Association between urinary C-megalin levels and progressive kidney dysfunction: a cohort study based on the diabetes distress and care registry at Tenri (DDCRT 24).

AIMS: The aim of this cohort study was to evaluate the association between urinary levels of C-megalin, a full-length form of megalin, and kidney dysfunction progression and its dependence on the urinary albumin-creatinine ratio (UACR) in individuals with diabetes. METHODS: We enrolled 1,547 individuals with diabetes who visited the ambulatory clinic at Tenri Hospital, a regional tertiary-care hospital in Tenri City, Nara Prefecture, Japan, with an estimated glomerular filtration (eGFR) of ≥ 30 mL/min/1.73 m2. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox proportional hazard models to examine the association between urinary C-megalin levels and eGFR decline by ≥ 40% from baseline. RESULTS: Urinary C-megalin level was not associated with ≥ 40% eGFR decline in an age-, sex-, eGFR-, systolic blood pressure-, hemoglobin-, and UACR-adjusted model in the 1,547 patients enrolled in the study. However, urinary C-megalin levels were associated with a ≥ 40% decline in eGFR when accounting for the relationship between urinary C-megalin levels and UACR in the model. This association was UACR-dependent. CONCLUSIONS: High urinary C-megalin levels were associated with progressive kidney dysfunction in individuals with diabetes, and this association was attenuated by high UACRs.

Effect of Intraprocedural Cortisol Measurement on ACTH-stimulated Adrenal Vein Sampling in Primary Aldosteronism.

Context: Adrenocorticotropin (ACTH) loading is used to increase the success rate of adrenal vein sampling (AVS). Objective: We aimed to determine the effect of intraprocedural cortisol measurement (ICM) on ACTH-stimulated AVS (AS-AVS) owing to a lack of reliable data on this topic. Methods: This multicenter, retrospective, observational study took place in 28 tertiary centers in Japan. Among 4057 patients enrolled, 2396 received both basal AVS (B-AVS) and AS-AVS and were divided into 2 groups according to whether ICM was used. The effect of ICM on AS-AVS was measured. Results: In patients who underwent both AVS procedures, the ICM group had significantly higher success rates for both B-AVS and AS-AVS than the non-ICM group did. However, the probability of failure of AS-AVS after a successful B-AVS and the probability of success of AS-AVS after a failed B-AVS were not significantly different in the 2 groups. For subtype diagnosis, propensity-score matching revealed no significant difference between the 2 groups, and the discrepancy rate between B-AVS and AS-AVS for subtype diagnosis was also not significantly different. Conclusion: ICM significantly increased the success rate of B-AVS and AS-AVS in protocols in which both AVS procedures were performed and had no effect on subtype diagnosis. However, in protocols in which both AVS procedures were performed, the results suggest ICM may not be necessary when performing AS-AVS if ICM is used only when B-AVS is performed. Our study suggests that ICM during AVS plays an important role and should be recommended.

Production of insulin antibody associated with relapsed hodgkin's lymphoma.

A 72-year-old man with type 2 diabetes mellitus with good glucose control for 20 years and maintained on oral hypoglycaemic agents was diagnosed with Hodgkin's Lymphoma (HL) and started on insulin glargine for glycaemic control. Despite increased doses of insulin, his blood glucose levels went up dramatically. The anti-insulin antibody test proved to be positive, and Scatchard plot analysis showed 2 binding sites with relatively low-affinity constants: K 1 = 0.0032, K 2 = 0.0002 (108/M); and high binding capacities: R 1 = 98.4, R 2 = 372 (10-8 M), which were compatible with the features of antibody of insulin autoimmune syndrome (IAS). However, hypoglycaemia was not noted throughout the course of treatment. Since the insulin binding ratio of the antibody decreased from 87.3% to 62% after the termination of insulin treatment, it was suggested that the antibody reacted mainly to exogenously injected insulin. Switching insulin preparations or introducing insulin secretagogues did not improve elevated blood glucose levels. The initiation of brentuximab vedotin (BV), a therapeutic agent for relapsed HL, resulted in a remarkable improvement in glycaemic control despite the absence of insulin therapy and partial remission of HL. This case suggested that HL triggered anti-insulin antibody production, which resulted in poor glycaemic control, and that BV could be a new treatment option for autoimmune diseases associated with HL. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-021-00550-1.

