bluuebunny/crossref_metadata_2025 huggingface dataset:
Principles of antibiotic therapy
Authors: Czachor John S.
Published: January 2022

This chapter reviews the very disturbing trend of antibiotic resistance seen among a wide variety of pathogens that are causing serious disease in patients residing in the community, in long-term care facilities, and in hospitals. The lines of acquisition of antibiotic resistance have begun to blur as less and less separation occurs between the nosocomial and community settings. The chapter also analyzes multidrug resistance, a global problem made worse by ease of worldwide travel and medical tourism, and that has made both the US Centers for Disease Control and the World Health Organization institute antibiotic risk notifications and grading systems that rank the severity of various threats to health.
Antibacterial agents
Authors: Watkins Richard R.
Published: January 2022

This chapter traces how the modern antibiotic era began with the discoveries of penicillin by Fleming in 1928 and sulfonamides by Domagk in 1932. It lists different classes of antibacterial agents that have been developed for the use in humans. It also describes the various antibacterial agents, including their mechanisms of action, clinical indications, and mechanisms of bacterial resistance. The chapter looks at the core structure of the penicillins, which consists of a thiazolidine ring attached to a β‎-lactam ring and an R-group side chain. It explains how the thiazolidine-β‎-lactam ring provides antibacterial activity while the side chain determines the antimicrobial spectrum and pharmacologic characteristics.
Uncertainty and the Certainty Bias
Authors: Silveira José , Rockman Patricia
Published: January 2022

All humans are afflicted with a set of peculiar tendencies in perceiving and thinking that, collectively, create an illusion that their judgments and beliefs are correct. These tendencies are the certainty bias, the overconfidence bias, and the optimism bias. This chapter discusses the various views of uncertainty in human judgment and the mind’s unexpected adaptation to it in the form of unwarranted certainty and confidence. These concepts are applied to clinical assessment. The concept of irreducible uncertainty is explained, and its pragmatic relevance to clinical judgment and decision making is discussed. Key factors contributing to irreducible uncertainty in clinical care are considered.
Humility
Authors: Covaleski Nicholas D.
Published: January 2022

Throughout history, humility has been marked with ambivalence, steadily oscillating between the statuses of virtue and vice. Recent scholarship in positive psychology, however, has begun to unveil the nuances of humility and its associations with human health and happiness. In particular, this limited but promising set of literature has persuasively shown that cultural, epistemic, and existential humility reliably corresponds with positive mental health outcomes in a variety of therapeutic contexts. Moreover, this same set of research strongly indicates that humility is positively associated with an array of traits and behaviors that promote overall well-being. Thus humility appears to be a key virtue for fostering human flourishing within mental health settings and beyond. Lastly, religious and spiritual traditions, many of which have dense histories of reflection on humility, may be particularly well equipped with the resources needed to cultivate humility and to enrich an understanding of this old and intricate virtue.
Hope (Optimism, Resilience)
Authors: Kinghorn Warren
Published: January 2022

Clinicians often debate whether hope is adaptive or maladaptive for patients who are confronting serious medical and mental health challenges. But these debates, which focus on hope as belief and/or emotion, sidestep the question of whether hope can be a virtue, that is, an embodied disposition to act with ease in particular circumstances in ways that contribute to flourishing. Drawing on Thomas Aquinas’s account of hope as a virtue that sits between the twin vices of despair and presumption, I argue that hope as a virtue is not simply emotion, cognitive or intellectual belief, wishing, positive thinking, or optimism. Hope, rather, is the capacity to rest in a not-yet-present, difficult-to-attain good future that will be brought about by an agent outside the self. Hope in Aquinas’s sense is therefore an exogenous virtue that forms courage and perseverance in the subject. The exogenous nature of hope is vividly displayed in the work of the poet, priest, and civil rights attorney Pauli Murray, in the speeches of Martin Luther King Jr., and in other black American Christian witnesses to hope. Understood as an exogenous virtue, hope enables clear-eyed appraisal of evil, the capacity to discern and to trust in a coming good future made possible by another, human solidarity and community, and the courageous capacity to act toward a good and just future that is not yet present but that will surely come.
Psychosocial and Spiritual Aspects of Care
Authors: Hallenbeck James L.
Published: January 2022

This chapter discusses the spiritual and psychosocial aspects of care using a narrative approach. It suggests that far more suffering in patients with advanced illness results from psychic rather than from physical distress, assuming physical symptoms are reasonably palliated. Categories of psychic distress described include depression, anxiety, and delirium. A discussion of anticipatory and bereavement grief is also presented. The chapter discusses how to assess these forms of psychic distress and provides recommendations for interventions. A discussion of altered states of consciousness in dying patients is presented along with an approach to analyzing and understanding these states, based on the level of consciousness, orientation, and the content of the altered state.
Prejudice and Discrimination Related to Mental Illnesses
Authors: Dobson Keith S. , Stuart Heather
Published: January 2022

