bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation-Induced Thyroid Disease
Authors: Yamashita Shunichi , Pacini Furio , Elisei Rossella 
Published: January 2022

Abstract
Radiation is a mitogen which may cause damage to the cell DNA. When sufficiently severe, the damage may result in cell death. When the damage is less severe, the consequences to the cell depend upon the gene and cell system that are affected. The thyroid gland is particularly sensitive to the effects of radiation and the evidence that radiation may damage the thyroid gland is overwhelming. Both external and internal radiation have been associated with thyroid diseases (cancer and hypothyroidism, with or without thyroid autoimmunity) both in vitro and in vivo. External radiation to the thyroid was first recognized as a cause of thyroid carcinoma in the 1950s, when incidences were found in individuals who had been given radiotherapy during childhood for an enlarged thymus. This chapter takes a look at the numerous studies which have confirmed and extended these initial observations.
Autoimmune Thyroid Disease
Authors: Weetman Anthony P. 
Published: January 2022

Abstract
Along with neoplasia, autoimmunity is the most common cause of endocrine disease, and of this group of disorders, thyroid autoimmunity is the most frequent. Conversely, the autoimmune thyroid diseases are the most common organ-specific or non-organ-specific autoimmune conditions affecting any site. This prevalence, the ease of access to the target organ, the often slow progression of disease, and the historical legacy of being the first distinctive autoimmune process to be defined, have ensured that there is now a reasonable understanding of the main factors involved in pathogenesis. This chapter reviews these factors and how they operate to cause Hashimoto’s thyroiditis, Graves’ disease, and related disorders. It also highlights the use of thyroid autoantibody measurement in the diagnosis of thyroid autoimmune disease.
Radioiodine Treatment of Hyperthyroidism
Authors: Luster Markus , Lassmann Michael 
Published: January 2022

Abstract
Radioiodine therapy was originally aimed at eliminating hyperthyroidism and thus leaving the patient euthyroid. Current strategies however established postradioiodine induction of hypothyroidism as treatment objective, thus included in the category of ‘cure’. This definition holds especially true for the management of Graves’ disease (GD) when long-term hypothyroidism was the rule and stabilization of euthyroidism failed in the majority of cases. In fact, the term ‘ablation’, meaning removal or destruction, has been increasingly used to characterize the outcome of RAIT and administration of larger amounts of radioiodine have tended to make this a self-fulfilling prophecy. Although many clinicians prefer that the end result of treatment should be the more easily managed hypothyroidism, others are still reluctant to give up the therapeutic ideal of euthyroidism as the preferred result of radioiodine therapy and continue their efforts to solve the enigma of thyroid radiosensitivity.
Surgery for Thyrotoxicosis
Authors: Perrier Nancy D. , Clark Orlo H. , Fisher Sarah B. 
Published: January 2022

Abstract
Antithyroid medications, radioactive iodine, or thyroidectomy are viable therapeutic options for the patient with thyrotoxicosis, with relative pros and cons for each modality varying with patient comorbidities and preferences, and the expertise of the treating physicians. Of the three modalities, surgery is the most invasive but also the most definitive, and is favoured for patients with symptomatic compression, concomitant documented/suspected malignancy, or coexisting hyperparathyroidism requiring surgical intervention. Thyroidectomy for treatment of thyrotoxicosis is also advantageous for women who are pregnant, lactating, or planning pregnancy, for patients with moderate to severe Graves’ orbitopathy, or when immediate control of symptoms is necessary. In experienced hands, thyroidectomy is performed with minimal morbidity and should be considered in the patient who places more relative emphasis on prompt and definitive control of symptoms with avoidance of radioactive therapy and/or medications, with less concerns regarding operative risks and/or need for lifelong thyroid hormone replacement.
Clinical Assessment and Systemic Manifestations of Hypothyroidism
Authors: Tonacchera Massimo , Chiovato Luca 
Published: January 2022

