulinaemia, increased very-low-density lipoprotein (VLDL) triglyceride, decreased high-density lipoprotein (HDL) cholesterol, and hypertension. He called this cluster ‘syndrome X’, and raised the possibility that resistance to insulin-stimulated glucose uptake and hyperinsulinaemia were involved in the aetiology of the metabolic abnormalities and the clinical diseases associated with them. Obesity and, particularly, visceral obesity have been recognized as a major contributor to the MetS since precise techniques to quantitate regional body composition became available. The MetS was initially thought of as an insulin resistance syndrome, implying that insulin resistance was the underlying unifying abnormality.
Diabetes in South Asians
Authors: Ramachandran A. , Snehalatha C.
Published: July 2011

Developing countries, mainly in the Indian subcontinent and China, contribute nearly 80% to the rising global diabetic population. Conservative estimates, based on population growth, ageing of population, and rate of urbanization in Asia, show that India and China will remain the top two countries with the highest number of people with diabetes by 2025: 71 and 38 million, respectively. Two other South Asian countries, Pakistan and Bangladesh, also are in the top ten list. The South Asian populations of Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, and Sri Lanka are racially heterogeneous, but all have high risk for diabetes and cardiovascular diseases. Type 1 diabetes is relatively less common, and nearly 95% of all diabetic cases in these regions are type 2 diabetes. The steady rise in the prevalence of diabetes seen in last three decades coincides with rapid urbanization and industrialization, and associated sociological and political changes, occurring in these countries (1). Among the populations, physical activity has reduced significantly, intake of energy-dense food has increased, and mental and physical stress factors associated with urban living have also increased. A tilt in the energy balance towards conservation and fat deposition has contributed to the alarming increase in the rate of obesity, both in adults and children.
Diabetes in sub-Saharan Africa and in Africans
Authors: Sobngwi Eugène
Published: July 2011

The prevalence of diabetes is drastically increasing in every part of the African continent where repeated surveys have been conducted. According to the International Diabetes Federation (IDF), the number of affected people in Africa will double within 20 years, from 12 million in 2010 to 24 million in 2030. Similarly, an increase is being observed in African diasporas of Western countries. In addition, there are some clinical presentations of diabetes that are predominantly observed in populations of African descent and that are difficult to classify. The most characteristic is ketosis-prone atypical diabetes, previously identified under ‘idiopathic type 1 diabetes’, which may represent up to 15% of all newly diagnosed diabetes in African-origin populations. This chapter, therefore, focuses on epidemiological specificities of diabetes in Africa, on the clinical specificities, and on atypical clinical presentations.
Structured education for people with type 2 diabetes mellitus
Authors: Heller Simon R. , Carey Marian E.
Published: July 2011

This chapter discusses how structured self-management education has become an integral component of the long-term care of type 2 diabetes in supporting individuals to initiate and sustain effective self-management.

We will briefly explore the background and context for structured education, identify and discuss its defining characteristics, and briefly comment on the evidence base as reported in the last 10 years. Finally, drawing on currently active structured self-management programmes in the UK and Europe as exemplars, we will examine the benefits of structured education in terms of the patient outcomes reported in some key research studies.
Metabolic surgery in the treatment of type 2 diabetes mellitus
Authors: Cummings David E.
Published: July 2011

Faced with the dual pandemics of obesity and type 2 diabetes mellitus, heath care providers require a broad array of treatment options. Diet, exercise, and medications remain the cornerstones of type 2 diabetes therapy, but long-term results with lifestyle modifications can be disappointing, and, despite an ever-increasing armamentarium of pharmacotherapeutics, adequate glycaemic control often remains elusive. Moreover, most diabetes medications promote weight gain, and using them to achieve tight glycaemic control introduces a proportionate risk of hypoglycaemia.

In cases where behavioural/pharmacological strategies prove insufficient, gastrointestinal surgery offers powerful alternatives for obesity and type 2 diabetes treatment (Fig. 13.4.5.1). Among severely obese patients, bariatric operations cause profound, sustained weight loss, ameliorating obesity-related comorbidities and reducing long-term mortality (1–4). Operations involving intestinal bypasses exert particularly dramatic antidiabetes effects. For example, approximately 84% of obese patients with type 2 diabetes experience diabetes remission after a Roux-en-Y gastric bypass (RYGB), maintaining euglycaemia off diabetes medications for at least 14 years (1, 5–8). Mounting evidence indicates that these effects result not only from weight loss, but also from weight-independent antidiabetic mechanisms (9).

