scholarly journals Primary Aldosteronism: The Next Five Years

2017 ◽  
Vol 49 (12) ◽  
pp. 977-983 ◽  
Author(s):  
John Funder

AbstractThe management of primary aldosteronism is widely varied within various published guidelines, with very little in the way of data supporting the choice of one variation over others. Current estimates of prevalence are probably accurate for aldosterone producing adenoma, but fall very short of that for bilateral adrenal hyperplasia. Discovery at the level of basic science has proven illuminating over the past 6 years in terms of unilateral disease and both somatic and germline mutations, with much less focus on the much more common bilateral disease; Attempts at harmonization have begun – for example, criteria for complete/partial/absent cure after adrenalectomy for unilateral disease; again focus on bilateral disease is muted. A number of possibilities are suggested as agenda for active consideration and change, across a wide range of areas – referral patterns, screening, confirmation and lateralization, what will be needed is discussion and agreement, to fill the lacunae within the current guidelines. Those involved will want to change to make such an agenda possible.

2018 ◽  
Vol 178 (3) ◽  
pp. R101-R111 ◽  
Author(s):  
Silvia Monticone ◽  
Fabrizio Buffolo ◽  
Martina Tetti ◽  
Franco Veglio ◽  
Barbara Pasini ◽  
...  

Aldosterone is the main mineralocorticoid hormone in humans and plays a key role in maintaining water and electrolyte homeostasis. Primary aldosteronism (PA), characterized by autonomous aldosterone overproduction by the adrenal glands, affects 6% of the general hypertensive population and can be either sporadic or familial. Aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH) are the two most frequent subtypes of sporadic PA and 4 forms of familial hyperaldosteronism (FH-I to FH-IV) have been identified. Over the last six years, the introduction of next-generation sequencing has significantly improved our understanding of the molecular mechanisms responsible for autonomous aldosterone overproduction in both sporadic and familial PA. Somatic mutations in four genes (KCNJ5, ATP1A1, ATP2B3 and CACNA1D), differently implicated in intracellular ion homeostasis, have been identified in nearly 60% of the sporadic APAs. Germline mutations in KCNJ5 and CACNA1H cause FH-III and FH-IV, respectively, while germline mutations in CACNA1D cause the rare PASNA syndrome, featuring primary aldosteronism seizures and neurological abnormalities. Further studies are warranted to identify the molecular mechanisms underlying BAH and FH-II, the most common forms of sporadic and familial PA whose molecular basis is yet to be uncovered.


2020 ◽  
Vol 52 (06) ◽  
pp. 379-385
Author(s):  
Lucie S. Meyer ◽  
Siyuan Gong ◽  
Martin Reincke ◽  
Tracy Ann Williams

AbstractPrimary aldosteronism (PA) is the most common form of endocrine hypertension. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1R-Abs) have been described in transplantation medicine and women with pre-eclampsia and more recently in patients with PA. Any functional role of AT1R-Abs in either of the two main subtypes of PA (aldosterone-producing adenoma or bilateral adrenal hyperplasia) requires clarification. In this review, we discuss the studies performed to date on AT1R-Abs in PA.


Endocrinology ◽  
2017 ◽  
Vol 158 (12) ◽  
pp. 4129-4138 ◽  
Author(s):  
Leticia Aragao-Santiago ◽  
Celso E Gomez-Sanchez ◽  
Paolo Mulatero ◽  
Ariadni Spyroglou ◽  
Martin Reincke ◽  
...  

Abstract Primary aldosteronism (PA) is a common form of endocrine hypertension that is characterized by the excessive production of aldosterone relative to suppressed plasma renin levels. PA is usually caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia. Somatic mutations have been identified in several genes that encode ion pumps and channels that may explain the aldosterone excess in over half of aldosterone-producing adenomas, whereas the pathophysiology of bilateral adrenal hyperplasia is largely unknown. A number of mouse models of hyperaldosteronism have been described that recreate some features of the human disorder, although none replicate the genetic basis of human PA. Animal models that reproduce the genotype–phenotype associations of human PA are required to establish the functional mechanisms that underlie the endocrine autonomy and deregulated cell growth of the affected adrenal and for preclinical studies of novel therapeutics. Herein, we discuss the differences in adrenal physiology across species and describe the genetically modified mouse models of PA that have been developed to date.