Urinary C-megalin as a novel biomarker of progression to microalbuminuria: A cohort study based on the diabetes Distress and Care Registry at Tenri (DDCRT 22).

AIMS: Megalin is a multiligand receptor expressed in proximal tubular cells that reabsorbs filtered albumin and correlates cross-sectionally with albuminuria. We investigated the association between urinary C-megalin levels and the incidence of microalbuminuria in patients with diabetes mellitus. METHODS: This cohort study included 752 patients with type 1 or 2 diabetes mellitus and a urinary albumin-to-creatinine (Cr) ratio (UACR) within the normoalbuminuric range (<30 mg/g Cr). The association between urinary C-megalin and persistent microalbuminuria, accounting for the possible interaction between baseline UACR and urinary C-megalin, was estimated using a Cox proportional hazards model. RESULTS: During a median follow-up period of 1.99 years, 179 cases of persistent microalbuminuria were observed. The association between urinary C-megalin and persistent microalbuminuria was UACR-dependent (P for interaction < 0.001), with the highest association observed in the absence of UACR (per 100 fM/gCr of urinary C-megalin: adjusted hazard ratio, 1.13; 95% CI 1.07-1.19), gradually decreasing as UACR increased to 30 mg/g Cr. UACR dependence was confirmed by sensitivity analyses according to low-normal (<10 mg/gCr) or high-normal (10-<30 mg/gCr) UACR. CONCLUSIONS: Urinary C-megalin is associated with progression to microalbuminuria, especially in those with low-normal UACR levels, and its usefulness to identify high risk patients requires further investigation.

Sex Difference in the Association of Osteoporosis and Osteopenia Prevalence in Patients with Adrenal Adenoma and Different Degrees of Cortisol Excess.

Objective: Osteoporosis and osteopenia (OS/OP) are frequent in patients with adrenal adenomas associated with cortisol excess (CE). However, the relationship between OS/OP and CE severity considering sex differences is unknown. Design: A cross-sectional observational study from January 2006 to December 2015. Patients. 237 patients with adrenal adenoma associated with CE, including Cushing's syndrome and mild autonomous cortisol secretion (MACS), diagnosed in 10 referral centers in Japan. MACS was defined by 1 mg overnight dexamethasone suppression test (DST) cortisol level >1.8 µg/dL. Measurements. Prevalence of fragility fractures, medication for osteoporosis, and bone mineral density. Results: In total, 112 of 237 patients, who were predominantly female (P < 0.001) and had lower BMI (P=0.013), had OS/OP. Patients with OS/OP was significantly affected by CE (P < 0.01) than those without. The adjusted odds ratio (OR) for predicting OS/OP was obtained in multivariate logistic regression analysis. Clinical measures of CE, 1 mg DST cortisol levels, were positively associated with OS/OP in total cases (OR 1.124, 95% CI: 1.070-1.181, P < 0.001) and the cases with MACS (OR 1.156, 95%CI: 1.046-1.278, P=0.005). A cutoff value of 1 mg DST cortisol level >5.0 µg/dL was associated with OS/OP differently between men and women. OS/OP risk in men with MACS was significantly affected only by 1 mg DST cortisol levels. However, OS/OP risk in women with MACS was significantly affected by 1 mg DST cortisol levels and age. Conclusions: CE severity in adrenal adenoma is positively associated with OS/OP. However, the associated factors of OS/OP in the patients with MACS are different between men and women.

Association of urinary C-megalin with albuminuria and renal function in diabetes: a cross-sectional study (Diabetes Distress and Care Registry at Tenri [DDCRT 21]).

BACKGROUND: A urinary biomarker sensitive to glomerular functional or structural changes in diabetic kidney disease is required. This study examined whether urinary C-megalin reflects renal function or albuminuria in diabetes. METHODS: This was a cross-sectional study involving 1576 patients with type 1 or 2 diabetes. The exposure variables were estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR), and the outcomes were urinary C-megalin excretion and concentration. Two-part models were used to examine the associations between eGFR and UACR with urinary C-megalin excretion or concentration. RESULTS: The UACR was linearly associated with urinary C-megalin excretion (per 100 mg/gCr of UACR; 11.8 fM/gCr [95% CI 8.9-14.7]). There was no association between decreasing eGFR and increasing urinary C-megalin excretion. The UACR was also linearly associated with the urinary C-megalin concentration (per 100 mg/gCr of UACR, 7.7 fM/L [95% CI 5.8-9.6]). At eGFR values > 60 mL/min/1.73 m2, the eGFR and urinary C-megalin concentration were inversely linearly related (per 10 mL/min/1.73 m2 decline, 7.7 fM/L [95% CI 0.2-15.1]). CONCLUSION: Urinary C-megalin excretion as well as concentration levels are potentially useful biomarkers to detect early changes in diabetic kidney disease.

