Endocrine Abstracts

Background: There is uncertainty as to whether glucocorticoid receptor (GCR) polymorphisms play a role in the development of glucocorticoid-related side-effects in individuals receiving hydrocortisone replacement for Addison’s disease.

Method: One-hundred-and-forty-seven Addison’s patients were age, gender, ethnicity and body mass index (BMI) matched with 147 control subjects. Genotyping was performed using polymerase chain reaction (PCR) for three single nucleotide polymorphisms, two of which are known to be sensitising Bcll and N363S and one polymorphism ER22/23EK is known to induce a degree of cortisol resistance. Associations with metabolic derangements were evaluated.

Results: The prevalence of the Bcll polymorphism occurred more frequently in whites than in any of the other ethnic groups, but was not associated with any metabolic derangement. The ER22/23EK polymorphism was associated with an increased BMI in both patients (29.4 vs. 24.7 kg/ m²; P <0.02) and control subjects (26.3 vs. 24.2 kg/ m²; P <0.001) compared with the wild-type. The heterozygous polymorphism was associated with lower low-density lipoprotein (LDL) cholesterol in controls vs. wild-type (3.46 mmol/l vs. 3.93 mmol/l; P=0.02). The N363S was not associated with any metabolic derangement.

Conclusion: The overall effect of the GCR polymorphisms was to increase the BMI in healthy control subjects and patients harbouring the ER22/23EK polymorphism, which was in contrast to what was expected. No associations between any of the polymorphisms and hydrocortisone doses were found, albeit that doses are prescribed on an empiric basis.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.