Diagnosis and management of primary aldosteronism: An updated review

Chao, Chia‐Ter; Wu, Vin‐Cent; Kuo, Chin‐Chi; Lin, Yen-Hung; Chang, Chin Chen; Chueh, Shih-Chieh; Wu, Kwan‐Dun; Pimenta, Eduardo; Stowasser, Michael

doi:10.3109/07853890.2013.785234

Cited by 108 publications

(86 citation statements)

References 72 publications

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“…PA patients can be classified into those with aldosterone-producing adenomas (APAs), idiopathic hyperaldosteronism, or familial hyperaldosteronism (FH), which is further divided into FH types 1-3 (FHI-FHIII) (5). In 1992, FHI was shown to result from a gene fusion of cytochrome P450, family 11, subfamily B, polypeptide 2 (CYP11B2: aldosterone synthase) and cytochrome P450, family 11, subfamily B, polypeptide 1 (CYP11B1; cortisol synthase) that resulted in zona fasciculata (ZF) expression of CYP11B2 and excess aldosterone production (6).…”

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Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands

Nishimoto

Tomlins

Kuick

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Primary aldosteronism (PA) represents the most common cause of secondary hypertension, but little is known regarding its adrenal cellular origins. Recently, aldosterone-producing cell clusters (APCCs) with high expression of aldosterone synthase (CYP11B2) were found in both normal and PA adrenal tissue. PA-causing aldosteroneproducing adenomas (APAs) harbor mutations in genes encoding ion channels/pumps that alter intracellular calcium homeostasis and cause renin-independent aldosterone production through increased CYP11B2 expression. Herein, we hypothesized that APCCs have APArelated aldosterone-stimulating somatic gene mutations. APCCs were studied in 42 normal adrenals from kidney donors. To clarify APCC molecular characteristics, we used microarrays to compare the APCC transcriptome with conventional adrenocortical zones [zona glomerulosa (ZG), zona fasciculata, and zona reticularis]. The APCC transcriptome was most similar to ZG but with an enhanced capacity to produce aldosterone. To determine if APCCs harbored APA-related mutations, we performed targeted next generation sequencing of DNA from 23 APCCs and adjacent normal adrenal tissue isolated from both formalin-fixed, paraffin-embedded, and frozen tissues. Known aldosterone driver mutations were identified in 8 of 23 (35%) APCCs, including mutations in calcium channel, voltage-dependent, L-type, α1D-subunit (CACNA1D; 6 of 23 APCCs) and ATPase, Na + /K + transporting, α1-polypeptide (ATP1A1; 2 of 23 APCCs), which were not observed in the adjacent normal adrenal tissue. Overall, we show three major findings: (i) APCCs are common in normal adrenals, (ii) APCCs harbor somatic mutations known to cause excess aldosterone production, and (iii) the mutation spectrum of aldosteronedriving mutations is different in APCCs from that seen in APA. These results provide molecular support for APCC as a precursor of PA.primary aldosteronism | aldosterone | adrenal | somatic mutations | aldosterone-producing cell cluster P rimary aldosteronism (PA) accounts for 8% of hypertension and is the most common adrenal disease (1-4). PA patients can be classified into those with aldosterone-producing adenomas (APAs), idiopathic hyperaldosteronism, or familial hyperaldosteronism (FH), which is further divided into FH types 1-3 (FHI-FHIII) (5). In 1992, FHI was shown to result from a gene fusion of cytochrome P450, family 11, subfamily B, polypeptide 2 (CYP11B2: aldosterone synthase) and cytochrome P450, family 11, subfamily B, polypeptide 1 (CYP11B1; cortisol synthase) that resulted in zona fasciculata (ZF) expression of CYP11B2 and excess aldosterone production (6). For almost two decades after the original report, no other genetic abnormalities were identified in the other forms of PA.First reported in 2011, exome sequencing identified a series of germ-line and somatic mutations in genes that altered adrenal cell intracellular Ca 2+ in PA. The most common mutations are somatic mutations of the gene encoding the potassium inwardly rectifying channel, subfamily J, member 5 (KCNJ5)...

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confidence: 99%

Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands

Nishimoto

Tomlins

Kuick

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

262

254

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“…1,2 Localizing the source of excessive aldosterone secretion is critical to select the appropriate therapy. Unilateral PA can be treated by laparoscopic adrenalectomy, which normalizes serum potassium concentrations in almost all cases and cures or improves hypertension in >80% of patients.…”

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Influence of Diagnostic Criteria on the Interpretation of Adrenal Vein Sampling

et al. 2015

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P atients with primary aldosteronism (PA) have either bilateral (idiopathic hyperplasia) or unilateral (aldosterone-producing adenoma or unilateral hyperplasia) adrenal disease. 1,2 Localizing the source of excessive aldosterone secretion is critical to select the appropriate therapy. Unilateral PA can be treated by laparoscopic adrenalectomy, which normalizes serum potassium concentrations in almost all cases and cures or improves hypertension in >80% of patients.3,4 By contrast, medical management with mineralocorticoid receptor antagonists is recommended as the first-line treatment in bilateral PA. 5Adrenal vein sampling (AVS) is currently considered the gold standard to differentiate unilateral from bilateral aldosterone hypersecretion and is recommended in almost all patients with PA who are eligible for surgical management. 5,6 The accuracy of catheter placement in the adrenal veins can be verified from the cortisol concentration in the adrenal veins divided by that in the inferior vena cava or a peripheral vein (selectivity index [SI]). If the SI reaches the predefined cut-off, the lateralization index (LI) is then used to classify PA into unilateral or bilateral disease. The LI is defined as the highest aldosterone/ cortisol concentration ratio (dominant adrenal vein) divided by the lowest aldosterone/cortisol concentration ratio (nondominant adrenal vein). Some investigators also propose the use of the contralateral suppression index, defined by the aldosterone/ cortisol concentration ratio of the nondominant adrenal vein divided by the peripheral aldosterone/cortisol concentration ratio.7 However, the protocol of AVS (simultaneous or sequential bilateral AVS, use of cosyntropin or not, and the protocol of cosyntropin infusion) and the SI and LI cut-offs used to interpret the results are not currently standardized. 7-9We have interpreted a large number of AVS procedures with criteria used in 4 reference centers or proposed by a recent consensus statement. 6,[10][11][12] The first objective of this study was to examine to which extent the interpretation of AVS may differ according to the criteria used for its interpretation. The second goal was to assess the reproducibility of this interpretation when multiple blood samples were drawn from the same adrenal vein. Methods PatientsThis retrospective study included all patients who underwent AVS in our hypertension referral center between January 2001 and July Abstract-Guidelines promote the use of adrenal vein sampling (AVS) to document lateralized aldosterone hypersecretion in primary aldosteronism. However, there are large discrepancies between institutions in the criteria used to interpret its results. This study evaluates the consequences of these differences on the classification and management of patients. The results of all 537 AVS procedures performed between January 2001 and July 2010 in our institution were interpreted with 4 diagnostic criteria used in experienced institutions where AVS is performed without cosyntropin (Brisbane, Padua, Paris, an...

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“…auch partiell erfolgen kann (Schlamp 2008). Bei beidseitiger Hyperplasie erfolgt die medikamentöse Therapie, da eine bilaterale Adrenalektomie unverhältnismäßig erscheint und unterbleiben sollte (Chao 2013).…”

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