2004 ◽  
Vol 48 (5) ◽  
pp. 674-681 ◽  
Author(s):  
Claudio E. Kater ◽  
Edward G. Biglieri

Primary aldosteronism (PA) is characterized by hypertension and suppressed renin activity with or without hypokalemia and comprises the aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia or idiopatic hyperaldosteronism (IHA). In recent series employing the aldosterone (aldo, ng/dL):renin (ng/mL·h) ratio (ARR) for screening, prevalence of PA among hypertensives soars to 8-20%; current predominance of IHA (>80%) over APA suggests the inclusion of former low-renin essential hypertensives (LREH), in whom plasma aldo can be reduced by suppressive maneuvers. We evaluated the test characteristics of the ARR obtained retrospectively from 127 patients with PA (81 APA; 46 IHA) and 55 with EH (30 LREH; 25 NREH) studied from 1975 to 1990. Using the combined ROC-defined cutoffs of 27 for the ARR and 12ng/dL for aldo, we obtained 89.8% sensitivity (Ss) and 98.2% specificity (Sp) in discriminating PA from EH: all APA and 72% of the IHA patients had values above these limits, but only one (3%) with LREH. Among the 46 IHA patients, 10 (21.7%) had ARR <27, four of whom with aldo <12ng/dL, virtually indistinguishable from LREH. Use of higher cutoff values (ARR >100; aldo >20) may attain 84%Ss and 82.6%Sp in separating APA from IHA. Because IHA and LREH ("the chaff") may be spectrum stages from the same disease, definite discrimination between these entities seems immaterial. However, precise identification of the APA ("the wheat") is critical, since it is the only surgically curable form of PA. Thus, while patients who may harbor an APA must be thoroughly investigated and surgically treated, non-tumoral disease (IHA and LREH) may be best treated with an aldo-receptor antagonist that will also prevent the aldo-mediated inflammatory effects involved in myocardial fibrosis and abnormal cardiac remodeling.


2020 ◽  
Vol 52 (06) ◽  
pp. 394-403
Author(s):  
Zsófia Tömböl ◽  
Péter István Turai ◽  
Ábel Decmann ◽  
Peter Igaz

AbstractMicroRNAs, the endogenous mediators of RNA interference, interact with the renin-angiotensin-aldosterone system, regulate aldosterone secretion and aldosterone effects. Some novel data show that the expression of some microRNAs is altered in primary aldosteronism, and some of these appear to have pathogenic relevance, as well. Differences in the circulating microRNA expression profiles between the two major forms of primary aldosteronism, unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia have also been shown. Here, we present a brief synopsis of these findings focusing on the potential relevance of microRNA in primary aldosteronism.


Author(s):  
Matthias Johannes Betz ◽  
Christoph Johannes Zech

Primary aldosteronism (PA) is the primary cause of secondary hypertension. The prevalence of PA has probably been underestimated in the past and recent studies suggest that PA could be present in up to 10% of patients suffering from hypertension. Aldosterone excess in PA can be caused by unilateral adrenal disease, usually adrenal adenoma, or bilateral adrenal hyperplasia. Differentiation between unilateral and bilateral disease is clinically important as the former can effectively be treated by removal of the affected adrenal. CT or MRI cannot reliably distinguish unilateral from bilateral disease. Therefore, adrenal vein sampling (AVS) is an important step of the diagnostic work-up in patients with PA. Current guidelines recommend PA in virtually all patients with biochemically diagnosed PA who would undergo adrenal surgery if unilateral PA was diagnosed. In this narrative review, we give an overview of the current technique used for AVS with a focus on the experience with this technique at the University Hospital Basel, Switzerland.


