Characteristics of Aldosterone-Producing Adenoma Responsive to Upright Posture.

Toraya, Shozo; Nomura, Kazuhiro; Kono, Atsushi K.; Aiba, Motohiko; Ogasawara, Makiko; Kikuchi, Chizu; Demura, Hiroshi

doi:10.1507/endocrj.42.481

Cited by 6 publications

(2 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous study has described a small subgroup of primary aldosteronism, named aldosterone-producing reninresponsive adenoma (AP-RA), have significant postural variation in concentration of aldosterone levels when subjected to upright posture. This might partially explain her symptom of supine polyuria (7). …”

Section: Discussionmentioning

confidence: 97%

Symptomatic Hypocalcemia in Primary Hyperaldosteronism: A Case Report

et al. 2009

View full text Add to dashboard Cite

The metabolic alterations caused by hyperaldosteronism are being increasingly recognized and have generated considerable interest among the medical fraternity. Hyperaldosteronism is suspected to have a pivotal role in the patho-physiology of congestive cardiac failure where it has been studied extensively. But its effects on calcium metabolism, parathyroid metabolism and renal handling of calcium are less well described. Recent experimental models have shed light into the roles played by previously unknown mechanisms in causing these metabolic alterations. We hereby report a case of primary hyperaldosteronism due to adrenal adenoma (Conn's syndrome) who presented with a myriad of clinical features including symptomatic hypocalcemia, significant weight loss along with uncontrolled hypertension for a prolonged period before eventually detected to have primary hyperaldosteronism. Surgical removal of the causative tumor resulted in prompt disappearance of all the symptoms and signs and regain of lost weight.

show abstract

Section: Discussionmentioning

confidence: 97%

Symptomatic Hypocalcemia in Primary Hyperaldosteronism: A Case Report

et al. 2009

View full text Add to dashboard Cite

show abstract

“…This has been utilized in a bedside posture test to differentiate between APA and IAH [58]. Patients with true Conn's syndrome (due to APA) were shown to have plasma aldosterone levels that tended to be responsive to ACTH but were insensitive to changes in circulating AngII [58,59]. Thus, aldosterone levels are relatively unchanged with assumption of erect posture (or indeed infusion of AngII), but instead they follow a circadian rhythm similar to that for cortisol.…”

Section: Primary Aldosteronismmentioning

confidence: 99%

Aldosterone and the Pathogenesis of Hypertension

Nyirenda¹,

Brown²,

Padfield³

2006

CHYR

View full text Add to dashboard Cite

Hypertension remains a major public health problem, affecting up to 20% of the adult population in Western societies. Despite progress in treatment, the rates of blood pressure control remain suboptimal. Hypertension is a heterogeneous disorder, and in the majority of cases, with so-called "essential" hypertension, no clear single identifiable cause is found. Syndromes of excessive mineralocorticoid production or activity are among the important causes of secondary hypertension. Aldosterone is the principal mineralocorticoid in humans, and primary aldosterone excess, when associated with an aldosterone secreting adenoma (Conn's tumor), is amenable to surgical cure. Classically, patient with Conn's tumor present with spontaneous hypokalemia and have a relative excess of aldosterone production with suppression of plasma levels of renin (a proxy for angiotensin II, the major trophic substance regulating aldosterone secretion). This combination of a high aldosterone and a low renin is however more commonly associated with 'nodular hyperplasia' of the adrenal glands, a condition not improved by surgery and variably responsive to the effects of mineralocorticoid antagonists such as spironolactone. Although primary aldosteronism was previously considered to be rare, recent studies have reported prevalence rates of up to 20% among hypertensive patients. This reflects the increasing use of the plasma aldosterone concentration to renin activity ratio (ARR), rather than spontaneous hypokalemia, as a screening tool for aldosteronism. Many patients with high ARR have normokalemia and, although renin activity is low, the level of aldosterone is usually within the normal range. This group of patients may thus include those who were previously classified as having low-renin essential hypertension. Recent data suggest that disturbances in aldosterone metabolism and regulation may not be uncommon in patients with essential hypertension. Thus, relatively high serum aldosterone levels within the reference range in normotensive individuals are associated with a substantially increased risk of developing hypertension, highlighting the potential role for aldosterone in the etiology of essential hypertension. The present review addresses the physiology of aldosterone action and its role in the pathogenesis of hypertension.

show abstract

Biochemical, Histopathological, and Genetic Characterization of Posture-Responsive and Unresponsive APAs

Nanba

Udager

McWhinney

et al. 2020

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

Context and Objective Posture-responsive and -unresponsive aldosterone-producing adenomas (APAs) account for approximately 40% and 60% of APAs, respectively. Somatic gene mutations have been recently reported to exist in approximately 90% of APAs. This study was designed to characterize the biochemical, histopathologic, and genetic properties of these two types of APA. Methods Plasma levels of aldosterone and hybrid steroids (18-oxocortisol and 18-hydroxycortisol) were measured by LC-MS/MS. Immunohistochemistry (IHC) for CYP11B2 (aldosterone synthase) and CYP17A1 (17α-hydroxylase) and DNA sequencing (Sanger and next-generation sequencing) were performed on APA tissue collected from 23 posture-unresponsive and 17 posture-responsive APA patients. Results Patients with posture-unresponsive APA displayed higher (P < 0.01) levels of hybrid steroids, recumbent aldosterone and cortisol, larger (P < 0.01) zona fasciculata (ZF)-like tumors with higher (P < 0.01) expression of CYP17A1 (but not of CYP11B2) than patients with posture-responsive APA (most of which were not ZF-like). Of 40 studied APAs, 37 (92.5%) were found to harbour aldosterone-driving somatic mutations (KCNJ5 = 14, 35.0%; CACNA1D = 13, 32.5%; ATP1A1 = 8, 20.0%; and ATP2B3 = 2, 5.0%), including 5 previously unreported mutations (3 in CACNA1D and 2 in ATP1A1). Notably, 64.7% (11/17) of posture-responsive APAs carried CACNA1D mutations, whereas 56.5% (13/23) of posture-unresponsive APAs harboured KCNJ5 mutations. Conclusions The elevated production of hybrid steroids by posture-unresponsive APAs may relate to their ZF-like tumor cell composition, resulting in expression of CYP17A1 (in addition to somatic gene mutation-driven CYP11B2 expression), thereby allowing production of cortisol which acts as the substrate for CYP11B2-generated hybrid steroids.

show abstract

Characteristics of Aldosterone-Producing Adenoma Responsive to Upright Posture.

Cited by 6 publications

References 14 publications

Symptomatic Hypocalcemia in Primary Hyperaldosteronism: A Case Report

Symptomatic Hypocalcemia in Primary Hyperaldosteronism: A Case Report

Aldosterone and the Pathogenesis of Hypertension

Biochemical, Histopathological, and Genetic Characterization of Posture-Responsive and Unresponsive APAs

Contact Info

Product

Resources

About