Role of glucocorticoid receptor polymorphism in adrenal incidentalomas.
BACKGROUND
Adrenal incidentalomas (AI) have been associated with and an increased prevalence of metabolic and bone complications. The N363S and BclI polymorphisms of the glucocorticoid receptor (GR) have been associated with an increased sensitivity to glucocorticoid (GC). This observational study aims to evaluate whether BclI and N363S polymorphisms play a role in the development of complications in AI.


METHODS
We enrolled 100 patients with AI (66 F; 34M). The presence of diabetes, arterial hypertension (AH), dyslipidaemia, osteoporosis and vertebral fracture (Fx), waist circumference and the Body Mass Index (BMI) were assessed. DNA samples were genotyped. Patients with wild-type BclI, wild-type N363S and heterozygous BclI polymorphism were classified as carriers of haplotype 1 (H1; n = 86), patients with homozygous BclI and heterozygous N363S polymorphism of GR of haplotype 2 (H2; n = 14).


RESULTS
We found no clinical or biochemical differences between haplotype 1 and 2 groups, but a higher prevalence of the simultaneous presence of Fx plus AH in H2 patients (H2 n = 7, H1 n = 16, P = 0.01). Logistic regression analysis showed that the presence of Fx and of AH and the combination of the presence of Fx plus AH were associated with the H2 genotype regardless of the degree of cortisol secretion, age, BMI and BMD (OR 4.88, 95%CI 1.47-18.40, P = 0.05; OR 8.25, 95%CI 0.98-69.52, P = 0.05; OR 7.25, 95%CI 1.57-35.78, P = 0.011; respectively).


CONCLUSIONS
In AI patients, the presence of the haplotype 2 of BclI and N363S is associated with the presence of AH, Fx and with the combination of Fx and AH.
Morelli
Valentina
V
Unit of Endocrinology and Diabetology, Department of Medical Sciences, University of Milan, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy.
Donadio
Francesca
F
Eller-Vainicher
Cristina
C
Cirello
Valentina
V
Olgiati
Luca
L
Savoca
Chiara
C
Cairoli
Elisa
E
Salcuni
Antonio Stefano
AS
Beck-Peccoz
Paolo
P
Chiodini
Iacopo
I
D000236:Adenoma / Q000150:complications / Q000235:genetics*; D000310:Adrenal Gland Neoplasms / Q000150:complications / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites / Q000235:genetics; D003920:Diabetes Mellitus / Q000453:epidemiology; D050171:Dyslipidemias / Q000453:epidemiology; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000453:epidemiology; D011110:Polymorphism, Genetic; D015995:Prevalence; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D013131:Spine
D011965:Receptors, Glucocorticoid