Association of achieved blood pressure after treatment for primary aldosteronism with long-term kidney function.

Little is known regarding the association of blood pressure (BP) after treatment for primary aldosteronism (PA) (i.e., adrenalectomy and mineralocorticoid receptor antagonists) with long-term renal outcomes, and whether the association is independent of BP before treatment. Using a dataset from a nationwide registry of PA in Japan, we assessed whether achieved BP levels 6 months after treatment for PA are associated with annual changes in estimated glomerular filtration rate (eGFR), rapid eGFR decline, and incident chronic kidney disease (CKD) during the 5-year follow-up period. The cohort included 1266 PA patients. In multivariable linear regression including systolic BP (SBP) levels before treatment for PA, estimates (95% confidence interval [CI]) for annual changes in eGFR after month 6 associated with one-standard deviation (1-SD) higher SBP at month 6 were -0.08 (-0.15, -0.02) mL/min/1.73 m2/year. After multivariable adjustment, the estimate (95% CI) for annual changes in eGFR after month 6 was -0.12 (-0.21, -0.02) for SBP ≥ 130 mmHg vs. SBP < 130 mmHg at month 6. Among 537 participants without CKD at baseline, a 1-SD higher SBP was associated with a higher risk for incident CKD events (hazard ratio [95% CI]: 1.40 [1.00, 1.94]). Higher SBP after treatment for PA was associated with a higher risk for kidney dysfunction over time, independently of BP levels before treatment. Achieving SBP lower than 130 mmHg after treatment for PA may be linked to better kidney outcomes.

Pheochromocytoma and paraganglioma with negative results for urinary metanephrines show higher risks for metastatic diseases.

PURPOSE: Few studies have assessed the clinical features of pheochromocytoma and paraganglioma (PPGL) not producing excessive catecholamine. We aimed to clarify the clinical characteristics of PPGL patients with negative results for urinary metanephrines. METHODS: This is a retrospective cross-sectional study. We established a database by combining datasets from the Nationwide Cohort Study on the Development of Diagnosis and Treatment of Pheochromocytoma in Japan (PHEO-J) and the Advancing Care and Pathogenesis of Intractable Adrenal diseases in Japan (ACPA-J). We compared the clinical differences between PPGL patients with negative results for urinary metanephrines and those with catecholamine-producing PPGL. RESULTS: Five hundred PPGL patients in the combined database were analyzed. Among them, 31 were negative for metanephrines. PPGL with negative results for urinary metanephrines was significantly associated with extra-adrenal disease (Odds ratio (OR) 6.58, 95% CI (confidence interval) 3.03-14.3, p < 0.001), the presence of metastatic disease (OR 4.22, 95% CI 1.58-11.3, p = 0.004), and negativity on meta-iodobenzylguanidine (MIBG) scintigraphy (OR 0.15, 95% CI 0.03-0.77, p = 0.023). CONCLUSIONS: Our findings demonstrate that PPGL patients with negative results for urinary metanephrines are associated with extra-adrenal lesions, metastatic disease, and negative MIBG findings. This suggests that PPGL patients with negative results for urinary metanephrines have a greater need for systemic whole-body imaging other than MIBG scintigraphy and close follow-up to monitor for metastasis than do patients with PPGL overtly producing excessive catecholamine.

Association of aldosterone and blood pressure with the risk for cardiovascular events after treatments in primary aldosteronism.

