bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stuck Between a Foot and a Soft Place
Authors: Thoendel Matthew J. , Tande Aaron J. 
Published: January 2022

Abstract
The potentially increased risk of hemolytic uremic syndrome (HUS) developing with antibiotic treatment of Shiga toxin−producing Escherichia coli (STEC) infections has been reported since STEC was identified as a cause of HUS. HUS is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. The increased risk of HUS development with antibiotic use remains a subject of investigation. The relative severity of HUS (compared with a typical postoperative infection) must be factored into the decision to use prophylactic antibiotics. The risk of HUS developing with antibiotic use also likely depends on the causative STEC strain.
Forgiveness
Authors: Worthington Everett L. 
Published: January 2022

Abstract
Forgiveness is considered a virtue by most people, and in today’s often-contentious society it can promote better relationships, better physical and mental health, and often better spirituality. People rarely present seeking treatment for forgiveness. Rather, it often surfaces as people deal with depression, anxiety, stress-related disorders, interpersonal anger, unforgiveness, couple and family conflict, self-condemnation, guilt, shame, and hopelessness. Treating issues in forgiveness is not tied to a particular treatment approach. Psychodynamic psychotherapists will find it particularly useful in family-of-origin issues. Cognitive-behavioral psychotherapists can incorporate most treatment protocols within their schema. One of the best ways to treat forgiveness issues is to use evidence-based treatments as adjuncts to psychotherapy (i.e., psychoeducational groups, workbooks, engagement with a faith community) and use psychotherapy to handle unresolved issues arising from adjunctive treatment. In this chapter, assessment, treatment, relevance for engaging other community resources like faith communities, and ethical issues are addressed.
Defiance
Authors: Potter Nancy Nyquist 
Published: January 2022

Abstract
Defiance has been praised, blamed, and vilified. This makes sense if one understands defiance as a virtue with vices and an intermediate condition. Yet social conditions frequently associate negative interpretations with people who are oppressed, including people who have mental challenges and distresses, such that it turns out that defiant mentally ill people, especially people whose social locations implicate race, gender, ethnic and religious minorities are interpreted as having a vice and clamped down rather than being listened to and treated as possibly giving a legitimate and reasonable response to oppressive or unjust interactions or conditions. Defiance is sometimes a virtue for people with mental illnesses. Therefore, they should not automatically be assumed to be either mad or bad for being defiant. Sometimes defiant behavior is even a step toward flourishing. Clinicians too are sometimes rightfully defiant, even though norms and practices of psychiatry may consider such behavior to be blameworthy.
Endocrine Practice Fundamentals
Authors: Loriaux Lynn 
Published: January 2022

Abstract
Medicine probably is the most rapidly evolving of all the professions. Said another way, it is probably the least stable. Progress is breathtaking, the ‘new information’ load is heavy, the work is never finished. In this intellectual maelstrom, however, there is a safe harbour—the physicians’ benchmark, the Oath of Hippocrates, teaching, physical examination, the doctor–patient covenant. These things are, for the most part, unchanging. This short chapter explains the interplay between change and permanence. We address the struggle and how it can be managed. It is written for physicians between the first and the last days of ‘the job’.
Environmental Influences on Endocrine Disease
Authors: Mastorakos George , Nezi Markella , Macut Djuro , Papagianni Maria 
Published: January 2022

Abstract
The impact of endocrine disruptors (EDs) has been a matter of concern for the last 60 years. However, the results of research remain controversial, mainly due to the diversity and multitude of environmental effects on humans, due to genetic variability among exposed organisms, and due to differing exposure, route, and duration for each ED. The exact time-point of exposure is crucial. In utero exposure seems to cause irreversible outcomes. Experimental studies in animals and studies in humans are sometimes discordant because exposure to EDs and physiology differs among species. Additional experimental and physiology research is needed to clarify mechanisms of EDs action. Nevertheless, humans must ultimately choose between the short-term benefits that technological advances offer and a more global quality of life based on the respect for the environment.
Functional Anatomy of the Hypothalamus and Pituitary
Authors: Morris John F. 
Published: January 2022