Abstract
Hypothyroidism is characterized by a deficient thyroidal production of thyroid hormone. It ranges from mild cases, in which biochemical abnormalities are present, to very severe cases. This condition comprises multiple functional or structural disorders, both congenital and acquired. The clinical expression of hypothyroidism varies between individuals, depending on the cause, duration, and severity of the hypothyroid state, but almost all organs and systems may be affected. It is influenced mainly by the age of the patient and the rate at which hypothyroidism develops, although being largely independent of its cause. Most adult patients complain of a slowing of physical and mental activity. This chapter describes the clinical manifestations of hypothyroidism in the adult and the peculiar clinical aspects due to different ages and aetiologies.
Causes and Laboratory Investigation of Hypothyroidism
Authors: Santini Ferruccio 
Published: January 2022

Abstract
Hypothyroidism is the clinical state that develops as a result of the lack of action of thyroid hormones on target tissues. Primary hypothyroidism occurs when inherited or acquired pathogenic events affect thyroid function by reducing the amount of functioning thyroid tissue or by inhibiting thyroid hormone production. Central hypothyroidism is caused by pituitary or hypothalamic abnormalities resulting in an insufficient stimulation of an otherwise normal thyroid gland. Autoimmune thyroiditis is the most common cause of spontaneous hypothyroidism in areas with adequate iodine intake. Severe environmental iodine deficiency is still crucial in the pathogenesis of hypothyroidism in some geographical areas. Permanent central hypothyroidism is rare and usually part of a disorder involving the secretion of other pituitary hormones, while transient functional abnormalities of TSH secretion are relatively common. Hormonal evaluation of hypothyroidism is mainly achieved by measurement of TSH and free thyroid hormones but additional testing may be required to achieve the proper diagnosis.
Papillary, Follicular, and Anaplastic Thyroid Carcinoma and Thyroid Lymphoma
Authors: Dobrescu Ruxandra , Badiu Corin 
Published: January 2022

Abstract
Thyroid cancer is the most common endocrine malignancy. Differentiated thyroid carcinoma (DTC) is the most frequent type of thyroid cancer and generally has a good prognosis. Diagnosis is based on neck ultrasound and fine needle aspiration biopsy (FNAB) which selects patients for thyroid surgery. Total thyroidectomy is required for large, invasive tumours with lymph node invasion; lobectomy is sufficient for small nodules without any suspicious features. Clinical and pathology data are used to stratify patients according to their risk of mortality and disease recurrence. Adjuvant therapy with radioiodine is indicated in high-risk groups. Follow-up is based on serial thyroglobulin measurements and ultrasound in a dynamic risk evaluation system. In case of disease persistence or recurrence radioiodine scans, high resolution cross-sectional imaging studies with computed tomography (CT) or MRI and 18FDG-PET are performed. Particular management is required for children and during pregnancy. Anaplastic thyroid carcinoma is a rare, aggressive malignancy, affecting older patients, rapidly evolving, and almost uniformly fatal. Prompt management is essential, involving early surgery followed by external radiotherapy, chemotherapy, and palliative care when needed. Thyroid lymphoma is a rare thyroid cancer that frequently occurs on the background of autoimmune thyroiditis. Management depends on histological subtype and stage. In localized forms radiotherapy alone may be sufficient; diffuse forms require a combination of radiotherapy and chemotherapy to improve survival and decrease the risk of recurrences.
Medullary Thyroid Carcinoma
Authors: Raue Friedhelm , Frank-Raue Karin 
Published: January 2022

Abstract
Medullary thyroid carcinoma (MTC) is a rare calcitonin (Ctn)-secreting tumour of the C cells of the thyroid. MTC often have the clinical and histological features of neuroendocrine tumours. They account for 3–5% of all thyroid carcinomas and occur in both sporadic (70%) and hereditary forms (30%). The familial variety of MTC is inherited as an autosomal dominant trait with a high degree of penetrance and is associated with multiple endocrine neoplasia type 2 syndrome. It is caused by germline-activating mutations of the RET proto-oncogene. Detection of MTC in patients has changed in recent years with the introduction of specific strategies: Ctn screening in patients with thyroid nodules and screening with molecular methods for RET proto-oncogene mutations in patients with apparently sporadic MTC and in family members at risk for MTC. By earlier identification of patients with MTC, the presentation has changed from clinical tumours to preclinical disease, resulting in a high cure rate of affected patients with much better prognosis. Surgery represents the only curative therapeutic strategy; the definitive treatment is a total thyroidectomy and, if necessary, central and lateral lymph node dissection. Tumour staging, either postoperatively or by imaging, and measuring the tumour markers Ctn and carcinoembryonic antigen (CEA), allows for the use of a dynamic risk-adapted stratification of follow-up procedures. In advanced metastatic MTC, molecular targeted therapy using tyrosine kinase receptor inhibitors helps controlling tumour progression and prolongs progression-free survival. The outcome for most MTC patients is excellent compared to those with other cancers.
Parathyroid Anatomy, Hormone Synthesis, Secretion, Action, and Receptors
Authors: Goltzman David , Hendy Geoffrey N. 
Published: January 2022

