bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral Oedema
Authors: Amann-Vesti Beatrice
Published: January 2022

Swelling of any part of the body may occur and be related to numerous diseases. In cardiovascular medicine swelling and oedema formation occurs most commonly in the lower limbs, for instance due to venous congestion in the context of heart failure, venous thrombosis, varicose veins, renal diseases, proteinuria, and liver disease with impaired protein synthesis. On the other hand, lymph oedema refers to the swelling that generally occurs in either one or both arms, or legs, due to a blockage of the lymphatic system leading to a feeling of heaviness and tightness, recurrent infection, and skin fibrosis. Lipoedema, on the other hand, runs in families like lymphoedema and commonly occurs due to genetic and hormonal factors, as well as being overweight or obese. While lymphoedema also involves the back of the foot and toes, lipoedema spares foot and toes. Finally, lipoedema particularly involves the lower legs and ankles.
Cardiac Resynchronization Therapy in Heart Failure
Authors: Hindricks Gerhard , Shamloo Allireza Sepehri
Published: January 2022

Patients with heart failure with reduced ejection fraction (HFrEF) develop electrical (i.e. left bundle branch block) and mechanical dyssynchrony of the ventricles of the heart. This further reduces pump function and can be corrected by simultaneous pacing of both ventricles, i.e. cardiac resynchronization therapy (CRT). The effectiveness and safety of CRT in patients with HFrEF have been documented in several large randomized trials documenting a marked improvement of quality-of-life and an important reduction in morbidity and mortality. CRT has progressive structural benefits, and can improve the left ventricular (LV) systolic function and promote LV reverse remodelling. This applies to heart failure patients with severe, and also to those with mild symptoms. Thus, CRT is now recommended in patients with wide QRS complex by the 2016 ESC Guidelines on the management of acute and chronic heart failure.
(Peri-)Myocarditis
Authors: Heidecker Bettina , Prasad Sanjay K. , Eriksson Urs
Published: January 2022

Myocarditis is an inflammation of the myocardium which may have an acute, sub-acute, or chronic clinical trajectory. If the pericardium is involved it is called perimyocarditis. Myocarditis may lead to acute heart failure, left ventricular remodelling, and eventually dilated cardiomyopathy. Myocarditis may be the consequence of viral or repeated bacterial infections, leading to autoimmune processes as well. In addition, parasites, drugs, and other unclear aetiologies may cause myocarditis. The diagnosis does eventually require endomyocardial biopsy, while imaging, particularly using magnetic resonance imaging and to a lesser extent echocardiography provide important information as well. The natural causes are quite diverse, but may lead to arrhythmias, heart failure, and sudden death.
The role of surgery in cancer pain management
Authors: Eldridge Paul , Bhargava Deepti
Published: January 2022

Patients suffering from cancer frequently experience pain, and this is often the primary presenting symptom. This chapter covers the surgical principles in the treatment of cancer pain, structural and symptomatic outcomes, and ends with a list of key learning points. A short analysis of the WHO analgesic ladder and its pitfalls is also included.
Diffuse cancer-related pain in lower half of body
Authors: Marley Kate
Published: January 2022

This chapter considers a complex case of refractory pain in a patient with advanced cancer which illustrates the challenges of balancing benefits and burdens of different treatment strategies. A variety of pain control methods such as ketamine, methadone and epidural analgesia are covered, as well as intrathecal drug delivery and pump implantation, before the chapter ends with a list of key learning points.
Upper gastrointestinal pain from invasive pancreatic cancer
Authors: Pushparaj Hemkumar
Published: January 2022

Close collaboration between multiple disciplines including disease-specific specialty, oncology, palliative care, and pain medicine is vital to offer appropriate diagnostics and range of pain control options. This chapter uses a case study to discuss pain presentation and assessment, management of cancer and pain recurrence, and pain related to cancer metastasis and management.
Intrathecal pump for cancer pain
Authors: Pushparaj Hemkumar
Published: January 2022