Abstract
The hypothalamus forms only a tiny part of the human brain but nevertheless controls, through feedforward and feedback connections with the pituitary gland, the autonomic nervous system, and other parts of the brain, nearly all the important aspects of our developing and adult life and enables us to respond appropriately to our changing environment. The hypothalamus influences our reproductive systems; the growth of the body, feeding behaviour, metabolic rate, and energy balance; our water and electrolyte balance; and our day–night rhythms. Not surprisingly it has links with the reward systems that influence behavioural and emotional responses including aggressive and affiliative/social behaviour. Whereas some neurons form distinct nuclei, others are more diffusely distributed and few obvious fibre bundles interconnect them. Therefore, although many clinical conditions have long been associated with hypothalamic dysfunction, it is only fairly recently that techniques such as genetic manipulation and optogenetic stimulation have enabled the functions and connections of defined groups of neurons to be unravelled.
The Neurohypophysis
Authors: Ball Stephen G. 
Published: January 2022

Abstract
The neurohypophysis is a complex neurohumoral system with a key role in body fluid homeostasis and reproductive function. This chapter will concentrate on the physiology and pathophysiology of the two hormones made by the neurohypophysis, vasopressin (VP), and oxytocin (OT); outlining the roles of both hormones together with the molecular, cellular, and anatomical basis of their regulation and action. The neurohypophysis consists of the supraoptic and paraventricular nuclei of the hypothalamus, the supraoptico-hypophyseal tract, and the posterior pituitary. Together, these constitute a functional neurohumoral unit with key roles in fluid balance and reproduction. The biology of the neurohypophysis and its individual elements is central to physiology and pathophysiology and in turn, to developing an approach to the management of disease that results from a breakdown in function.
Development of the Pituitary and Genetic Forms of Hypopituitarism
Authors: Gregory Louise C. , Dattani Mehul T. 
Published: January 2022

Abstract
Human embryonic hypothalamo-pituitary (HP) development consists of complex molecular pathways reliant on an array of genes expressed at specific time points. The resulting intertwined signalling molecules work in synchronization to give rise to the five specialized anterior pituitary cell types that secrete the six vital hormones responsible for growth and homeostasis. Congenital hypopituitarism (CH) involves deficiencies in one or more of these hormones, and exists in many forms of severity ranging from an inability to sustain life, to mild hormone deficiencies that may go unnoticed. Accompanying phenotypic features affecting various target tissues, intellectual disability and dysmorphic features are often apparent in such patients, depending on the genes mutated. The rapid evolution in next generation sequencing (NGS) technology has revolutionized genotyping in such individuals, and stem cell research and CRISPR-Cas9 gene editing will doubtless allow a more detailed and physiologically relevant characterization of mutations identified. Future studies are likely to reveal an expanding list of new candidate genes associated with HP development. In this part we will focus on known genetic causes of CH and related disorders.
Molecular Pathogenesis of Pituitary Tumours
Authors: Melmed Shlomo 
Published: January 2022

Abstract
Pituitary tumours and arise from highly differentiated anterior pituitary cell types and are invariably benign. They may be clinically silent or secrete specific trophic hormones which elicit unique clinical phenotypes. These include acromegaly (GH), prolactinomas (PRL), Cushing’s disease (ACTH), gonadotroph adenomas (FSH and LH), and rarely thyrotrophinomas (TSH). Some tumours may be non-secreting and do not result in excess peripheral hormone levels. Sporadic non-familial adenomas are not associated with classic oncogene mutations and likely arise due to chromosomal, epigenetic, and signalling disruptions leading to cell cycling defects coupled with enhanced specific hormone gene transcription. Accordingly, both hypothalamic and intrinsic pituitary signals determine pathogenesis of these unique tumour types.
Thyroid Imaging
Authors: Bonnema Steen Joop , Hegedüs Laszlo 
Published: January 2022