Abstract
Parathyroid hormone (PTH) is produced in the parathyroid glands and is released as an 84 amino acid polypeptide whose bioactivity resides in its amino-terminal domain. PTH secretion is controlled by the parathyroid calcium-sensing receptor (CaSR), and inactivating or activating mutations in this receptor lead to inherited hypercalcaemic and hypocalcaemic disorders, respectively. PTH regulates extracellular fluid calcium homeostasis through its renal calcium-conserving action, and its bone resorbing actions. Adenomas or hyperplasia of the parathyroid glands can lead to dysregulated PTH secretion and the disorder hyperparathyroidism. Intermittently administered PTH, however, exerts a bone anabolic effect and has found use in the clinic in the treatment of osteoporosis. Both PTH (and the gene family member, parathyroid hormone-related protein or PTHrP) act through a G-protein-coupled receptor, the type 1 PTH/PTHrP receptor (PTHR1) that is widely expressed and signals through multiple second messenger pathways. Inactivating mutations in the PTHR1 cause Blomstrand’s lethal chondrodysplasia, whereas activating mutations are found in Jansen’s metaphyseal chondrodysplasia.
Familial Hypocalciuric Hypercalcaemia Types 1–3 and Neonatal Severe Primary Hyperparathyroidism
Authors: Babey Muriel , Shoback Dolores M. 
Published: January 2022

Abstract
The calcium-sensing receptor (CaSR) plays a key role in maintaining calcium homeostasis. The CaSR regulates parathyroid hormone (PTH) secretion and calcium reabsorption by the kidney. Loss-of-function CASR mutations on chromosome 3q21.1 cause familial hypocalciuric hypercalcaemia type 1 (FHH1). FHH1 patients are usually asymptomatic. Biochemically, FHH1 is characterized by mild-to-moderate hypercalcaemia, inappropriately low urinary calcium excretion and a normal or mildly elevated circulating PTH level. Loss-of-function GNA11 mutations on chromosome 19p13.3 lead to FHH2. GNA11 gene encodes Gα-11 which mediates downstream CaSR signalling. Patients with FHH2 mutations display a mild FHH phenotype. Loss-of-function AP2S1 mutations on chromosome 19q.13.3 give rise to FHH3. AP2S1 gene encodes the adaptor-related protein complex 2 sigma (AP2σ) which is crucial for clathrin-mediated endocytosis, CaSR signalling, and trafficking. FHH3 may be a more severe form of FHH that may produce symptomatic hypercalcaemia, low bone mineral density, and cognitive dysfunction. Calcimimetic therapy may be considered for patients with FHH types 1–3.
Hypocalcaemic Disorders, Hypoparathyroidism, and Pseudohypoparathyroidism
Authors: Hannan Fadil M. , Clarke Bart L. , Thakker Rajesh V. 
Published: January 2022

