bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics of Primary Aldosteronism and Other Steroid-Related Causes of Endocrine Hypertension
Authors: Zennaro Maria Christina , Fernandes-Rosa Fabio , Boulkroun Sheerazed 
Published: January 2022

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
Female Infertility
Authors: Oktay Kutluk , Taylan Enes 
Published: January 2022

Abstract
Fertility preservation is an emerging field which aims to develop and utilize effective treatment options for women under risk of ovarian insufficiency (OI) due to a wide range of conditions from chromosomal disorders to antineoplastic treatments and surgical interventions that can cause loss of ovarian follicle reserve. Irreversible loss of fertility and ovarian endocrine function can have a negative impact on women’s physiological and psychosocial health. Therefore, preservation of fertility in reproductive age women is a critical component of modern healthcare and improved quality of life. In this chapter, we will review the current status and future perspectives of the field of fertility preservation as an emerging branch of assisted reproductive technologies.
Hormonal Contraception
Authors: Chin Jennifer , Kaneshiro Bliss 
Published: January 2022

Abstract
The birth control pill, the first hormonal contraceptive method widely available to the public, transformed the way society viewed childbearing and sexuality. Since the 1960s, many different types of hormonal contraceptives have been developed and are now available to women. There are two main categories of hormonal contraceptives, combined hormonal contraceptives, which consist of oestrogen and progestin, and progestin-only contraceptives. Within each category, various methods and formulations exist, each with a different mechanism of action, efficacy, and side effect profile. Emergency contraception offers a post-coital method that can be used in cases where women did not use contraception at the time of intercourse or had a method failure (i.e. condom breakage). Several contraceptive methods have non-contraceptive benefits. Most methods decrease the risk of endometrial cancer and combined hormonal contraceptives decrease the risk of ovarian cancer. Many methods have been used in the treatment of abnormal uterine bleeding, dysmenorrhoea, premenstrual syndrome, and acne.
General Considerations Relating to Thyroid Disease in Pregnancy
Authors: Taylor Peter N. , Premawardhana L.D.K.E. , Lazarus John H. 
Published: January 2022

Abstract
Thyroid hormone is essential for maintaining a pregnancy and ensuring fetal development. Thyroid disorders are common in women of childbearing age and as pregnancy has a substantial impact on the hypothalamic–pituitary–thyroid axis, abnormal thyroid function is frequently encountered in antenatal clinics. It is also well established that overt thyroid disease is associated with adverse obstetric and offspring neuro-developmental outcomes. There is now growing concern that more marginal degrees of thyroid dysfunction particularly subclinical hypothyroidism (elevated TSH and normal fT4 concentration) and isolated hypothyroxinaemia (normal TSH and low fT4) are also associated with fetal loss, prematurity and impaired offspring cognitive function. In some studies, maternal thyroid autoimmunity has also been identified as a potential risk for fetal loss even in euthyroid women. Correction of overt hypothyroidism and hyperthyroidism dramatically reduces the risk of major adverse obstetric outcomes including fetal loss and premature birth.
Thyroid Disease During Pregnancy
Authors: Korevaar Tim I.M. , Peeters Robin P. 
Published: January 2022

Abstract
Thyroid physiology undergoes major changes during pregnancy, understanding of which improves the clinical assessment of thyroid function during pregnancy and the clinical decision-making process regarding the follow-up and treatment of gestational thyroid disease. Although thyroid function is frequently assessed before and during pregnancy, accurate clinical assessment, and interpretation of maternal (and fetal) thyroid function during pregnancy is complicated by the maternal–placental–fetal interaction. Given this complexity, it remains difficult how and when to evaluate for thyroid dysfunction, as well as if and how to treat (mild) thyroid disease during pregnancy. This chapter discusses current insights on physiology, diagnosis, risk of adverse outcomes, and treatment options.
Thyroid Disorders in Newborns
Authors: van Trotsenburg A.S. Paul , Zwaveling-Soonawala Nitash 
Published: January 2022