Whereas diabetes is traditionally viewed as a relentless disease in which delay of end-organ complications is the major treatment goal, gastrointestinal surgery offers a novel endpoint: complete disease remission. Consequently, conventional bariatric procedures and experimental gastrointestinal manipulations are being used worldwide to treat type 2 diabetes in association with obesity, and, increasingly, among less obese or merely overweight patients (8). Gastrointestinal surgery also offers valuable research opportunities to improve knowledge of diabetes pathogenesis and help develop less invasive procedures and novel pharmaceuticals.

This chapter discusses the effects of gastrointestinal operations on type 2 diabetes, and focuses on potential antidiabetic mechanisms that mediate those effects.
Hypoglycaemia in the treatment of diabetes mellitus
Authors: Choudhary Pratik , Amiel Stephanie A.
Published: July 2011

Hypoglycaemia (low blood glucose concentration) is the most important acute complication of the pharmacological treatment of diabetes mellitus. Low blood glucose impairs brain (and, potentially, cardiac) function. The brain has minimal endogenous stores of energy, with small amounts of glycogen in astroglial cells. The brain is therefore largely dependent on circulating glucose as the substrate to fuel cerebral metabolism and support cognitive performance. If blood glucose levels fall sufficiently, cognitive dysfunction is inevitable. In health, efficient glucose sensing and counterregulatory mechanisms exist to prevent clinically significant hypoglycaemia. These are impaired by diabetes and by its therapies. Patients with diabetes rank fear of hypoglycaemia as highly as fear of chronic complications such as nephropathy or retinopathy (1). Fear of hypoglycaemia, hypoglycaemia itself and attempts to avoid hypoglycaemia limit the degree to which glycaemic control can be intensified to reduce the risk of chronic complications of diabetes both for type 1 and type 2 diabetes.
Diabetic neuropathy
Authors: Tesfaye Solomon
Published: July 2011

Diabetic neuropathy is a major complication of diabetes and a cause of considerable morbidity and mortality (1). Diabetic neuropathy is not a single entity but includes several neuropathic syndromes (Fig. 13.5.4.1). In clinical practice, the commonest presentation of neuropathy is chronic distal symmetrical polyneuropathy, also known as diabetic peripheral neuropathy (DPN). The neuropathic syndromes depicted in Fig. 13.5.4.1 have varied presentations and pathogenesis. This chapter will cover these syndromes although the main focuses will be: (1) DPN, which is the main initiating factor for foot ulceration and a cause of troublesome painful neuropathic symptoms; and (2) autonomic neuropathy.
Hypertension in diabetes mellitus
Authors: Williams Bryan
Published: July 2011

High blood pressure (hypertension) is arguably the most important preventable cause of premature microvascular and macrovascular disease and the associated morbidity and mortality in people with diabetes. This chapter will review key aspects of the epidemiology and pathophysiology of hypertension in people with diabetes, as well as recommended approaches to its clinical evaluation and treatment.
Depression and diabetes mellitus
Authors: Ismail Khalida , Petrak Frank
Published: July 2011

There is a high prevalence of co-morbid depression in people with diabetes. Depression is a mental disorder that is associated with worse physical outcomes in diabetes, in particular higher rates of diabetes complications and mortality, but it is often undetected and undertreated. The mechanisms underlying the high rates of depression and its adverse effects are not well understood but appear to include both biological and psychological processes. Depression may have a more chronic course in people with diabetes compared to those without diabetes. The current evidence for the treatment of depression in diabetes suggests that treating depression improves mood but its effectiveness in improving glycaemic control is poor.
Organizing a diabetes service
Authors: Gough Stephen C. L.
Published: July 2011

The increasing worldwide incidence and prevalence of diabetes is placing substantial pressures on health care systems and economies. As a consequence individuals involved in the care of people with diabetes are looking at services currently being provided and examining ways in which care can be organized in the most cost-effective manner. Whilst the degree to which diabetes care is delivered differs from country to country, similar fundamental questions are being asked by those involved in the delivery of care, including: What are we currently providing? What do we need to provide? What are we able to provide? Although the answers to these questions are quite different not just between countries but often within specific localities within a country, the ultimate aim is the same: to provide the best possible care to as many people with diabetes as possible.

