bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenesis of Non-Toxic Goitre
Authors: Führer Dagmar , Jäschke Holger 
Published: January 2022

Abstract
In clinical terms goitre is a thyroid enlargement above the gender- and age specific reference range and may present with euthyroid, hyperthyroid, or hypothyroid function. On morphological grounds, goitre may be diffuse or nodular. Histologically, thyroid nodules are distinguished by morphological criteria according to the World Health Organization (WHO) classification. On functional grounds, nodules are classified as either ‘cold’, ‘normal’, or ‘hot’ depending whether they show decreased, normal, or increased uptake of radioactive nuclides such as technetium on scintiscan. In contrast to solitary nodular thyroid disease, which has a more uniform clinical, pathological, and molecular picture, multinodular goitre (MNG) usually comprises a mixed group of nodular entities. The aetiology of non-toxic goitre includes extrinsic factors like dietary iodine and intrinsic factors like age, gender, or genetic disposition. This chapter discusses the interplay of the aforementioned aspects in the pathogenesis of benign non-toxic goitre.
Management of Non-Toxic Multinodular Goitre
Authors: Graf Hans , Paz-Filho Gilberto 
Published: January 2022

Abstract
Multinodular goitre (MNG) is a common thyroid disorder associated with more than one thyroid nodule. The clinical presentation varies from a completely asymptomatic goitre to a life-threatening disease with upper airway compression. Patients should have a careful clinical evaluation, thyroid function tests, ultrasonography, cross-sectional imaging, and fine-needle aspiration. The best therapeutic approach will depend on the size and location of the goitre, the presence of compressive symptoms and the clinical status. The recommended treatments include clinical observation, surgery, and administration of radioactive iodine (131I). Suppressive treatment with levothyroxine is discouraged due to its low efficacy compared with surgery or 131I and adverse effects. Total thyroidectomy is effective, but surgical complications may occur. The use of radioiodine after the elevation of thyroid-stimulating hormone (TSH) levels, either via the exogenous administration of recombinant human TSH or through the induction of transient primary subclinical hypothyroidism by antithyroid drugs, are relative novel alternative treatments.
Rickets and Osteomalacia (Acquired and Heritable Forms)
Authors: Whyte Michael P. 
Published: January 2022

Abstract
Rickets and osteomalacia refer to the consequences of generalized impairment of skeletal mineralization during growth and adult life, respectively. Among the complications can be deformity, fracture, weakness, and pain. The many acquired or heritable causes typically involve low circulating levels of inorganic phosphate (Pi), often with hypocalcaemia and secondary hyperparathyroidism. Commonly, the pathogenesis features deficiency of vitamin D leading to malabsorption of dietary calcium (Ca). Especially rare forms involve aberrant bioactivation or action of vitamin D, elevated circulating levels of a phosphatonin (typically fibroblast growth factor 23) that cause renal Pi wasting and hypophosphatemia, or alkaline phosphatase deficiency. All types have some medical treatment, but success depends on correcting the aetiology or effectively addressing the pathogenesis, often requiring supplementation with vitamin D or an analogue together with Ca or Pi. Although general guidelines for therapy may be available, skilled personalized treatment and follow-up are key to safe and successful outcomes.
Management of Primary Aldosteronism
Authors: Drake William M. , Brown Morris J. 
Published: January 2022

Abstract
Major advances have been made since Jerome Conn first described the meticulous assessment and surgical treatment of a patient with severe primary aldosteronism (PA) more than 60 years ago. Diagnostic criteria, although still imperfect, have been refined; high definition cross-sectional imaging is widely available; adrenal vein sampling (AVS) is practised to a high standard in selected centres; low-morbidity laparoscopic adrenalectomy (replacing open surgery involving rib resection) is now routine; preliminary data are emerging about the utility of radiofrequency ablation of adrenal nodules as an alternative to surgery; and the range of medical therapies, available or in development, is expanding. Despite this, based on current prevalence estimates, it remains the case that under 1% of patients with PA are fully evaluated and treated. Given the evidence that PA is associated with substantial excess cardiometabolic morbidity over and above that conferred by elevated blood pressure alone, this underprovision of clinical care represents a major public health issue. This chapter will describe the current approach to the management of PA (from its initial suspicion, diagnosis, differential diagnosis, treatment, and evaluation of the success of treatment) and highlight areas of particular uncertainty and controversy.
Cushing's Syndrome
Authors: Newell-Price John 
Published: January 2022