This chapter discusses the concept of stigma and its history as applied to the topic of mental illness. Public, self, and structural stigma are defined as variations on the application of stigma to various contexts, and it is noted that stigma includes attitudinal, emotional and behavioral/discriminatory aspects. A matrix model is presented as a way to graphically demonstrated the many different ways in which stigma can be presented. The importance of a social justice perspective related to stigma is highlighted because this perspective helps to ensure that concerns about social inequities and care are considered in discussions about stigma.
Measuring Structural Stigma
Authors: Ungar Thomas , Knaak Stephanie
Published: January 2022

Structural stigma is a relatively recent focus in work on stigma, related to the activities of organizations that create and maintain social inequalities. This chapter elucidates models to measure this construct and presents eight measurement prototypes to enhance awareness and assessment of structural stigma. These prototypes include cognitive bias training, audit tools, performance dashboards, surveys, equity scorecards and other current methodologies. The development of a novel and multifaceted measure of structural stigma is recommended for the field. It is argued that structural stigma reflects an unconscious cognitive bias or set of implicit systemic inequities and that assessment must be developed to minimize measurement resistance and therefore increase the likelihood of transformative learning.
The Assessment of Mental Health Stigma in the Workplace
Authors: Dobson Keith S. , Szeto Andrew C. H.
Published: January 2022

Although the workplace is commonly cited as a stressful environment and one where stigma related to mental illness can have significant repercussions, the evaluation of workplace stigma is relatively underdeveloped. This chapter details efforts to measure mental health stigma in the workplace and describes in detail a novel assessment tool. Other measures related to self-stigma, structural stigma, and presenteeism and absenteeism in the workplace are also discussed. It is suggested that this area of stigma evaluation requires significant investment of resources.
Homelessness and mental health in Hungary
Authors: Braun Eszter , Ungvari Gabor S. , Gazdag Gábor
Published: January 2022

Homelessness in Hungary has become a major social issue since the demise of the communist system in 1989. Yet, homelessness is not a new phenomenon as it was ushered in with the period of industrialization at the end of the nineteenth century. The number of homeless people was estimated to be about 8600 in Hungary in 2018 by the non-governmental organization, the ‘3rd of February Working Party’. The system of care for the homeless is regulated by the 1/2000. (I.7.) Government Directive. Under this legislation, temporary homeless shelters and rehabilitation centres are considered to be specialized institutions, which, in addition to providing food and housing, are also obliged to provide professional social care. In 2014, a survey was conducted in Budapest to assess the psychiatric condition of homeless people and the impact of their psychiatric illness on social relations, employment, and substance use. The main finding of the survey was that the prevalence of severe psychiatric disorders in homeless people is very high, which is in line with the results of other similar surveys conducted in other countries. The poor engagement of homeless people with psychiatric services indicates that the traditional care model is not appropriate for this particular population. Homeless psychiatric patients form a special subgroup and looking after them is a complex problem which demands complex solutions. Their care can only be provided by a highly trained interdisciplinary team who follow their clients to continue helping them with social integration even after they have left the shelter.
Chronic pain in homeless persons
Authors: Vogel Marc , Schütz Christian G. , Hwang Stephen W.
Published: January 2022

Chronic pain and its role in homelessness is an under-researched but critical issue. This chapter aims to summarize the scant evidence on this topic. It examines underlying factors for the association of homelessness with chronic pain, which occurs much more often in homeless individuals than in the general population. Chronic pain impacts a variety of health aspects such as activities of daily living and mental health, thus contributing to the perpetuation of homelessness and unstable housing. The bidirectional relationship of chronic pain with psychiatric and in particular substance use disorders in homeless populations is discussed. Finally, we describe existing barriers to effective care and make the case for an integrated treatment of chronic pain and mental health issues.
Care of the patient with heart failure
Authors: Jaarsma Tiny , Stromberg Anna , Lambrinou Ekaterini , Protopapas Andreas , Hill Loreena , Ljubas Ana , Thompson David R.
Published: January 2022

Heart failure is a major and growing health problem that imposes a significant human and economic burden on individuals, families, and society through the associated high mortality, morbidity, and hospital readmission rates. It also impairs the quality of life and well-being of patients, families, and carers. The management of patients with heart failure depends on a detailed, systematic clinical assessment of their clinical presentation. Although treatments, especially pharmacological ones, but also devices, are increasingly effective, patients with heart failure and their families need education and support to help them understand and cope with treatments and any complications, make adjustments to their lifestyle, adhere to treatments, and take responsibility for their self-care.
Patient education and communication
Authors: Astin Felicity , Harris Emma , Neubeck Lis , Gallagher Robyn , Jones Jennifer
Published: January 2022

Nurses and allied health professionals play a key role in communicating and educating patients and informal carers. Comprehensive therapeutic patient education requires planning, delivery, evaluation, and documentation. Informal carers should be involved in all aspects of therapeutic education. Communication skills training for health professionals can improve patient satisfaction with care. Therapeutic education is more likely to be effective if best practice communication and teaching skills are applied in clinical practice which includes a learning needs assessment. Single sessions of therapeutic education are less effective than multiple sessions with follow-up. Problematic health literacy is a major obstacle to therapeutic patient education. Universal health literacy precautions should be implemented to reduce health inequalities. Effective therapeutic patient education has the potential to reduce unnecessary health resource use by patients and adverse events.
Looking forward: the future of cardiovascular care
Authors: Thompson David R. , Neubeck Lis , Gallagher Robyn
Published: January 2022

