bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iodine Deficiency Disorders
Authors: Zimmermann Michael B. 
Published: January 2022

Abstract
Iodine deficiency has multiple adverse effects on growth and development due to inadequate thyroid hormone production that are termed the iodine deficiency disorders. The most serious adverse effect of iodine deficiency is damage to the fetus. Iodine deficiency remains one of the most common causes of preventable mental impairment worldwide. Four methods are generally recommended for assessment of iodine nutrition: urinary iodine concentration, the goitre rate, and blood concentrations of thyroid-stimulating hormone and thyroglobulin. In nearly all countries, the best strategy to control iodine deficiency is salt iodization, one of the most cost-effective ways to contribute to economic and social development. When salt iodization is not possible, iodine supplements can be targeted to vulnerable groups. Introduction of iodine to regions of chronic iodine deficiency may transiently increase risk of hyperthyroidism, but this relatively small risk is far outweighed by the substantial benefits of correcting iodine deficiency.
Thyrotoxic Storm
Authors: Wartofsky Leonard , Ylli Dorina , Klubo-Gwiezdzinska Joanna 
Published: January 2022

Abstract
Thyroid storm is a rare presentation of exaggerated manifestations of thyrotoxicosis and represents a complex endocrine emergency with a high mortality rate. Multiple organs are affected leading to multisystemic decompensation. To facilitate early diagnosis, a scoring system has been developed based on thermoregulation dysfunction, central nervous system alteration, gastrointestinal symptoms, cardiovascular involvement, and presence of precipitating event. Treatment delay increases the likelihood of irreversible progression and ultimate demise. Hence, when the diagnosis is likely but indefinite, treatment for thyrotoxic storm should be initiated. Management is based on four main strategies directed to reducing thyroid gland hormone production and release, managing the effects of circulating thyroid hormone in the periphery, addressing the systemic decompensation and the precipitating event.
Subclinical Hypothyroidism
Authors: Vaidya Bijay , Daumerie Chantal 
Published: January 2022

Abstract
Subclinical hypothyroidism is a common condition associated with a raised serum thyroid-stimulating hormone (TSH) but normal serum free thyroxine and triiodothyronine. It is more prevalent in women and people with advancing age. Most patients with subclinical hypothyroidism are asymptomatic. About 2.5% patients progress to overt hypothyroidism annually although the rate of progression is higher in the presence of thyroid autoantibodies. Subclinical hypothyroidism is associated with an increased risk of coronary heart disease, heart failure and cerebrovascular disease in younger patients (&lt;65 years), particularly in those with TSH ≥10.0 mU/L. Currently, there is no randomized controlled trial evidence that levothyroxine prevents these complications, although a large observational study has shown that levothyroxine may reduce the risk of coronary heart disease in younger patients (&lt;70 years). The treatment decision for subclinical hypothyroidism requires careful consideration of the patients’ age as well as the presence of symptoms, thyroid autoantibodies, and cardiovascular risk factors.
Syndromes of Resistance to Thyroid Hormone
Authors: Moran Carla , Gurnell Mark , Chatterjee Krishna 
Published: January 2022

Abstract
Disorders of cellular uptake, metabolism, or action of thyroid hormones comprise syndromes of resistance to thyroid hormone. Reduced entry of thyroid hormones into the central nervous system via a membrane transporter mediates severe mental and psychomotor retardation associated with peripheral hyperthyroidism. Failure of selenocysteine incorporation into 25 different proteins results in a multisystem, selenoprotein deficiency, disorder associated with abnormal thyroid function due to impaired activity of deiodinase selenoenzymes. Resistance to Thyroid Hormone β, due to thyroid hormone β receptor mutations, is characterized by elevated circulating thyroid hormones, impaired feedback inhibition of thyroid-stimulating hormone (TSH) secretion and variable hormone resistance in peripheral tissues. Thyroid hormone receptor α defects cause resistance to thyroid hormone α, characterized by features of hypothyroidism in specific tissues but paradoxically associated with near-normal thyroid hormone levels. We describe the genetic basis, clinical features, pathogenesis, and management of these disorders.
Pathology of Thyroid Cancer
Authors: Basolo Fulvio , Ugolini Clara 
Published: January 2022