Abstract
Harvey Cushing described the first case of Cushing’s syndrome with a severe phenotype in 1912. Since that time, investigation and management of Cushing’s syndrome has remained a significant clinical challenge and patients suspected of this diagnosis warrant referral to major centres. Endogenous Cushing’s syndrome is due the chronic, excessive, and inappropriate secretion of cortisol. When presentation is florid, diagnosis is usually straightforward, but in modern practice Cushing’s syndrome is frequently and increasingly considered in mild cases in the absence of the classical signs in the context of osteoporosis, diabetes, and hypertension, as well as in the context of gynaecological and psychiatric clinics. Achieving a diagnosis can be difficult. Appropriate management of Cushing’s syndrome is dependent on correctly identifying the cause of excess cortisol. Separating ACTH-independent causes (adrenal tumours) from ACTH-dependent causes (pituitary or ectopic secretion of ACTH) is usually simple. However, many ectopic sources are occult and the identification of the source of ACTH secretion may require meticulous and repeated investigations. In most circumstances the mainstay of therapy remains surgery to either an ACTH-secreting tumour or directly to the adrenal glands, but additional treatment with cortisol-lowering or opposing drugs and tumour-directed therapy is often needed.
Management of Adrenal Insufficiency
Authors: Arlt Wiebke 
Published: January 2022

Abstract
In 1855, Thomas Addison identified a clinical syndrome characterized by wasting and hyperpigmentation as the result of adrenal gland destruction. This landmark observation paved the way for progress in understanding and treating adrenal insufficiency, with the introduction of adrenal extracts for treatment of Addison’s disease by the groups of Hartman and Pfiffner in 1929. However, long-term survival of patients with adrenal insufficiency only became possible after the seminal work of Edward Kendall, Philip Hench, and Tadeus Reichstein on the characterization and therapeutic use of cortisone. In 1946, Lewis Sarrett, a Merck scientist, achieved a partial synthesis of cortisone, which marked the beginning of industrial-scale production of cortisone. In 1948, in a fundamental clinical experiment at the Mayo Clinic, the first patient with Addison’s received intravenous injections of Kendall’s Compound E, cortisone, resulting in ‘notable improvement of his condition’. This was followed by ground-breaking trials on the use of cortisone in rheumatoid arthritis. In November 1950, cortisone was made available to all physicians in the United States, which culminated in the award of the 1950 Nobel Prize in Medicine to Kendall, Hench, and Reichstein. This progress reached other countries and widespread availability of cortisone in the United Kingdom was achieved by joint efforts of Glaxo and the Medical Research Council. Though almost 150 years have passed since Addison’s landmark observations and 60 years since the introduction of life-saving cortisone, there are still advances and challensges in the management of adrenal insufficiency, summarized in this chapter.
Overview and Pathophysiology of Neuroendocrine Neoplasms
Authors: Srirajaskanthan Rajaventhan , Rindi Guido 
Published: January 2022

Abstract
Neuroendocrine neoplasms are increasing in incidence and prevalence. Recent epidemiological data suggests an overall incidence of 7 per 100 000 population in USA. Symptoms can be diverse with a number of tumours causing distinct clinical syndromes, most commonly carcinoid syndrome. Investigations to aid diagnosis include biochemical, cross-sectional, and functional imaging. Histology remains the gold standard for diagnosis. Treatment options are dependent in part of the site of the primary tumour. Surgery remains the only chance of cure and should be offered to all patients when appropriate. There are a number of systemic palliative treatment therapies and a number of local regional therapies that can be employed for liver metastases. For patients with carcinoid syndrome or functional tumours somatostatin analogues can be very effective a reducing hormone secretion. Median overall survival has been improving over the last 30 years to 9.3 years.
Gastrinoma
Authors: Toumpanakis Christos , Caplin Martyn E. 
Published: January 2022