Abstract
Nuclear medicine techniques, like iodine uptake measurements, planar scintigraphy, and positron emission tomography (PET), are very helpful in the management of a number of thyroid disorders. The thyroid gland can trap radioactive iodine as well as the widely used 99mTc isotope. Non-iodine radioactive isotopes are also useful, primarily in the context of PET. The emission of γ -photons enables detection by a gamma camera, resulting in the generation of a two- or three-dimensional thyroid image. In contrast to most other imaging methods, nuclear medicine techniques reflect the functional status of the thyroid tissue. Among other advantages, this feature aids in the management of patients with thyroid nodular diseases in order to diagnose thyroid malignancy. In patients with established thyroid cancer, various techniques, like radioiodine whole-body scan or PET, are very sensitive for detection and localizing of residual malignant thyroid tissue. This chapter focuses on and discusses advantages and limitations of nuclear medicine techniques in thyroid diseases.
Clinical Assessment and Systemic Manifestations of Thyrotoxicosis
Authors: Marcocci Claudio , Cetani Filomena 
Published: January 2022

Abstract
The term ‘thyrotoxicosis’ refers to the clinical syndrome due to excessive serum concentrations of free thyroxine, free triiodothyronine, or both. Potential causes of thyrotoxicosis include destructive thyroiditis, excessive ingestion of thyroid hormones, or secretion of thyroid hormones from ectopic sites. The term ‘hyperthyroidism’ is used when thyrotoxicosis is due to hormone overproduction by the thyroid gland, Graves’ disease being the most common. Other diseases responsible for thyrotoxicosis are destructive thyroiditis, excessive ingestion of thyroid hormones or secretion of thyroid hormones from ectopic sites. The clinical features depend on the severity and duration of the disease, the age of the patient, the presence or absence of extrathyroidal manifestations, and the specific thyrotoxic disorder.
Management of Graves’ Hyperthyroidism
Authors: Orgiazzi Jacques 
Published: January 2022

Abstract
Graves’ disease could be seen as a long lasting, quasichronic disease. Treatment of Graves’ disease is a dilemma, be it medical conservative but successful in less than 50% of the cases, or radical destructive with, however, no possibility to insure the preservation of a subsequent normal thyroid function apart from long-term levothyroxine treatment. It is no surprise, then, that surveys had shown large therapeutic option disparities between countries and cultures and traditions, not to forget patient’s preference and concerns, physicians’ personal bias, and local availability of experienced team in thyroid surgery and nuclear medicine department These differences, however, tend to level off, antithyroid drug being from now on considered as the more appropriate first-line treatment in most of thyroid centres all over the world.
Graves’ Orbitopathy and Dermopathy
Authors: Wiersinga Wilmar M. 
Published: January 2022

Abstract
Graves’ orbitopathy (GO) is characterized by enlarged extraocular muscles and increased orbital fat, causing swelling and redness of eyelids and conjunctiva, exophthalmos, double vision, and sometimes corneal lesions and optic neuropathy. Quality of life is severely impaired. Orbital fibroblasts (OF) are the target cells of the immune attack, most likely driven by autoimmunity against the thyroid stimulating hormone (TSH) receptor. OF respond by excessive secretion of hydrophobic glycosaminoglycans and a subset differentiates into mature adipocytes. About 20% of Graves’ hyperthyroid patients develop GO (mild in 15% and more severe in 5%). Risk factors for GO are high levels of TSH receptor antibodies, smoking, and radioactive iodine. Restoration of euthyroidism (preferably by antithyroid drugs or thyroidectomy), local measures (like artificial tears), and discontinuation of smoking should always be established. Management of GO depends on disease severity and disease activity. In mild GO a wait-and-see policy can be considered, or selenium administration. Moderate-to-severe and active GO qualifies for immunosuppression: intravenous methylprednisolone pulses are still the gold standard, but novel treatments with rituximab or teprotumumab are promising. Rehabilitative surgery can be performed when the disease has become inactive.
Myxoedema Coma
Authors: Wartofsky Leonard , Ylli Dorina , Klubo-Gwiezdzinska Joanna 
Published: January 2022