Abstract
Thyroid malignant lesions include a heterogeneous group of pathologies with different origins, different morphological aspects, and different outcomes. They can originate from follicular cells or from parafollicular C cells. Papillary and follicular thyroid carcinomas arise from follicular cell while medullary cancer develops from the C cell. Papillary cancer can show several variants with different morphological aspects. The most frequent are the classical variant with a typical papillary growth pattern and the follicular variant with an exclusive follicular growth pattern. The different variants show common cytological and nuclear features fundamental for diagnosis of papillary thyroid carcinoma. Follicular carcinoma may present minimal or wide invasion. The widely invasive follicular carcinoma can invade extrathyroidal tissues and organs showing a poor outcome. Other thyroid tumours, like poorly differentiated and anaplastic cancer, show marked cellular anaplasia and atypia, vascular and extrathyroidal tissue invasion, and a very poor prognosis. Fine needle aspiration cytology is the election analysis for preoperative diagnosis of thyroid cancer.
Genetics of Phaeochromocytomas, Paragangliomas, and Neuroblastoma
Authors: Maher Eamonn R. , Casey Ruth T. 
Published: January 2022

Abstract
Phaeochromocytomas, paragangliomas, and neuroblastomas are the main primary tumours that arise from the autonomic nervous system. The autonomic nervous system is subdivided into the sympathetic and parasympathetic systems. Phaeochromocytomas arise from sympathetic nervous system (chromaffin) cells in the adrenal medulla. Paragangliomas may arise from the sympathetic or parasympathetic system. The former, previously known as extra-adrenal phaeochromocytomas but referred herein as paragangliomas, typically occur along the sympathetic chain and, like phaeochromocytomas, are usually secretory and most commonly present with symptoms of excess catecholamine secretion. Parasympathetic ganglia-derived paragangliomas (herein referred to as head and neck paraganglioma, HNPGL) develop along branches of the vagal and glossopharyngeal nerves (e.g. carotid body tumours, glomus jugulare) and are only rarely secretory. Phaeochromocytoma, paraganglioma, and HNPGL are rare in childhood but neuroblastomas, which are derived from neuroblasts in the developing sympathetic nervous system and are most common in children under the age of 5 years. Familial forms of neuroblastoma are rare but a major feature of phaeochromocytoma and paraganglioma (PPGL) and HNPGL is the high frequency of inherited cases and the major inherited syndromic and non-syndromic disorders that predispose to these tumours are described in Chapter 6.13.
Molecular and Clinical Characteristics of the McCune–Albright Syndrome
Authors: Levine Michael A. , Lietman Steven A. 
Published: January 2022

Abstract
The McCune–Albright syndrome (MAS) is characterized by the clinical triad of polyostotic fibrous dysplasia, café-au-lait pigmented skin lesions, and endocrinopathy. MAS is due to postzygotic mutation of the GNAS gene that leads to activation of Gαs, the alpha chain of the heterotrimeric G protein, Gs. Cells that carry the activating GNAS mutation, termed gsp, are distributed in a mosaic pattern, and the extent of the distribution of mutation-bearing cells is based on the timing of the mutational event. Thus, gsp mutations that occur late in development can cause mono-ostotic fibrous dysplasia or an isolated endocrine lesion, whereas earlier mutational events lead to widespread distribution of lesional cells and MAS. Molecular studies now enable the detection of somatic GNAS mutations in circulating cells from most patients with MAS as well as many patients who have only one affected tissue, and therefore diagnosis of MAS continues to rely upon clinical assessment.
Neuroendocrinology of Reproduction
Authors: McCartney Christopher R. , Marshall John C. 
Published: January 2022

Abstract
Gonadotropin-releasing hormone (GnRH)-secreting neurons represent the final common pathway for central neuroendocrine control of reproduction. Pulsatile GnRH secretion from the hypothalamus governs luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from pituitary gonadotropes, which subsequently directs ovarian function. Higher-level afferent inputs (e.g. neurons releasing kisspeptin, neurokinin B, and dynorphin) substantially impact GnRH neuron function and largely mediate sex steroid negative feedback and the reproductive effects of altered nutrition, physiological stress, and lactation. These complex hypothalamic–pituitary–ovarian interactions achieve ovarian follicular development; episodic presentation of ova for possible fertilization (ovulation); and physiological preparation for possible pregnancy (e.g. endometrial decidualization).
Ovarian and Uterine Development from Fetal Life to Puberty
Authors: Piltonen Terhi , Tapanainen Juha 
Published: January 2022

