High Prevalence of Diabetes in Patients With Primary Aldosteronism (PA) Associated With Subclinical Hypercortisolism and Prediabetes More Prevalent in Bilateral Than Unilateral PA: A Large, Multicenter Cohort Study in Japan

Akehi, Yuko; Yanase, Toshihiko; Motonaga, Ryoko; Umakoshi, Hironobu; Tsuiki, Mika; Takeda, Yoshiyu; Yoneda, Takashi; Kurihara, Isao; Itoh, Hiroshi; Katabami, Takuyuki; Ichijo, Takamasa; Wada, Norio; Shibayama, Yuki; Yoshimoto, Takanobu; Ashida, Kenji; Ogawa, Yoshihiro; Kawashima, Junji; Sone, Masakatsu; Inagaki, Nobuya; Takahashi, K.; Fujita, Megumi; Watanabe, Minemori; Matsuda, Yuichi; Kobayashi, Hiroki; Shibata, Hirotaka; Kamemura, Kohei; Otsuki, Michio; Fujii, Yukihiko; Yamamoto, Kōichi; Ogo, Atsushi; Okamura, Shintaro; Miyauchi, Shozo; Fukuoka, Tatsunari; Izawa, Shoichiro; Hashimoto, Shigeatsu; Yamada, Masanobu; Yoshikawa, Yuichiro; Kai, Tatsuya; Suzuki, Tomoko; Kawamura, Takashi; Naruse, Mitsuhide

doi:10.2337/dc18-1293

Cited by 84 publications

(72 citation statements)

References 36 publications

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“…One further mechanism underlying the impairment in glucose metabolism in PA is glucocorticoid co-secretion. Although recent studies showed that higher prevalence of DM in PA patients might be associated mainly with SH [27,28], our result showed PA patients without SH, and thus with aldosterone excess alone, had a higher prevalence of DM than do sex-, age-, and BMI-matched controls. Interestingly, the DM prevalence and FPG levels were significantly decreased after ADX in PA patients without SH.…”

Section: Discussioncontrasting

confidence: 99%

“…Third, findings regarding parameters to assess glucose metabolism in PA were not fully consistent [16,[21][22][23][24][25][26]. Fourth, recent studies showed that possible cortisol co-secretion rather than only aldosterone excess itself could contribute to the impairment of glucose metabolism in patients with PA [27,28]. Finally, comparisons of the effects of adrenalectomy (ADX) and mineralocorticoid receptor antagonist (MRA) therapy on glucose metabolism in PA have only sparsely been studied.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Primary Aldosteronism and Different Therapeutic Modalities on Glucose Metabolism

Kwak

Lee

Kim

et al. 2019

JCM

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Despite findings that aldosterone impairs glucose metabolism, studies concerning the effect of primary aldosteronism (PA) and its treatment on glucose metabolism are controversial. We aimed to determine glucose metabolism in PA and the effect of the treatment modality. We compared glucose metabolism between PA patients (N = 286) and age-, sex-, and body mass index-matched controls (N = 816), and the changes in glucose metabolism depending on the treatment modality (adrenalectomy vs. spironolactone treatment). Hyperglycemia including diabetes mellitus (DM; 19.6% vs. 13.1%, p = 0.011) was more frequent in PA patients. Hyperglycemia was also more frequent in PA patients without subclinical hypercortisolism (SH: p < 0.001) and in those regardless of hypokalemia (p < 0.001-0.001). PA patients and PA patients without SH had higher DM risk (odds ratio (OR); 95% confidence interval (CI): 1.63; 1.11-2.39 and 1.65; 1.08-2.51, respectively) after adjusting confounders. In PA patients, there was significant decrease in the DM prevalence (21.3% to 16.7%, p = 0.004) and fasting plasma glucose (p = 0.006) after adrenalectomy. However, there was no significant change in them after spironolactone treatment. Adrenalectomy was associated with more improved glucose status than spironolactone treatment (OR; 95% CI: 2.07; 1.10-3.90). Glucose metabolism was impaired in PA, regardless of hypokalemia and SH status, and was improved by adrenalectomy, but not spironolactone treatment.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Primary Aldosteronism and Different Therapeutic Modalities on Glucose Metabolism

Kwak

Lee

Kim

et al. 2019

JCM

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“…The proportions of DM patients in the PA and SCS groups increased, which resulted to nullify a statistically significant difference in the proportion of DM patients between the 2 study groups. The fact that the risk for DM is increased in PA patients with mild glucocorticoid excess has been reported [30][31][32]; the finding was also described in Japanese patients with PA and patients with PASCS [33].…”