The global diversity of diabetes health care need is enormous and while the solutions will be equally diverse, the approach to the development of a diabetes service will, for many organizations, be similar. The main focus of this chapter is based upon the model or the strategic approach developed in the UK, but many of the individual component parts are present in most health care settings.
General concepts of hypothalamus-pituitary anatomy
Authors: Bernabeu Ignacio , Marazuela Monica , Casanueva Felipe F.
Published: July 2011

The hypothalamus is the part of the diencephalon associated with visceral, autonomic, endocrine, affective, and emotional behaviour. It lies in the walls of the third ventricle, separated from the thalamus by the hypothalamic sulcus. The rostral boundary of the hypothalamus is roughly defined as a line through the optic chiasm, lamina terminalis, and anterior commissure, and an imaginary line extending from the posterior commissure to the caudal limit of the mamillary body represents the caudal boundary. Externally, the hypothalamus is bounded rostrally by the optic chiasm, laterally by the optic tract, and posteriorly by the mamillary bodies. Dorsolaterally, the hypothalamus extends to the medial edge of the internal capsule (Fig. 2.1.1) (1).

The complicated anatomy of this area of the central nervous system (CNS) is the reason why, for a long time, little was known about its anatomical organization and functional significance. Even though the anatomy of the hypothalamus is well established it does not form a well-circumscribed region. On the contrary, it is continuous with the surrounding parts of the CNS: rostrally, with the septal area of the telencephalon and anterior perforating substance; anterolaterally with the substantia innominata; and caudally with the central grey matter and the tegmentum of the mesencephalon. The ventral portion of the hypothalamus and the third ventricular recess form the infundibulum, which represents the most proximal part of the neurohypophysis. A bulging region posterior to the infundibulum is the tuber cinereum, and the zone that forms the floor of the third ventricle is called the median eminence. The median eminence represents the final point of convergence of pathways from the CNS on the peripheral endocrine system and it is supplied by primary capillaries of the hypophyseal portal vessels. The median eminence is the anatomical interface between the brain and the anterior pituitary. Ependymal cells lining the floor of the third ventricle have processes that traverse the width of the median eminence and terminate near the portal perivascular space; these cells, called tanycytes, provide a structural and functional link between the cerebrospinal fluid (CSF) and the perivascular space of the pituitary portal vessels.

The conspicuous landmarks of the ventral surface of the brain can be used to divide the hypothalamus into three parts: anterior (preoptic and supraoptic regions), middle (tuberal region), and caudal (mamillary region). Each half of the hypothalamus is also divided into a medial and lateral zone. The medial zone contains the so-called cell-rich areas with well-defined nuclei. The scattered cells of the lateral hypothalamic area have long overlapping dendrites, similar to the cells of the reticular formation. Some of these neurons send axons directly to the cerebral cortex and others project down into the brainstem and spinal cord.
Development of the pituitary and genetic forms of hypopituitarism
Authors: Alatzoglou Kyriaki S. , Dattani Mehul T.
Published: July 2011

Pituitary development occurs in distinct and sequential developmental steps, leading to the formation of a complex organ containing five different cell types secreting six different hormones. During this process the sequential temporal and spatial expression of a cascade of signalling molecules and transcription factors play a crucial role in organ commitment, cell proliferation, patterning, and terminal differentiation. Complex regulatory networks govern the process during which distinct cell types emerge from a common primordium. The mechanisms are not fully elucidated but it seems that opposing signalling gradients induce expression of interacting transcriptional regulators (activators or repressors) in overlapping patterns that act synergistically. Spontaneous or artificially induced mutations in the mouse and identification of mutations associated with human pituitary disease have contributed to defining the genetic cascades responsible for pituitary development.
Imaging of the pituitary
Authors: Byrne J. V.
Published: July 2011