Abstract
Myxoedema coma is a rare but life-threatening condition resulting from severe thyroid hormone deficiency. Despite having a low incidence, the mortality rate may be as high as 30–60%. The prompt recognition of clinical presentation and precipitating events allows earlier diagnosis and treatment reducing the probability of an adverse outcome. The risk of myxoedema coma is greatest in hypothyroid older patients exposed to a precipitating event such as infection or a systemic superimposed illness. The effect of thyroid hormone deficiency on multiple systems (cardiovascular, respiratory, gastrointestinal, renal, neuropsychiatric, haematologic and thermoregulatory) often blurs the diagnosis resulting in treatment delay. Proper treatment includes thyroid hormone administration and a multifaceted approach to the multiple metabolic derangements in order to optimize survival.
Treatment of Hypothyroidism
Authors: Nygaard Birte 
Published: January 2022

Abstract
The goals for treatment of primary hypothyroidism are to restore euthyroidism with normalization of serum thyroid-stimulating hormone (TSH) and fT4 concentrations and to eliminate symptoms. Thyroxine, as levothyroxine sodium (L-T4), is the therapy of choice, and its use in most patients’ treatment is straightforward. In a minor patient group, persistent symptoms are present although thyroid function parameters are normalized. In these patients, it is pertinent to search for alternative explanations for the symptoms other than thyroid disease. A possible effect of a combination of L-T4 and L-T3 is disputed. Overtreatment with suppressed serum TSH must be avoided due to risks of cardiovascular disease, osteoporosis, and dementia.
Hypercalcaemia
Authors: Marcocci Claudio , Saponaro Federica , Cetani Filomena 
Published: January 2022

Abstract
Calcium homeostasis is maintained by the equilibrium among renal excretion, bone resorption, and intestinal absorption of calcium. Hypercalcaemia, which develops when the renal calcium overload exceeds its capacity to reabsorb calcium. Hyperparathyroidism is one of the most common causes of hypercalcaemia in free-living individuals, whereas hypercalcaemia of malignancy is the second cause of hypercalcaemia and the most common in hospitalized patients. The principal challenge in the evaluation of hypercalcaemia is distinguishing parathyroid hormone-related hypercalcaemia from other causes. Symptoms generally, but not always, correlate with the severity of hypercalcaemia and time course. The management of hypercalcaemia should be addressed at the underlying cause/mechanisms. When hypercalcaemia in moderate to severe the aim is also and most importantly directed to decrease hypercalcaemia, by increasing renal calcium excretion and decreasing bone resorption and intestinal calcium absorption. Severe hypercalcaemia represents an emergency and treatment is urgently required.
Primary Hyperparathyroidism
Authors: Bilezikian John P. 
Published: January 2022

Abstract
Primary hyperparathyroidism is a common endocrine disease characterized by excessive secretion of parathyroid hormone from one or more of the four parathyroid glands. In most patients, a single, benign adenoma is responsible for the disease, but in a small percentage of subjects, four-gland hyperplasia is evident. Most patients present with sporadic disease but familial multiple endocrine gland syndromes are well known, with genetic bases that have been characterized. The clinical presentation of primary hyperparathyroidism has changed by virtue of the use of automated biochemical screening, in which the serum calcium is routinely measured as well as by a proactive approach to the investigation of known or suspected metabolic bone disease. As a result, three phenotypes of primary hyperparathyroidism are seen throughout the world. Symptomatic disease with skeletal and renal involvement is limited primarily to countries in which biochemical screening is not used and where vitamin D deficiency is endemic. Mild hypercalcaemia is the most common biochemical presentation in subjects who are discovered incidentally. The normocalcaemic variant of primary hyperparathyroidism is recognized in patients whose disease is manifest by elevated levels of parathyroid hormone in the absence of secondary causes. With recent advances in our ability to investigate in detail the two major target organs of primary hyperparathyroidism, namely bone and kidney, a more complete assessment of patients with this disease is now possible.
Osteoporosis
Authors: Eastell Richard 
Published: January 2022

Abstract
Osteoporosis is an important public health problem. It is defined in the individual by a low bone mineral density and a high risk of fracture. It is a consequence of a low peak bone mass or accelerated bone loss, or both. Oestrogen deficiency and ageing are important causes of accelerated bone loss as are a number of drugs and diseases. Treatments for osteoporosis are effective at reducing the risk of further fracture and these include drugs that work by inhibiting bone resorption or stimulating bone formation. Bisphosphonates are the drugs most commonly used for osteoporosis and most guidelines recommend a drug holiday after treatment for 5 years.
Paget’s Disease of Bone
Authors: Papapoulos Socrates E. 
Published: January 2022

