Sporadic solitary aldosterone- and cortisol-co-secreting adenomas: endocrine, histological and genetic findings in a subtype of primary aldosteronism

Willenberg, Holger S.; Späth, Martin Richard; Maser-Gluth, Christiane; Engers, Rainer; Anlauf, Martin; Dekomien, Gabriele; Schott, M.; Schinner, Sven; Cupisti, Kenko; Scherbaum, Werner A.

doi:10.1038/hr.2010.18

Cited by 23 publications

(13 citation statements)

References 53 publications

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“…However, no significant gender difference was detected in our previous study [7]. Furthermore, we and others reported the co-secretion of cortisol in approximately 30% of Japanese patients with APAs, which was markedly higher than that in patients in Western countries [19][20][21][22][23][24]. In an attempt to identify biochemical differences between Japanese and Western APA patients, we examined the clinicopathological features of patients with APAs with and without KCNJ5 mutations and also analyzed several steroidogenic enzyme mRNAs including CYP11B2 (aldosterone synthetize), CYP11B1, CYP17A1, CYP12A2, HSD3B2, (3β-hydroxysteroid dehydrogenase), and CYP11A1 (cholesterol side chain cleavage cytochrome P-450), which may reflect the production of hormones and the adrenal zone of origin.…”

Section: Immunohistochemistrymentioning

confidence: 82%

Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations

et al. 2017

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PRIMARY ALDOSTERONISM (PA) has been reported to affect at least 6~10% of patients with essential hypertension [1][2][3][4][5] and is caused mostly by an adrenal adenoma (aldosterone-producing adenoma, APA) or by adrenal hyperplasia (idiopathic hyperaldosteronism, IHA). Although the tumorigenesis of APA remained unclear, somatic mutations of the potassium Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations Abstract. Somatic mutations in KCNJ5 gene have been identified in patients with adrenal aldosterone-producing adenomas (APAs). We previously reported that Japanese patients with APAs had distinct characteristics from patients in Western countries; i.e. they had a high frequency of KCNJ5 mutations and exhibited a frequent association with cortisol cosecretion. Therefore, APAs among Japanese patients may have different features from those in Western countries. We added recent cases, examined 47 cases (43% male) of APAs, including clinicopathological features, KCNJ5 mutations, and the mRNA levels of several steroidogenic enzymes, and compared the results obtained to those reported in other countries. While the prevalence of KCNJ5 mutations is approximately 40% in Western countries, 37 APA cases (78.7%) showed mutations: 26 with p.G151R and 11 with p.L168R. Although a significant gender difference has been reported in the frequency of KCNJ5 mutations in Europe, we did not find any gender difference. However, the phenotypes of Japanese patients with mutations were similar to those of patients in Western countries; patients were younger and had higher plasma aldosterone levels, lower potassium levels, and higher diastolic blood pressure. Reflecting these phenotypes, APAs with mutations had higher CYP11B2 mRNA levels. However, in contrast to APAs in Western countries, Japanese APAs with mutations showed lower CYP11B1, CYP17A1, and CYP11A1 mRNA levels. These findings demonstrated that Japanese APA patients may have distinct features including a higher prevalence of KCNJ5 mutations, no gender difference in the frequency of these mutations, and characteristics similar to the zona glomerulosa.

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Section: Immunohistochemistrymentioning

confidence: 82%

Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations

et al. 2017

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“…Here, the CYP11B1/CYP11B2 hybrid gene was not found, and mutations in the aldosterone synthase gene or a remarkable family history could be excluded (13). Thus, A/CPAs may also oversecrete 'hybrid' steroids such as 18-OH-F, an observation that may be of diagnostic value.…”

Section: Clinical Presentation Of Cases With A/cpamentioning

confidence: 92%

“…APAs that solely consist of zona glomerulosa cells are very rare and usually, APAs are composed of different cell types (73)(74)(75). Thus, APAs seem to have the potential of excess co-secretion of both aldosterone and cortisol (13,76). Hence, in A/CPAs, the co-secretion of cortisol may become apparent for three different reasons.…”

Section: Subtype Differentiation and Radiological Findings In Patientmentioning

confidence: 99%

Aldosterone- and cortisol-co-secreting adrenal tumors: the lost subtype of primary aldosteronism