2004 ◽  
pp. 305-308 ◽  
Author(s):  
PF Plouin ◽  
X Jeunemaitre

Fifty years ago, Jerome Conn described 'a new clinical syndrome which is designated temporarily as primary aldosteronism' in a young patient with hypertension, severe hypokalaemia and a benign adrenocortical tumour, for whom an adrenalectomy cured both the hypertension and hypokalaemia. His report identified the condition known as aldosterone-producing adenoma, a form of curable hypertension. According to Conn, the prevalence of primary aldosteronism in the hypertensive population referred to his department was 20%, but this estimate was subject to referral bias. Primary aldosteronism has long been considered rare, with an estimated prevalence of 0.5-2% among unselected hypertensive patients. During the past 10 years, however, the apparent prevalence of the condition increased dramatically, up to 30% in some series. Overall, the prevalence of primary aldosteronism in series dealing with at least 100 screened hypertensive patients averaged 6%, with one patient in two harbouring an aldosterone-producing adenoma. This increase in prevalence reflects the fact that hypokalaemic and normokalaemic patients are now screened for primary aldosteronism, with the aldosterone to renin ratio used as a screening tool. The current 'epidemic' of primary aldosteronism raises several questions and concerns.


2019 ◽  
Vol 181 (4) ◽  
pp. R147-R153 ◽  
Author(s):  
Benjamin Lechner ◽  
Katharina Lechner ◽  
Daniel Heinrich ◽  
Christian Adolf ◽  
Finn Holler ◽  
...  

In patients with primary aldosteronism, specific treatment provides prognostic benefit over optimal antihypertensive therapy and is therefore crucial to reduce mortality and morbidity in this subgroup of patients with hypertension. Prognostic relevance has been shown for adrenalectomy in unilateral disease and for medical treatment with mineralocorticoid receptor antagonists in bilateral adrenal hyperplasia. Collectively, evidence points to the superiority of surgical treatment compared to medical treatment. The causal approach of removing the mineralocorticoid excess, as well as the often-accompanying glucocorticoid excess, might provide one biologically plausible explanation for the observation of slightly better outcomes with surgical therapy. However, in patients living with primary aldosteronism, medical treatment is often insufficient for three major reasons. First and foremost, no marker of sufficient aldosterone blockade has yet been established and therefore adequate treatment of the aldosterone excess is often dismissed as a treatment goal. Second, side effects often limit patient compliance. Third, as recommendations differ from other indications like heart failure, drug dosing is often inadequate. The aim of this review is first to provide an overview over medical treatment options and second to review potential markers for treatment surveillance in patients with primary aldosteronism.


2020 ◽  
Vol 10 (1-s) ◽  
pp. 79-82
Author(s):  
El-Reshaid Kamel ◽  
Shaikha Al-Bader

Over the past 4 and 1/2 years, a total of 97 patients had hypertension yet lacked clinical, laboratory and radiological evidence of renal, renovascular and endocrine disease were investigated for A/R ratio.  High A/R was detected in 30 patients.  Five patients had unilateral adrenal adenoma and 1 had cancer while 24 patients (24.7%) had bilateral enlargements indicating bilateral adrenal hyperplasia (BAH).  Our study has shown that BAH is: (a) easily diagnosed with a combination of A/R ratio and CT scan of the adrenal gland, (b) responsible for 24.7% of hypertension cases, (c) associated with moderate to severe hypertension that may require 2-4 antihypertensives, (d) associated with hypokalemia in only in 54% of the cases, (e) not controlled with a single daily dose of Spironolactone (S) and ½ the cases require 50 mg/day.   Moreover, it has shown that S treatment was not associated with significant hyperkalemia yet gynecomastia and erectile dysfunction were common side effects.  Interestingly; and despite normalization of A/R ratio, most patients continue to require antihypertensive drugs though the number and dosage were less.  The latter phenomenon was more evident in those with higher initial A/R ratio and longer duration of hypertension.  Nephroangiosclerosis is the most plausible explanation for it.  In conclusion; BAH is not a rare disease and should be considered in cases of refractory hypertension.  Keywords: Aldosterone, Aldosterone/Renin ratio, hypertension, Spironolactone.


Sign in / Sign up

Export Citation Format

Share Document