bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung 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.
Familial Syndromes and Genetic Causes of Paraganglioma and Phaeochromocytoma
Authors: Maher Eamonn R. , Casey Ruth T. 
Published: January 2022

Abstract
A phaeochromocytoma is a tumour arising from the adrenal medulla and a paraganglioma refers to its extra-adrenal counterpart, which can develop from sympathetic or parasympathetic tissue anywhere from the skull base to the pelvis. Phaeochromocytomas and paragangliomas (PPGL) are considered to be the most heritable tumours as up to 40% of patients who develop these tumours have a hereditary predisposition. This chapter provides an update on the clinical and molecular genetics of PPGL and related syndromes, as well as offering a guideline for genetic testing and surveillance of those individuals identified as carriers for a known PPGL predisposition gene.
Cowden Syndrome
Authors: Yehia Lamis , Malhotra Shreya , Eng Charis 
Published: January 2022

Abstract
Cowden syndrome (CS) is a multiple hamartoma syndrome characterized by high risks of benign and malignant tumours of the thyroid, breast, kidney, and endometrium, as well as neurodevelopmental disorders such as autism spectrum disorder (ASD). Affected individuals typically have macrocephaly at birth, and mucocutaneous features evident by the late 20s. The tumour suppressor gene PTEN, encoding an ubiquitously expressed phosphatase classically counteracting the PI3K/AKT/mTOR growth-promoting cascade, is the first and currently only clinically actionable CS susceptibility gene. Individuals with germline PTEN mutations have diverse phenotypes, can have different syndromic names, and fall under the umbrella term PTEN hamartoma tumour syndrome (PHTS). Ongoing investigations in the research arena are uncovering other susceptibility genes in PTEN mutation-negative patients. Clinicians play a critical role in recognizing ‘red flag’ signs and symptoms to establish a CS diagnosis. Timely diagnosis is key, as early recognition enables high-risk cancer surveillance and related medical management.
Disorders of Gonadotropin Secretion
Authors: Berga Sarah L. 
Published: January 2022

Abstract
Gonadal function sufficient to support gametogenesis requires appropriate gonadotropin-releasing hormone (GnRH) input to drive appropriate pituitary secretion of LH and FSH. Alterations in GnRH drive either cause or reflect gonadal dysfunction. Hypothalamic hypogonadism in men and women results from functional, theoretically reversible, reductions in GnRH drive that are linked to stress, that is, cognitions and behaviours that activate the limbic hypothalamic–pituitary–adrenal axis. Common manifestations of insufficient GnRH drive in women include anovulation and amenorrhea. Amelioration of adrenal activation has been shown to restore ovulatory ovarian function in women with functional hypothalamic amenorrhea.
Polycystic Ovary Syndrome
Authors: Chang R. Jeffrey 
Published: January 2022

Abstract
Polycystic ovary syndrome (PCOS) is a reproductive-metabolic disorder that is the most common endocrinopathy of women in their reproductive years of life. The reproductive phenotype includes hirsutism, irregular menstrual bleeding, and polycystic ovaries. Because of chronic anovulation, infertility is a major concern. Commonly, these features are accompanied by obesity, hyperlipidaemia, insulin resistance, and an increased risk for type 2 diabetes mellitus. In addition, there is increased prevalence of depression and anxiety disorders, acne, acanthosis nigricans, sleep apnoea, and metabolic syndrome. Genetic markers for PCOS have not been identified. The pathophysiology has been well described, but the underling basis for PCOS is unknown. The onset of symptoms occurs during or soon after puberty and there is a familial inheritance pattern. Long-term health concerns include an increased risk for uterine and cancer cardiovascular disease.
Female Hypogonadism
Authors: Yasmin Ephia , Conway Gerard S. 
Published: January 2022

Abstract
The natural lifespan of the ovary is occasionally interrupted by pathological processes, some known but many unknown. Premature ovarian insufficiency (POI) may be caused by genetic and chromosomal defects, autoimmune damage, and cancer treatments. POI can be a devastating diagnosis for a teenager or for someone who has yet to start a family. Knowledge of the pathogenesis of the condition, as well as treatment options in terms of hormones and assisted fertility require a multidisciplinary team comprising reproductive medicine, endocrinology, clinical psychology, and specialists in assisted conception. Premature ovarian failure is a complex condition that requires specialist services. The diagnostic work-up is aimed at determined the aetiology where possible and is followed by a screen for syndromic conditions. Oestrogen replacement and fertility options need to be reassessed at intervals and clinicians have to be vigilant for psychological sequelae.
Female Hypogonadism
Authors: Paschou Stavroula A. , Anagnostis Panagiotis , Goulis Dimitrios G. 
Published: January 2022

