New-onset diabetes mellitus risk associated with concurrent autonomous cortisol secretion in patients with primary aldosteronism.

Concurrent autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA patients) is not uncommon. This work aimed to determine the effect of cortisol levels on incident new-onset type 2 diabetes mellitus (NODM) in PA patients. Using the prospectively designed observational TAIPAI cohort, the PA patients were grouped by cortisol level after an overnight low-dose dexamethasone suppression test (1-mg DST). Of the 476 PA patients, 387 (43.7% men; mean age 52.8 years) did not have baseline DM. After a mean follow-up of 4.3 ± 2.9 years, 32 patients (8.3%) developed NODM. The cutoff value obtained via a generalized additive model showed that a serum cortisol level ≥ 2.65 µg/dL after 1-mg DST was a risk factor for developing NODM (HR, 3.5, p = 0.031) by Cox proportional- hazards model.. In PA patients with a higher body mass index (>25 kg/m2; HR, 3.16), lower estimated glomerular filtration rate (<90 ml/min/1.73 m2; HR, 3.18), longer hypertension duration (>7 years; HR, 3.34), and higher waist-to-hip ratio (>0.9; HR, 3.07), a concomitant cortisol level ≥ 2.65 µg/dL after 1-mg DST were more likely to develop NODM. The high-cortisol group of patients with aldosterone-producing adenoma (APA) using mineralocorticoid receptor antagonist (MRA) was associated with an increased risk of NODM (HR, 5.72). Our results showed that PA patients with a concomitant cortisol level ≥ 2.65 µg/dL after 1-mg DST, independent of the aldosterone level, had a higher incidence of NODM. Such PA patients should be carefully evaluated and managed to achieve better glucose control and prevent metabolic syndrome.

Urinary sodium potassium ratio is associated with clinical success after adrenalectomy in patients with unilateral primary aldosteronism.

BACKGROUND: The urinary sodium potassium (NaK) ratio is associated with dietary sodium and potassium intake and blood pressure, and it also reflects the activity of aldosterone. Herein we evaluated the value of the urinary NaK ratio in predicting the surgical outcomes of patients with unilateral primary aldosteronism (uPA). METHODS: This non-concurrent prospective cohort study was conducted from 2011 to 2017 and included 241 uPA patients who had undergone adrenalectomy. Predictors of successful clinical outcomes were analyzed using logistic regression. RESULTS: Among the 241 uPA patients, 197 (81.7%) achieved clinical complete or partial success. A urinary sodium potassium ratio <3 (odds ratio (OR): 2.5; 95% confidence interval (CI): 1.2-5.4; p = 0.015), body mass index <25 kg/m2 (OR: 2.82; 95% CI: 1.31-6.06; p = 0.008), renin <1 ng/mL/h (OR: 2.51; 95% CI: 1.01-6.21; p = 0.047) and mean preoperative blood pressure >115 mmHg (OR: 5.02; 95% CI: 2.10-11.97; p < 0.001) could predict clinical success after adrenalectomy. Furthermore, higher pre-treatment plasma aldosterone (OR: 1.014; 95% CI 1.005-1.024; p = 0.002) or lower serum potassium (OR: 0.523; 95% CI: 0.328-0.836; p = 0.007) were correlated with lower urinary NaK ratio (<3), and log urinary NaK ratio was positively correlated with serum C-reactive protein (ß value 2.326; 95% CI 0.029-4.623; p = 0.047). CONCLUSIONS: uPA patients with a lower urinary NaK ratio, due to high plasma aldosterone and low serum potassium concentrations, were more likely to have clinical success after adrenalectomy. uPA patients with a higher urinary NaK ratio were associated with more severe inflammatory status, and possibly more resistant hypertension post-operatively.

Risk of Fracture in Primary Aldosteronism: A Population-Based Cohort Study.