BACKGROUND AND AIMS: We used a dataset from a Japanese nationwide registry of patients with primary aldosteronism, to determine which of the parameters of hyperaldosteronism and blood pressure before or after treatments for primary aldosteronism (i.e., surgical adrenalectomy or a medication treatment) are important in terms of cardiovascular prognosis. METHODS: We assessed whether plasma aldosterone-to-renin ratio and pulse pressure levels before treatment and 6 months after treatment were associated with composite cardiovascular disease events during the 5-year follow-up period. RESULTS: The cohort included 1987 patients (mean age was 53.2 years, 52.0% were female, 37.2% had undergone surgical treatment, and the remainder had been treated with mineralocorticoid receptor antagonists). In the Cox proportional hazard model, the covariate-adjusted hazard ratio (95% confidence interval) for the composite cardiovascular disease events risk for each one-standard-deviation increase in the aldosterone-to-renin ratio or pulse pressure before treatment, those after treatment, or the duration of hypertension were 1.24 (1.05, 1.48), 0.74 (0.54, 1.02), and 1.07 (0.79, 1.44), 1.43 (1.07, 1.92), and 1.52 (1.19, 1.95), respectively. Patients with a high pre-treatment aldosterone-to-renin ratio of more than 603 and a large post-treatment pulse pressure of more than 49 mmHg showed approximately three-fold higher hazard ratios for cardiovascular events risk compared to those with a lower aldosterone-to-renin ratio and smaller pulse pressure. CONCLUSIONS: Higher aldosterone-to-renin ratio before treatments, higher pulse pressure after treatments, and longer duration of hypertension were prognostic factors for cardiovascular diseases. Early intervention may be important for preventing cardiovascular disease among patients with primary aldosteronism.

Age-stratified comparison of clinical outcomes between medical and surgical treatments in patients with unilateral primary aldosteronism.

Although adrenalectomy (ADX) is an established treatment for unilateral primary aldosteronism (uPA), the influence of age on the surgical outcomes is poorly understood. Therefore, we aimed to elucidate how age affects the clinical outcomes after treatments. We analyzed 153 older (≥ 65 years) and 702 younger patients (< 65 years) with uPA, treated either with ADX or mineralocorticoid receptor antagonist (MRA) in the Japan PA Study, and compared the estimated glomerular filtration rate (eGFR) or blood pressure over a 36-month period after treatments. ADX-treated patients showed severer biochemical indicators than MRA-treated patients. During 6 and 36 months, the eGFR decreased more prominently in older but not in younger patients with ADX than in those with MRA, which remained significant after adjustment with the inverse probability of treatment weighting (IPTW). There was a significant interaction between the age-groups and the treatment choices in the change of the eGFR with IPTW-adjusted analysis. The post-treatment dose of antihypertensive medication was lower in younger and higher in older patients with ADX than those with MRA. The clinical benefit of ADX differed between younger and older patients with uPA. These findings indicate the need for further validation on whether ADX can benefit older patients with uPA.

Diverse pathological lesions of primary aldosteronism and their clinical significance.

Primary aldosteronism (PA) is mainly clinically classified as unilateral aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism. Immunohistochemistry for aldosterone synthase reveals a diverse PA pathology, including pathological APA and aldosterone-producing cell clusters. The relationship between PA pathology and adrenalectomy outcomes was examined herein. Data from 219 unilaterally adrenalectomized PA cases were analyzed. Pathological analyses revealed diverse putative aldosterone-producing lesions. Postoperative biochemical outcomes in 114 cases (test cohort) were classified as complete success (n = 85), partial success (n = 19), and absent success (n = 10). Outcomes in the large and small PA lesion groups, rather than between PA lesion types, were compared at five threshold values for PA lesion sizes (2-6 mm with 1-mm increments) to streamline the results. The proportion of complete success was significantly higher in the large PA lesion group than in the small PA lesion group at the 5-mm threshold only. The proportion of absent success was significantly higher in the small PA lesion group than in the large PA lesion group at all thresholds. Univariate and multivariate analyses of the test cohort identified serum K as an independent predictive factor for the small PA lesion group, which was confirmed in the 105-case validation cohort. Chi-squared automatic interaction detector analysis revealed that the best threshold of serum K for predicting large PA lesions was 2.82 mEq/L. These results will be beneficial for treating PA in clinical settings because patients with low serum K levels and apparent adrenal masses on CT may be subjected to adrenalectomy even if the adrenal venous sampling test is unavailable.

Predictive Validity of Each Item of the 8-Item Short-Form Health Survey for All-Cause Mortality in Japanese patients with type 2 diabetes: A prospective Cohort Study (Diabetes Distress and Care Registry at Tenri [DDCRT 19]).