Abstract
Thyroid hormone is essential for normal brain development starting in the early embryonic period and continuing throughout the first years of life. Untreated congenital hypothyroidism leads to permanent intellectual and motor disabilities. Neonatal screening programmes have proven to be very successful in preventing brain damage by early detection and treatment of congenital hypothyroidism. Congenital hypothyroidism may be of thyroidal (primary) or of hypothalamic–pituitary (central) origin. Primary congenital hypothyroidism accounts for approximately 90–95% of all cases and may be due to abnormal thyroid gland formation (dysgenesis) or defective thyroid hormone syntheses by a structurally normal gland (dyshormonogenesis). Central congenital hypothyroidism has a reported incidence of up to one in 16 000 live births and may occur in isolation, but in the majority of cases is accompanied by additional pituitary hormone deficiencies. In this chapter the aetiology, diagnostics, and treatment of congenital hypothyroidism are discussed.
Sex Determination and Differentiation
Authors: Hiort Olaf , Werner Ralf 
Published: January 2022

Abstract
The biological sex of a human being is dependent on a genetic pathway starting from the chromosomal set that determines the differentiation of the gonads. In this chapter the current knowledge of the physiological genetic regulation of gonadal development, termed sex determination is described, followed by the endocrine differentiation into the usual phenotypes of male and female. The delicate complexity of these pathways is not only dependent on the genetic composition, but needs to occur in a stringent step-wise and time-dependent manner, therefore dependent on hitherto often unknown regulatory mechanisms. Deviations and disruptions of these pathways may lead to disorders or differences of sex development (DSD), demonstrating that the poles of female and male may be not robust, but are subject to high variability even within the usual sex development.
Recognizing Normal and Disordered Pubertal Development
Authors: Rogol Alan D. , Fuqua John S. 
Published: January 2022

Abstract
Pubertal maturation is a time of dramatic physical, reproductive, and psychological changes, including the development of secondary sex characteristics and changes in body composition. It requires a complex series of hormonal changes initiated by alterations in hypothalamic regulatory mechanisms that are incompletely understood, culminating in gonadal sex steroid secretion and associated maturation. While genetics play a major role in the timing and progression of pubertal maturation, other inputs such as nutrition, environmental factors, and social milieu yield individualized variations in the maturational pattern. It is likely that these factors are in part responsible for changes in timing and tempo of pubertal maturation noted over the last few decades. When a child begins to mature at the earliest or latest extremes of the normal ranges, the clinician must determine if the child is undergoing normal puberty, a non-pathologic variation, or a medically concerning condition that requires further investigation or treatment.
Pubertal Delay and Hypogonadism
Authors: Rogol Alan D. , Fuqua John S. 
Published: January 2022

Abstract
Delayed puberty occurs when no signs of pubertal maturation are seen by 14 years of age in boys or 13 years in girls. Although constitutional delay of growth and puberty is commonly seen and is often regarded as benign, there are many other causes of pubertal delay that ultimately result in permanent hypogonadism, and these must be differentiated from self-limited delays in maturation. Causes of hypogonadism include disorders affecting the gonads (primary hypogonadism) and abnormalities of pituitary or hypothalamic function (hypogonadotropic hypogonadism). Hypogonadotropic hypogonadism may be part of a more global set of pituitary deficiencies or may be the only endocrine axis affected. A rapidly growing array of genetic disorders accounts for isolated hypogonadotropic hypogonadism. Treatment of delayed puberty often consists of short-term administration of sex steroids to those with constitutional delay, while individuals with permanent hypogonadism require long-term testosterone or oestradiol replacement.
Transition in Endocrinology
Authors: Gleeson Helena K. , Wright Rohana J. 
Published: January 2022