Abstract
Human fetal organogenesis is a complex process starting 4 weeks post conception. The gender specific gonads can be distinguished as early as by the GW 8 and the process is driven by the sex determining region on the Y-chromosome (SRY) among other genes that drive fetal testosterone and AMH effects. In the absence of anti-Müllerian hormone (AMH) the Müllerian ducts will develop to uterus and fallopian tubes, and without androgen influence the urogenital sinus will form as female external genitalia. Ovarian primordial follicles reach the highest number of 7 million around mid-gestation after which the number starts to decrease by means of apoptosis and only 2 million primordial follicles are left at the time of birth and less than half of million at puberty. The pituitary–ovarian axis of the fetus is activated at mid-gestation, after which levels of gonadotropins decrease towards the term, and become activated again after birth resulting in minipuberty. The quiescent period in gonadotrophins and sex steroid production remains during childhood ends before puberty as a consequence of maturation of the hypothalamus–pituitary–ovarian axis. During reproductive life around 400 follicles will ovulate with concomitant decrease of follicle pool through apoptosis. The follicle reserve is exhausted around the age of 50 years resulting into menopause.
Laboratory Evaluation
Authors: Dumesic Daniel , Al-Safi Zain 
Published: January 2022

Abstract
A variety of laboratory assessment and imaging studies can be ordered to guide the management of patients with suspected endocrine abnormality. These are selected based on the clinical presentation. In this chapter, we thereby classify them into hormonal evaluation (e.g. β-hCG, oestradiol, progesterone, LH and FSH, androgens (testosterone, DHEAS), 17 α-hydroxyprogesterone (17 OHP), prolactin, growth hormone, anti-Mullerian hormone (AMH), thyroid hormone, cortisol), imaging studies (e.g. head, ovarian, adrenal, bone density, and thyroid), and other assessments (e.g. karyotype, fragile X testing, autoimmune testing, insulin resistance testing) that are helpful in diagnosing these conditions and evaluating for other associated abnormalities. A full references list and illustrative tables provide further reading and information.
Polycystic Ovary Syndrome
Authors: Mumusoglu Sezcan , Yildiz Bulent Okan 
Published: January 2022

Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 6–10% of the reproductive age women worldwide. It is a complex multifactorial syndrome with polygenic inheritance and epigenetic alterations. PCOS is characterized by clinical and/or biochemical hyperandrogenism (HA), ovulatory dysfunction (OD), and polycystic ovarian morphology (PCOM). Different sets of diagnostic criteria are available, and the syndrome could present with various phenotypes. Therefore, diagnosis of PCOS is a challenge for clinical practitioners and researchers alike. Accurate and early diagnosis is essential in women with PCOS, in order to address presenting complaints and prevent long-term health consequences of the syndrome. This chapter outlines definition, clinical features, diagnosis, clinical features, phenotypes, prevalence, and genetics of PCOS.
Polycystic Ovary Syndrome
Authors: Ehrmann David A. , Sam Susan 
Published: January 2022

Abstract
Insulin resistance is common among women with PCOS independent of adiposity. However, the severity of insulin resistance in these women worsens with obesity especially in those who present with the classical phenotype of PCOS (NIH criteria) consisting of hyperandrogenism and menstrual irregularity. Hence, obese women with PCOS, especially those with the classic phenotype of PCOS, are at high risk for metabolic complications. These complications include type 2 diabetes (DM2), metabolic syndrome, dyslipidaemia and obstructive sleep apnoea (OSA). Additionally, these women are at increased risk for cardiovascular disease even though the exact risk for this complication is not established. Due to heightened risk for metabolic disorders, close screening and follow-up for development of glucose intolerance, metabolic syndrome, and OSA is essential and is supported by current guidelines. Management of women with PCOS is individualized and should depend on the patient’s symptoms as well as their risk for development of various complications.
Polycystic Ovary Syndrome
Authors: Pignatelli Duarte , Azziz Ricardo , Yildiz Bulent Okan 
Published: January 2022

