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Physiological Research Sep 2020The adrenal glands produce significant amounts of steroid hormones and their metabolites, with various levels of androgenic activities. Until recently, the androgenic... (Review)
Review
The adrenal glands produce significant amounts of steroid hormones and their metabolites, with various levels of androgenic activities. Until recently, the androgenic potency of these adrenal-derived compounds were not well known, but some recent studies have shown that the production of 11-oxo- and 11beta-hydroxy-derived testosterone and dihydrotestosterone evidently have high androgenic activity. This fact has clinical importance, for instance, in various types of congenital adrenal hyperplasia with androgenization or polycystic ovarian syndrome, and laboratory determinations of these substances could help to better evaluate the total androgen pressure in patients with these disorders. Another area of concern is the treatment of prostate cancer with androgen deprivation, which loses effectiveness after a certain time. The concurrent blocking of the secretion of adrenal C(19)-steroids, whether using corticoids or adrenostatics, could increase the effectiveness of androgen-deprivation therapy.
Topics: Adrenal Hyperplasia, Congenital; Androgen Antagonists; Androgens; Animals; Humans; Male; Molecular Targeted Therapy; Prostatic Neoplasms; Testosterone
PubMed: 33094617
DOI: 10.33549/physiolres.934516 -
Ugeskrift For Laeger Mar 2024Congenital adrenal hyperplasia (CAH) arises from genetic enzyme defects, often in CYP21A2, causing primary adrenal insufficiency. In this case report, a man in his late...
Congenital adrenal hyperplasia (CAH) arises from genetic enzyme defects, often in CYP21A2, causing primary adrenal insufficiency. In this case report, a man in his late 20s with lifelong CAH faced challenges in adhering to medication. Suboptimal treatment led to the development of testicular adrenal rest tumours, diagnosed by ultrasound, and hypogonadism. Enhanced adherence restored hormone levels, promoting eugonadism. Adherence plays a crucial role in diminishing tumour size and preventing complications, potentially necessitating orchiectomy in severe cases.
Topics: Humans; Male; Adrenal Hyperplasia, Congenital; Adrenal Rest Tumor; Hypogonadism; Steroid 21-Hydroxylase; Testicular Neoplasms; Adult
PubMed: 38533865
DOI: 10.61409/V12230794 -
Current Opinion in Endocrinology,... Jun 2021The introduction of synthetic glucocorticoids 70 years ago made survival possible in classic 21-hydroxylase deficiency (21OHD). The currently used glucocorticoid... (Review)
Review
PURPOSE OF REVIEW
The introduction of synthetic glucocorticoids 70 years ago made survival possible in classic 21-hydroxylase deficiency (21OHD). The currently used glucocorticoid therapy may lead to unphysiological dosing with negative consequencies on health in addition to the problems that may arise due to androgen over-exposure.
RECENT FINDINGS
Fertility in females with 21OHD seemed to be impaired, especially in the salt-wasting (SW) phenotype but when pregnancies did occur there was a higher risk for gestational diabetes and cesearean section. Increased fat mass, body mass index, insulin resistance and frequency of autoimmune disorders as well as impaired echocardiographic parameters and lower bone mineral density were found in 21OHD compared to controls. Negative effects on cognitive functions have been identified. Adrenal tumors, especially myelolipomas, were prevalent. Increased knowledge on steroid metabolism in 21OHD and urine steroid profiling may improve assessment of treatment efficacy. Nevanimibe, abiraterone acetate and anastrozole may have a place in the future management of 21OHD. Long-acting glucocorticoids may be a less favorable, especially dexamethasone.
SUMMARY
The various clinical outcomes need regular monitoring. Negative consequencies are to large extent the result of the unphysiological glucocorticoid replacement. Modern management with improved follow-up and future addition of new drugs may improve outcomes.
Topics: Adrenal Hyperplasia, Congenital; Female; Glucocorticoids; Humans
PubMed: 33741777
DOI: 10.1097/MED.0000000000000625 -
Endocrinology and Metabolism (Seoul,... Aug 2022A plethora of negative long-term outcomes have been associated with congenital adrenal hyperplasia (CAH). The causes are multiple and involve supra-physiological gluco-... (Review)
Review
A plethora of negative long-term outcomes have been associated with congenital adrenal hyperplasia (CAH). The causes are multiple and involve supra-physiological gluco- and mineralocorticoid replacement, excess adrenal androgens both intrauterine and postnatal, elevated steroid precursor and adrenocorticotropic hormone levels, living with a congenital condition as well as the proximity of the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene to other genes. This review aims to discuss the different long-term outcomes of CAH.
Topics: Adrenal Hyperplasia, Congenital; Humans; Steroid 21-Hydroxylase
PubMed: 35799332
DOI: 10.3803/EnM.2022.1528 -
Radiographics : a Review Publication of... 2021
Topics: Adrenal Hyperplasia, Congenital; Humans; Hyperplasia
PubMed: 34197246
DOI: 10.1148/rg.2021210118 -
Frontiers in Endocrinology 2022Pediatric adrenocortical hyperplasias are rare; they usually present with Cushing syndrome (CS); of them, isolated micronodular adrenal disease and its variant, primary... (Review)
Review
Pediatric adrenocortical hyperplasias are rare; they usually present with Cushing syndrome (CS); of them, isolated micronodular adrenal disease and its variant, primary pigmented adrenocortical disease are the most commonly encountered. Most cases are due to defects in the cyclic AMP/protein kinase A (cAMP/PKA) pathway, although a few cases remain without an identified genetic defect. Another cause of adrenal hyperplasia in childhood is congenital adrenal hyperplasia, a group of autosomal recessive disorders that affect steroidogenic enzymes in the adrenal cortex. Clinical presentation varies and depends on the extent of the underlying enzymatic defect. The most common form is due to 21-hydroxylase deficiency; it accounts for more than 90% of the cases. In this article, we discuss the genetic etiology of adrenal hyperplasias in childhood.