Abstract
Gastrinomas are functional neuroendocrine tumours, characterized by autonomous release of gastrin by the tumour cells, which results in symptoms not only due to the tumour growth per se, but also due to gastric acid hypersecretion. Gastrinomas can either be sporadic or can be associated with multiple endocrine neoplasia type 1 (MEN-1) syndrome in 25% of cases. The duodenum (especially the first and the second part) is the most common location for both sporadic and MEN-1 associated gastrinomas. Most of the symptoms in patients with gastrinomas include peptic ulcers resistant to treatment, erosive oesophagitis, and chronic diarrhoea. Fasting serum gastrin levels of &gt;10-fold the upper normal limit in the presence of gastric p H&lt;2 or basal acid output (BAO)&gt;15 mmol/h confirm the clinical suspicion, of a gastrinoma. Precise localization of primary tumour as well as metastatic deposits can be achieved through the new molecular imaging studies (68Ga-DOTA PET) in combination with good quality cross-sectional imaging studies and endoscopic ultrasound. Once the diagnosis is established, it is important to control gastric acid hypersecretion and prevent its complications, by using high-doses proton pump inhibitors. The aim of surgery in patients with sporadic gastrinomas is curative resection, in order to decrease the risk of development of distant metastases, as well as to completely control the hormonal symptoms. The benefit of surgery in gastrinomas associated with MEN-1 syndrome is controversial. All patients with advanced and inoperable disease should have systemic antitumour treatment (somatostatin analogues, molecular targeted agents, chemotherapy, peptide receptor radionuclide therapy) in order to prolong the survival rates.
Insulinoma and Hypoglycaemia
Authors: Mak Ingrid Y.F. , Grossman Ashley B. 
Published: January 2022

Abstract
Hypoglycaemia is a clinical syndrome with diverse aetiologies. While the list of possible causes is extremely long, excluding patients with diabetes then the most frequent cause in patients who are otherwise well is an insulinoma. Insulinomas are the most common functioning pancreatic islet cell tumour and may be part of the multiple endocrine neoplasia type 1 syndrome. Patients present with episodic symptoms of neuroglycopaenia and catecholamine responses, and diagnosis is confirmed by evidence of endogenous hyperinsulinaemic hypoglycaemia with tumour localization by CT, MRI, endoscopic ultrasound, functional imaging, and/or intra-arterial calcium stimulation with venous sampling. Most tumours are benign and solitary, making surgical cure and long-term remission possible with complete resection. Diazoxide, everolimus, and somatostatin analogues are the major medical options for hormonal control in metastatic disease, while peptide receptor radionuclide therapy, chemotherapy, and liver-debulking procedures are reserved for the more aggressive tumours. Important differential diagnoses of hypoglycaemia without apparent causes include medications, non-insulinoma pancreatogenous hypoglycaemic syndrome, autoimmune hypoglycaemia, and non-islet cell tumour hypoglycaemia.
Somatostatinoma
Authors: Wass John A.H. 
Published: January 2022

Abstract
Somatostatinomas are rare neuroendocrine tumours they may be sporadic or familial. About half are pancreatic somatostatinomas which are often large and associated with features of somatostatin excess. Slightly less than half are duodenal tumours which are much more amenable to surgical resection. The main features of pancreatic somatostatinoma are hyperglycaemia, cholelithiasis, diarrhoea, abdominal pain, and weight loss. These rumours are best localized with 68ga-dotatate. The treatment is optimally with surgery and if not possible by surgical debulking. Somatostatin analogues relieve symptoms and may inhibit growth. Overall survival is 75.2% at 5 years. Without metastases there is a high survival rate.
Management of Thyroid Disorders After Pregnancy
Authors: Amino Nobuyuki , Arata Naoko 
Published: January 2022