Cardiovascular care is evolving rapidly in an era of unprecedented demand. Nurses are increasingly caring for a growing number of people who are older, present with multiple chronic conditions, and are socially isolated. This is against a backdrop of public, political, economic, and professional pressures to work more effectively and efficiently, ensuring cost containment or value for money for health services and better outcomes and experiences for patients. Health services and healthcare professionals are being exhorted, when and where possible, to keep people out of hospital; reduce waiting times and hospital stays; speed up, shorten, and avoid duplication of diagnostics, treatments, and clinic visits; make care processes more patient-centred and coordinated; and ensure monitoring and follow-up, including linking with other sectors such as social services. In summary, to make healthcare services more responsive and patient driven, we need to change the way we think and work so that we think more creatively, work more smartly, and exploit technology and other resources appropriately, while at all times being cognizant of patient and family needs, values, and preferences, and aiming to improve outcomes and experiences.
Global Cardiovascular Risk
Authors: Lüscher Thomas F. , Deanfield John E.
Published: January 2022

Cardiovascular risk is determined by many factors including genetics predisposition, environmental factors, and lifestyle. These need to be considered when evaluating risk of future cardiovascular events in an individual patient. The important modifiable risk factors are diabetes, cholesterol, smoking and blood pressure which together with family history and lifestyle influences (stress, obesity, alcohol, physical activity) account for more than 90% of heart attacks and strokes. The ScoreCard of the European Society of Cardiology can be used now to determine the 10-year risk of a major cardiovascular event, such as myocardial infarction, stroke, and cardiovascular death and this can be used as a guide to choice of treatment. Other important factors, such as noise, pollution, socio-economic status will influence cardiovascular risk, but are difficult to incorporate when managing an individual patient.
Hypertensive Emergencies
Authors: Sudano Isabella , Hermann Matthias
Published: January 2022

Acute elevation of blood pressure is defined as a hypertensive crisis, if blood pressure is >220/120 mmHg or as a hypertensive emergency, if blood pressure is >220/120 mmHg with concomitant acute end organ damage. End organ damage may involve encephalopathy, acute coronary syndrome, acute heart failure, and aortic dissection among others. Triggers may be drugs, oral contraceptives, certain medications, renal disease, and pheochromocytoma among other conditions. Medical blood pressure lowering should be achieved rapidly or urgently, depending on clinical presentation.
Ischaemia with Non-Obstructive Coronary Artery Disease (INOCA) – Microvascular Angina
Authors: Kaski Juan-Carlos , Barton Jack , Al-Rubaye Hussein
Published: January 2022

Around half of patients with stable angina and one in ten with acute coronary syndromes have normal or non-obstructed coronary arteries. It is suspected that this is due to structural or functional microcirculatory dysfunction or myocardial factors, such as left ventricular hypertrophy, increased myocardial pressure among others. Risk factors for INOCA are age, peri -and post-menopausal status, diabetes or dyslipidaemia, hypertension and left ventricular hypertrophy, as well as endothelial dysfunction and inflammation. The diagnosis relies on documentation of ischaemia during exercise, on ECG or imaging in the presence of non-obstructed coronary arteries. Outcomes may be good or impaired in a sub-group of patients, particularly those with markedly reduced coronary flow reserve. The management is currently not evidence-based and involves lifestyle changes, as well as a variety of anti-anginal drugs with mixed effectiveness.
Antithrombotics for Acute and Chronic Coronary Syndromes
Authors: Guttmann Oliver P. , Binder Ronald , Gämperli Oliver , Baumbach Andreas
Published: January 2022

Thrombus formation involves activation of aggregating platelets as well as the formation of fibrin after activation of the coagulation cascade. Fibrin eventually binds to glycoprotein IIB/IIIA receptors on platelets thereby forming a very solid occlusive clot. There are several molecules interfering with platelet activation: (1) aspirin, which blocks the formation of thromboxane A2; (2) clopidogrel, prasugrel, and ticagrelor which block P2Y12 receptors and their activation by ADP; (3) glycoprotein inhibitors that interfere with glycoprotein IIB/IIIA on platelets, the final common pathway of platelet activation, and finally (4) thrombin inhibitors blocking PAR-1 receptors on platelets. Commonly, after an acute coronary syndrome (ACS) or after percutaneous coronary interventions (PCI) or even bypass surgery, dual antiplatelet therapy (DAPT) is recommended consisting of aspirin plus a P2Y12 inhibitor. The duration of treatment after the acute event is commonly 12 months for those with ACS and 6 months for those with a high bleeding risk. In patients with high ischaemic risk, prolonged DAPT treatment can be considered, but often such patients also have a high bleeding risk. Intravenous platelet inhibitors, such as Reopro, tirofiban, and others, are used mainly during PCI, particularly in patients with ACS. Inhibitors of coagulation cascade, such as factor Xa or factor II inhibitors or vitamin K antagonists are mainly used in patients with ACS and concomitant atrial fibrillation. In these patients, mainly aspirin or in some the P2Y12 inhibitor is skipped for some weeks or months.
Raynaud’s Phenomenon
Authors: Amann-Vesti Beatrice
Published: January 2022