AIMS: While health-related quality of life (HRQOL) is reported to be associated with mortality, this assessment was made using surveys with a large number of questions, not specifically focused on populations with diabetes, or in western countries alone. We thus evaluated the predictive validity of summary scores, and each item score of the 8-Item Short-Form Health Survey in Japanese individuals with type-2 diabetes. MATERIALS AND METHODS: Longitudinal data from 3269 individuals with diabetes were obtained from a large Japanese diabetes registry. To assess the independent correlation between the 10-point scores of the SF-8 physical component summary (PCS) and mental component summary (MCS), each item score, and all-cause mortality, the Cox proportional hazards model was used with adjustment for potential confounders. RESULTS: Mean cohort parameters included age (64.9 years [SD 11.2]), body mass index (24.6 kg/m2 [SD, 3.9]), and HbA1c level (7.5% [SD, 1.2]; or 58.6 mmol/mol [SD, 12.7]). We recorded 248 deaths during the median follow-up of 7.2 years (incidence ratio, 12.2 per 1000 person-years). Multivariable-adjusted HRs for all-cause mortality were 0.780 (95%CI, 0.674-0.902; p=0.001) and 0.776 (95%CI, 0.656-0.917; p=0.003), respectively, for 10-point increment of PCS and MCS scores. Higher score of any single item of SF-8 was associated with lower risk of all-cause mortality even after adjusting for possible confounders. CONCLUSIONS: As assessed by the SF-8, higher PCS, MCS, and any single 1-item scores were associated with lower risk of all-cause mortality in Japanese individuals with type 2 diabetes.

The joint association of diabetes distress and depressive symptoms with all-cause mortality in Japanese individuals with type 2 diabetes: a prospective cohort study (Diabetes Distress and Care Registry in Tenri [DDCRT 20]).

AIMS/HYPOTHESIS: The independent association of depressive symptoms and diabetes distress with mortality risk in individuals with diabetes has not been evaluated. We examined the temporal joint association of diabetes distress and depressive symptoms at baseline and the subsequent risk of all-cause mortality. METHODS: The longitudinal data of 3118 individuals with type 2 diabetes were obtained from a large Japanese diabetes registry. To assess the joint association of diabetes distress and depressive symptoms at baseline with the subsequent risk of all-cause mortality, the Cox proportional hazards model was used with adjustment for potential confounders. RESULTS: The mean age, BMI and HbA1c levels were 64.7 years, 24.6 kg/m2 and 58.6 mmol/mol (7.5%), respectively, and 38.1% of the participants were women. In the multivariable-adjusted models evaluating the diabetes distress and depressive symptoms separately, the HRs for all-cause mortality were 1.67 (95% CI 1.14, 2.43; p = 0.008) and 1.40 (95% CI 1.05, 1.85; p = 0.020), respectively. In such models evaluating the joint association of diabetes distress and depressive symptoms, compared with individuals without diabetes distress or depressive symptoms (DD-/DS-), the HRs for all-cause mortality for the group without diabetes distress but with depressive symptoms (DD-/DS+), with diabetes distress but without depressive symptoms (DD+/DS-), and with diabetes distress and depressive symptoms (DD+/DS+) were 1.34 (95% CI 0.99, 1.86; p = 0.056), 1.96 (95% CI 1.10, 3.50; p = 0.023) and 1.71 (95% CI 1.06, 2.77; p = 0.029), respectively. We did not observe a significant interaction between diabetes distress and depressive symptoms with all-cause mortality risk (p = 0.2636). In the stratified analysis by sex, a significant joint association of diabetes distress and depressive symptoms with the risk of all-cause mortality was observed only in men. CONCLUSIONS/INTERPRETATION: Diabetes distress and depressive symptoms were independently associated with all-cause mortality risk in male participants with type 2 diabetes, but we did not observe a significant interaction between diabetes distress and depressive symptoms in relation to all-cause mortality. Graphical abstract.