There are several choices of analgesic interventions for patients with cancer-related pain. The likely life expectancy of the patient, site of the pain, cause of the pain, and likely tumour progression are relevant factors to consider. This chapter uses a case study to discuss intrathecal pumps, bacteraemia and meningism following pump revision, and loss of pump efficacy, and ends with some key learning points.
Intrathecal drug delivery for cancer pain
Authors: Titterington John
Published: January 2022

Intrathecal drug delivery (ITDD) has been an option for the management of persistent cancer pain since the 1980s. The discovery of opioid receptors in the central nervous system was the impetus for early attempts to deliver opioids intra-spinally. This chapter will describe ITDD and the available drug delivery systems, with a focus on practicalities rather than theory. Bleeding diatheses, psychiatric and psychological problems, and types of intrathecal drug delivery systems are discussed, and the chapter ends with a list of key learning points.
Spinal neurolysis
Authors: Chaudhari Mahesh
Published: January 2022

This chapter focuses on the role of intrathecal neurolytic blocks for the management of intractable cancer pain. Generally, well localized primary somatic pain responds well to such blocks with neurolytics such as alcohol and phenol. This chapter includes discussion of the anatomical consideration for spinal neurolysis, technique of intrathecal neurolysis, informed consent, and complications, before concluding with key learning points.
Peripheral nerve blocks including neurolytic blocks
Authors: Vas Lakshmi , Sharma Manohar
Published: January 2022

Patients with cancer may suffer from pain due to neuralgia in a nerve distribution that may be directly due to the cancer or its treatment. A successful nerve block may give considerable relief in these patients. This chapter covers a variety of different common nerve blocks such as intercostal nerve block, suprascapular nerve block, and femoral nerve block. This chapter also addresses pain service and nerve blocks in hospice settings and includes a list of key learning points.
Collaboration with palliative medicine
Authors: Marley Kate , Pushparaj Hemkumar
Published: January 2022

Adequate pain relief can be obtained in 70-90% of patients with cancer pain by using the WHO cancer pain ladder. Intractable pain or severe side effects from opioids and adjuvant medication may warrant alternative pain management strategies. This chapter includes a discussion of the Liverpool model of collaboration between pain and palliative medicine, a case study that illustrates the benefits of such collaboration, and practical aspects of service delivery, before ending with a summary of the key learning points.
Endocrine Practice Fundamentals
Authors: Loriaux Lynn
Published: January 2022

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Multiple endocrine neoplasia type 1 (MEN 1) is characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumours. Some patients may also develop other neuroendocrine tumours (lung and bowel), adrenal cortical tumours, meningiomas, facial angiofibrosmas, collagenomas, and lipomas. MEN 1is inherited as an autosomal dominant disorder that is due to mutations in the tumour suppressor gene MEN 1, which encodes a 610-amino acid protein, menin. Patients with MEN 1 have a decreased life expectancy. Moreover, the finding of MEN 1 in a patient also has important implications for family members, because first-degree relatives have a 50% risk of developing the disease, and these at-risk relatives can be identified by MEN 1 mutational analysis. The prognosis of MEN 1 patients and that of the at-risk relatives may be improved by presymptomatic detection of the tumour and with implementation of earlier and specific treatments for the MEN 1 tumours.
Carney’s Complex
Authors: Stratakis Constantine A. , Faucz Fabio R.
Published: January 2022

Carney complex (CNC) is a rare autosomal dominant syndrome that was first described in 1985 and is characterized by pigmented lesions of the skin and mucosa, cardiac, cutaneous, and other myxomas, and multiple endocrine tumours. The disease is mostly caused by inactivating mutations or large deletions of the PRKAR1A gene located at 17q22–24 coding for the regulatory subunit type I alpha of protein kinase A (PKA) gene but other causative genetic defects on chromosome 2p16 and perhaps elsewhere remain unknown. Most recently, components of the complex have been associated with defects of other PKA subunits, such as the catalytic subunits PRKACA (adrenal hyperplasia) and PRKACB (pigmented spots, myxomas, pituitary adenomas). The chapter reviews CNC, its clinical features, diagnosis, treatment, and molecular aetiology.
Menstrual Cycle and Ovulation
Authors: Bozdag Gurkan , Ata Baris , Türkgeldi Engin
Published: January 2022