Raynaud’s phenomenon is defined as an intermittent ischaemia of the fingers, either primarily functional in nature due to vasospasms or secondary in the context of any underlying vascular disease, most commonly scleroderma among others. The primary Raynaud’s phenomenon is characterized by acute attacks of white fingers with pain, commonly with exemption of the thumb and rarely involving toes. The attacks are usually triggered by cold temperature or psychological stress and occur primarily in females. In contrast, secondary Raynaud’s phenomenon affects different patient populations that are characterized by painful tropic lesions due to tissue ischaemia with ulcerations or point-like tissue lesions of the fingertips, ischaemic symptoms of hands, arms, feet, or lower legs, commonly with signs of inflammation. The underlying systemic diseases are typically collagenases, such as scleroderma, thromboangiitis obliterans (Buerger’s disease), hypothenar hammer syndrome, haematological diseases, and different forms of vasculitis.
Acute Deep Venous Thrombosis
Authors: Amann-Vesti Beatrice
Published: January 2022

Deep vein thrombosis may be associated with severe mild, or even no symptoms. Typical symptoms are acute leg pain, calf swelling, and red or discoloured skin with visible superficial veins, as well a feeling of warmth and increased symptoms upon standing. Acute deep vein thrombosis occurs in the context of an active cancer, bed-ridden status, or major surgery among others. It is diagnosed clinically as well as using duplex sonography of the deep venous system. Treatment mainly involves oral anticoagulation with NOACs or vitamin K antagonists. Initially, often heparin or low molecular weight heparin is used. Furthermore, bandaging of the affected leg is recommended. The duration of anticoagulation depends on the clinical context. It should be performed for at least 3 months and longer in the context of the history of previous deep vein thrombosis or other comorbidities.
Atrial Fibrillation
Authors: Guarguagli Silvia , Ernst Sabine
Published: January 2022

Atrial fibrillation is the most common atrial arrhythmia with a prevalence of approximately 1–2% in the general population with a marked increase with age. It is caused by uncoordinated atrial activation and associated with an irregular ventricular response. It can be classified as new onset, paroxysmal persistent long-standing and permanent or chronic atrial fibrillation. It may present with no, mild, severe, or disabling symptoms. It is associated with an increased mortality, especially cardiovascular mortality, mortality due to sudden cardiac death, heart failure, and stroke. The major causes are hypertensive, valvular, ischaemic, and other types of structural heart disease, including congenital heart disease. Lone atrial fibrillation accounts for approximately 50% of cases. The evaluation involves ECGs, long-term ECG monitoring, and cardiac imaging, in particular, trans-thoracic echocardiography, as well as blood tests. Rate control involves primarily beta receptor antagonists, digoxin and/or calcium channel blockers of the verapamil or diltiazem type. Rhythm control requires electrical cardioversion in general followed by anti-arrhythmic agents and, today, more and more catheter or less commonly surgical ablation.
Removal (Extraction) of Pacemakers and ICD Leads
Authors: Haldar Shouvik
Published: January 2022

Most cardiac implantable electronic devices (CIEDs) use leads or electrodes to connect the device generator to cardiac tissues, and as such, they are foreign bodies that can activate coagulation, thrombus formation, or be a site of infection, as bacteria attached to leads are difficult for the immune system to reach. Risk factors for complications are diabetes, renal disease, and COPD among others. Suspected infection has to be evaluated carefully using transoesophageal echocardiography, blood cultures, wound swabs inflammatory markers and often the CIEDs have to be removed if suspicion is confirmed. Removal can be achieved today with special technology and requires the experience and skills of the operator to avoid major complications, particularly bleeding.
Channelopathies and Sudden Cardiac Death
Authors: Schwartz Peter J. , Keller Dagmar I.
Published: January 2022

Channelopathies are arrhythmogenic disorders of genetic origin due to mutations on genes and coding for ion channels and characterized by typical ECG features. They are often life threatening and their recognition is clinically important because without therapy such patients may have a high mortality due to Sudden Cardiac Death (SCD). Channelopathies usually manifest at a young age or are associated with syncope, cardiac arrest (CA), and SCD, and show clinical and genetic heterogeneity. The inheritance is often autosomal-dominant, and ICD implantation is sometimes required. Channelopathies may involve the long-QT syndrome, the short-QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia.
Scores, Classifications, and Severity Levels
Authors: Davies Allan , Schmied Christian
Published: January 2022

The scores described are those used routinely in cardiovascular practice and help practitioners in classifying severity of disease, assessing risk and determining the appropriate course of clinical management.
Definition and pathophysiology of complex cancer pain
Authors: Bennett Michael I.
Published: January 2022

This chapter covers the definition of pain, its epidemiology, prevalence and aetiology in the context of cancer. It then describes the severity and impact of pain, pathophysiology, and complex pain syndromes. It then discusses pain in the context of cancer-specific areas of the body, including bone, spinal cord compression, the chest wall, brachial plexopathy, pancreatic pain, lumbosacral plexopathy, and pelvic pain. It concludes with key learning points for the reader.
The pharmacological management of cancer pain
Authors: Bennett Michael I. , Farquhar-Smith Paul
Published: January 2022