Obesity predicts persistence of resistant hypertension after surgery in patients with primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) is considered a major cause of resistant hypertension (RHT). The prevalence of RHT has been recently reported to reach 18% in general hypertension. However, little is known about the prevalence and the outcomes after adrenalectomy of RHT in PA. Therefore, we aimed to clarify the prevalence and surgical outcomes in patients with both PA and RHT. PATIENTS AND DESIGN: Among 550 patients who underwent adrenalectomy for unilateral PA in the Japan PA Study, RHT was defined as an uncontrolled blood pressure (≥140/90 mm Hg) despite treatment with at least any three antihypertensives or hypertension controlled with at least four drugs. Surgical outcome was assessed by the biochemical and clinical outcome. RESULTS: Although 40 (7.3%) patients fulfilled the criteria for preoperative RHT, this should be underestimated because only 36% of patients with postoperative RHT were classified as having preoperative RHT. The prevalence of preoperative RHT was approximately 20% when estimated using the total number of patients with postoperative RHT and the ratio of postoperative RHT in patients with preoperative RHT. Although an improvement in hypertension was achieved in approximately 80% of patients with preoperative RHT, 20% of these exhibited persistent RHT. These patients were more obese than those for whom RHT improved after surgery. Notably, body mass index of ≥25 kg/m2 was an independent predictor of postoperative RHT. CONCLUSIONS: The prevalence of RHT in PA was lower than expected even with the adjustment for underestimation. Furthermore, obesity is an independent factor predicting the postoperative persistence of RHT.

Nadir Aldosterone Levels After Confirmatory Tests Are Correlated With Left Ventricular Hypertrophy in Primary Aldosteronism.

Left ventricular hypertrophy (LVH) is often seen in patients with primary aldosteronism (PA), and the prevalence of LVH is reportedly higher among patients with PA than patients with essential hypertension. However, the correlation between aldosterone levels and LVH is undefined, and how aldosterone affects LVH in patients with PA remains unclear. We, therefore, retrospectively assessed a large PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) to reveal the factors associated with LVH in patients with PA without suspected autonomous cortisol secretion. In the 1186 patients with PA studied, the basal plasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio did not significantly correlate with left ventricular LV mass index (LVMI) in single or multiple regression analyses. However, the plasma aldosterone concentration after the captopril challenge test or saline-infusion test, which are associated with autonomous aldosterone secretion, correlated significantly with LVMI, even after adjusting for patients' backgrounds, including age and blood pressure. In addition, hypokalemia and the unilateral subtype also correlated with LVMI. Longitudinal subanalysis of medically or surgically treated patients with PA showed significant reductions in LVMI in both the surgery (63.0±18.1 to 55.3±19.5 g/m2.7, P<0.001) and drug treatment (56.8±14.1 to 52.1±13.5 g/m2.7, P<0.001) groups. Our results suggest the autonomous aldosterone secretion level, not the basal aldosterone level itself, is relevant to LVH in patients with PA. In addition, the elevated LVMI seen in patients with PA is at least partially reversible with surgical or medical treatment.

Baseline Plasma Aldosterone Level and Renin Activity Allowing Omission of Confirmatory Testing in Primary Aldosteronism.

CONTEXT: Previous studies have proposed cutoff value of baseline plasma aldosterone concentration (bPAC) under renin suppression that could diagnose primary aldosteronism (PA) without confirmatory testing. However, those studies are limited by selection bias due to a small number of patients and a single-center study design. OBJECTIVE: This study aimed to determine cutoff value of bPAC and baseline plasma renin activity (bPRA) for predicting positive results in confirmatory tests for PA. DESIGN: The multi-institutional, retrospective, cohort study was conducted using the PA registry in Japan (JPAS/JRAS). We compared bPAC in patients with PA who showed positive and negative captopril challenge test (CCT) or saline infusion test (SIT) results. PATIENTS: Patients with PA who underwent CCT (n = 2256) and/or SIT (n = 1184) were studied. MAIN OUTCOME MEASURES: The main outcomes were cutoff value of bPAC (ng/dL) and bPRA (ng/mL/h) for predicting positive CCT and/or SIT results. RESULTS: In patients with renin suppression (bPRA ≤ 0.3), the cutoff value of bPAC that would give 100% specificity for predicting a positive SIT result was lower than that for predicting a positive CCT result (30.85 vs 56.35, respectively). Specificities of bPAC cutoff values ≥ 30.85 for predicting positive SIT and CCT results remained high (100.0% and 97.0%, respectively) in patients with bPRA ≤ 0.6. However, the specificities of bPAC cutoff values ≥ 30.85 for predicting positive SIT and CCT results decreased when patients with bPRA > 0.6 were included. CONCLUSION: Confirmatory testing could be omitted in patients with bPAC ≥ 30.85 in the presence of bPRA ≤ 0.6.

Historical changes and between-facility differences in adrenal venous sampling for primary aldosteronism in Japan.