Understanding the physiology of follicular development is important in order to extrapolate the preclinical data to the clinical side. In this context, there has been an increasing effort to figure out the autocrine/paracrine signalling and microenvironment that will determine the fate of a follicle. The processes of atresia or further development to later stages reaching to a dominant follicle appear to be regulated by highly complicated system that consists oocyte and granulosa cell derived factors, peptides, cytokines, and sex steroids. Additionally, recent research on the menstrual cycle that yields the presence of more than one wave of follicular cohort growing within a single period will undoubtedly implicate our perception on reproductive function, hormonal contraception, and ovarian stimulation during an assisted reproduction treatment. This chapter reviews the current knowledge that reflects the timetable of a follicle throughout the early ages to the formation of dominant follicle and corresponding endometrial changes.
Hyperprolactinaemia
Authors: Davis Julian , Święcicka Agnieszka
Published: January 2022

Hyperprolactinaemia is a common clinical problem with important effects on reproductive function. The condition is often drug-induced but potential pituitary disease, including micro- and macroprolactinoma and non-tumoural hyperprolactinaemia, requires evaluation. Treatment is usually with dopamine agonist drugs such as cabergoline, which suppress hyperprolactinaemia in most patients, and allow restoration of regular ovulation in women. Even large pituitary tumours usually display marked shrinkage with dopamine agonist treatment, hence pituitary surgery is rarely necessary. Women who become pregnant with dopamine agonists usually discontinue the drug during pregnancy, but have a small risk of significant pituitary enlargement.
Premenstrual Syndrome
Authors: Lavu Deepthi , Indusekhar Radha , O’Brien Shaughn
Published: January 2022

Millions of women and their families around the world are affected by premenstrual disorders. These conditions cause significant impairment for women, resulting in emotional, somatic, and/or behavioural symptoms in the luteal phase of the menstrual cycle. Following the recent International Society for Premenstrual Disorders (ISPMD) consensus, these disorders have been divided into core and variant premenstrual disorders. Diagnosis is complex as there are no objective tests. Use of a prospective symptom scoring chart, by women, to record their daily symptoms is recommended to support a definitive diagnosis in addition to a multidisciplinary team approach for management of women with premenstrual syndrome (PMS). Treatments are broadly divided into two categories, based on ovulation suppression and neuroendocrine manipulation. These include lifestyle modifications, cognitive behaviour therapy, combined oral contraception, selective serotonin reuptake inhibitors, oestradiol, and progesterone, gonadotrophin-releasing hormone analogues and surgery (bilateral salpingo-ophorectomy and hysterectomy) as a last resort.
Exogenous Factors and Female Reproductive Health
Authors: Gambineri Alessandra , Ibarra-Gasparini Daniela
Published: January 2022

Female infertility affects 8–15% of reproductive-aged couples worldwide and ovulatory disorders account of more than a quarter of cases. It is defined as the failure to establish a clinical pregnancy after 12 months of regular and unprotected sexual intercourse in women younger than 35 and after six months in women over the age of 35. The ovaries and the uterus are under the control of many hormones such as LH, FSH, thyroid hormones, GH, prolactin, glucocorticoids, and sex steroids. Thus, an excess or defect of these hormones may account for female infertility. This chapter explains in detail the mechanisms by which each hormone regulates folliculogenesis, uterus decidualization, and embryo implantation in order to understand the complex regulation of female reproduction and of its alteration.
Tall Stature
Authors: Sävendahl Lars , Benyi Emelie
Published: January 2022

Tall stature is usually constitutional depending on the height of the father and mother. In some cases, there is an underlying condition affecting the complex regulation of growth which causes tall stature. For some individuals, extreme tall stature is associated with psychosocial problems and therapies aiming to reduce further growth have been available for decades, but some have been associated with undesired serious side effects. This chapter gives an overview of the aetiology behind and possible consequences of extreme tallness. The assessment of a tall child as well as treatment methods to reduce growth are summarized and ethical considerations regarding treatment are also discussed.
Disorders of Sex Development (DSD) in the Newborn
Authors: Ahmed S. Faisal , Ali Salma R.
Published: January 2022