MRI is the optimum method of imaging the pituitary of patients with suspected pituitary disease though CT is an acceptable alternative. The advantages of MRI are: direct multiplanar scanning, lack of ionizing radiation, and good anatomical tissue discrimination. Imaging the pituitary gland and hypothalamus is best performed in the sagittal and coronal planes because they show the relationships between gland and adjacent structures. Scanning in the axial plane alone is a poor technique for demonstrating vertical relationships between structures lying between the floor of the third ventricle and sella turcica. Computer-generated three-dimensional (3D) reconstructions of axially acquired data (by MR or CT) and can be viewed in any plane can compensate but usually direct scanning gives better resolution images.
Perisellar tumours including cysts, hamartomas, and vascular tumours
Authors: Honegger Jürgen , Beschorner Rudi , Ernemann Ulrike
Published: July 2011

Approximately 80% of symptomatic tumours in the pituitary region are pituitary adenomas and further 10% are craniopharyngiomas. Among the remaining 10%, a considerable number of rare tumour entities have to be considered (Box 2.4.3.1) which makes the differential diagnosis sometimes difficult. Endocrinological, neuroradiological, and ophthalmological evaluation is the indispensable diagnostic triad to identify typical features in nonadenomatous perisellar tumours, and to provide diagnostic accuracy. This chapter presents typical clinical aspects of various nonadenomatous sellar tumours and the differential diagnostic value of specific symptoms. The current therapeutic strategies are also described.
Lymphocytic hypophysitis and other inflammatory conditions of the pituitary
Authors: Kravarusic Jelena , Molitch Mark E.
Published: July 2011

Inflammatory lesions of the pituitary are far less common than pituitary adenomas. Although the most common of these, lymphocytic hypophysitis, is limited to the pituitary and pituitary stalk, many of the other lesions are usually part of a systemic process. Nonetheless, even these lesions, such as Langerhans’ cell histiocytosis (LCH) and sarcoidosis, sometimes present as part of disease limited to the central nervous system (CNS) and, rarely, present as isolated lesions of the hypothalamic/pituitary area. When lesions are located in the base of the hypothalamus or in the stalk, they commonly present with a combination of diabetes insipidus and hypopituitarism. In some cases, hypothalamic infiltration may be more widespread, affecting a variety of additional hypothalamic functions, such as satiety, sleep, and temperature regulation. These inflammatory lesions tend to be progressively destructive, resulting ultimately in fibrosis but the rate of progression is highly variable. When hypopituitarism or diabetes insipidus occur, they rarely recover even if the underlying process is directly treated. Thus, these lesions present more with endocrine hypofunction than with mass effects, although in early stages lymphocytic hypophysitis may well present with mass effects to the point where it can be confused with a pituitary adenoma.
Endocrinology and alcohol
Authors: Proescholdt Margit G. , Walter Marc
Published: July 2011

Alcohol has widespread effects on multiple organs, including the endocrine organs, potentially impairing endocrine function and affecting the entire endocrine milieu. Endocrine impairment may be observed with acute alcohol ingestion, excessive chronic alcohol consumption, and during alcohol withdrawal. Whereas many effects of alcohol on the endocrine organs are reversible following cessation of alcohol consumption, some changes may extend into abstinence. Importantly, endocrine dysfunction observed in alcoholism, is no longer considered to simply result from hepatic failure or chronic malnutrition, but, at least partially, from direct, toxic actions of alcohol on the endocrine organs themselves. In addition, there is increasing evidence that the endocrine system itself may play a crucial role in the pathogenesis of addictive behaviour.

Ethanol and its metabolite acetaldehyde directly affect cell membranes and influences intracellular metabolism. Indirect effects include stress, nausea, and vomiting during acute intoxication and withdrawal. Whereas the list of alcohol-induced endocrine dysfunction is long, scientific and epidemiological evidence is frequently controversial. Controversies may result from the highly heterogenic group of alcohol-dependent individuals regarding dose and duration of alcohol consumption, periods of abstinence, age, gender, nutritional status, cigarette smoking, use of other drugs, presence of other diseases, particularly liver disease, and the complexity of endocrine regulation in general.
The history and iconography relating to the thyroid gland
Authors: Volpé Robert , Sawin Clark
Published: July 2011

This chapter is a brief summary of the history and art related to the thyroid gland. The reader is referred to other sources for an exhaustive exposition of these matters (1–3).