Primary aldosteronism (PA) is associated with increased urinary calcium excretion and osteoporosis prevalence. We studied the long-term effect of hyperaldosterone on fracture risk and possible risk mitigation via treatments, by comparing PA patients and their essential hypertension (EH) counterparts extracted by propensity score match. We used a longitudinal population database from the Taiwan National Health Insurance, and used a validated algorithm to identify PA patients diagnosed in 1997-2010. Our sample included 2533 PA patients, including 921 patients with aldosterone-producing adenoma (APA). Our methods for assessing excessive fracture risk included multivariable Cox regression and the competing risk regression. The incidence rate of fracture at any site was 14.4 per 1000 person-years for PA, and 11.2 per 1000 person-years for APA. In contrast, the incidence rate of fracture at any site was 8.3 per 1000 person-years in EH controls for PA, and 6.5 per 1000 person-years in EH controls for APA. Mineralocorticoid receptor antagonist (MRA) treatment might be associated with higher risk of osteoporotic fracture in the whole female PA cohort (subdistribution hazard ratio [SHR] = 2.12, p = 0.008) as well as female APA patients (SHR = 1.15, p = 0.049). As to fracture at any site, MRA treatment was also associated with higher risk; the SHR was 1.88 (p < 0.001) in the whole female PA cohort, and 2.17 (p = 0.019) in female APA patients. PA is tightly associated with higher risk of bone fracture, even in the case where the competing risk of death was controlled. Particularly, female PA patients treated with MRA were confronted with significantly higher risk in bone fracture than their EH controls. © 2017 American Society for Bone and Mineral Research.

Circulating tissue inhibitor of matrix metalloproteinase-1 is associated with aldosterone-induced diastolic dysfunction.

OBJECTIVE: To test if collagen markers are associated with aldosterone-induced diastolic dysfunction. BACKGROUND: Although primary aldosteronism is associated with more prominent cardiac remodeling and diastolic dysfunction, the reversibility of diastolic function is unclear. In addition, there is no known biomarker associated with aldosterone-induced diastolic dysfunction. METHODS: We enrolled 27 patients with aldosterone-producing adenoma (APA) preparing for adrenalectomy, and 27 patients with essential hypertension prospectively from October 2006 to March 2010 at a tertiary referral center. Plasma matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured, and echocardiography including tissue Doppler images was performed in both groups and 1 year after receiving adrenalectomy in the APA group. RESULTS: The baseline plasma TIMP-1 level (88.4 ±â€Š38.7 vs. 63.6 ±â€Š32.5 ng/ml; P = 0.014), left ventricular mass index (LVMI), and E/E' ratio (11.5 ±â€Š2.9 vs. 9.0 ±â€Š2.1; P < 0.001) were significantly higher in the APA group. The baseline plasma TIMP-1 level significantly correlated with the E/E' ratio, LVMI, interventricular septum, and left atrial diameter. The plasma MMP-2 level did not correlate with the left ventricular structure parameters, except for interventricular septum thickness. After adrenalectomy, LVMI and E/E' ratio improved significantly. The postadrenalectomy plasma TIMP-1 levels, but not MMP-2 levels, also decreased. The change of plasma TIMP-1 levels was negatively associated with the postadrenalectomy E/E' ratio after adjustment for age, sex, BMI, and mean blood pressure (ß-coefficient = - 3.6, P = 0.004). CONCLUSION: Excess of aldosterone induces cardiac diastolic dysfunction, which is reversible by adrenalectomy. TIMP-1 is associated with the aldosterone-induced diastolic dysfunction.

Administrative data on diagnosis and mineralocorticoid receptor antagonist prescription identified patients with primary aldosteronism in Taiwan.

OBJECTIVES: To develop algorithms of locating patients with primary aldosteronism (PA) using insurance reimbursement data and to validate the algorithms using medical charts. STUDY DESIGN AND SETTING: We extracted National Health Insurance (NHI) reimbursement data and medical charts in seven enrolled hospitals and analyzed diagnosis-related information for 1999-2010. The NHI codes PA as 255.1x, using the International Classification of Diseases, Ninth Revision, Clinical Modification. Confirmation of PA was based on suppression tests. RESULTS: We reviewed medical charts for 1,094 cases with at least one PA diagnosis. PA was confirmed for 563 cases. Compared with patients with essential hypertension, PA patients had higher systolic blood pressure, higher aldosterone, lower renin activity, and lower potassium level (all P-values <0.05). An algorithm based on PA diagnosis reported in at least one hospital stay or three outpatient visits had modest performance (sensitivity = 0.94 and specificity = 0.20). The best additional condition for the algorithm was use of mineralocorticoid receptor antagonist (MRA; sensitivity = 0.89 and specificity = 0.88). CONCLUSION: Using information on PA diagnosis and MRA prescription reported in insurance claims data can precisely locate PA patients in high-risk groups. This algorithm can construct a reliable PA sample for conducting research in various fields, including epidemiology and clinical practice.