The newborn infant with a suspected disorder of sex development (DSD) presents a challenging scenario. It is paramount that any such chid is assessed by an expert with adequate knowledge about the range of variation in the physical appearance of genitalia, the underlying pathophysiology of disorders of sex development and the strengths and weaknesses of the tests that can be performed in early infancy. By working within a multidisciplinary team, the DSD expert can ensure that the parents’ needs for information are comprehensively addressed and that appropriate investigations are performed in a timely fashion. In the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration so that any evidence for future changes in practice have a stronger foundation than that which is currently available.
The Endocrine Response to Stress
Authors: Henley David , Upton Thomas , Lightman Stafford L.
Published: January 2022

Reaction to stress is characterized by a series of interlinked, dynamic, and organized responses that function to restore homeostasis. Rapid activation of the sympathoadrenomedullary and hypothalamic–pituitary–adrenal (HPA) axes occurs following acute stress exposure in order to appropriately respond to, adapt, or escape the threat. The dynamic, pulsatile nature of the HPA axis is crucial to the function of glucocorticoids which modulate many of the complex neurocognitive and physiological changes that occur in acute and chronic stress states. Maladaptive long-term activation of the stress response is associated with numerous pathological states including mood and sleep disorders, obesity, and metabolic syndrome. The altered stress dynamics that occur in critical illness remain poorly understood.
Hormones and the Kidney
Authors: Nataatmadja Melissa , Cho Yeoungjee , Johnson David W.
Published: January 2022

Chronic kidney disease (CKD) is a growing global health problem and affects approximately 10–15% of the world’s population. The interactions between kidney disease and endocrine systems are complex, and endocrine abnormalities are common in patients with CKD. In particular, abnormalities in the renin–angiotensin–aldosterone system, parathyroid function, and erythropoietin production and responsiveness are common. In addition, thyroid disease, sexual dysfunction and abnormalities in prolactin, growth hormone, and insulin-like growth factor-1 are often seen. Here in this chapter, we outline common endocrine abnormalities seen in patients with CKD and their pathophysiology, and discuss important aspects of management of these conditions including screening and treatment.
Endocrine Complications of Biological Cancer Therapies
Authors: Moran Carla
Published: January 2022

In recent years, modulation of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways has resulted in significant improvements in cancer outcomes. Immune-related adverse events (IrAEs), including endocrinopathies, are common toxicities associated with use of these immune checkpoint inhibitors, with agents affecting the CTLA-4 pathway typically causing hypophysitis, and those affecting the PD-1 pathway most commonly causing thyroid dysfunction. Notably, due to non-specific and ill-defined symptoms, these endocrine-associated IrAEs can escape detection, such that surveillance for these side effects is warranted. Although these endocrinopathies may be irreversible, they are rarely life-threatening and there is emerging evidence that individuals experiencing such side effects have better cancer outcomes. With likely increasing use of these agents over the coming decade, endocrinologists can expect to diagnose and manage these side effects more frequently.
Endocrine Treatment of Breast Cancer
Authors: Sheri Amna , Morrison Laura
Published: January 2022

Endocrine manipulation is a well-recognized treatment modality for breast cancer and better understanding of the role of oestrogen in breast cancer pathogenesis has enabled advances in both early and metastatic breast cancer treatment. Two key pathways are used to reduce oestrogen levels—competition for the oestrogen receptor at the cell surface and by reducing peripheral androgen conversion. Adjuvant therapy with the oestrogen receptor antagonist tamoxifen shows improved disease-free and overall survival when given for ten years. Aromatase inhibitors have shown further benefits in the adjuvant setting either alone (in postmenopausal women) or in conjunction with ovarian suppression (in younger, premenopausal women). Endocrine therapy has had a significant impact on breast cancer treatment, but resistance develops in many patients. The mechanisms for this resistance are being investigated and there are a number of emerging treatment options that may help to overcome resistance although this is a complicated area of research.
Management of Obesity in Children and Young People
Authors: White Billy , Viner Russell M.
Published: January 2022