Abstract
Healthcare professionals are increasingly aware that the transition from childhood to adulthood requires special consideration, in terms of meeting the needs of young people with any long-term condition, both through healthcare design and delivery and the need for a specific skill and behaviour set in order to do this effectively. Young people can be a forgotten group, not adequately considered in paediatric or adult service development strategies resulting in disrupted care. This phase of life is key, as it is when a young person develops their ideas about, and relationships with the healthcare system and their own health condition, thus setting the scene for future interactions. Young people with endocrine conditions, whether onset is in early childhood or during adolescence, often require lifelong care, and therefore both paediatric and adult healthcare professionals require knowledge about: biopsychosocial development and how it can both affect and be affected by having an endocrine condition; key aspects of adolescent health; developmentally appropriate healthcare; effective transition between paediatric and adult services; endocrine-specific care during adolescence and young adulthood.
Paraneoplastic Endocrine Syndromes
Authors: Ray David W. 
Published: January 2022

Abstract
Hormone production from non-endocrine glands poses a diagnostic and management challenge. With improvements in hormone assay precision, and diagnostic imaging, the clinician is better equipped now to manage the patient. Here, we review the underlying biology of ectopic hormone production, and aberrant regulation. Ectopic adrenocorticotrophic hormone (ACTH) syndrome is a prevalent disorder, but in most cases remains undiagnosed, and is managed as part of treatment for small cell undifferentiated cancer. Humoral hypercalcaemia of malignancy is also commonly encountered, but with PTHrP assay, and bisphosphonate therapy can be effectively managed. SIADH is a frequent diagnosis in medical inpatients, here the danger is frequently overtreatment. Hormone-dependent cancers are primarily managed by oncology services, but the role of hormones in breast and prostate development, and the hormonal manipulations used in their management are important. Here, we review the state of the art in hormone-dependent cancers.
Hormonal Therapy for Prostate Cancer
Authors: Vasilevskaya Irina A. , Schiewer Matthew J. , Knudsen Karen E. 
Published: January 2022

Abstract
First-line therapy for metastatic prostate cancer (PCa) is targeted at the androgen receptor (AR), which governs gene expression programmes that impact pro-tumorigenic phenotypes, including proliferation, survival, and DNA repair. As is the case for many cancers, ageing is one of the most significant risk factors for PCa. PCa develops mainly in older men, with a significantly higher frequency in African-American men. Diagnosis rarely occurs in men younger than 40 years old, with the majority of new cases diagnosed between the ages of 65 and 79. Current data suggest that only up to 10% of PCa cases are hereditary, especially in early onset disease, while other risk factors proposed in some studies, such as smoking and excess body weight, have not been universally accepted. This chapter will outline the mechanistic underpinnings of response and resistance to AR-directed therapy, including androgen deprivation therapy (ADT) and AR antagonists.
Obesity as a Public Health Problem
Authors: Bauman Adrian 
Published: January 2022

Abstract
Public health approaches to obesity are distinctly different, but complementary, to clinical management. The history of describing obesity as a public health problem is lengthy, preceding the 1990s high-income country ‘obesity epidemic’. Overweight and obesity now affect half to two-thirds of developed country populations, and rates are still increasing in middle-income countries. Patterns and socioeconomic correlates of obesity differ across countries at different stages of industrial development. In relation to health outcomes, obesity is consistently related to non-communicable disease, especially diabetes. Risk increases across all levels of obesity, but increases exponentially for extreme obesity. Population-wide increases are likely due to a complex system of environmental, societal, economic, and cultural factors, and these need to be addressed in implementing upstream primary prevention solutions. Working outside of the health sector will be required, posing challenge to the implementation of national obesity prevention plans.
Epidemiology and Public Health
Authors: Mayer-Davis Elizabeth J. , Igudesman Daria 
Published: January 2022

Abstract
Diabetes mellitus is a collection of endocrine disorders that involve insufficient or dysfunctional insulin production. Their causes include genetic and environmental factors that vary from one individual to another, and across populations. Trends in incidence and prevalence of diabetes and its complications also vary by geographic region, and by demographic factors such as gender, race, and ethnicity. While type 1 and type 2 diabetes onset tend to occur more frequently in children and adults, respectively, relative proportions of the two may be difficult to measure accurately in middle- and low-income countries. Gestational diabetes is a third diabetes type that is on the rise, partially due to increases in obesity among women of childbearing age. Prevention and treatment efforts should include a combination of pharmacologic and lifestyle interventions, and should be targeted based upon resource availability and feasibility. Economic impact is discussed both nationally and internationally.
Presentation and Natural History of Type 2 Diabetes
Authors: Taylor Roy 
Published: January 2022