Section: Discussionmentioning

confidence: 71%

Clinical characterization of patients with primary aldosteronism plus subclinical Cushing’s syndrome

Yasuda¹,

Hikima²,

Kabeya³

et al. 2020

BMC Endocr Disord

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Background: Primary aldosteronism (PA) plus subclinical Cushing's syndrome (SCS), PASCS, has occasionally been reported. We aimed to clinically characterize patients with PASCS who are poorly profiled. Methods: A population-based, retrospective, single-center, observational study was conducted in 71 patients (age, 58.2 ± 11.2 years; 24 males and 47 females) who developed PA (n = 45), SCS (n = 12), or PASCS (n = 14). The main outcome measures were the proportion of patients with diabetes mellitus (DM), serum potassium concentration, and maximum tumor diameter (MTD) on the computed tomography (CT) scans. Results: The proportion of DM patients was significantly greater in the PASCS group than in the PA group (50.0% vs. 13.9%, p < 0.05), without a significant difference between the PASCS and SCS groups. Serum potassium concentration was significantly lower in the PASCS group than in the SCS group (3.2 ± 0.8 mEq/L vs. 4.0 ± 0.5 mEq/L; p < 0.01), without a significant difference between the PASCS and PA groups. Among the 3 study groups of patients who had a unilateral adrenal tumor, MTD was significantly greater in the PASCS group than in the PA group (2.7 ± 0.1 cm vs. 1.4 ± 0.1 cm; p < 0.001), without a significant difference between the PASCS and SCS groups. Conclusions: Any reference criteria were not obtained that surely distinguish patients with PASCS from those with PA or SCS. However, clinicians should suspect the presence of concurrent SCS in patients with PA when detecting a relatively large adrenal tumor on the CT scans.

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“…Using data from a nationwide PA registry (the Japan Primary Aldosteronism Study [JPAS] and Japan Rare/Intractable Adrenal Diseases Study [JRAS]), 7,10,11 we assessed whether changes in circulating aldosterone levels and BP were associated with changes in eGFR after surgical or MR antagonist treatment, respectively.…”

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Associations Between Changes in Plasma Renin Activity and Aldosterone Concentrations and Changes in Kidney Function After Treatment for Primary Aldosteronism

Kobayashi

Haze

Yano

et al. 2020

Kidney International Reports

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Introduction: Greater reduction in estimated glomerular filtration rate (eGFR) after specific treatment for primary aldosteronism (PA) reflects improvement in glomerular hyperfiltration associated with PA and leads to better patient outcomes. However, little is known regarding the mechanisms underlying eGFR reduction after treatment for PA. Methods: We analyzed data from the nationwide PA registry in Japan. Patients were assigned to adrenalectomy (n ¼ 438) and mineralocorticoid receptor (MR) antagonist (n ¼ 746) groups. We assessed associations between changes in blood pressure (BP), plasma renin activity (PRA) and plasma aldosterone concentrations (PAC), and eGFR before and 6 months after treatment for both groups. Results: In a multivariable linear regression, the adjusted b values (95% confidence interval [CI]) for change in eGFR after treatment were À2.76 (À4.29, À1.22) ml/min per 1.73 m 2 for PRA (per 3.2 ng/ml per hour), and 1.97 (1.08, 2.85) ml/min per 1.73 m 2 for PAC (per 236.1 pg/ml) in the adrenalectomy group; and À0.45 (À0.89, À0.01) ml/min per 1.73 m 2 for PRA and À0.72 (À1.62, 0.18) ml/min per 1.73 m 2 for PAC in the MR antagonist group. Change in mean arterial pressure after treatment was not significantly associated with change in eGFR in either group. Changes in PRA and PAC but not BP before and 6 months after treatment for PA were associated with greater reductions in eGFR. Conclusion: Post-treatment improvements in glomerular hyperfiltration may be attributable to decreased MR activity in the kidneys, but not to reductions in systemic BP.

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High Prevalence of Diabetes in Patients With Primary Aldosteronism (PA) Associated With Subclinical Hypercortisolism and Prediabetes More Prevalent in Bilateral Than Unilateral PA: A Large, Multicenter Cohort Study in Japan

Cited by 84 publications

References 36 publications

Effects of Primary Aldosteronism and Different Therapeutic Modalities on Glucose Metabolism

Effects of Primary Aldosteronism and Different Therapeutic Modalities on Glucose Metabolism

Clinical characterization of patients with primary aldosteronism plus subclinical Cushing’s syndrome

Associations Between Changes in Plasma Renin Activity and Aldosterone Concentrations and Changes in Kidney Function After Treatment for Primary Aldosteronism

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