Comparisons of plasma aldosterone and renin data between an automated chemiluminescent immunoanalyzer and conventional radioimmunoassays in the screening and diagnosis of primary aldosteronism.

Determining values of plasma renin activity (PRA) or plasma active renin concentration (ARC), plasma aldosterone concentration (PAC), and aldosterone-to-renin ratio (ARR) is essential to diagnose primary aldosteronism (PA), but it takes several days with conventional radioimmunoassays (RIAs). Chemiluminescent enzyme immunoassays for PAC and ARC using the Accuraseed® immunoanalyzer facilitated the determination, but relations between Accuraseed® immunoanalyzer-based and RIA-based values in samples of PA confirmatory tests and adrenal venous sampling remained to be elucidated. We addressed this issue in the present study. This is a prospective, cross-sectional study. ARC and PAC values were measured by the Accuraseed® immunoanalyzer in samples, in which PRA and PAC values had been measured by the PRA-FR® RIA and SPAC®-S Aldosterone kits, respectively. The relations between Accuraseed® immunoanalyzer-based and RIA-based values were investigated with regression analyses. The optimal cutoff of Accuraseed® immunoanalyzer-based ARR for PA screening was determined by the receiver operating characteristic analysis. After log-log transformations, linear relations with high coefficients of determination were observed between Accuraseed® immunoanalyzer-based and RIA-based data of renin and aldosterone. Following the PA guidelines of Japan Endocrine Society, Accuraseed® immunoanalyzer-based cutoffs were calculated from the regression equations: the basal PAC for PA screening >12 ng/dL, PAC for the saline infusion test >8.2 ng/dL, ARC for the furosemide-upright test <15 pg/mL, and ARR for the captopril challenge test >3.09 ng/dL per pg/mL. The optimal cutoff of Accuraseed® immunoanalyzer-based ARR for PA screening was >2.43 ng/dL over pg/mL not to overlook bilateral PA patients. The present study provided conversion formulas between Accuraseed® immunoanalyzer-based and RIA-based values of renin, aldosterone, and ARR, not only in basal samples but also in samples of PA confirmatory tests and adrenal venous sampling. Although validation studies are awaited, the present study will become priming water of harmonization of renin and aldosterone immunoassays.

Parameters of captopril challenge test can predict results of other confirmatory tests for primary aldosteronism and propose the next test to be done.

In Japan, primary aldosteronism (PA) is diagnosed if any one of the captopril challenge test (CCT), saline infusion test (SIT), furosemide-upright test (FUP), and oral salt-loading test (OST) is positive. The present study aimed to investigate if parameters of CCT, the safest confirmatory test, could predict decisions of other tests and propose the next test to diagnose PA in CCT-negative patients. In a cross-sectional design, 142 patients, who were referred to our hospital for the scrutiny of PA and underwent at least two confirmatory tests, were enrolled. While 123 patients underwent all of the CCT, SIT, and FUP, the OST was successfully done in only six patients and excluded from further analyses. CCT parameters showing correlations of higher degrees with SIT and FUP parameters were selected, and their powers to predict SIT and FUP decisions were investigated by receiver operating characteristic analyses. Proposals of the next test based on the CCT parameters were validated with SIT and FUP decisions in subsets of CCT-negative patients divided by cut-offs of the CCT parameters. The plasma aldosterone concentration and plasma renin activity 60 min after the load of CCT (CCT60-PAC and CCT60-PRA) were selected, and CCT60-PAC ≤59.0 pg/mL and CCT60-PRA ≥1.05 ng/mL/h could predict negativities of SIT and FUP, respectively, with >95% specificities. Based on the validation, the present study suggested the SIT as the next test to be done if the CCT-negative patient belonged to the subset with CCT60-PAC >59.0 pg/mL and CCT60-PRA ≥1.05 ng/mL/h, otherwise the FUP should be selected.

Effect of human leukocyte antigen class II genes on Hashimoto's thyroiditis requiring replacement therapy with levothyroxine in the Japanese population.

Contribution of the human leukocyte antigen (HLA) subtype to Hashimoto's thyroiditis (HT) that requires replacement therapy with levothyroxine remains unclear in the Japanese population. The frequencies of HLA DR-DQ haplotypes were compared between patients with HT requiring levothyroxine replacement therapy and the control individuals. We studied 82 patients with HT requiring levothyroxine replacement therapy. The frequencies of DRB1*08:03-DQB1*06:01 and DRB1*09:01-DQB1*03:03 haplotypes were significantly higher in HT patients, whereas those of DRB1*13:02-DQB1*06:04 and DRB1*15:01-DQB1*06:02 haplotypes were significantly lower in these patients than in the controls. Deduced from known linkage disequilibria, DRB1*13:02-DQB1*06:04 and DRB1*15:01-DQB1*06:02 haplotypes share the same DQA1*01:02 allele. Since DQB1*06:02 and DQB1*06:04 molecules differ in the beta chain by 7 residues, these DQB1 genes are very similar. The DQA1*01:02-DQB1*06 (DQB1*06:02 or DQB1*06:04) haplotype might play a pivotal role in the resistance to HT.

The age of onset of diabetes and glutamic acid decarboxylase titer measured long after diagnosis are associated with the clinical stage of slow-onset type 1 diabetes.

AIMS: Diabetes mellitus is divided into 3 clinical stages: not insulin requiring, insulin requiring for control, and insulin requiring for survival. We investigated the clinical characteristics of patients with slow-onset type 1 diabetes (T1D) to examine which clinical factors influence the clinical stage. METHODS: One hundred fifty patients with slow-onset T1D were divided into 3 groups based on disease stage, and clinical features were compared among these groups. The patients were also divided into 4 groups based on the age of onset and the glutamic acid decarboxylase antibody (GAD-Ab) titer, which was measured long after diagnosis (mean, 9.2 years). The frequencies of the 3 stages were compared among these 4 groups. RESULTS: The age of onset and the log (GAD-Ab) titer differed significantly among the 3 stages. The number of patients not requiring insulin was significantly higher and the number of those requiring insulin for survival was significantly lower in the group in which the age of onset was ≥50 and the log (GAD-Ab) titer <0.6, while the opposite pattern was observed in the group in which the age of onset was <50 and the log(GAD-Ab) titer ≥0.6. CONCLUSIONS: Our results suggest that the combination of the age of onset and GAD-Ab titer measured long after diagnosis might predict the clinical stage of slow-onset T1D.

Effect of human leukocyte antigen class II genes on insulin deficiency in slow-onset type 1 diabetes in the Japanese population.

The aim of this study is to determine the contribution of human leukocyte antigen (HLA) class II genes to insulin deficiency in slow-onset type 1 diabetes (T1D). Our results suggest that the susceptibility conferred by HLA subtypes to slow-onset T1D differs between insulin-deficient patients and non-insulin-deficient patients.