This chapter addresses methods and approaches to managing cancer pain. It begins with the assessment and classification of pain, then the principles that underpin effective pain management and the barriers that may prevent this from happening. A systemic approach to prescribing in cancer pain is included, then the chapter goes on to the methods and pharmacological interventions used. This includes non-opioids and weak opioids, and the administration of opioids and managing adverse effects. Switching to strong opioid alternatives or to morphine is explained, and then various opioids and their administration and management are described. Adjuvants, co-analgesics, steroids, anticonvulsants and antidepressants are all covered, and the chapter finishes with the key learning points.
Oncological management of cancer pain
Authors: Eswar Chinnamani
Published: January 2022

Appropriate and timely oncological management of the primary tumour and any secondaries can result in a significant improvement in pain. This chapter covers both systemic forms of cancer treatment such as chemotherapy, and locoregional treatments such as radiotherapy and surgery. Hormonal and targeted agents, bisphosphonates, and radioisotopes are also addressed, and the chapter ends with some key learning points.
Molecular Aspects of Hormone Regulation
Authors: Siddle Kenneth , Brierley Gemma V.
Published: January 2022

Hormones travel in the bloodstream to exert effects on target tissues, which are often anatomically remote from the site of hormone secretion. They achieve this by binding and activating receptors, which usually are highly selective or specific. Receptors are grouped into several families according to their molecular structure and mechanism of action. Common classes of receptors important in endocrinology include cell surface G-protein-coupled receptors, receptor tyrosine kinases, and cytokine-like receptors, and intracellular nuclear hormone receptors. In this chapter the basic anatomy of the signalling pathways emanating from these receptors is described, and the principles and mechanisms of information coding and transmission, and how these may go awry in endocrine disease, are discussed.
Pituitary Assessment Strategy
Authors: Drake William M. , Keevil Brian , Trainer Peter J.
Published: January 2022

Accurate assessment of anterior pituitary function requires a sound knowledge of its normal physiology together with careful integration of clinical and biochemical information. The optimum methods of testing anterior and posterior pituitary function and the interpretation of the results are subjects of continuing debate. The syndromes associated with and consequences of hypo- and hyperpituitarism; and the diagnosis and treatment of diabetes insipidus are all discussed elsewhere in this book. The intention of this chapter is to describe the physiological basis and evidence in favour of the various available tests of anterior pituitary function, while at the same time acknowledging their limitations and appreciating the importance of the clinical context of testing.
Acromegaly
Authors: Wass John A.H. , Trainer Peter J. , Korbonits Márta
Published: January 2022

Acromegaly is a disease with a long history; with gigantism this is particularly so. It is uncommon. Significant genetic advances have been made in regard to the causation of the tumour but more needs to be known and understanding the genetic basis of these tumours is not universal. The most important asset of this disease is early recognition. It presents to a number of different specialties. The mainstay of treatment is transsphenoidal hypophysectomy. Not infrequently, even in the hands of experienced surgeons, acromegaly persists and drug therapy with dopamine agonists, somatostatin analogues, and pegvisomant are needed. New drugs are being developed in the field of acromegaly. Radiotherapy may occasionally be necessary to control the tumour and/or growth hormone levels in the absence of response to some medical therapies. Nowadays it is possible however in the majority of patients to control IGF1 secretion with adequate doses of pegvisomant.
Hypothalamic Dysfunction (Hypothalamic Syndromes)
Authors: Gan Hoong-Wei , Cerbone Manuela , Dattani Mehul T.
Published: January 2022

Despite its small size, the hypothalamus is one of00 the most complex and vital structures of the human brain. Through its intimate connection with the pituitary gland and other areas of the brain, the hypothalamus acts as the master regulator of various neuroendocrine systems while integrating endocrine and neural signals which regulate superior functions such as appetite, thirst, circadian rhythms, arousal, memory, and behaviour. Consequently, acquired damage to or maldevelopment of this area can have widespread consequences on a variety of homeostatic mechanisms. Hypothalamic dysfunction can present with heterogeneous clinical features including hypopituitarism necessitating pituitary hormone replacement, a spectrum of weight disorders ranging from hypothalamic obesity to diencephalic syndrome/anorexia, temperature and sleep dysregulation, behavioural difficulties, and memory and autonomic dysfunction. Targeted treatment for hypothalamic obesity and the ‘non-endocrine’ manifestations of hypothalamic dysfunction has proven difficult, and supportive care and avoidance of acquired hypothalamic damage are the only strategies currently available for these patients.
Perisellar Tumours Including Cysts, Hamartomas, and Vascular Tumours
Authors: Honegger Jürgen , Ernemann Ulrike , Beschorner Rudi
Published: January 2022

