PMID- 34446274
OWN - NLM
STAT- MEDLINE
DCOM- 20211111
LR  - 20211111
IS  - 1873-4111 (Electronic)
IS  - 0378-5122 (Linking)
VI  - 151
DP  - 2021 Sep
TI  - The association of glucocorticoid receptor polymorphism with metabolic outcomes 
      in menopausal women with adrenal incidentalomas.
PG  - 15-21
LID - S0378-5122(21)00116-X [pii]
LID - 10.1016/j.maturitas.2021.06.011 [doi]
AB  - OBJECTIVES: To investigate whether BclI polymorphism in the glucocorticoid 
      receptor gene influences hypothalamic-pituitary-adrenal (HPA) axis regulation, 
      body composition and metabolic parameters in women with adrenal incidentalomas 
      (AIs). STUDY DESIGN: A cross-sectional study. MAIN OUTCOME MEASURES: We analyzed 
      106 women with AIs. Insulin resistance was assessed using a homeostasis model 
      while HPA activity was assessed using dexamethasone suppression tests (DST), 
      basal ACTH, urinary free cortisol, and midnight serum cortisol level. Body 
      composition was analyzed using dual-energy X-ray absorptiometry. DNA was obtained 
      from peripheral blood leucocytes and BclI polymorphism was detected using PCR, 
      RFLP and DNA sequencing. RESULTS: BclI carriers in comparison with those with 
      wild-type BclI had less suppressed cortisol after DST-0.5 mg (126.4 +/- 111.4 vs 
      80.9 +/- 75.7 nmol/l, p = 0.026) and had a lower prevalence of impaired glucose 
      tolerance and of type 2 diabetes mellitus (T2DM). BclI carriers had a higher 
      percentage of leg fat mass (FM), lower left-sided limb muscle mass and a decline 
      in total lean body mass. Duration of menopause remained a strong predictor of 
      appendicular lean mass index (ALMI) (beta=-0.125, p = 0.034). BclI polymorphism was 
      significantly associated with sum of legs FM percentage (beta=0.327, p = 0.048). 
      T2DM was negatively associated with BclI polymorphism, after adjusting for age, 
      truncal FM, ALMI, and sum of legs FM (OR=0.158, 95%CI 0.031-0.806, p = 0.027). 
      CONCLUSIONS: BclI polymorphism is associated with tissue-specific glucocorticoid 
      sensitivity, relative glucocorticoid resistance of the HPA axis and peripheral 
      adipose tissue, and glucocorticoid hypersensitivity at the muscle level. By 
      modulating glucocorticoid and insulin sensitivity, BclI polymorphism appears to 
      reduce the risk of T2DM in women with AIs.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Ognjanovic, Sanja
AU  - Ognjanovic S
AD  - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of 
      Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
FAU - Antic, Jadranka
AU  - Antic J
AD  - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of 
      Serbia, Belgrade, Serbia.
FAU - Pekmezovic, Tatjana
AU  - Pekmezovic T
AD  - Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, 
      Serbia.
FAU - Popovic, Bojana
AU  - Popovic B
AD  - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of 
      Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
FAU - Isailovic, Tatjana
AU  - Isailovic T
AD  - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of 
      Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
FAU - Antic, Ivana Bozic
AU  - Antic IB
AD  - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of 
      Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
FAU - Bogavac, Tamara
AU  - Bogavac T
AD  - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of 
      Serbia, Belgrade, Serbia.
FAU - Kovacevic, Valentina Elezovic
AU  - Kovacevic VE
AD  - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of 
      Serbia, Belgrade, Serbia.
FAU - Ilic, Dusan
AU  - Ilic D
AD  - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of 
      Serbia, Belgrade, Serbia.
FAU - Opalic, Milica
AU  - Opalic M
AD  - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of 
      Serbia, Belgrade, Serbia.
FAU - Macut, Djuro
AU  - Macut D
AD  - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of 
      Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic 
      address: djmacut@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20210629
PL  - Ireland
TA  - Maturitas
JT  - Maturitas
JID - 7807333
RN  - 0 (Receptors, Glucocorticoid)
RN  - WI4X0X7BPJ (Hydrocortisone)
RN  - Adrenal incidentaloma
SB  - IM
MH  - Adrenal Gland Neoplasms/*genetics/pathology
MH  - Adult
MH  - Aged
MH  - Cross-Sectional Studies
MH  - Diabetes Mellitus, Type 2/*prevention & control
MH  - Female
MH  - Genes, bcl-1/*genetics
MH  - Humans
MH  - Hydrocortisone
MH  - Hypothalamo-Hypophyseal System
MH  - *Menopause
MH  - Middle Aged
MH  - Pituitary-Adrenal System
MH  - Polymorphism, Single Nucleotide
MH  - Receptors, Glucocorticoid/*genetics
OTO - NOTNLM
OT  - Adrenal incidentaloma
OT  - BclI polymorphism
OT  - Body composition
OT  - Glucocorticoid receptor
OT  - Insulin sensitivity
EDAT- 2021/08/28 06:00
MHDA- 2021/11/12 06:00
CRDT- 2021/08/27 05:48
PHST- 2021/03/12 00:00 [received]
PHST- 2021/06/21 00:00 [revised]
PHST- 2021/06/26 00:00 [accepted]
PHST- 2021/08/27 05:48 [entrez]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/11/12 06:00 [medline]
AID - S0378-5122(21)00116-X [pii]
AID - 10.1016/j.maturitas.2021.06.011 [doi]
PST - ppublish
SO  - Maturitas. 2021 Sep;151:15-21. doi: 10.1016/j.maturitas.2021.06.011. Epub 2021 
      Jun 29.