Hypersecretion of a New Corticosteroid, 18–Hydroxycortisol in Two Types of Adrenocortical Hypertension

Ulick, Stanley; Chu, Michael D.

doi:10.3109/10641968209061640

Cited by 81 publications

(35 citation statements)

References 9 publications

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“…In the 1980s, patients with APA or FH-I were found to differ from those with BAH by demonstrating elevated levels of "hybrid" steroids, 18-hydroxy-cortisol and 18-oxocortisol (191,202,487,533,534,579). The demonstration of normal levels of "hybrid" steroids in patients with PA, although requiring assays not easy to perform and not widely available, thus potentially represented a means by which BAH could be diagnosed and differentiated from other subtypes.…”

Section: Biochemical Approachesmentioning

confidence: 99%

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

Stowasser

Gordon

2016

Physiological Reviews

127

134

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In the 60 years that have passed since the discovery of the mineralocorticoid hormone aldosterone, much has been learned about its synthesis (both adrenal and extraadrenal), regulation (by renin-angiotensin II, potassium, adrenocorticotrophin, and other factors), and effects (on both epithelial and nonepithelial tissues). Once thought to be rare, primary aldosteronism (PA, in which aldosterone secretion by the adrenal is excessive and autonomous of its principal regulator, angiotensin II) is now known to be the most common specifically treatable and potentially curable form of hypertension, with most patients lacking the clinical feature of hypokalemia, the presence of which was previously considered to be necessary to warrant further efforts towards confirming a diagnosis of PA. This, and the appreciation that aldosterone excess leads to adverse cardiovascular, renal, central nervous, and psychological effects, that are at least partly independent of its effects on blood pressure, have had a profound influence on raising clinical and research interest in PA. Such research on patients with PA has, in turn, furthered knowledge regarding aldosterone synthesis, regulation, and effects. This review summarizes current progress in our understanding of the physiology of aldosterone, and towards defining the causes (including genetic bases), epidemiology, outcomes, and clinical approaches to diagnostic workup (including screening, diagnostic confirmation, and subtype differentiation) and treatment of PA.

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Section: Biochemical Approachesmentioning

confidence: 99%

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

Stowasser

Gordon

2016

Physiological Reviews

127

134

View full text Add to dashboard Cite

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“…Possuem também atividade MC a 19-Nor-DOC (2), um potente esteróide produzido no fígado pela oxigenação da DOC, e os compostos 18-oxigenados derivados do cortisol, 18-hidroxicortisol (18-OHF) e 18-oxocortisol (18-oxoF) (3,4).…”

Section: Como Agem Os Mineralocorticóidesunclassified

“…O bloqueio na oxidação do cortisol para formar cortisona é a anormalidade primária do SEAM (4,6,75). Assim, o diagnóstico baseia-se no aumento da relação dos metabólitos urinários de cortisol sobre os de cortisona (normalmente igual a 1) (75) e/ou da relação cortisol:cortisona plasmática.…”

Section: Síndrome Do Excesso Aparente De Mineralocorticóides (Seam) (unclassified