Pituitary adenomas are prevailing among perisellar tumours. That is why other perisellar tumours are often misinterpreted as pituitary adenomas. Careful consideration of the characteristic endocrinological and magnetic resonance imaging (MRI) findings are of paramount importance to differentiate between various tumours encountered in the perisellar region. With knowledge of the typical and occasionally pathognomonic signs of the different perisellar tumour entities, the correct diagnosis can often be made with a high degree of certainty even before histological confirmation of diagnosis. Diagnostic accuracy is decisive for purposeful clinical decision-making. In parallel, histopathological classification in surgical cases has further developed and molecular markers have been implemented allowing a more precise distinction and definition of tumour entities. Extended transsphenoidal skull base approaches have expanded the surgical options in the treatment of perisellar tumours. Radiotherapeutic modalities have been refined and the experience with radiosurgery or fractionated radiotherapy for perisellar tumours has significantly increased over the past 10 years. Novel targeted therapies are emerging as additional therapeutic options for solid tumours. The endovascular techniques for treatment of aneurysms including stent-assisted coiling and flow diversion have rapidly advanced. The characteristic clinical findings, the current diagnostic and therapeutic strategies, and the outcome with the advanced treatment options in non-adenomatous perisellar tumours are presented in this chapter.
The History and Iconography Relating to the Thyroid Gland
Authors: Volpé Robert , Sawin Clark
Published: January 2022

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 at the end of the chapter in its References. Knowledge of goitre (which was not known to be a thyroid enlargement until about the sixteenth century) goes back into antiquity. From this early documentation of goitre and cretinism in prehistoric times, to the discovery of iodine at the beginning of the nineteenth century and beyond, thyroid conditions and their treatment—including hyper- and hypothyroidism, cretinism, Graves’ disease, goitre, myxoedema, and fibrous thyroiditis—have been known by humankind for millennia.
Biosynthesis, Transport, Metabolism, and Actions of Thyroid Hormones
Authors: Visser W. Edward
Published: January 2022

This chapter looks at the thyroid, which produces thyroid hormone, the common name for prohormone thyroxine (T4) and the bioactive hormone 3,3ʹ,5-triiodothyronine (T3). Thyroid hormone biosynthesis takes place in thyroid follicular cells. The bioavailability of thyroid hormone in target tissues depends to a large extent on the supply of plasma T4 and T3, the activity of plasma membrane transporters mediating the cellular uptake and/or efflux of these hormones, as well as the activity of deiodinases and other enzymes catalysing their activation or inactivation. The actions of thyroid hormone are mediated by binding of T3 to the nuclear thyroid hormone (or T3) receptors (TRs).
The Complex Genetics of Thyroid Disease
Authors: Davies Terry F. , Menconi Francesca , Tomer Yaron
Published: January 2022

Significant progress has been made in the identification and characterization of susceptibility genes for the autoimmune thyroid diseases (AITD) which includes Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), and are among the commonest autoimmune endocrine diseases, affecting up to 5% of the general population. There is a strong familial aggregation with these diseases, a high sibling risk ratio, and a high concordance rate in monozygotic twins. Several major AITD susceptibility genes have been identified which can be categorized by the disease phenotype or their function. In the group of immune regulatory genes, HLA-DR3 was shown long ago to be associated with GD and HT, and the presence of arginine at position 74 of the HLA-DRβ chain is now known to be the specific sequence variant conferring risk. Three additional susceptibility genes related to immune regulation have also been revealed—CTLA-4, CD40, and PTPN22, as well as two thyroid-specific genes: thyroglobulin and the TSH receptor (TSHR). While CTLA-4, PTPN22, and thyroglobulin confer susceptibility to both GD and HT, CD40 and TSHR are specific for GD.
Environmental Factors
Authors: Köhrle Josef
Published: January 2022

The thyroid gland, its feedback regulation within the hypothalamus–, pituitary–, thyroid–periphery axis, and the action of thyroid hormones belong to the most vulnerable components of the endocrine system affected by our environment. Thyroid hormone synthesis critically depends on live long nutritional availability of three essential trace elements (i.e. iodine, selenium, and iron). The complex, evolutionary highly conserved system, utilizing the uptake, organification, storage, and fine-tuned mobilization and activation of iodine as the main chemical constituent of and environmentally dependent thyroid hormones, provides a number of possibilities for nutritive, industrial and environmental compounds (endocrine disruptors) to interfere with these reactions and to cause adverse effects. Thyroid hormones are critical for brain development already in utero and represent potent permissive regulators of growth, energy metabolism, regulation of body temperature, and turnover of biomolecules. Deficiency or excess of thyroid hormones due to exposure with endocrine disrupting compounds is associated with various thyroid-related diseases.
Thyroiditis
Authors: Pearce Elizabeth N. , Farwell Alan P.
Published: January 2022

Thyroiditis comprises a diverse group of disorders that are among the most common endocrine abnormalities encountered in clinical practice. These disorders range from the extremely common chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis) to the extremely rare invasive fibrous thyroiditis (Riedel’s thyroiditis). Clinical presentations are also diverse, ranging from an incidental finding of a goitre to potentially life-threatening illness, from hypothyroidism to thyrotoxicosis. This chapter reviews the pathogenesis, clinical manifestations, diagnosis, and treatment of chronic lymphocytic thyroiditis, subacute thyroiditis, infectious thyroiditis, and sclerosing thyroiditis (Riedel’s thyroiditis, which may be linked to immunoglobulin G4-related disease).
Subclinical Hyperthyroidism
Authors: Pearce Simon H.S.
Published: January 2022

