Correlation of lower 2 h C-peptide and elevated evening cortisol with high levels of depression in type 2 diabetes mellitus

Background A number of studies have explored the association between depression and ghrelin, leptin, and cortisol; further, postprandial C-peptide levels have a therapeutic effect on type 2 diabetes mellitus (T2DM). However, the relationship between C-peptide and depression in patients with diabetes, remains unclear. The aim of this study was to explore the association between depression and ghrelin, leptin, cortisol, and C-peptide in patients with diabetes. Methods We enrolled 50 adults without T2DM, 77 non-depressed adults with T2DM (free of Axis-I psychiatric disorders as assessed using the Mental Illness Needs Index (MINI), Patient Health Questionnaire (PHQ-9 score ≤ 4)) and 59 patients with T2DM and depression (PHQ-9 ≥ 7 and positive by the Structured Clinical Interview for DSM-5). The age range of the participants was 45–59 years of age. We compared the above three groups and explored the association between ghrelin, leptin, cortisol, C-peptide, and depression in patients with diabetes. A post-hoc power-analysis was finished. Results Compared with the non-depression T2DM group, the depression T2DM group had significantly higher blood glucose fluctuations. Further, compared with the non-depression T2DM and non-diabetic groups, the depression T2DM group had significantly lower levels of post-meal 2-h C-peptide and elevated evening cortisol (p < 0.01). Regression analysis revealed a significant negative correlation between depression severity and 2-h postprandial C-peptide in patients with diabetes (p < 0.01) and a significant positive correlation with midnight cortisol levels (p < 0.01). A post hoc power analysis showed that we had an adequate sample size and met the minimum requirement to attain 80% power. A post hoc power calculation also demonstrated that this study basically achieved power of 80% at 5% alpha level. Conclusions Our findings indicate a correlation of low fasting levels of 2-h C-peptide as well as higher midnight cortisol levels with higher depression severity in middle-aged patients with T2DM.

MON-193 Glucocorticoid Excess and Its Association with Metabolic and Cardiovascular Complications in Primary Aldosteronism

Objective: To investigate autonomous cortisol secretion in patients with primary aldosteronism and its effect on metabolism and cardiovascular events (CVE) in patients with primary aldosteronism (PA). Methods: This study included 163 patients with PA and 105 sex- and age-matched patients with essential hypertension (EH). Clinical and laboratory data were collected. The expression of cortisol synthase (CYP11B1) and aldosterone synthase (CYP11B2) was investigated in adenoma tissues from 44 patients with aldosterone-producing adenoma (APA) by employing immunohistochemistry. Results: 1) CYP11B2 was expressed in 36 patients with APA and was absent in 8 patients, while CYP11B1 immunoreactivity was detected in all tested patients with APA; 2) Compared with patients with EH, midnight cortisol concentration (104.81±90.86 vs 76.87±65.86), 24-h urine free cortisol level (726.04±309.87 vs 630.65±168.2), and cortisol level after 1mg-DST [35.6(27.6,75.73)vs 27.6(27.60,29.27)]were all significantly increased in patients with PA(all P&lt;0.01); 3) Midnight cortisol concentration is positively associated with systolic blood pressure (SBP) (r=0.147 P&lt;0.05), LDL-C (r=0.194 P&lt;0.05), HOMA-IR (r=0.262 P&lt;0.05), HOMA-β (r=0.313 P&lt;0.05) and fasting insulin level (r=0.329 P&lt;0.05) in patients with PA. In multiple linear regression analysis, midnight cortisol concentration was a postitive predictor for SBP (β=0.185 P&lt;0.05), HOMA-IR (β=0.331 P&lt;0.05) and HOMA-β (β=0.390 P&lt;0.05); 4) Of the 163 patients with PA, 35 had a history of CVE, including 22 with stroke, eight with myocardial infarction, three with atrial fibrillation, and two with heart failure. The multivariate logistic-regression analyses revealed older age (OR 1.160 95%CI 1.041-1.294 P &lt;0.001) and higher serum aldosterone level (OR 1.013 95%CI 1.000-1.026 P &lt;0.05) were independent risk factors of CVE, serum cortisol level was not associated with the increased risk of CVE in patients with PA (OR 0.997 95%CI 0.985-1.009 P =0.570). Conclusion: Excess cortisol secretion was common in PA. Cortisol excretion is correlated with metabolic disorders, but not associated with increased risk of CVE in patients with PA.

