TY  - JOUR
A1  - Vetrivel, Sharmilee
A1  - Zhang, Ru
A1  - Engel, Mareen
A1  - Altieri, Barbara
A1  - Braun, Leah
A1  - Osswald, Andrea
A1  - Bidlingmaier, Martin
A1  - Fassnacht, Martin
A1  - Beuschlein, Felix
A1  - Reincke, Martin
A1  - Chen, Alon
A1  - Sbiera, Silviu
A1  - Riester, Anna
T1  - Circulating microRNA Expression in Cushing’s Syndrome
JF  - Frontiers in Endocrinology
N2  - Context
Cushing’s syndrome (CS) is a rare disease of endogenous hypercortisolism associated with high morbidity and mortality. Diagnosis and classification of CS is still challenging.

Objective
Circulating microRNAs (miRNAs) are minimally invasive diagnostic markers. Our aim was to characterize the circulating miRNA profiles of CS patients and to identify distinct profiles between the two major CS subtypes.

Methods
We included three groups of patients from the German Cushing’s registry: ACTH-independent CS (Cortisol-Producing-Adenoma; CPA), ACTH-dependent pituitary CS (Cushing’s Disease; CD), and patients in whom CS had been ruled out (controls). Profiling of miRNAs was performed by next-generation-sequencing (NGS) in serum samples of 15 CS patients (each before and after curative surgery) and 10 controls. Significant miRNAs were first validated by qPCR in the discovery cohort and then in an independent validation cohort of 20 CS patients and 11 controls.

Results
NGS identified 411 circulating miRNAs. Differential expression of 14 miRNAs were found in the pre- and postoperative groups. qPCR in the discovery cohort validated 5 of the significant miRNAs from the preoperative group analyses. Only, miR-182-5p was found to be significantly upregulated in the CD group of the validation cohort. Comparing all CS samples as a group with the controls did not reveal any significant differences in expression.

Outcome
In conclusion, our study identified miR-182-5p as a possible biomarker for CD, which has to be validated in a prospective cohort. Furthermore, our results suggest that presence or absence of ACTH might be at least as relevant for miRNA expression as hypercortisolism itself.
KW  - cortisol
KW  - ACTH
KW  - miRNA
KW  - biomarker
KW  - cortisol-producing adenoma
KW  - miR-182-5p
KW  - hypercortisolism
KW  - miR-183 cluster
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229761
SN  - 1664-2392
VL  - 12
ER  - 
TY  - JOUR
A1  - Drechsler, Christiane
A1  - Ritz, Eberhard
A1  - Tomaschitz, Andreas
A1  - Pilz, Stefan
A1  - Schönfeld, Stephan
A1  - Blouin, Katja
A1  - Bidlingmaier, Martin
A1  - Hammer, Fabian
A1  - Krane, Vera
A1  - März, Winfried
A1  - Allolio, Bruno
A1  - Fassnacht, Martin
A1  - Wanner, Christoph
T1  - Aldosterone and cortisol affect the risk of sudden cardiac death in haemodialysis patients
JF  - European Heart Journal
N2  - Background: Sudden cardiac death is common and accounts largely for the excess mortality of patients on maintenance dialysis. It is unknown whether aldosterone and cortisol increase the incidence of sudden cardiac death in dialysis patients.

Methods and results: We analysed data from 1255 diabetic haemodialysis patients participating in the German Diabetes and Dialysis Study (4D Study). Categories of aldosterone and cortisol were determined at baseline and patients were followed for a median of 4 years. By Cox regression analyses, hazard ratios (HRs) were determined for the effect of aldosterone, cortisol, and their combination on sudden death and other adjudicated cardiovascular outcomes. The mean age of the patients was 66 ± 8 years (54% male). Median aldosterone was <15 pg/mL (detection limit) and cortisol 16.8 µg/dL. Patients with aldosterone levels >200 pg/mL had a significantly higher risk of sudden death (HR: 1.69; 95% CI: 1.06–2.69) compared with those with an aldosterone <15 pg/mL. The combined presence of high aldosterone (>200 pg/mL) and high cortisol (>21.1 µg/dL) levels increased the risk of sudden death in striking contrast to patients with low aldosterone (<15 pg/mL) and low cortisol (<13.2 µg/dL) levels (HR: 2.86, 95% CI: 1.32–6.21). Furthermore, all-cause mortality was significantly increased in the patients with high levels of both hormones (HR: 1.62, 95% CI: 1.01–2.62).

Conclusions: The joint presence of high aldosterone and high cortisol levels is strongly associated with sudden cardiac death as well as all-cause mortality in haemodialysed type 2 diabetic patients. Whether a blockade of the mineralocorticoid receptor decreases the risk of sudden death in these patients must be examined in future trials.
KW  - mortality
KW  - kidney disease
KW  - cardiovascular events
KW  - sudden cardiac death
KW  - cortisol
KW  - aldosterone
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132562
VL  - 34
ER  -