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Influence of antihypertensive drugs in the subtype diagnosis of primary aldosteronism by adrenal venous sampling

Nagasawa, Motonoria,*; Yamamoto, Koichia,*; Rakugi, Hiromia; Takeda, Masaoa; Akasaka, Hiroshia; Umakoshi, Hironobub; Tsuiki, Mikab; Takeda, Yoshiyuc; Kurihara, Isaod; Itoh, Hiroshid; Ichijo, Takamasae; Katabami, Takuyukif; Wada, Noriog; Shibayama, Yuig; Yoshimoto, Takanobuh; Ogawa, Yoshihiroh; Kawashima, Junjii; Sone, Masakatsuj; Inagaki, Nobuyaj; Takahashi, Katsutoshik,l; Fujita, Megumim; Watanabe, Minemorin; Matsuda, Yuichio; Kobayashi, Hirokip; Shibata, Hirotakaq; Kamemura, Koheir; Otsuki, Michios; Fujii, Yuichit; Ogo, Atsushiu; Okamura, Shintarov; Miyauchi, Shozow; Yanase, Toshihikox; Suzuki, Tomokoy; Kawamura, Takashiz; Naruse, Mitsuhideb JPAS Study Group

doi: 10.1097/HJH.0000000000002047
ORIGINAL PAPERS: Secondary hypertension

Objectives: Because of the influence on the renin–angiotensin–aldosterone system, it is recommended to avoid, if possible, the use of angiotensin-converting-enzyme inhibitors, angiotensin II type 1 receptor blockers, diuretics, β-blockers, and mineralocorticoid receptor antagonists during the diagnostic period of primary aldosteronism. A laterality index more than 4 in adrenocorticotropic hormone (ACTH)-stimulated adrenal venous sampling (ACTH-AVS) is a widely used classification of the unilateral subtype that can benefit from adrenalectomy. Here, we revealed clinical features of patients taking drugs that could affect the primary aldosteronism diagnosis (DAPD) and investigated whether the classification with laterality index more than 4 in ACTH-AVS is applicable to these patients.

Patients and methods: Using a large database of primary aldosteronism patients in Japan, we analyzed 2122 patients with successful ACTH-AVS.

Results: Patients who received any DAPD (n = 209) showed higher prevalence of comorbidity burdens and took more antihypertensive drugs compared with patients without DAPD. In patients taking DAPD, those with laterality index more than 4 had a higher prevalence of hypokalemia, a higher aldosterone-to-renin ratio and a higher prevalence of adrenal mass than those with laterality index of 4 or less. Adrenalectomy was performed in 76% patients with laterality index more than 4 and 20% with laterality index of 4 or less. Patients who underwent adrenalectomy showed biochemical cure in 89% with laterality index more than 4 and 50% with laterality index of 4 or less (P = 0.001). Multivariate regression analysis showed that laterality index more than 4 was an independent predictor of a biochemical cure. Biochemical cure rate in patients with laterality index more than 4 was consistently high, irrespective of the potential effect of individual DAPD on laterality index.

Conclusion: Our findings suggest that in primary aldosteronism patients to whom DAPD were administrated due to severe clinical features, laterality index more than 4 in ACTH-AVS could accurately predict a biochemical cure after adrenalectomy.

aDepartment of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka

bDepartment of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto

cDepartment of Internal Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa

dDepartment of Endocrinology, Metabolism and Nephrology, School of Medicine Keio University, Tokyo

eDepartment of Endocrinology and Metabolism, Saiseikai Yokohamashi Tobu Hospital, Yokohama

fDivision of Metabolism and Endocrinology, Department of Internal Medicine, St. Marianna University School of Medicine Yokohama City Seibu Hospital, Yokohama

gDepartment of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo

hDepartment of Molecular Endocrinology and Metabolism, Tokyo Medical and Dental University, Tokyo

iDepartment of Metabolic Medicine, Faculty of Life Science, Kumamoto University, Kumamoto University, Kumamoto

jDepartment of Diabetes, Endocrinology and Nutrition Kyoto University, Kyoto

kDivision of Nephrology and Endocrinology, University of Tokyo School of Medicine

lDivision of Metabolism, Showa General Hospital

mDivision of Nephrology and Endocrinology, University of Tokyo, Tokyo

nDepartment of Endocrinology and Diabetes, Okazaki City Hospital, Okazaki

oDepartment of Cardiology, Sanda City Hospital, Sanda

pDivision of Nephrology, Hypertension and Endocrinology, Nihon University School of Medicine, Tokyo

qDepartment of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu

rDepartment of Cardiology, Akashi Medical Center, Akashi

sDepartment of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka

tDepartment of Cardiology, JR Hiroshima Hospital, Hiroshima

uClinical Research Institute, National Hospital Organization Kyusyu Medical Center, Fukuoka

vDepartment of Endocrinology, Tenriyorozu Hospital, Nara

wDepartment of Internal Medicine, Uwajima City Hospital, Uwajima

xDepartment of Endocrinology and Diabetes Mellitus, Faculty of Medicine, Fukuoka University, Fukuoka

yDepartment of Public Health, School of Medicine, International University of Health and Welfare, Narita

zKyoto University Health Service, Kyoto, Japan

Correspondence to Koichi Yamamoto, MD, PhD, Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. E-mail:

Abbreviations: ACE, angiotensin-converting-enzyme; ACTH, adrenocorticotropic hormone; APA, aldosterone-producing adenoma; ARB, angiotensin II type 1 receptor blocker; ARC, plasma active renin concentration; ARR, aldosterone-to-renin ratio; AVS, adrenal venous sampling; BP, blood pressure; CCB, calcium channel blocker; CT, computed tomography; DAPD, drugs that could affect the primary aldosteronism diagnosis; MRA, mineralocorticoid receptor antagonist; PAC, plasma aldosterone concentration; PRA, plasma renin activity

Received 4 October, 2018

Revised 5 December, 2018

Accepted 18 December, 2018

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