Abstract
Hirsutism is defined as excess growth of body or facial terminal (coarse) hair in females, in a male-like pattern. In addition to its possible association with conditions such as polycystic ovary syndrome (PCOS) and the associated risk of cardiometabolic diseases and infertility, hirsutism has a significant negative impact on a woman’s self-esteem and on her quality of life. Hirsutism affects 5–15% of the women, and is the most commonly used clinical diagnostic criterion of androgen excess or hyperandrogenism. Depending on age and race/ethnicity, 80–90% of women with hirsutism will have an androgen excess disorder, most often PCOS, but also non-classic congenital adrenal hyperplasia (NCAH), and androgen-secreting neoplasms, among others. Current treatment of hirsutism may consist of: suppression of androgen production; blockade of peripheral androgen action; and mechanical and cosmetic means of hair removal. This chapter outlines androgen metabolism in women, physiology and pathophysiology of hair growth, epidemiology of hirsutism and differential diagnosis of its multiple aetiologies, and the clinical investigation, and treatment of the hirsute patient.
Exogenous Factors and Female Reproductive Health
Authors: Diamanti-Kandarakis Evanthia , Kandaraki Eleni A. 
Published: January 2022

Abstract
Endocrine disruptors (EDCs) and glycotoxins or advanced glycosylated end products (AGEs) have raised one of the most controversial environmental question of recent decades that requires urgent answers, since there is now better appreciation that both AGEs and EDCs exposure from food, depends on methods of food processing packaging and nutrient composition. The Western diet and lifestyle can be a significant environmental source of these toxicants that are potentially involved in the pathogenesis of female reproductive axis deregulation. Acute or prolonged exposure to EDCs and AGEs through different life cycle stages may result in destabilization of the hormonal homeostasis and lead to disruption of reproductive functions. Extensive data from different scientific models, collected in recent years, have confirmed their negative role. Therefore, strategies and strong recommendations should be targeted to reduce human exposure in order to protect current as well as next generations from steadily rising adverse health effects.
Adrenal Disease in Pregnancy
Authors: Torpy David J. , O’Reilly Michael W. , De Sousa Sunita M.C. 
Published: January 2022

Abstract
Diagnosis of adrenal gland dysfunction in pregnancy is complex, and confounded by physiological gestational changes in maternal adrenal hormone metabolism. Management of newly diagnosed or pre-existing adrenal disease in pregnant women requires intensive input from the endocrinologist, and close collaboration with the obstetrician or fetal medicine specialist. Maternal adrenal gland dysfunction during pregnancy encompasses adrenocortical disorders resulting in glucocorticoid and mineralocorticoid deficiency or excess, and medullary disease resulting in catecholamine excess. The aim of this chapter is to review clinical aspects of the most common adrenal disorders in pregnancy, and to discuss approaches to diagnosis and management. Both benign and malignant diseases of the adrenal cortex and medulla will also be discussed.
Endocrine Bone Disease in Pregnancy
Authors: Cox Jeremy , Robinson Stephen 
Published: January 2022

Abstract
Fetal and neonatal calcium requirements are high. To meet this need requires marked changes in maternal calcium physiology and bone metabolism during pregnancy and lactation. The import of widespread vitamin D deficiency and low calcium diets has been difficult to ascertain in the context of these changes, despite extensive studies. The impact goes beyond simple calcium homeostasis, with associations of low Vitamin D levels to worse maternal, fetal, and neonatal outcomes, including neonatal hypocalcaemia and pre-eclampsia. Other less common disorders of calcium metabolism, such as diseases involving the parathyroid axis, that are stable outside of pregnancy are markedly affected both by pregnancy and lactation and may cause serious complications to mother and fetus, requiring much closer monitoring and possible intervention. The normal physiological changes in calcium control during pregnancy and lactation may themselves cause disease, particularly osteoporosis, but also rarer entities such as pseudohyperparathyroidism.
Short Stature in Children Born Small for Gestational Age
Authors: Hokken-Koelega Anita C.S. 
Published: January 2022