Abstract
Menopause marks the permanent cessation of menstruation and the transition to the non-reproductive stage of a woman’s life, after completion of 12 months of amenorrhoea or immediately after bilateral oophorectomy. The purpose of this chapter is to provide current knowledge regarding the different stages preceding and following the final menstrual period, the physiology of the endocrine changes occurring during the menopausal transition, the clinical manifestations, diagnosis, and differential diagnoses, as well as the pros and cons of its medical management. Hormone replacement therapy (HRT) is the treatment of choice for most. Additionally, it may be considered for osteoporosis treatment and fracture risk reduction, but only for women who present with VMS. In cases of hysterectomy, oestrogen-only formulations should be used, whereas for women with intact uterus progestogen needs to be added to counteract the harmful effects of oestrogen on the endometrium. Postmenopausal women should also be managed with lifestyle interventions, including diet, exercise, smoking cessation, and decrease in alcohol consumption, with a particular focus on bone and cardiovascular health. Alternatively, drug or non-pharmaceutical therapies may be considered for the alleviation of VMS in cases, when HRT is contraindicated. The ultimate goal of the healthcare providers should be an integrated plan for the postmenopausal women, bearing in mind that most of them will spend more than one-third of their lifespan in menopausal status.
Female Infertility and Assisted Reproduction
Authors: Balen Adam H. , Jacob Susie 
Published: January 2022

Abstract
Infertility is common. Female age remains the single most important factor determining the ability to conceive. General investigations address all aspects of fertility including tubal assessment, ovarian reserve, and semen analysis. Assisted conception techniques with gamete preparation enhances fertility by either bypassing absolute obstruction or boosting fecundity above that expected without treatment. Limitation of the serious complication of ovarian hyperstimulation syndrome must occur. Cryopreservation has provided a credible option for those wishing to preserve or delay fertility, with success rates equivocal with fresh treatment options. Pre-implantation genetic testing and surrogacy further widen treatment options for previously untreatable conditions. This chapters provides a brief synopsis of fertility investigation and outlines one of the main treatment options, in vitro fertilization.
Exogenous Factors and Female Reproductive Health
Authors: Lim Siew , Mousa Aya , Shorakae Soulmaz , Moran Lisa 
Published: January 2022

Abstract
Undernutrition adversely affects fertility. A low body weight is associated with delayed conception. When conception does occur, undernutrition could also adversely affect pregnancy outcomes. Low prepregnancy BMI (&lt;18.5 kg/m2) is associated with increased risk of early miscarriage, preterm labour, anaemia, insufficient weight gain, and impaired intrauterine fetal growth. On the other hand, overweight and obesity are associated with increased risk of gestational diabetes, pre-eclampsia, and other complications during pregnancy and delivery. Weight loss through energy restriction, with or without exercise, improves reproductive function in overweight or obese women. Aside from body weight and energy status, maternal macronutrient, and micronutrient intakes before and during pregnancy would also influence pregnancy outcomes. Studies in mostly nutritionally at-risk women reported that balanced energy/protein supplementation (&lt;25% energy from protein) is associated with higher birth weights but high protein supplementation (&gt; 25% energy from protein) may increase the risk of small-for-gestational-age (SGA) infants. Reducing glycaemic index or glycaemic load of maternal diet may reduce the risk of large-for-gestational-age (LGA) births or gestational diabetes. In terms of micronutrients, current evidence supports folic acid supplementation (at least 400 µg/day) to reduce the risk of fetal abnormalities, iodine supplementation for women at risk of iodine deficiency to prevent complications in fetal physical and mental development, and iron supplementation to reduce the risk of maternal anaemia where required.
Management of Thyroid Disorders Before Assisted and Spontaneous Pregnancies
Authors: Poppe Kris , Veltri Flora , Unuane David 
Published: January 2022

Abstract
Severe thyroid dysfunction may lead to menstrual disorders and infertility. Fertility problems may persist even after restoring normal thyroid function, and then an assisted reproductive technology (ART) may be considered as a therapeutic option. Prior to an ART treatment, an ovarian hyperstimulation is performed, leading to high oestradiol levels, which may lead to hypothyroidism in women with thyroid autoimmunity (TAI), necessitating thyroid hormone supplements (LT4) before pregnancy. Moreover, women with the polycystic ovarian syndrome and idiopathic infertility have a higher prevalence of TAI. Women with a known hypothyroidism before pregnancy and treated with LT4 should have a serum TSH &lt;2.5 mIU/L, both in case of assisted and spontaneous pregnancies. Women with Graves’ disease desiring pregnancy should be advised of the increased risk of maternal and fetal complications and about the possible side effects of antithyroid drugs. If necessary, pregnancy must be postponed until euthyroidism is reached and confirmed. With the exception of women planning ART or those known to have TAI, at present there are no recommendations regarding universal screening for thyroid function in the preconception phase.
Pituitary Tumours in Pregnancy
Authors: Huang Wenyu , Molitch Mark E. 
Published: January 2022