Subclinical hyperthyroidism is a biochemical diagnosis, defined by a serum thyroid stimulating hormone (TSH) below the reference range coupled with normal serum free thyroid hormones. It rarely causes symptoms and affects around 1% of people, becoming more prevalent in individuals over 80 years of age. It is most frequently a transient condition owing to non-thyroidal illness or medication use. Many observational population-based studies of older people have shown that subclinical hyperthyroidism is associated with a poor long-term outcome, including an excess of atrial fibrillation, heart failure, osteoporosis, dementia, and death. This is likely to reflect that serum TSH is a biomarker of ageing and thus low TSH defines a group of people with more morbidity or frailty. However, if the serum TSH is fully suppressed (<0.05 mU/L) then it can represent a state of mild thyroid autonomy and treatment should be considered.
Management of Toxic Multinodular Goitre and Toxic Adenoma
Authors: Führer Dagmar , Jäschke Holger
Published: January 2022

Toxic adenoma (TA) and toxic multinodular goitre (TMNG) represent the clinically important presentations of thyroid autonomy. Thyroid autonomy is a condition where thyrocytes produce thyroid hormones independently of thyrotropin (TSH) and in absence of TSH receptor stimulating antibodies (TSAb). This prevalence of thyroid autonomy is linked with dietary iodine supply and is a common finding in areas with iodine deficiency. Genetic alterations frequently determined in patients with TA or TMNG are activating somatic mutations in the TSH receptor or the Gs alpha protein subunit resulting in a loss of pituitary control of the thyroid. This chapter discusses beside epidemiology and pathology also the clinical presentation, diagnosis, and treatment options for patients with TA or TMNG.
Pathogenesis of Thyroid Cancer
Authors: Santoro Massimo , Jarzab Barbara , Krajewska Jolanta , Rusinek Dagmara
Published: January 2022

Thyroid cancers (TCs) include a wide spectrum of cancer types, from indolent papillary microcarcinomas, through well-differentiated TCs to aggressive and treatment-refractory poorly and undifferentiated TCs. TC, mostly papillary microcarcinoma, features one of the most rapid incidence increases compared to other malignant neoplasms. This phenomenon is mainly explained by a widespread use of diagnostic tools (neck ultrasound, fine needle aspiration biopsy). However, it is possibly also a consequence of the impact of environmental and genetic factors. This chapter summarizes the current knowledge concerning environmental and in particular molecular factors related to TC pathogenesis. The use of high throughput methods showed a wide spectrum of genetic and epigenetic alterations as well as their associations in TC. Notwithstanding our better understanding of the molecular pathology of TC, numerous questions still remain open.
Hypercalcaemic and Hypocalcaemic Syndromes in Children
Authors: Ardeshirpour Laleh , Carpenter Thomas O. , Robinson Cemre
Published: January 2022

Mineral requirements vary considerably throughout life, reflecting the intensive mineral accretion that occurs in during childhood. The correct diagnosis of bone and mineral disorders as well as the monitoring of relevant therapies requires an understanding of the age-dependent changes in serum minerals and calciotropic hormones. Many heritable disorders of mineral homeostasis become evident in infancy and childhood and are best recognized when viewed within the appropriate context of mineral requirements and the hormonal milieu during the early stages of life. Thus, an understanding of the relevant physiology is central to formulating age-specific approaches to management of these various clinical problems. This chapter reviews features of calcium homeostasis specific to children, and the diagnosis and management of various inherited and acquired syndromes of hypocalcaemia and hypercalcaemia, in the context of physiology specific to childhood.
Thyroid Disorders and Bone Disease
Authors: Watts Laura M. , Freudenthal Bernard , Bassett J.H. Duncan , Williams Graham R.
Published: January 2022

Thyroid hormones have important effects on bone that are mediated by thyroid hormone receptor alpha. Hypothyroidism in children causes growth retardation and delayed bone age, whereas juvenile thyrotoxicosis accelerates growth and skeletal maturation. In adults, hyperthyroidism increases bone resorption and formation disproportionately and results in high bone turnover osteoporosis and an increased susceptibility to fracture. Thus, thyroid hormones stimulate anabolic responses during skeletal growth but have catabolic effects in adults. Overt thyrotoxicosis, subclinical hyperthyroidism, and overtreatment of hypothyroid patients with thyroxine all result in bone loss and varying degrees of osteoporosis and susceptibility to fracture. Furthermore, population studies demonstrate that thyroid status within the upper normal reference range is associated with low bone mass and an increased risk of fracture. Taken together, it is evident that thyroid hormones are essential for skeletal growth and adult bone maintenance, and the skeleton remains exquisitely sensitive to thyroid hormones throughout life.
Adrenal Surgery
Authors: Palazzo Fausto , Mihai Radu
Published: January 2022