The management of obesity in childhood and adolescence poses challenges unique to this age group. Compared to adults, obesity-related comorbidities are relatively rare, yet risk factors are increasingly prevalent, frequently undetected, and poorly managed. The evidence base for weight loss interventions and management of comorbidities is limited, with short duration of follow-up only reported, and few randomized controlled trials. Bariatric surgery in adolescents results in the largest magnitude of weight loss, with outcomes similar to those seen in adults. Lifestyle intervention studies have relatively modest outcomes, with unknown long-term outcomes. Only one pharmaceutical agent (orlistat) is licenced in this age group, with generally poor outcomes.
Disorders of Carbohydrate Metabolism
Authors: Lachmann Robin H.
Published: January 2022

Sugar molecules play many roles in metabolism. Glucose is an essential source of energy in the body, but carbohydrates also have important structural and signalling functions as constituents of glycoproteins, glycolipids, and glycosaminoglycans. Disorders of carbohydrate metabolism, although caused be defects in individual enzymes, are best viewed as disorders of metabolic pathways. Their tissue pathology can be due to deficiency of a product of metabolism, but just as often it is due to accumulation of toxic molecules which cannot be metabolized. In this chapter, a number of monogenic diseases will be described which involve the monosaccharides glucose, galactose, and fructose, and their roles in intermediary metabolism. The many other inherited metabolic diseases which affect the formation of glycosylated macromolecules (the congenital disorders of glycosylation) or their breakdown (lysosomal storage disorders) will not be discussed.
Prevention of Type 2 Diabetes
Authors: Wareham Nicholas J.
Published: January 2022

The rising prevalence of type 2 diabetes and the costs of managing the condition in developed and developing countries alike has driven an increased focus on the potential to design and implement preventive interventions. Meta-analyses of randomized controlled trials of individual-level behavioural interventions aimed at changing dietary and physical activity behaviour, mediated in most but not all populations by weight loss, have unequivocally established that these interventions are efficacious under the ideal circumstances that exist in clinical trials. Achieving comparable effectiveness in real-world settings has been much more challenging and there are as yet few examples of effective, scalable, and inexpensive interventions. Even in settings where individual-level interventions are affordable, such approaches need to be complemented by whole population approaches to prevention that implicitly acknowledge that the public health problem of diabetes cannot be dealt with by clinical approaches alone and needs a balanced approach of individual and societal-level action.
“Closed Loop” Insulin Delivery
Authors: Hovorka Roman , Boughton Charlotte
Published: January 2022

Glycaemic control with insulin therapy is influenced by multiple factors, contributing to the notable variability in insulin requirements and making self-management of type 1 diabetes (T1D) challenging. As a result, the majority of people with T1D are unable to achieve their recommended therapeutic goals. Rapid progress has been made over the past decade with the development of a closed-loop insulin delivery system, also known as the ‘artificial pancreas’ which emulates the glucose-responsive functionality of the pancreatic beta cell. A control algorithm autonomously and continually increases and decreases subcutaneous insulin delivery based on real-time sensor glucose levels to achieve normoglycaemia while mitigating hyper- and hypoglycaemia. Randomized clinical studies in outpatient and home settings have demonstrated improved glycaemic outcomes, reduced risk of hypoglycaemia, and positive user attitudes. The Food and Drug Administration (FDA) approval of the first hybrid closed-loop system in 2017 marks a new era in the management of T1D using diabetes technology.
Macrovascular Disease in Type 2 Diabetes
Authors: Sattar Naveed
Published: January 2022