Abstract
Pituitary adenomas are commonly found in general population. The impact of pituitary tumour on fertility are mainly due to over-secretion and/or under-secretion of pituitary hormones due to the tumour secretion per se or compression of pituitary stalk and normal pituitary tissue by the tumour. Diagnosing and managing pituitary tumours during pregnancy are faced with many challenges, including the effect of either hormone excess or hormone deficiency on pregnancy outcome, changes in the pituitary or pituitary-related hormones during pregnancy, changes in tumour size during pregnancy, and the impact of various treatments of pituitary tumours on maternal and fetal outcomes. This chapter will discuss the diagnosis and treatment of patients with prolactinomas, acromegaly, Cushing’s disease and other pituitary tumours during pregnancy.
Other Disorders of the Pituitary and Hypothalamus in Pregnancy
Authors: Carroll Paul V. , Karavitaki Niki , Lithgow Kirstie 
Published: January 2022

Abstract
Pregnancy results in significant alteration of pituitary anatomy and hormone physiology. Prolactin-producing lactotroph cells undergo progressive and significant hyperplasia throughout pregnancy contributing to increase in size of the anterior pituitary. Changes in pituitary hormone production, binding protein levels and target hormone action occur during pregnancy. As a result of these alterations, the assessment of pituitary status in the pregnant woman is complex and differs from the non-pregnant state. Disorders of hormone function may be well established prior to pregnancy or less frequently develop during pregnancy. These conditions may impact on maternal and fetal outcomes and influence pregnancy management. The physiology of pregnancy may also influence behaviour of endocrine conditions. Several disorders are specifically associated with pregnancy, lymphocytic hypophysitis, and Sheehan’s syndrome being particular examples.
Imaging for Endocrine Diseases in Pregnancy
Authors: Lowe Sandra 
Published: January 2022

Abstract
Imaging for endocrine diseases in pregnancy requires a detailed understanding of the risks and benefits of the imaging options. As in the non-pregnant subject, non-ionizing radiation options such as ultrasound and magnetic resonance imaging should be considered first. In almost all cases, radiation and contrast risks are negligible and therefore the most sensitive and specific imaging should be performed at the most appropriate time, whether during or after pregnancy. For practical purposes, no specific counselling is required for women undergoing diagnostic imaging with a predicted fetal absorbed dose of less than 10 mGy. This includes all X-ray and CT scanning not involving the abdomen and most nuclear scans. Despite widely held concerns, even at an estimated fetal dose of 50 mGy, the additional risk of childhood cancer is at worst 1.1–3.0 cases per 1000 patient exposures.
Disorders of the GH-IGF Axis
Authors: Jorge Alexander A.L. , Correa Fernanda A. , Scalco Renata C. 
Published: January 2022

Abstract
Disorders of the GH-IGF axis include a large heterogeneous group of conditions with distinct phenotypes. Each of the defects identified in this axis is responsible for a rare and specific condition that endocrinologists need to be familiar with. Traditionally, clinical and hormonal evaluations are the cornerstones of their diagnosis but in recent years, molecular genetic tests are becoming an important tool for the investigation of GH-IGF axis disorders. In this chapter, we will focus on genetic causes and highlight their main characteristics and the diagnostic approaches for each of them. The expansion of our knowledge in this field may lead to treatment based on the molecular defect.
Precocious Puberty
Authors: Léger Juliane , Carel Jean-Claude 
Published: January 2022

Abstract
Precocious puberty (PP) is defined as the onset of clinical signs of puberty before the age of 8 years in girls and 9.5 years in boys. It may be caused by central or peripheral mechanisms. Central PP (CPP) results from premature reactivation of the hypothalamo–pituitary–gonadal axis, with a hormonal pattern similar to that of normal puberty. CPP may be due to hypothalamic lesions or idiopathic in most cases, particularly in girls. It may have consequences for growth and psychosocial development. Thorough evaluation is required to identify its cause and potential for progression. Gonadotropin-releasing hormone agonists are the standard treatment for progressive CPP. The available data indicate that this treatment does not seem to cause or aggravate obesity or have repercussions for body composition, bone mineral density and fertility. Recent studies have implicated a genetic cause for paternally transmitted familial CPP, but such defects do not underlie maternally transmitted CPP and are rarely involved in sporadic forms.
Management of Sexual Dysfunction
Authors: Rochira Vincenzo , Carani Cesare , Granata Antonio R.M. 
Published: January 2022