Abstract
Hypocalcaemia ranges from an asymptomatic biochemical abnormality to a life-threatening disorder, and may be caused by vitamin D deficiency, chronic renal failure, hypomagnesaemia, hypoparathyroidism, and pseudohypoparathyroidism. Hypoparathyroidism may occur as part of a pluriglandular autoimmune disorder or a complex congenital defect, such as the autosomal dominant DiGeorge or Hypoparathyroidism-deafness-renal anomalies (HDR) syndromes. In addition, hypoparathyroidism may occur as an isolated endocrinopathy, with autosomal dominant, autosomal recessive, and X-linked inheritances. Molecular genetic studies of hypoparathyroidism have elucidated important roles for: transcription factors (e.g. TBX1, GATA3, GCMB, and AIRE), the tubulin-specific chaperone (TBCE), and the mitochondrial genome in determining parathyroid development and function; the calcium-sensing receptor (CaSR) and G-protein subunit α-11 (Gα11) in regulating extracellular calcium and parathyroid hormone (PTH) secretion; and PTH gene expression for synthesis and secretion of PTH. Pseudohypoparathyroidism, an autosomal dominant disorder associated with PTH resistance, is due to abnormalities of Gαs, which mediates PTH1 receptor signalling.
Bones and the Kidney
Authors: Miller Paul D. , Pazianas Michael 
Published: January 2022

Abstract
Management of osteoporosis in patients with chronic kidney disease (CKD) is often very challenging and it should consider the pathophysiology of both disorders. Patients with stage 4–5 CKD are especially at very high risk for fragility fractures and secondary increase in mortality. Discriminating between osteoporosis and CKD-MBD is best accomplished with quantitative bone histomorphometry but biochemical markers of bone turnover, especially intact parathyroid hormone (PTH) and bone-specific alkaline phosphatase, also may be helpful. The one renal bone disease where antiresorptive osteoporosis therapies would be potentially unsafe is idiopathic renal adynamic bone disease. The two renal bone diseases where an osteoporosis pharmacological agent would not be advised are osteomalacia and primary hyperparathyroid bone disease which can be excluded by defining the underlying cause of a high bone-specific alkaline phosphatase or defining the cause of a very high intact PTH. If a stage 4–5 CKD patient with fragility fractures is felt to have osteoporosis as the major underlying metabolic bone disease causing fractures, FDA approved pharmacological agents for the treatment of osteoporosis can be beneficial on or off label.
Glucocorticoid-Induced Osteoporosis
Authors: Mazziotti Gherardo , Canalis Ernesto , Bilezikian John P. 
Published: January 2022

Abstract
Glucocorticoid-induced osteoporosis (GIO), the most frequent form of secondary osteoporosis, is caused by chronic exposure to glucocorticoid excess. Glucocorticoids have several direct and indirect effects on the skeleton making multifactorial the pathogenesis of GIO. Fragility fractures occur early in GIO and antiosteoporotic drugs along with calcium and vitamin D should be started soon after exposure to glucocorticoid excess. Despite several guidelines and consensus recommendations stating that patients are at a remarkably increased fracture risk, little attention is paid to this risk and guidelines are frequently not applied in real-life clinical practice. This chapter deals with the pathophysiological, clinical, and therapeutic aspects of exogenous and endogenous GIO.
Adrenal Imaging
Authors: Guest Peter 
Published: January 2022

Abstract
Evaluating the adrenal gland with imaging can be challenging. The adrenal glands may be morphologically within normal limits even in the presence of clear hyperfunction. Hyperplasia and small nodules may coexist. Non-functioning nodules are frequent and need to be differentiated from hyperfunctioning adenomas or malignancy. However, the high-resolution anatomical imaging provided by computed tomography (CT) and magnetic resonance imaging (MRI), together with the functional characterization afforded by radionuclide imaging, allows correlation with clinical and endocrine parameters. The use of these modalities in various adrenal disorders is detailed with illustrative images. In this chapter, the anatomy of the adrenal glands is reviewed, while imaging modalities in common modern use are described with their advantages and limitations.
Adrenal Incidentaloma
Authors: Bancos Irina , Terzolo Massimo , Arlt Wiebke 
Published: January 2022

Abstract
Adrenal incidentalomas are adrenal tumours discovered incidentally on around 5% of cross-sectional imaging studies performed for indications unrelated to adrenal disease. The incidental discovery of an adrenal mass has evolved into a common problem, because of the increasingly widespread use of cross-sectional imaging in current clinical practice. Over the last two decades, the number of abdominal CT and MRI imaging studies performed for various reasons quadrupled, and increasing resolution of these imaging studies allows for detection of ever smaller tumours, explaining the growing numbers of patients with adrenal incidentaloma. Any patient with a newly detected adrenal mass requires further evaluation to assess: (1) whether the adrenal mass is functioning (i.e. overproducing adrenal hormones), and (2) whether the adrenal mass is malignant or benign.
Adrenocortical Cancer
Authors: Jouinot Anne , Libè Rossella , Bertherat Jérôme 
Published: January 2022