Disease of large blood vessels is a major cause of premature deaths in type 2 diabetes. On average the risk for macrovascular outcomes is approximately double in type 2 diabetes. Risk is heterogeneous, with relative risks higher in earlier onset type 2 diabetes, women, and certain ethnicities as well with longer duration of disease or the presence of microvascular complications. Over the last 2–3 decades, more aggressive risk factor management and earlier diagnosis have lowered myocardial infarctions and stroke risk in type 2 diabetes more so than in the general population in high income countries but CVD death rate reductions have been similar. The result is that other common cardiovascular complications including heart failure and peripheral arterial disease have grown in profile in type 2 diabetes. Going forwards, more aggressive management of younger patients, and increasing use of newer therapies with cardiovascular benefits, should help further lessen CVD risks in type 2 diabetes.
Hypertension in Diabetes Mellitus
Authors: Williams Bryan
Published: January 2022

High blood pressure (hypertension) is very common in people with diabetes. There is moreover an association between hypertension and diabetes that tracks through life, while the blood glucose concentration of young non-diabetic individuals has been shown to predict risk of future hypertension. Conversely, people with hypertension are twice as likely to develop type 2 diabetes over their lifetime. High blood pressure (hypertension) is arguably the most important preventable cause of premature microvascular and macrovascular disease and their associated morbidity and mortality in people with diabetes. This chapter will review key aspects of the epidemiology and pathophysiology of hypertension in people with diabetes, as well as recommended approaches to its clinical evaluation and treatment.
Diabetes Service Organization
Authors: Valabhji Jonathan
Published: January 2022

The World Health Organization has estimated that globally, 422 million adults were living with diabetes in 2014, compared to 108 million in 1980. Increasing prevalence of diabetes has required evolution of healthcare delivery systems. While the lens of the current article is the National Health Service in England, the challenges posed by increasing diabetes prevalence, and the implications to sustainability of healthcare systems, will be broadly applicable. Strategies to achieve sustainability may include: prevention of type 2 diabetes, including both interventions for those at high risk, as well as population level interventions; prevention of the complications of diabetes through better organization of care delivery; empowerment of individuals with diabetes to better self-manage their condition; establishment of digital technologies for healthcare provision; and achievement of integration of care delivery across the organizations that constitute healthcare systems. Models of diabetes service delivery that aim to achieve these policy goals are described.
Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibodies in Australia After the First Epidemic Wave in 2020: A National Survey
Authors: Vette Kaitlyn M , Machalek Dorothy A , Gidding Heather F , Nicholson Suellen , O’Sullivan Matthew V N , Carlin John B , Downes Marnie , Armstrong Lucy , Beard Frank H , Dwyer Dominic E , Gibb Robert , Gosbell Iain B , Hendry Alexandra J , Higgins Geoff , Hirani Rena , Hueston Linda , Irving David O , Quinn Helen E , Shilling Hannah , Smith David , Kaldor John M , Macartney Kristine
Published: January 2022

Background

As of mid-2021, Australia’s only nationwide coronavirus disease 2019 (COVID-19) epidemic occurred in the first 6 months of the pandemic. Subsequently, there has been limited transmission in most states and territories. Understanding community spread during the first wave was hampered by initial limitations on testing and surveillance. To characterize the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroprevalence generated during this time, we undertook Australia’s largest national SARS-CoV-2 serosurvey.

Methods

Between June 19 and August 6, 2020, residual specimens were sampled from people undergoing general pathology testing (all ages), women attending antenatal screening (20–39 years), and blood donors (20–69 years) based on the Australian population’s age and geographic distributions. Specimens were tested by Wantai total SARS-CoV-2-antibody assay. Seroprevalence estimates adjusted for test performance were produced. The SARS-CoV-2 antibody-positive specimens were characterized with microneutralization assays.

Results

Of 11 317 specimens (5132 general pathology; 2972 antenatal; 3213 blood-donors), 71 were positive for SARS-CoV-2-specific antibodies. Seroprevalence estimates were 0.47% (95% credible interval [CrI], 0.04%–0.89%), 0.25% (CrI, 0.03%–0.54%), and 0.23% (CrI, 0.04%–0.54%), respectively. No seropositive specimens had neutralizing antibodies.

Conclusions

Australia’s seroprevalence was extremely low (<0.5%) after the only national COVID-19 wave thus far. These data and the subsequent limited community transmission highlight the population’s naivety to SARS-CoV-2 and the urgency of increasing vaccine-derived protection.