Role of endogenous ACTH on circadian aldosterone rhythm in patients with primary aldosteronism

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Abstract

We recently reported that stimulation with high-dose ACTH caused different responses in terms of aldosterone secretion in aldosterone-producing adenomas (APAs) and idiopathic hyperaldosteronism (IHA) in patients with primary aldosteronism (PA). However, the role of endogenous ACTH in aldosterone secretion in PA has not been systematically evaluated. In this study, we examined diurnal changes in plasma aldosterone concentration (PAC), and changes in PAC after dexamethasone administration in patients with suspected PA, in order to evaluate the effect of endogenous ACTH on aldosterone secretion. Seventy-three patients admitted to Kyoto University Hospital with suspected PA were included. The patients were classified into non-PA, IHA, and APA groups according to the results of captopril challenge test and adrenal venous sampling. PAC at 0900 h (PAC ₀₉₀₀), 2300 h (PAC ₂₃₀₀), and after 1-mg dexamethasone suppression test (PAC _dex) was measured and compared among the three groups. The PAC ₂₃₀₀/PAC ₀₉₀₀ and PAC _dex/PAC ₀₉₀₀ ratios were also analyzed. PAC ₂₃₀₀ and PAC _dex were lower than PAC ₀₉₀₀ in all three groups. There were no significant differences in PAC ₂₃₀₀/PAC ₀₉₀₀ among the three groups. However, PAC _dex/PAC ₀₉₀₀ was significantly lower in the APA group compared with the non-PA and IHA groups. The results of this study indicate that aldosterone secretion in APA patients is more strongly dependent on endogenous ACTH than in IHA and non-PA patients. The results also suggest that factors other than ACTH, such as clock genes, may cause diurnal changes in aldosterone secretion in IHA and non-PA patients.

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A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients.

Gian Paolo Rossi, Giampaolo Bernini, Chiara Caliumi … (2006)

We prospectively investigated the prevalence of curable forms of primary aldosteronism (PA) in newly diagnosed hypertensive patients. The prevalence of curable forms of PA is currently unknown, although retrospective data suggest that it is not as low as commonly perceived. Consecutive hypertensive patients referred to 14 hypertension centers underwent a diagnostic protocol composed of measurement of Na+ and K+ in serum and 24-h urine, sitting plasma renin activity, and aldosterone at baseline and after 50 mg captopril. The patients with an aldosterone/renin ratio >40 at baseline, and/or >30 after captopril, and/or a probability of PA (by a logistic discriminant function) > or =50% underwent imaging tests and adrenal vein sampling (AVS) or adrenocortical scintigraphy to identify the underlying adrenal pathology. An aldosterone-producing adenoma (APA) was diagnosed in patients who in addition to excess autonomous aldosterone secretion showed: 1) lateralized aldosterone secretion at AVS or adrenocortical scintigraphy, 2) adenoma at surgery and pathology, and 3) a blood pressure decrease after adrenalectomy. Evidence of excess autonomous aldosterone secretion without such criteria led to a diagnosis of idiopathic hyperaldosteronism (IHA). A total of 1,180 patients (age 46 +/- 12 years) were enrolled; a conclusive diagnosis was attained in 1,125 (95.3%). Of these, 54 (4.8%) had an APA and 72 (6.4%) had an IHA. There were more APA (62.5%) and fewer IHA cases (37.5%) at centers where AVS was available (p = 0.002); the opposite occurred where AVS was unavailable. In newly diagnosed hypertensive patients referred to hypertension centers, the prevalence of APA is high (4.8%). The availability of AVS is essential for an accurate identification of the adrenocortical pathologies underlying PA.

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Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan.