Abstract
Paget’s disease of bone is a focal disorder of bone remodelling that progresses slowly and leads to changes in the shape and size of affected bones and to skeletal, articular, and vascular complications. Paget’s disease affects typically older people, slightly more men than women, and seldom presents before the age of 35 years. Its prevalence increases with age and it affects 1 to 5% of those above 50 years of age. However, only a small proportion of individuals with Paget’s disease comes to clinical attention, most commonly these with symptomatic or severe disease. In some parts of the world it is the second most common bone disorder after osteoporosis, although in recent years its prevalence and severity appeared to decrease. The disease is easily diagnosed and effectively treated but its pathogenesis remains incompletely understood.
Genetics of Congenital Adrenal Hyperplasia
Authors: Krone Nils P. 
Published: January 2022

Abstract
Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive disorders causing impaired cortisol biosynthesis. The phenotypic expression of different CAH forms depends on the underlying enzyme deficiency. Steroid 21-hydroxylase (CYP21A2) and 11β-hydroxylase (CYP11B1) deficiencies only affect adrenal steroidogenesis, whereas 17α-hydroxylase (CYP17A1) and 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) also impair gonadal steroid biosynthesis. P450 oxidoreductase deficiency (PORD) presents with apparent combined CYP17A1-CYP21A2 deficiency. In contrast to other CAH forms, PORD also causes skeletal malformations and severe genital ambiguity in both sexes. Three further conditions have been traditionally classified as CAH. Steroidogenic acute regulatory protein (StAR) deficiency results in Lipoid CAH (CLAH), and has the unique feature of adrenal and gonadal lipid accumulation. P450 side-chain cleavage (CYP11A1) deficiency resembles the CLAH phenotype; however, patients have normal-sized or absent adrenals. Aldosterone synthase (CYP11B2) deficiency manifests with isolated aldosterone deficiency.
Carcinoid Syndrome
Authors: Clement Dominique , Srirajaskanthan Raj , Caplin Martyn E. 
Published: January 2022

Abstract
Carcinoid syndrome occurs in approximately 20% of patients with neuroendocrine tumours. Its pathophysiology is not completely understood; however, it is thought to arise from secretion of serotonin and kinins from the neuroendocrine tumour cells. In patients with liver metastases these hormones are not metabolized by the liver and consequently lead to the symptoms of carcinoid syndrome. The most common symptoms are diarrhoea, flushing, abdominal pain, and wheezing. Management of carcinoid syndrome is centred around control of tumour growth and symptoms. First line treatment is with somatostatin analogues, more recently Telotristat ethyl has been licensed for refractory syndrome. A number of complications can arise secondary to serotonin and kinin secretion these include nutritional deficiency, mesenteric fibrosis, and carcinoid heart disease. Carcinoid crisis which comprises of severe haemodynamic instability can occur during times of stress or surgery. Careful preoperative management needs to be considered prior to surgery in this cohort of patients.
Multiple Endocrine Neoplasia Type 1
Authors: Thakker Rajesh V. 
Published: January 2022

Abstract
Multiple endocrine neoplasia type 1 (MEN 1) is characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumours. Some patients may also develop other neuroendocrine tumours (lung and bowel), adrenal cortical tumours, meningiomas, facial angiofibrosmas, collagenomas, and lipomas. MEN 1is inherited as an autosomal dominant disorder that is due to mutations in the tumour suppressor gene MEN 1, which encodes a 610-amino acid protein, menin. Patients with MEN 1 have a decreased life expectancy. Moreover, the finding of MEN 1 in a patient also has important implications for family members, because first-degree relatives have a 50% risk of developing the disease, and these at-risk relatives can be identified by MEN 1 mutational analysis. The prognosis of MEN 1 patients and that of the at-risk relatives may be improved by presymptomatic detection of the tumour and with implementation of earlier and specific treatments for the MEN 1 tumours.