Abstract
Sexual dysfunction in men may be related to multiple factors according to the type of sexual problems (e.g. low desire, erectile, or ejaculatory disturbances). Organic and psychological factors both contribute to the development of male sexual dysfunction. Among organic causes, endocrine disorders (the most important of which is hypogonadism) may contribute to the occurrence of male sexual dysfunction, but are much less frequent than other organic causes (i.e. vascular, neurological, and drug-induced). Clinical assessment (including a sexual history) is important for identifying patients with hormonal (e.g. testosterone deficiency) or other disorders (e.g. vascular or neurological) who may present with symptomatic sexual dysfunction. The aetiology(ies) underlying the sexual dysfunction will guide the most appropriate treatment in individual cases. Management of male sexual dysfunction may include psychological counselling, pharmacological therapy (e.g. PDE5Is), surgery, and testosterone replacement therapy in cases of well-documented hypogonadism. Despite the recent improvements due to the use of PDE5Is, in the management of erectile dysfunction remains largely unsatisfactory for a significant proportion of patients so there is still a major treatment gap and challenge ahead.
Introduction to Transgender and Gender Diverse People
Authors: Arcelus Jon , Bouman Walter Pierre 
Published: January 2022

Abstract
This chapter provides an introduction to transgender health. It starts with a brief historical and cultural overview concerning those people who identify as transgender or gender diverse, followed by a description of current language and terminology in transgender health with a glossary of transgender-related nomenclature. The classification of transgender and gender-diverse identifying people is described in the context of the International Classification of Diseases of the World Health Organization (WHO) and the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (APA). This is followed by a description of prevalence studies in clinical populations, as well as in the general population, regarding transgender and gender-diverse identifying people. The chapter further discusses transgender health services, including assessment and gender-affirming medical treatments, and concludes with a short presentation of mental health problems in the transgender population.
The Endocrinology of Liver Disease
Authors: George Jacob , Eslam Mohammed 
Published: January 2022

Abstract
Liver and endocrine diseases are common in the general population and intimately linked, such that diseases of both organ systems frequently coexist. Thus, disease in one can modulate the phenotypic manifestations or progression of the other and share pathogenic mechanisms. The common liver diseases, non-alcoholic fatty liver disease, viral hepatitis and haemochromatosis have unique extrahepatic endocrine manifestations, including diabetes mellitus, thyroid dysfunction, osteoporosis, and gonadal dysfunction. Conversely, the liver is frequently a target of a variety of endocrinopathies, including hypothyroidism, hypercortisolaemia, polycystic ovarian syndrome (PCOS), hypopituitarism, growth hormone deficiency, and hypogonadism. It is therefore incumbent on both gastroenterologists and endocrinologists to consider these reciprocal interrelationships in daily practice, to provide better clinical care. Prospective studies are required to reveal if we need to change current guidelines on screening for endocrine disease in patients with liver dysfunction and vice versa, at least in high risk groups. In the following chapter, we summarize this bidirectional relationship.
Effect of Opioids on Adrenal and Reproductive Endocrinology
Authors: Armeni Eleni , Grossman Ashley B. , Khoo Bernard 
Published: January 2022

Abstract
Endogenous opioids and opioid receptors play key neuroendocrinological roles in regulating the body’s response to stress and pain. As part of this function, endogenous opioids regulate the hypothalamo–pituitary–adrenal (HPA), hypothalamo—pituitary–gonadal axes (HPG) axes and posterior pituitary function. Exogenous opioids have been used from ancient times as analgesics but have a well-known addictive potential. Opiate dependency is now a widespread global problem, driven by the easy availability of both prescribed and illegal opiates. As a consequence, the endocrine complications from opiates are becoming more common and chronic opiate users are at high risk of developing hypoadrenalism and hypogonadism. A robust screening protocol for these endocrinopathies, in collaboration between pain specialists and endocrinologists, is essential for appropriate replacement treatment and the prevention of morbidities and possibly mortality, especially from hypoadrenalism.
The Breast
Authors: Clarke Robert , Greenhalgh Alice 
Published: January 2022

Abstract
Breast cancer is the most common form of cancer in women. In order to fully understand the molecular causes of breast cancer, it is critical to understand the underlying mechanisms which regulate and dictate normal breast development. Both pituitary and ovarian steroid hormones are required to regulate and govern breast development. Progesterone is an ovarian steroid hormone and is considered to be a major risk factor for the development of breast cancer, since it controls proliferation of stem and progenitor cells. The human breast is organized as an epithelial network of ducts opening at the nipple and these form a tree-like structure ending in lobuloalveolar glands located within the collagenous and adipose tissue of the mammary gland. Upon pregnancy, specialized luminal cells develop in the alveoli which go on to secrete milk proteins and lipids during lactation. Breast development occurs in three well-defined stages: embryonic, pubertal, and reproductive.