Jun-ichi Saito, Masao Omura, Y Kakuta … (2004)

Secondary hypertension (SH) including endocrine hypertension has been reported to be uncommon. We estimated the prevalence of SH among hypertensive patients. We prospectively studied 1,020 hypertensive patients. As an initial screening, we measured plasma aldosterone concentration, plasma renin activity, serum cortisol concentration and plasma catecholamine concentration and conducted abdominal ultrasonography (US). As a secondary screening, we performed furosemide plus upright test, captopril renography, dexamethasone suppression test, 24-h urine catecholamine measurement and abdominal CT. Finally, primary aldosteronism with the exception of idiopathic hyperaldosteronism, pheochromocytoma, and Cushing's syndrome were diagnosed by histopathological examination of surgical specimens. Idiopathic hyperaldosteronism was clinically diagnosed by adrenocorticotrophic hormone (ACTH)-stimulated adrenal venous sampling and renovascular hypertension by renal arteriography. There were 61 patients with primary aldosteronism, 5 with renovascular hypertension, 11 with Cushing's syndrome, 10 with preclinical Cushing's syndrome and 6 with pheochromocytoma, and the prevalence of SH was 9.1% among 1,020 hypertensive patients. In 76 (82%) of 93 patients with SH, hypertension was cured or improved after unilateral adrenalectomy, transsphenoidal pituitary adenectomy or percutaneous transluminal angioplasty. With the exception of US and CT, all initial and secondary screening tests were found to be sensitive and specific for differentiating SH from essential hypertension (EH). In conclusion, the measurement of various hormone concentrations was very sensitive for ruling out SH--a condition for which, in the present study, there were few specific signs or symptoms--while CT and US examinations were not always useful for differentiating SH from EH. The prevalence of curable SH among hypertensive subjects was higher in this study, which was conducted by our simple method of screening tests, than in previous reports. Hypertensive patients should be screened for SH and the underlying disease treated appropriately to avoid long-term use of antihypertensive drugs and risks of atherosclerotic complications.

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Long-term renal outcomes in patients with primary aldosteronism.

Leonardo A Sechi, Marileda Novello, Roberta Lapenna … (2006)

Experimental animal studies indicate that exposure to increased aldosterone levels might result in renal damage, but the clinical evidence supporting this role of aldosterone is preliminary. To determine the long-term outcome of renal function in patients with primary aldosteronism after surgical or medical treatment. Prospective study conducted at an Italian university medical center among a consecutive sample of 50 patients who were diagnosed as having primary aldosteronism between January 1994 and December 2001 and who were followed up for a mean of 6.4 years after treatment with adrenalectomy or spironolactone. Patients with primary aldosteronism were compared with 100 patients with essential hypertension, matched for severity and duration of hypertension. All patients were treated with antihypertensive drugs to reach a target blood pressure of less than 140/90 mm Hg. Primary outcome measures were rates of change of glomerular filtration rate and albuminuria during follow-up. Detection of new-onset microalbuminuria and restoration of normal albumin excretion during follow-up were considered as secondary outcomes. At baseline, glomerular filtration rate and albuminuria were higher in patients with primary aldosteronism than those with essential hypertension. The mean blood pressure during the study was 136/81 mm Hg in the primary aldosteronism group and 137/81 mm Hg in the essential hypertension group. Glomerular filtration rate and albuminuria declined during the initial 6-month period in both groups, with a change that was significantly greater (P<.001 for both variables) in patients with primary aldosteronism. Subsequent rate of decline of glomerular filtration was comparable in the 2 groups, whereas albuminuria did not progress in the remainder of the follow-up. Restoration of normal albumin excretion from microalbuminuria was significantly more frequent in primary aldosteronism than in essential hypertension (P = .02). In the majority of patients in this study, primary aldosteronism was characterized by partially reversible renal dysfunction in which elevated albuminuria is a marker of a dynamic rather than structural renal defect.

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Author and article information

Journal

Journal ID (nlm-ta): Endocr Connect

Journal ID (iso-abbrev): Endocr Connect

Journal ID (publisher-id): EC

Title: Endocrine Connections

Publisher: Bioscientifica Ltd (Bristol )

ISSN (Electronic): 2049-3614

Publication date (Electronic): 19 September 2014

Publication date Collection: 01 December 2014

Volume: 3

Issue: 4

Pages: 173-179

Affiliations

[1 ]Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine , 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

Author notes

Correspondence should be addressed to M Sone Email: sonemasa@ 123456kuhp.kyoto-u.ac.jp

Article

Publisher ID: EC140086

DOI: 10.1530/EC-14-0086

PMC ID: 4168680

PubMed ID: 25239966

SO-VID: 7199bee1-b4ca-46a7-9e1a-f366c22d68ba

License:

This work is licensed under a Creative Commons Attribution 3.0 Unported License

History

Date received : 11 August 2014

Date accepted : 10 September 2014

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