Topics: Adrenal Cortex; Adrenal Cortex Diseases; Adrenal Hyperplasia, Congenital; Child; Cushing Syndrome; Humans; Hyperplasia
PubMed: 35992119
DOI: 10.3389/fendo.2022.937793 -
Reviews in Endocrine & Metabolic... Apr 2023Adrenal insufficiency (AI) is a severe endocrine disorder characterized by insufficient glucocorticoid (GC) and/or mineralocorticoid (MC) secretion by the adrenal... (Review)
Review
Adrenal insufficiency (AI) is a severe endocrine disorder characterized by insufficient glucocorticoid (GC) and/or mineralocorticoid (MC) secretion by the adrenal glands, due to impaired adrenal function (primary adrenal insufficiency, PAI) or to insufficient adrenal stimulation by pituitary ACTH (secondary adrenal insufficiency, SAI) or tertiary adrenal insufficiency due to hypothalamic dysfunction. In this review, we describe rare genetic causes of PAI with isolated GC or combined GC and MC deficiencies and we also describe rare syndromes of isolated MC deficiency. In children, the most frequent cause of PAI is congenital adrenal hyperplasia (CAH), a group of adrenal disorders related to steroidogenic enzyme deficiencies, which will not be included in this review. Less frequently, several rare diseases can cause PAI, either affecting exclusively the adrenal glands or with systemic involvement. The diagnosis of these diseases is often challenging, due to the heterogeneity of their clinical presentation and to their rarity. Therefore, the current review aims to provide an overview on these rare genetic forms of paediatric PAI, offering a review of genetic and clinical features and a summary of diagnostic and therapeutic approaches, promoting awareness among practitioners, and favoring early diagnosis and optimal clinical management in suspect cases.
Topics: Child; Humans; Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Adrenal Glands
PubMed: 36763264
DOI: 10.1007/s11154-023-09784-7 -
Hormone Research in Paediatrics 2022The adrenal has played a major role in the history of pediatric endocrinology. Cases of congenital adrenal hyperplasia (CAH) were reported in the 19th century, leading... (Review)
Review
The adrenal has played a major role in the history of pediatric endocrinology. Cases of congenital adrenal hyperplasia (CAH) were reported in the 19th century, leading to the understanding that the adrenal influenced sexual phenotypes as well as being mysteriously required for survival. Numerous adrenal steroids were isolated in the early 20th century, and bioassays eventually distinguished glucocorticoids, mineralocorticoids, and androgens. Treatment of CAH with cortisone in 1950 by Wilkins and by Bartter and Albright revolutionized clinical endocrinology and launched a productive era of pediatric adrenal research. Through careful clinical studies, Wilkins established the contemporary approach to treating CAH. Alfred Bongiovanni identified defective 21-hydroxylation in CAH in 1957, followed by deficiencies of 3β-hydroxysteroid dehydrogenase and 11β-hydroxylase. P450 enzymes were described in 1962-1964, and 21-hydroxylation was the first activity ascribed to a P450. Accurate assays for 17OH-progesterone in newborns and in response to ACTH permitted the diagnosis of CAH in children and families. Application of the techniques of molecular genetics elucidated genetic and biochemical bases of these disorders from 1984 to 2004. Pediatric endocrinologists played central roles in identifying the genes responsible for both common and rare forms of congenital adrenal hyperplasia and determining their most appropriate treatments.
Topics: Humans; Adrenal Hyperplasia, Congenital; Mineralocorticoids; Endocrinology; Glucocorticoids; Androgens
PubMed: 36446323
DOI: 10.1159/000526468 -
The Journal of Clinical Endocrinology... Aug 2023The most common form of congenital adrenal hyperplasia is 21-hydroxylase deficiency (21OHD), which in the classic (severe) form occurs in roughly 1:16 000 newborns... (Review)
Review
The most common form of congenital adrenal hyperplasia is 21-hydroxylase deficiency (21OHD), which in the classic (severe) form occurs in roughly 1:16 000 newborns worldwide. Lifelong treatment consists of replacing cortisol and aldosterone deficiencies, and supraphysiological dosing schedules are typically employed to simultaneously attenuate production of adrenal-derived androgens. Glucocorticoid titration in 21OHD is challenging as it must balance the consequences of androgen excess vs those from chronic high glucocorticoid exposure, which are further complicated by interindividual variability in cortisol kinetics and glucocorticoid sensitivity. Clinical assessment and biochemical parameters are both used to guide therapy, but the specific purpose and goals of each biomarker vary with age and clinical context. Here we review the approach to medication titration for children and adults with classic 21OHD, with an emphasis on how to interpret adrenal biomarker values in guiding this process. In parallel, we illustrate how an understanding of the pathophysiologic and pharmacologic principles can be used to avoid and to correct complications of this disease and consequences of its management using existing treatment options.
Topics: Child; Adult; Humans; Infant, Newborn; Adrenal Hyperplasia, Congenital; Glucocorticoids; Hydrocortisone; Steroids; Biomarkers; Disease Management; Steroid 21-Hydroxylase
PubMed: 36950738
DOI: 10.1210/clinem/dgad134 -
International Heart Journal 2024
Topics: Humans; Adrenal Hyperplasia, Congenital; Hyperplasia
PubMed: 38296561
DOI: 10.1536/ihj.23-647