Abstract
Clinical presentation of type 2 diabetes are described. The natural history of the three phases of type 2 diabetes—prediabetes, diabetes itself, and the post-diabetic state—are presented in terms of clinical features and underlying pathophysiology. The dangerous, asymptomatic phase of prediabetes is a high risk state for cardiovascular disease. This is also true for type 2 diabetes, with the additional microvascular complication risks. If weight loss is not achieved and maintained after diagnosis, the diabetic state steady progresses, requiring sequential addition of antidiabetic agents. In the past decade clear information on the potential reversibility of the processes underlying diabetes has become available. It is now possible to describe the post-diabetic state. Provided that substantial weight loss is achieved and maintained, non-diabetic glycaemic control can be stable for several years. Longer-term observation is required of cardiovascular outcomes, although risk indices indicate return to background levels.
Monogenic Forms of Diabetes Resulting from Beta-Cell Dysfunction
Authors: Hattersley Andrew , Patel Kashyap A. , Besser Rachel 
Published: January 2022

Abstract
Monogenic diabetes refers to diabetes resulting from mutations in a single gene. This chapter discusses monogenic disorders causing beta-cell dysfunction, which accounts for the majority of cases. Patients can usually be divided into three clinical categories; maturity-onset diabetes of the young (MODY) which is dominantly inherited familial diabetes, neonatal diabetes diagnosed under the age of 6 months and monogenic diabetes syndromes which are characterized by multiple non-pancreatic features. In each clinical category there are several aetiological genes, which usually result in a discrete clinical phenotype. Genetic diagnosis is now possible in &gt;80% of cases and is crucial in determining appropriate management, predicting clinical course, screening affected relatives, and genetic counselling of unaffected family members. Importantly, in many of the most common causes of monogenic beta-cell diabetes, making a diagnosis can result in greatly improved treatment. However diagnosis can be challenging because of low prevalence rates in a diabetes clinic (1–3%) and the majority of patients are therefore misdiagnosed as having type 1 (T1D) or type 2 diabetes (T2D). Features that distinguish these disorders are discussed.
Pathogenesis of Microvascular Complications
Authors: Shore Angela 
Published: January 2022

Abstract
The microvascular complications of diabetes, seen clinically as diabetic retinopathy, nephropathy, and neuropathy are preceded by subclinical microvascular dysfunction and abnormalities in other cells in the neurovascular units. Once microvascular complications are established both structural (e.g. thickened capillary basement membrane, acellular capillaries, pericyte loss, tissue remodelling, fibrosis, mesangial expansion) and functional changes (e.g. reduced perfusion, impaired endothelial function, leukocyte sticking and migration, increased vascular permeability) occur. The mechanisms underlying the formation and progression of microvascular complications are complex, and vary both with the stage of disease and an individual’s susceptibility to complications due to both their genetic risk and environmental factors.
Management of Idiopathic Male Infertility
Authors: Tournaye Herman , Popovic-Todorovic Biljana 
Published: January 2022

Abstract
Male reproductive deficiency may result from factors that affect sperm production, sperm quality and function, or sperm transport. However, in about 30–40% of men the cause for these impairments remain unexplained, but increasingly, genetic causes are being discovered. In general, although largely unproven, a healthy lifestyle may improve sperm quality. Currently, there is no evidence of beneficial effect of food supplements and oral antioxidant preparations in management of idiopathic male infertility. Empiric hormonal treatment has no role in unexplained male infertility. Assisted reproduction technologies (ART) are relatively successful and increasingly used as the management of choice in the idiopathic male infertility.