Abstract
Subclinical autoimmune thyroiditis exacerbates after delivery through immune rebound mechanism and may result in five types of thyroid dysfunction. Overall, the prevalence is around 5% in most countries. Typically, an exacerbation induces destructive thyrotoxicosis followed by transient hypothyroidism, defined as postpartum thyroiditis. Late development of permanent hypothyroidism is found frequently and patients should have thyroid function testing once every 1 to 2 years. Destructive thyrotoxicosis in postpartum thyroiditis should carefully be differentiated from postpartum Graves’ disease. Onset time of postpartum thyroiditis is 1–6 months after parturition but Graves’ disease typically develops at 3–12 months postpartum. Anti-TSH receptor antibodies are raised and thyroid blood flow is increased in Graves’ disease but not in postpartum thyroiditis. Postpartum Graves’ disease should be treated with antithyroid drugs.
Recognizing Normal and Disordered Growth
Authors: Butler Gary 
Published: January 2022

Abstract
Normal growth is a good marker of a child’s well-being. Growth takes place differently during infancy, childhood, or adolescence. Infantile growth is the most rapid period. Childhood growth is slower but with mini-growth spurts. Pubertal physical changes are linked to the rapid acceleration and deceleration of adolescent growth. Puberty is assessed by Tanner staging, but a simpler non-invasive system of the assessing the puberty phases (prepuberty, in puberty, and completing puberty) may be more helpful in daily practice. Weight is multicomponent and body mass index may be a more helpful evaluation tool. WHO growth charts are suitable for use from birth to 5 years as they reflect the true pathway of early growth. Thereafter, local, UK or NCHS charts may be suitable. Specialist charts are available for preterm infants and specific syndromes (e.g. Down, Turner, achondroplasia). Additional useful tools include mid-parental or target height calculation, adult height prediction possibly by bone age estimation.
Management of Gynaecomastia
Authors: Braunstein Glenn D. 
Published: January 2022

Abstract
Gynaecomastia, the benign enlargement of the breast glandular tissue in a male, is a common clinical condition, caused in most instances by an imbalance between the breast stimulatory effects of oestrogen and the inhibitory effects of androgens. It is a normal physiological process in infancy, puberty, and senescence. A number of medications have been associated with gynaecomastia, as has several pathological conditions leading to increased oestrogen action or decreased androgen action. Gynaecomastia should be distinguished from pseudogynaecomastia, representing breast enlargement due to fat deposition and not glandular enlargement, and breast cancer through a careful breast examination. The cause of gynaecomastia may be elucidated through the history, general physical examination, and a few laboratory tests. Treating an underlying pathologic cause may lead to resolution of the gynaecomastia, especially if it is of short duration (less than 6 months). Otherwise, a trial of an antioestrogen such as tamoxifen may decrease pain, tenderness, and breast enlargement. Tamoxifen or breast radiotherapy may be used to prevent the development of gynaecomastia in men receiving hormonal therapy for prostate cancer. For chronic fibrotic gynaecomastia or gynaecomastia unresponsive to medical therapy or failing to spontaneously resolve over time, plastic surgical removal can give acceptable cosmetic results.
Long-Term Endocrine Sequalae of Cancer Therapy
Authors: Higham Claire E. , Murray Robert D. 
Published: January 2022

Abstract
There are an increasing number of patients living with and beyond cancer (LWBC) who are susceptible to both short- and long-term cancer therapy related side effects. Long-term endocrine sequelae of cancer therapies occur in up to 50% of childhood cancer survivors and may occur decades after the treatment has been delivered. These consequences of treatment can cause significant morbidity and increased mortality if not diagnosed and appropriately managed. This chapter will provide an overview of these endocrine sequalae include disturbances of growth and puberty, hypothalamo-pituitary (HP) dysfunction, hypogonadism, thyroid dysfunction, benign and malignant thyroid nodules, hyperparathyroidism, and bone effects. The relative contributions of cancer treatment modalities such as radiotherapy and chemotherapy and patient factors are discussed. Appropriate screening, diagnostic testing, and treatment algorithms are also described.
Medical Complications of Obesity
Authors: Jassil Friedrich C. , Batterham Rachel L. 
Published: January 2022