Primary aldosteronism (PA) is a common curable cause of hypertension. Adrenal venous sampling (AVS) is recommended for subtype diagnosis but is a difficult procedure. Recently, an increased prevalence of PA was reported, creating a greater demand for treatment of the condition in clinical facilities. The aim of the present study was to identify the historical changes over time and the differences between facilities in the success rate and subtype diagnosis of PA. The database of the PA registry developed by the Japan PA Study (JPAS) was used. A total of 2599 patients with PA who underwent AVS were evaluated. The overall success rate of AVS was 88%. The bilateral subtype was the dominant subtype, comprising 69% of cases. During the period 2004-2011 to 2011-2017, there were significant changes in the total number of AVS procedures (from 562 to 1732), ratio of ACTH administration with AVS (75 to 97%), success rate (79 to 90%), and proportion with bilateral subtype diagnosis (53 to 72%). There were also significant inter-facility differences in the number of AVS procedures (6 to 322), success rate (59 to 97%), and proportion with the bilateral subtype (44 to 86%). The principal enrolled department was Endocrinology (86%), and the ratio of unilateral PA was significantly higher in this department than in others (32% vs. 25%). In conclusion, the number of AVS procedures performed, the success rate, and the proportion with the bilateral subtype increased over time after normalizing the centre difference. Significant differences were observed between the centres.

Lateralizing Asymmetry of Adrenal Imaging and Adrenal Vein Sampling in Patients With Primary Aldosteronism.

CONTEXT: In patients with primary aldosteronism (PA), it remains unclear whether aldosterone-producing adenomas are likely to develop in the left or right adrenal gland. OBJECTIVE: To investigate left-right differences of PA laterality diagnoses via CT imaging and adrenal vein sampling (AVS). DESIGN: Retrospective, observational study. PATIENTS: From the Japan Primary Aldosteronism Study, 1493 patients with PA were enrolled who underwent CT and ACTH-stimulated AVS. MEASUREMENTS: Left or right adrenal nodular lesion distribution and laterality observed on CT scans and from AVS were noted. RESULTS: Both on CT scans and AVS, unilateral results were observed more frequently on the left side than on the right side (25.1% vs 15.4% and 17.3% vs 13.5%, respectively; P < 0.01for both diagnostic techniques). There was no significant difference in the concordance rate for CT and AVS between patients with left and right unilateral nodular lesions observed on CT scans (44.1% and 50.9%, respectively; P = 0.15). In patients with nodules <20 mm, the concordance rate was significantly greater on the right side than the left side (45.8% vs 56.4%; P = 0.03). In patients with bilateral results of AVS, unilateral nodular lesions were detected more frequently on the left side than the right side (17.8% vs 9.4%; P < 0.01). CONCLUSION: These results suggest aldosterone-producing adenomas and nonfunctioning tumors are more likely to develop on the left side in patients with PA and that misdiagnosis of CT-based lateralization may occur more frequently on the left side.

Renal impairment is closely associated with plasma aldosterone concentration in patients with primary aldosteronism.

OBJECTIVE: Several clinical studies have reported that renal impairments are sometimes observed in patients with primary aldosteronism (PA). We analyzed the prevalence of renal impairments in PA patients and identified parameters that increase the risk for them. DESIGN: This is a retrospective cross-sectional study. We assessed the PA database established by the multicenter Japan PA study (JPAS). Data were also collected from patients with essential hypertension (EHT). METHODS: We compared the prevalences of proteinuria and lowered estimated glomerular filtration rate (eGFR) between patients with PA and age, sex, blood pressure and duration of hypertension-matched patients with EHT. We also performed logistic regression analysis to identify parameters that increase the risk for these renal impairments. RESULTS: Among 2366 PA patients, the prevalences of proteinuria and lowered eGFR were 10.3 and 11.6%, respectively. The prevalence of proteinuria was significantly higher in PA patients than matched-EHT patients (16.8 vs 4.4%), whereas there was no significant difference in the prevalence of lowered eGFR (17.2 vs 15.0%). The logistic regression analysis also showed that the plasma aldosterone concentration (PAC) significantly increases the risk of proteinuria and lowered eGFR, independent of other known risk factors. CONCLUSION: Plasma aldosterone levels are closely associated with renal impairment in patients with PA. This is contrast to our earlier finding that the PAC was not itself linearly associated with cardiovascular events such as stroke or ischemic heart disease. The mechanism underlying the kidney damage in patients with PA may differ from that affecting the cardiovascular system.