Abstract
Adrenocortical cancer (ACC) is among the most aggressive endocrine tumours with an overall poor prognosis. Morbidity and mortality can be secondary to tumour-related steroid hormone excess and/or tumour growth and metastases. This potentially poor outcome explains why the early detection of adrenocortical malignancy is paramount for the investigation of adrenal masses, alongside exclusion of hormone excess. The diagnosis of adrenocortical carcinoma relies on careful investigations of clinical, endocrine, and imaging features before surgery, and histopathological examination after tumour removal. Appropriate management and follow-up by an expert multidisciplinary team is critical to improve prognosis and drive progress for this rare cancer.
Management of Phaeochromocytoma and Paraganglioma
Authors: Timmers Henri 
Published: January 2022

Abstract
Phaeochromocytomas and paragangliomas (PPGLs) are rare catecholamine producing tumours. The pathophysiology of PPGL is largely driven by genomic alterations. At least 35% of PPGLs occur as part of a hereditary syndrome. Catecholamine excess may lead to severe hypertension and potentially lethal cardiovascular complications. Therefore, prompt diagnosis is essential for effective treatment, usually by surgical resection. Biochemical testing should include analysis of plasma-free metanephrines or urinary fractionated metanephrines. Additional testing using the clonidine-suppression test is indicated in case of mildly elevated test results that cannot be explained by faulty sampling conditions, patient preparation, or by use of interfering medication. Following a biochemical diagnosis of PPGL, tumour localization can be achieved by CT or MRI. This chapter describes the imaging and treatment modalities that can be employed in the effective management of phaeochromocytoma and paraganglioma.
Modern Management of Congenital Adrenal Hyperplasia and Prospects for the Future
Authors: Auchus Richard J. 
Published: January 2022

Abstract
Congenital adrenal hyperplasia (CAH) refers to a group of genetic cortisol biosynthesis defects, with 21-hydroxylase deficiency (21OHD) being the most common form. The treatment of CAH first involves replacing the deficient hormones of adrenal and sometimes also gonadal origin. In addition, the accumulation of cortisol precursors typically leads to excess androgen and/or mineralocorticoid production. Thus, the second goal is to attenuate the production of unwanted adrenal steroids or to block their action in target tissues. Historically, the two goals were primarily accomplished with glucocorticoid therapy, both to replace the cortisol deficiency and to lower adrenocorticotropin secretion and the production of unwanted steroids. This chapter will review the principles and practical approaches to therapy for patients with CAH, focusing on the adult with 21OHD and their transition from paediatric care. The later sections will review differences in treatment strategies for other forms of CAH and potential novel therapies for the future.
Neuroendocrine Tumour Markers
Authors: Dhillo Waljit , Bech Paul 
Published: January 2022

Abstract
Neuroendocrine cells occur throughout the body, they are particularly prominent in the gastrointestinal tract, pancreas, C cells of the thyroid, adrenal medulla, parathyroid tissue, respiratory tract, skin, and genitourinary system. Neuroendocrine cells are characterized by the presence of dense core secretory vesicles in the cytoplasm which are used to store, process, and secrete hormones. Neuroendocrine tumours (NETs) occur in all these tissues. Due to thseir rarity, heterogeneity, varied and vague symptoms, and often slow-growing tumours, NETs can be a diagnostic challenge. Tumour biomarkers are required for diagnosis and follow-up. An ideal NET biomarker would be one that is secreted exclusively by the tumour cells and can be used for screening, prognostic indication, estimation of tumour burden, and surveillance. Although none of the currently available biomarkers completely fits this ideal, when measured in combination, they are useful for diagnosis, monitoring response to therapy and surveillance. Due to NET defective processing of pro-hormones, any new biomarker should also be able to detect these aberrant forms to increase the sensitivity of the test.