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Mineralocorticoid receptor (MR) blockers are very beneficial for patients with hypertension and primary aldosteronism (PA). We investigated the efficacy and safety of a newly available nonsteroidal MR blocker, esaxerenone, in Japanese patients with hypertension and PA. A multicenter, open-label study was conducted in Japan between October 2016 and July 2017. Patients with hypertension and PA received 12 weeks of treatment with esaxerenone, initiated at 2.5 mg/day and escalated to 5 mg/day during week 2 or 4 of treatment, based on individual response. The only other permitted antihypertensive therapies were stable dosages of a Ca 2+ channel blocker or α-blocker. The primary efficacy outcome was a change in sitting systolic and diastolic blood pressure (SBP/DBP) from baseline to the end of treatment. Forty-four patients were included; dose escalation to 5 mg/day was implemented for 41 of these patients. Significant decreases in SBP and DBP were observed (point estimates [95% confidence interval] -17.7 [-20.6, -14.7] and -9.5 [-11.7, -7.3] mmHg, respectively; both p < 0.0001 at the end of treatment). Significant BP reductions were evident from week 2 and continued through to week 8; BP remained stable until week 12. The antihypertensive effect of esaxerenone on SBP was significantly greater in females and in patients receiving monotherapy. The major drug-related adverse events were serum K + increase and estimated glomerular filtration rate decrease (both 4.5%, n = 2); no gynecomastia or breast pain was observed. We conclude that esaxerenone is a potent MR blocker with favorable efficacy and safety profiles in patients with hypertension and PA.

Patients with poorly controlled hypertension despite taking at least three different kinds of anti-hypertensive drugs, including diuretics, are considered to have resistant hypertension (RH). The prevalence of RH was reported to be 13% in the Japanese J-HOME study. The incidences of RH in younger and older Japanese individuals should be prospectively investigated in the near future. RH is associated with poor outcomes and various cardiovascular events. In addition, it is frequently associated with older age, obesity, sleep apnea, long-term hypertension, diabetes, dyslipidemia, reduced renal function, microalbuminuria and left ventricular hypertrophy. Some cases of RH exhibit high levels of aldosterone and cortisol, suggesting that endocrine hypertension should be ruled out among RH patients. Carotid baroreceptor activation and renal sympathetic denervation have recently been developed as treatments for RH. In conclusion, we should consider the possibility of RH during the treatment of hypertensive patients who do not achieve appropriate blood pressure control, in order to avoid the early onset of fatal cardiovascular events and reduce medical costs.

Primary aldosteronism (PA) due to aldosterone-producing adenoma (APA) is a form of surgically curable secondary hypertension, and distinguishing APA from idiopathic hyperaldosteronism (IHA) is important for treatment. We made a differential diagnosis between APA and IHA using imaging tests such as adrenal CT and MRI as well as adrenal venous sampling (AVS) in all 93 cases of PA presenting at our institutions over the last decade. We identified 27 patients with aldosterone-producing microadenoma (APmicroA), all of whom could be diagnosed by AVS but not by the imaging tests. Then, we compared the clinical and roent-genological findings of these 27 patients with those of 42 patients with aldosterone-producing macroadenoma (APmacroA) and of 24 patients with IHA. Using surgically removed adrenal tissues, histopathological examinations and immunohistochemical analyses of steroidogenic enzymes were conducted. The findings for APmicroA were similar to those for APmacroA, except with respect to the diameter of the adrenal adenomas. Endocrinological and roentgenological findings for APmicroA were similar to those for IHA, but not to those for APmacroA. The rate of cure of hypertension was much greater in patients with APmicroA than in patients with APmacroA after the unilateral adrenalectomy (odds ratio, 4.0; p=0.028). In conclusion, it is important to accurately diagnose APmicroA, in which the laterality of the hyperproduction of aldosterone is only detectable by AVS, and to treat these patients by unilateral adrenalectomy in order to avoid long-term medical treatment and prevent hypertensive vascular complications.

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.