Abstract
Obesity is a chronic progressive condition. It is associated with adverse health outcomes affecting the cardiovascular, endocrine, gastrointestinal, urinary, respiratory, nervous, musculoskeletal, and reproductive systems. Obesity also increases the risk of certain malignancies and psychological comorbidities. The aetiopathogenesis of obesity-linked diseases is complex and not yet fully elucidated, however, clinical and experimental observations, as well as epidemiological studies, have identified a key role for adipocyte-derived factors, in particular from visceral adipose tissue and ectopic lipid deposition. These factors drive low-grade chronic systemic inflammation and mediate the development of at least some obesity-associated diseases. Increasing understanding of the mechanisms whereby obesity leads to a myriad of complications is urgently required to pave the way for development of novel evidence-based preventative and therapeutic strategies.
Hyperinsulinaemic Hypoglycaemia
Authors: Hussain Khalid , Galcheva Sonya 
Published: January 2022

Abstract
In hyperinsulinaemic hypoglycaemia (HH) insulin secretion is dysregulated so that insulin secretion persists in the presence of low blood glucose concentration. HH is a common cause of severe and persistent hypoglycaemia in neonates and children and early diagnosis is essential to avoid hypoglycaemic brain injury. Mutations in 14 different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1, PPM2, CACNA1D, FOXA2) have been linked to congenital forms of HH. Histologically, congenital HH can be divided into two main types namely diffuse and focal. Accessibility of rapid molecular genetic testing, pancreatic imaging with 18F-DOPA PET/CT and the availability of novel medical therapies has changed the clinical approach to patients with HH.
Haemochromatosis and Other Inherited Diseases of Iron Metabolism
Authors: Deugnier Yves , Bardou-Jacquet Edouard 
Published: January 2022

Abstract
Haemochromatosis was described centuries ago, yet the biological mechanisms involved were delineated only recently. Mutation in genes involved in iron metabolism (HFE in the most frequent form) leads to systemic iron overload which particularly affect the liver, pancreas, heart, joints, and pituitary. This can lead to cirrhosis, hepatocellular carcinoma, diabetes, heart failure, hypogonadism, and arthropathy. The diagnosis now relies on definite genetic testing, allowing earlier diagnosis and family screening. This chapter looks at how this lifelong treatment is based on bloodletting to normalize body iron stores and, provided it is initiated before the onset of massive iron overload, allows a normal life expectancy.
The Porphyrias
Authors: Badminton Michael N. , Schulenburg-Brand Danja 
Published: January 2022

Abstract
The porphyrias are a group of mainly inherited metabolic conditions resulting from partial deficiency, or in one condition increased activity, of individual enzymes of haem biosynthesis. Clinical presentation is either with acute neurovisceral attacks, skin photosensitivity, or both, due to overproduction of pathway intermediates. Diagnosis is based on biochemical testing, preferably during or soon after symptomatic periods. Penetrance in autosomal dominant acute porphyrias is low. They predominantly affect adult females and are managed by treatment of acute symptoms and intravenous haematin to suppress hepatic overproduction of precursors. Cutaneous porphyrias present in two distinct patterns of skin photosensitivity; acute painful photosensitivity (protoporphyrias) and fragile skin (bullous porphyrias). Treatment includes photoprotection against visible light (sunlight) especially for the erythropoietic porphyrias. Porphyria cutanea tarda (PCT) may be the first manifestation of liver disease and skin lesions can be effectively treated.
Presentation and Natural History of Type 1 Diabetes
Authors: Brooks Augustin 
Published: January 2022

Abstract
Type 1 diabetes results from loss of pancreatic β-cell function, producing a state of insulin insufficiency that results in spontaneous hyperglycaemia and ketone formation. Genetically susceptible individuals are believed to encounter an (as yet undefined) environmental trigger which initiates an autoimmune process, leading to autoantibody formation, activation of autoreactive T-lymphocytes and pancreatic β-cell destruction. Onset occurs at any age beyond 6 months, with two peak incidences at 5–7 years and during puberty. Incidence is increasing by 3–4% per year, implying a causative role for non-genetic factors. Symptomatic onset with polyuria, polydipsia, and weight loss later leads to presentation with diabetic ketoacidosis if untreated. The discovery of insulin transformed type 1 diabetes from a terminal disease to a manageable medical condition, although exogenous insulin replacement cannot fully mimic the natural regulatory ability of β-cells. Microvascular and macrovascular complications of chronically elevated glucose continue to cause premature morbidity and mortality, with mean reduction in life expectancy estimated at 11–13 years.