Association of glucocorticoid receptor polymorphism A3669G with decreased risk of developing diabetes in patients with Cushing's syndrome

ObjectiveGlucocorticoid receptor (GR) polymorphisms alter glucocorticoid (GC) sensitivity and have been associated with altered metabolic profiles. We evaluate the prevalence of the fourGR(NR3C1) polymorphisms BclI, N363S, ER22/23EK, and A3669G in patients with Cushing's syndrome (CS) compared with healthy controls (HC) and we investigate their role in the development of metabolic abnormalities in patients with CS according to their hormonal profile.Patients and methodsSixty-one patients with CS and 71 sex- and age-matched HC were genotyped.ResultsBclI variant was markedly higher in patients with CS compared with HC (62 vs 41%,P<0.05) while no significant differences were found among other polymorphisms. A very low frequency of N363S and the ER22/23EK was observed.In CS patients, despite the significantly increased levels of morning serum cortisol in BclI carriers compared with wild type no clinical or metabolic differences were found.In contrast, A3669GGRcarriers showed a significantly reduced prevalence of type 2 diabetes mellitus compared with wild type (19 vs 68%,P=0.001) despite the higher levels of both serum morning (21.7±6 vs 27.3±8.6 μg/dl,P=0.009) and midnight cortisol (18.8±5.8 vs 24.0±8.0 μg/dl,P=0.01). The negative association between diabetes and A3669GGRpolymorphism remained significant when data were adjusted for potential confounding factors.ConclusionsThe A3669G polymorphism of theGRgene plays a protective role in patients with CS, attenuating the effects of GC excess on glucose metabolism as shown by their reduced risk of diabetes.

Sequential hormonal changes in 21 patients with recurrent Cushing's disease after successful pituitary surgery

ObjectiveTo describe the sequence of hormonal changes during recurrence of Cushing's disease (CD) after successful transsphenoidal surgery (TSS).DesignRetrospective study in a single center.Patients and methodsWe studied 101 of the 127 patients treated by TSS for CD between 1996 and 2009, who had hypocortisolism or eucortisolism for at least 3 months post-TSS. We arbitrarily defined ‘overt recurrence’, as presence of two classical parameters of excess cortisol (increased midnight – either serum or salivary – and 24 h urinary cortisol (UC)), leading to further specific therapeutic action, and ‘mild recurrence’, as presence of a single classical parameter, leading to simple surveillance.ResultsOf the 101 patients, 21 (20.8%) presented with recurrence, ‘mild’ or ‘overt’, during long-term follow-up (median 50.4 months, range 7–99). Recurrence occurred less frequently (16.8 vs 50%, P=0.02), and later (mean 44.7 months, median 43, range 7–94 vs mean 21.5 months, median 17, range 3–61, P=0.05), in patients with early post-TSS hypocortisolism compared with those with eucortisolism. Increase in midnight cortisol occurred in a mean time of 38.2 months, while UC elevation was observed at 50.6 months. Vasopressin analogs and CRH tests were eventually positive in 85 and 93% of all patients respectively; a positive response to one of the two dynamic tests preceded the increase in midnight cortisol or UC in 71 and 64% of the patients respectively.ConclusionA positive response to vasopressin analogs and/or CRH tests occurs early in recurrence, followed by an increase in midnight cortisol, while UC elevation is at a later stage.

Accuracy of Diagnostic Tests for Cushing’s Syndrome: A Systematic Review and Metaanalyses

Context: The diagnosis of Cushing’s syndrome (CS) requires the use of tests of unregulated hypercortisolism that have unclear accuracy. Objective: Our objective was to summarize evidence on the accuracy of common tests for diagnosing CS. Data Sources: We searched electronic databases (MEDLINE, EMBASE, Web of Science, Scopus, and citation search for key articles) from 1975 through September 2007 and sought additional references from experts. Study Selection: Eligible studies reported on the accuracy of urinary free cortisol (UFC), dexamethasone suppression test (DST), and midnight cortisol assays vs. reference standard in patients suspected of CS. Data Extraction: Reviewers working in duplicate and independently extracted study characteristics and quality and data to estimate the likelihood ratio (LR) and the 95% confidence interval (CI) for each result. Data Synthesis: We found 27 eligible studies, with a high prevalence [794 (9.2%) of 8631 patients had CS] and severity of CS. The tests had similar accuracy: UFC (n = 14 studies; LR+ 10.6, CI 5.5–20.5; LR− 0.16, CI 0.08–0.33), salivary midnight cortisol (n = 4; LR+ 8.8, CI 3.5–21.8; LR− 0.07, CI 0–1.2), and the 1-mg overnight DST (n = 14; LR+ 16.4, CI 9.3–28.8; LR− 0.06, CI 0.03–0.14). Combined testing strategies (e.g. a positive result in both UFC and 1-mg overnight DST) had similar diagnostic accuracy (n = 3; LR+ 15.4, CI 0.7–358; LR− 0.11, CI 0.007–1.57). Conclusions: Commonly used tests to diagnose CS appear highly accurate in referral practices with samples enriched with patients with CS. Their performance in usual clinical practice remains unclear.