O espectro das síndromes de hipertensão esteróide na infância e adolescência

Kater

Costa-Santos

2001

Arq Bras Endocrinol Metab

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RESUMOHipertensão arterial não é privilégio de adultos. Além de causas renais e vasculares, doenças adrenocorticais ou correlatas devem ser consideradas na investigação da criança e adolescente hipertensos. O receptor mineralocortidóide (MC) pode ser ativado tanto por MC típicos como pelo cortisol, e mesmo funcionar de maneira autônoma, decorrente de distúrbio nos canais de sódio. Assim, hiperatividade MC (hipertensão, hipocalemia e supressão de renina) pode resultar do excesso de: (1) aldosterona, (2) deoxicorticosterona (DOC) e (3) cortisol. O primeiro grupo, denominado hiperaldosteronismo primário (HAP), inclui o adenoma, o carcinoma e a hiperplasia produtora de aldosterona, além de causa familiares: HA supressível por dexametasona (ou tipo I) e o tipo II. O segundo grupo engloba os tumores produtores tanto de DOC, como de andrógenos ou estrógenos, e a produção de DOC secundária ao excesso de ACTH (síndrome de Cushing, hiperplasia adrenal congênita por deficiência de 11β-e 17α-hidroxilases e síndrome de resistência periférica ao cortisol). Na síndrome do excesso aparente de MC, cortisol age como um MC graças à deficiência congênita ou à inibição (pelo alcaçuz) da enzima 11β-hidroxisteróide desidrogenase, responsável pela oxidação do cortisol em cortisona. Sódio e fluidos podem ser absorvidos nos túbulos renais de forma inapropriada, tanto na síndrome de Liddle (mutações ativadoras do gene do canal epitelial de sódio) como na de Arnold-Healy-Gordon (onde a hiperreabsorção de cloretos e sódio no túbulo renal impede a excreção de H+ e K+, produzindo hipertensão com acidose e hipercalemia). Todo este espectro de doenças adrenais hipertensivas, apesar de pouco prevalentes, deve ser lembrado com possível causa da hipertensão que pode ocorrer na infância e adolescência. ABSTRACTArterial hypertension is not a privilege of adults. Besides renal and vascular causes, adrenocortical and correlated diseases must be considered when investigating a hypertensive child or adolescent. The mineralocorticoid (MC) receptor can be activated by typical MC as well as by cortisol, and even run autonomously, as a result of disturbances in the sodium channel. Thus, MC hyperactivity (hypertension, hypokalemia and renin suppression) may result from excess of: (1) aldosterone, (2) deoxycorticosterone (DOC), and (3) cortisol. The first group, called primary hyperaldosteronism (PHA), includes aldosterone-producing adenoma, carcinoma and hyperplasia, in addition to familial causes: dexamethasone suppressible HA (or type I) and type II familial PAH. The second group encompasses DOC-producing, as well as androgen-and estrogen-producing tumors, and ACTH-dependent DOC hypersecretion (Cushing's syndrome, congenital adrenal hyperplasia due to 11β-and 17α-hydroxylase deficiencies and the syndrome of peripheral cortisol

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“…The synthesis of hybrid steroids, 18-oxocortisol and 18-hydroxycorticosterone, requires the action of 17a-hydroxylase on aldosterone, an enzyme expressed only in the zona fasciculata, suggesting that aldosterone is synthesised in the zona fasciculata in this disorder (44). Higher blood pressure in the offspring of affected mothers rather than affected fathers has been attributed to the effects of high maternal aldosterone on the fetus rather than imprinting (45,46).…”

Section: Familial Hyperaldosteronism Type Imentioning

confidence: 99%

Familial hyperaldosteronism

Torpy

Stratakis

Chrousos³

2000

Braz J Med Biol Res

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Aldosterone, the major circulating mineralocorticoid, participates in blood volume and serum potassium homeostasis. Primary aldosteronism is a disorder characterised by hypertension and hypokalaemia due to autonomous aldosterone secretion from the adrenocortical zona glomerulosa. Improved screening techniques, particularly application of the plasma aldosterone:plasma renin activity ratio, have led to a suggestion that primary aldosteronism may be more common than previously appreciated among adults with hypertension. Glucocorticoid-remediable aldosteronism (GRA) was the first described familial form of hyperaldosteronism. The disorder is characterised by aldosterone secretory function regulated chronically by ACTH. Hence, aldosterone hypersecretion can be suppressed, on a sustained basis, by exogenous glucocorticoids such as dexamethasone in physiologic range doses. This autosomal dominant disorder has been shown to be caused by a hybrid gene mutation formed by a crossover of genetic material between the ACTH-responsive regulatory portion of the 11ß-hydroxylase (CYP11B1) gene and the coding region of the aldosterone synthase (CYP11B2) gene. Familial hyperaldosteronism type II (FH-II), so named to distinguish the disorder from GRA or familial hyperaldosteronism type I (FH-I), is characterised by autosomal dominant inheritance of autonomous aldosterone hypersecretion which is not suppressible by dexamethasone. Linkage analysis in a single large kindred, and direct mutation screening, has shown that this disorder is unrelated to mutations in the genes for aldosterone synthase or the angiotensin II receptor. The precise genetic cause of FH-II remains to be elucidated.

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Hypersecretion of a New Corticosteroid, 18–Hydroxycortisol in Two Types of Adrenocortical Hypertension

Cited by 81 publications

References 9 publications

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

O espectro das síndromes de hipertensão esteróide na infância e adolescência

Familial hyperaldosteronism

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