This chapter looks at how the past two decades have witnessed a significant increase in the diagnosis of both functioning and non-functioning adrenal tumours. The widespread use of cross-sectional imaging has unveiled a previously undiagnosed reservoir of as many as 10% of adults with enlarged adrenal glands. Increasingly sensitive oncological staging has led to the identification of patients with previously undiagnosed solitary adrenal metastases. The (slow) acceptance of screening of hypertensive populations for hyperaldosteronism has been encouraged by the recognition of the potential benefits of adrenal surgery in hyperaldosteronism. All of these changes have increased the number of patients considered for adrenal surgery.
Genetics of Primary Aldosteronism and Other Steroid-Related Causes of Endocrine Hypertension
Authors: Zennaro Maria Christina , Fernandes-Rosa Fabio , Boulkroun Sheerazed
Published: January 2022

Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. It represents a major target for personalized treatment and prevention of cardiovascular complications. Recent years have brought important insights into the genetic mechanisms responsible for inherited forms of PA and aldosterone-producing adenoma (APA). Genetic defects affect genes coding for ion channels and pumps, involved in maintaining cell membrane potential and ion homoeostasis in adrenal zona glomerulosa. The pathogenic mechanisms imply increased calcium signalling as a trigger for increased aldosterone production. In addition, genetic mutations in components of the Wnt/β-catenin pathway may lead to APA development. Some rare monogenic disorders also lead to steroid dependent hypertension. These include 11β-hydroxylase (CYP11B1) and 17α-hydroxylase (CYP17A1) deficiencies, as well as rare diseases affecting steroid actions in the kidney. In this chapter we will describe the genetics of PA and the other steroid-related causes of hypertension and address perspectives for diagnosis and treatment.
Non-Functioning Pancreatic Neuroendocrine Tumours
Authors: Lim Kok Haw Jonathan , Valle Juan W. , Mansoor Wasat
Published: January 2022

This chapter will focus on neuroendocrine tumours (NETs) of the lung and pancreas (panNETs) (non-functioning) summarizing the current understanding, diagnosis, and management recommendations of these two subgroups NETs (functioning panNETs and other NET subtypes will be covered separately in subsequent chapters). Lung NETs are the most common subtype of NETs outside the gastroenteropancreatic (GEP) axis, and there has been an alarming rise in its incidence in recent years. Lung NETs are categorized into well-differentiated typical carcinoid (TC), well-differentiated atypical carcinoid (AC), poorly differentiated small cell lung carcinoma (SCLC) and poorly differentiated large cell neuroendocrine carcinoma (LCNEC); which has a significant implication on the treatment recommended. Meanwhile panNETs are classified morphologically into well-differentiated NETs (grades 1-3) and poorly differentiated NECs (grade 3). The majority of lung NETs and panNETs are non-functioning by virtue of absence of carcinoid syndrome and lack of positive serum neuroendocrine biomarkers. In both, histopathological, biochemical, and complete radiological work-up including the use of nuclear medicine imaging are pivotal in confirming the diagnosis. The last decade has witnessed rapid advances in systemic treatment options available for both lung NETs and panNETs with the advent of somatostatin analogues (SSAs), various targeted therapies, and chemotherapy; and also liver-directed therapies and other nuclear medicine ‘theranostics’. In view of the heterogeneity in NETs, each patient’s treatment pathway should be personalized, and it is recommended for all subtypes of NETs to be managed in high-volume centres in close partnership with a specialized multidisciplinary team.
Vasointestinal Polypeptide Secreting Tumours
Authors: Munir Alia
Published: January 2022

Vasointestinal polypeptide (VIP) secreting tumours (VIPomas) are rare functioning neuroendocrine tumours (NET) The majority arise from the tail of pancreas. Frequently they have metastasized at presentation and may prove challenging to diagnose and manage. The VIP causes a syndrome of profound and chronic, watery diarrhoea which persists despite fasting. Characteristic electrolyte abnormalities occur including: dehydration, hypokalaemia, achlorhydria, acidosis with hypercalcaemia, and hyperglycaemia. These may be life-threatening. Patients may also present with lethargy, weakness, nausea, abdominal pain, and weight loss. Diagnosis requires the clinical picture, fasting VIP level, multimodal imaging including CT, somatostatin receptor scintigraphy, and MRI. Treatment goals are to initially correct dehydration and electrolyte abnormalities. Control of diarrhoea may be achieved using octreotide. Surgical resection with curative intent should be offered where able. For metastatic disease options should be discussed in a NET specific multidisciplinary team meeting (MDT) and include targeted, loco-regional, and peptide receptor radionuclide therapies.
Clinical Evaluation of Patients with Suspected Reproductive Endocrine Disorders
Authors: Roberts Rachel , Franks Steve , Jayasena Channa
Published: January 2022

Female reproductive endocrine disorders are common, and can result in significant morbidity for women due to their impact on fertility, in addition to physical, psychological, and sexual consequences. It is therefore important that women with menstrual disorders are recognized, receive thorough clinical evaluation, and have access to appropriate services to facilitate prompt diagnosis so that hormone levels are maintained and the potential health consequences on fertility, bone, and cardiovascular health are minimized. Clinical assessment is often sufficient to determine the likely cause of female reproductive disorders or infertility, and allow subsequent diagnostic evaluation to be performed in a more targeted manner. This chapter will provide a practical and systematic guide to interpreting clinical assessment of female reproductive endocrine disorders.