Abstract
Small-for-gestational-age (SGA) is defined as a birth weight and/or length &lt;–2 SDS. As the aetiology of SGA is multifactorial and includes maternal lifestyle and obstetric factors, placental dysfunction, and numerous (epi)genetic abnormalities, SGA-born children comprise a heterogeneous group. The majority of SGA-born infants show catch-up growth to a normal stature, but 10% remains short. For more than 30 years, studies have been performed in short children after SGA birth, including children with Silver–Russell syndrome (SRS). Studies have generally excluded short SGA children with major dysmorphic features or a (suspected) syndrome, primordial dwarfism, or DNA repair disorder. Thus present knowledge and management, particularly on GH treatment, are based on the results in non-syndromic short SGA/SRS children. This chapter presents our current knowledge of the (epi)genetic causes of short stature for those born SGA, the health consequences of SGA, and the diagnostic approach and management of short SGA-born children, including the efficacy and safety of GH treatment.
Growth Disorders with No Defined Aetiology
Authors: George Minu , Chernausek Steven 
Published: January 2022

Abstract
Short stature is one of the most common conditions presenting to paediatric endocrinology clinics. After careful history, physical examination, and standard laboratory diagnosis, the majority are classified as having idiopathic short stature. The extent to which the condition is detrimental to the well-being of the child, as well as the effectiveness, benefit, and safety of treatments remain incompletely delineated. There is evidence that administration of human growth hormone stimulates skeletal growth and increases adult stature, however, the response is variable and so the challenge has been to identify those for whom treatment may be warranted. The chapter addresses these issues and describes a diagnostic strategy that incorporates newer genetic testing to identify the basis of the growth disorder for select patients. With such an approach a definitive diagnosis can be reached 25–40% of patients labelled as idiopathic short stature and thereby aid in their management.
Endocrine Treatment of Transgender Youth
Authors: Klink Daniel 
Published: January 2022

Abstract
Transgender adolescent healthcare is a relatively novel part of endocrine medicine. Treatment protocols have emerged since the late1990’s and outcome data have become available more recently. A multidisciplinary approach with psychology and endocrinology is required to accommodate the specific needs of developing transgender adolescents and their primary caretakers. Therefore, treatment is ideally provided by specialized centres. However, with a growing population in numbers, all physicians should be familiar with treatment protocols. The endocrine treatment of transgender youth differs from that of transgender adults. The first step of treatment is a phase of gonadal suppression using either gonadotropin hormone-releasing hormone analogues (GnRHa) or, alternatively, progestogens, or antiandrogens. Second step is the induction of sexual characteristics of the affirmed gender using synthetic sex steroids in increasing dosages to mimic a pubertal fase. These specific therapeutics approaches of the transgender adolescent are outlined in this chapter.
Hormone Therapy in Transgender Women
Authors: Tangpricha Vin , Sineath Craig 
Published: January 2022

Abstract
When a transgender woman decides to begin medical transition, she will meet with a physician to begin the steps of starting gender-affirmation therapy via hormone replacement. This process involves an initial evaluation that includes psychological evaluation, a complete history and physical exam, and baseline lab values. There are many medications available for transgender women to take for their transition; in general, a transgender woman will begin an oestrogen agent and a testosterone-lowering agent. This combination of medications has effects on the body including breast development, redistribution of body fat, dermatological effects, and changes to the genitalia and sexual desire. While these drugs are considered safe, there are some lab values that must be monitored longitudinally depending on which regiment the patient is taking. This chapter outlines the overall process of starting hormone therapy, what effects the therapy will have on the patient, and longitudinal monitoring.
Hormone Therapy in Transgender Men
Authors: T’Sjoen Guy , Defreyne Justine 
Published: January 2022

Abstract
Currently, transgender medicine is not a strong part of the medical curriculum, although a large number of transgender persons will search for some kind of gender-affirming care. As psychopathology is clearly reduced in transgender persons after the initiation of hormone therapy, we believe all endocrinologists should become familiar with endocrinological care for transgender persons. In transgender men, testosterone therapy is initiated, aimed at achieving cisgender male reference values of serum testosterone in order to induce virilization. Although gender-affirming hormonal therapy with testosterone is considered safe, endocrinological follow-up is advised in all transgender people receiving gender-affirming hormonal care and will be discussed in this chapter for transgender men.