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Adrenal in the adult male
Published in Barry G. Wren, Progress in the Management of the Menopause, 2020
Besides the adrenal androgens, the adrenal cortex also secretes the vital corticosteroids cortisol and aldosterone, and also minor amounts of other C21-steroids. If adrenal steroids affect testicular testosterone synthesis, this may be either by regulating or modulating testicular activity or by providing raw material for testicular androgen synthesis. It is well known that high doses of glucocorticoids inhibit testicular T secretion: Cushing’s disease, exogenous adrenocorticotropic hormone (ACTH) stimulation, insulin-induced hypoglycemia and exogenous glucocorticoids are all accompanied by low T levels in men. The inhibitory mechanisms seem to vary with the nature of hypercortisolism and include interference of glucocorticoids with the luteinizing hormone (LH) receptors in the Leydig cells, increased metabolic clearance rate of T and also interference with the pituitary–gonadal axis3–6. However, corticosteroids inhibit testicular T secretion only at supraphysiological levels and there are no reports of an influence of normal cortisol levels on testicular T synthesis. In fact, recent studies from some groups including our own rather seem to indicate the reverse (see below).
Adrenoleukodystrophy
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
The course of ALD has usually been relentless, and no therapeutic measures appear to be effective. Symptomatic therapy is important [91], and support groups may be helpful to families. Physiologic amounts of adrenal steroid replacement therapy are effective in the management of the adrenal disease.
Steroids and Infection
Published in Herman Friedman, Thomas W. Klein, Andrea L. Friedman, Psychoneuroimmunology, Stress, and Infection, 2020
Yoshimasa Yamamoto, Herman Friedman
The steroids secreted by the adrenal cortex are crucial for survival in that they are necessary for the response to a threatening environment. The main adrenal steroids are those such as mineralocorticoid, glucocorticoid and some sex steroids, mainly androgens. Since glucocorticoids affect metabolism, water and various electrolyte balance, and organ systems, and have anti-inflammatory as well as immunosuppressive activities, they have been widely used as a therapeutic agent. The main endogenous glucocorticoids are hydrocortisone and corticosterone. The importance of glucocorticoids in homeostasis has been recognized in diseases of abnormal glucocorticoid production. Addison’s disease is caused by a deficiency in production characterized by muscular weakness, low blood pressure, depression, anorexia, loss of weight and hypoglycemia. In contrast, an excess of glucocorticoid activity results in Cushing’s syndrome. This is usually due to hyperplasia of the adrenal glands but a somewhat similar picture can be produced by prolonged or continued administration of steroids. High level of glucocorticoid in patients is frequently associated with severe infections which may be due to the immunosuppressive effect of glucocorticoids. In this chapter, susceptibility of individuals to infections caused by steroids, such as glucocorticoids, will be discussed.
Socioeconomic status and fertility treatment outcomes in high-income countries: a review of the current literature
Published in Human Fertility, 2023
Rachel Imrie, Srirupa Ghosh, Nitish Narvekar, Kugajeevan Vigneswaran, Yanzhong Wang, Mike Savvas
There are many theories as to how differences in socioeconomic status have an impact on an individual (the ‘biology of social adversity’) and their response to disease and medical treatments (Boyce et al., 2012). The term ‘allostatic load’ refers to the cumulative wear and tear throughout life on the body after exposure to chronic and recurrent stress (McEwen & Stellar, 1993). Exposure to psychological chronic stressors, especially in early childhood, can cause epigenetic changes (Lam et al., 2012) that impact lifelong biological responses. Short-term protection from acute stressors provided by hormones such as adrenal steroids and glucocorticoids can, in the long-term, negatively impact health. These factors combined are thought to account for socially mediated discrepancies in behaviour, immune responses (Slopen et al., 2015), inflammatory cascades and cardiovascular and metabolic health (McCrory et al., 2015). In particular, it is thought that environmental factors can influence the epigenome of spermatozoa which may be a factor in any socioeconomic differences in fertility treatment outcomes (Donkin & Barrès, 2018). It is currently not known whether any difference in outcomes between SES groups is because of gamete quality and the subsequent embryos that are created through ART, or the physiological environment to which they are transferred (e.g. pelvic infections are higher in lower SES groups (Leichliter et al., 2013) which may influence implantation).
A rare intronic mutation in the splice acceptor site of the CYP17A1 gene in a patient with 17α-hydroxylase/17,20-lyase deficiency
Published in Gynecological Endocrinology, 2021
Xudong Guo, Hanbo Wang, Yuzhu Xiang, Xiangbin Ren, Shaobo Jiang
Owing to excessive production of corticosterone, a weak glucocorticoid compared to cortisol, 17OHD usually remains undiagnosed until the patients are evaluated because of delayed puberty, sexual infantilism, hypertension or hypokalemia when they enter adolescence or early adulthood. Thus, a patient with mild symptoms is unlikely to be identified and easily misdiagnosed. The diagnosis is usually preliminarily made due to special characteristics of adrenal steroids with confirmation by molecular mutation analysis. The onset age and severity of hypertension, hypokalemia, and sexual development are variable, even among patients with completely inactive P450c17 protein or with the same genotype [14]. The onset of hypertension and hypokalemia may occur in infants, teenagers or individuals in their thirties, and the severity may range from mild to severe [3]. In contrast, approximately 10–15% of patients with 17OHD manifest as normotensive and/or normokalemic at diagnosis [15].
New and emerging drug therapies for Cushing’s disease
Published in Expert Opinion on Pharmacotherapy, 2018
Sylvère Störmann, Jochen Schopohl
Imidazoles are cyclic compounds that comprise a group of diverse drugs, including ketoconazole and etomidate (see the next section). Ketoconazole is an antifungal drug that has been used clinically since the early 1980s. Its capacity to block adrenal steroid synthesis was discovered several years ago [145]. It does so by blocking the enzymes: cholesterol side-chain cleavage enzyme, 11β-hydroxylase, 17α-hydroxylase, and 18-hydroxylase [146]. It has widely been used as an off-label option in otherwise untreatable CD patients since the 1980s. A recent publication which presented the largest retrospective analysis to date provided information regarding 200 patients on monotherapy with ketoconazole for CD. Almost 50% of these patients had normalized UFC at their last follow-up [147]. Of the remaining 101 ‘non-normalized’ patients, 51 had a decrease of at least 50%in UFC compared to baseline values by the end of the study. Prior studies performed during the 1980s and 1990s showed similar results [34].