Späth

Korovkin

Antke³

et al. 2011

European Journal of Endocrinology

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109

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Current guidelines suggest proving angiotensin-independent aldosterone secretion in patients with primary aldosteronism (PA). It is further recommended to demonstrate unilateral disease because of its consequence for therapy. A general screening for excess secretion of other hormones is not recommended. However, clinically relevant autonomous aldosterone production rarely originates in adrenal tumors, compromised of zona glomerulosa cells only. This article reviews published data on aldosterone-and cortisol-co-secreting tumors and shows that pre-operative diagnosis of such a lesion is beneficial for patients. Overt or subclinical glucocorticoid hypersecretion may interfere with diagnostic studies, e.g. adrenal venous sampling, screening of familial forms of PA on the basis of serum 18-hydroxy-cortisol (18-OH-F) determination, and provoke glucocorticoid deficiency after surgical removal of the tumor. In addition, knowledge from histological and molecular studies in patients with aldosterone-and cortisol-co-secreting tumors challenges some concepts of the development of adrenal autonomy. The presence of an aldosterone-and cortisol-co-secreting adrenocortical tumor should be considered if a patient has i) PA and an adenoma that is larger than 2.5 cm, ii) cortisol that is nonsuppressible with overnight low-dose dexamethasone, or iii) grossly elevated serum levels of hybrid steroids, such as 18-OH-F.

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“…Many cases of PA with hypercortisolism reported thus far [29][30][31][32][33] are due to a solitary adenoma co-secreting aldosterone and cortisol, as in Cases 1 and 7. However, aldosterone hypersecretion as confirmed by AVS in our 4 patients (Cases 2, 3, 5, 6) was from the contralateral side of the adrenal lesions by imaging side detected by CT imaging in all 8 PA/SCS patients, which is compatible with concomitant cortisol-and/or aldosterone-producing tumors.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological features of primary aldosteronism associated with subclinical Cushing's syndrome

et al. 2011

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Primary aldosteronism (PA) is characterized by autonomous aldosterone hypersecretion from adrenal gland, resulting in low-renin hypertension often accompanied by hypokalemia and metabolic alkarosis. Recent epidemiologic studies have revealed that PA is more common cause of secondary hypertension than previously thought with its higher prevalence (5-15 %) in patients with hypertension [1][2][3][4][5]. Subclinical Cushing's syndrome (SCS) is characterized as subtle cortisol hypersecretion from adrenal tumor but lack of specific signs or symptoms of overt abstract. Primary aldosteronism (PA), an autonomous aldosterone hypersecretion from adrenal adenoma and/or hyperplasia, and subclinical Cushing syndrome (SCS), a mild but autonomous cortisol hypersecretion from adrenal adenoma without signs or symptoms of Cuhing's syndrome, are now well-recognized clinical entities of adrenal incidentaloma. However, the clinicopathological features of PA associated with SCS (PA/SCS) remain unknown. The present study was undertaken to study the prevalence of PA/SCS among PA patients diagnosed at our institute, and characterize their clinicopathlogical features. The prevalence of PA/SCS was 8 of 38 PA patients (21%) studied. These 8 PA/SCS patients were significantly older and had larger tumor, higher serum potassium levels, lower basal plasma levels of aldosterone, ACTH and DHEA-S as well as lower response of aldosterone after ACTH stimulation than those in 12 patients with aldosterone-producing adenoma without hypercortisolism. All 8 PA/SCS patients showed unilateral uptake by adrenal scintigraphy at the ipsilateral side, whereas the laterality of aldosterone hypersecretion as determined by adrenal venous sampling varied from ipsilateral (3), contralateral (2), and bilateral side (2). 6 PA/SCS patinets who underwent adrenalectomy required hydrocortisone replacement postoperatively. Histopathological analysis of the resected adrenal tumors from 5 PA/SCS patients revealed a single adenoma in 3, and double adenomas in 2, with varying degrees of positive immunoreactivities for steroidgenic enzymes (3β-HSD, P450 C17 ) by immunohistochemical study as well as CYP11B2 mRNA expression as measured by real-time RT-PCR. In conclusion, PA/SCS consists of a variety of adrenal pathologies so that therapeutic approach differs depending on the disease subtype.

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Sporadic solitary aldosterone- and cortisol-co-secreting adenomas: endocrine, histological and genetic findings in a subtype of primary aldosteronism

Cited by 23 publications

References 53 publications

Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations

Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations

Aldosterone- and cortisol-co-secreting adrenal tumors: the lost subtype of primary aldosteronism

Clinicopathological features of primary aldosteronism associated with subclinical Cushing's syndrome

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