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  - Adolf, Christian
A1  - Braun, Leah T.
A1  - Fuss, Carmina T.
A1  - Hahner, Stefanie
A1  - Künzel, Heike
A1  - Handgriff, Laura
A1  - Sturm, Lisa
A1  - Heinrich, Daniel A.
A1  - Schneider, Holger
A1  - Bidlingmaier, Martin
A1  - Reincke, Martin
T1  - Spironolactone reduces biochemical markers of bone turnover in postmenopausal women with primary aldosteronism
JF  - Endocrine
N2  - Context
Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Besides its deleterious impact on cardiovascular target organ damage, PA is considered to cause osteoporosis.

Patients and methods
We assessed bone turnover in a subset of 36 postmenopausal women with PA. 18 patients had unilateral PA and were treated by adrenalectomy, whereas 18 patients had bilateral PA and received mineralocorticoid receptor antagonist (MRA) therapy respectively. 18 age- and BMI-matched females served as controls. To estimate bone remodeling, we measured the bone turnover markers intact procollagen 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin and tartrate resistant acid phosphatase 5b in plasma by chemiluminescent immunoassays at time of diagnosis and one year after initiation of treatment.

Study design
Observational longitudinal cohort study.

Setting
Tertiary care hospital.

Results
Compared with controls, patients with PA had mildly elevated osteocalcin at baseline (p = 0.013), while the other bone markers were comparable between both groups. There were no differences between the unilateral and the bilateral PA subgroup. One year after initiation of MRA treatment with spironolactone bone resorption and bone formation markers had significantly decreased in patients with bilateral PA. In contrast, patients adrenalectomized because of unilateral PA showed no significant change of bone turnover markers.

Conclusion
This study shows that aldosterone excess in postmenopausal women with PA is not associated with a relevant increase of bone turnover markers at baseline. However, we observed a significant decrease of bone markers in patients treated with spironolactone, but not in patients treated by adrenalectomy.
KW  - aldosterone
KW  - osteocalcin
KW  - osteoporosis
KW  - hyperparathyroidism
KW  - cortisol
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-315966
SN  - 1355-008X
SN  - 1559-0100
VL  - 69
IS  - 3
ER  -