MON-190 Telomere Length as a Novel Prognostic Marker of Cushing Complications

Abstract

Telomeres are small sequences at the end of chromosomes, protecting them from abnormal degradation. Certain conditions, like cancer, have been associated with changes in telomere length (TL), which, in turn, may predict outcomes of the disease. Studies on the effect of cortisol on TL have not led to conclusive results or are limited in stress induced hypercortisolemia. Moreover, no study has focused on effects of persistent endogenous hypercortisolemia during childhood, a known important period for telomere modifications.We hypothesized that TL is affected in pediatric patients with endogenous Cushing syndrome (CS) and it correlates with markers and complications of hypercortisolemia.We studied 10 pediatric patients (mean age: 13.3 years, 7 females), diagnosed and treated successfully for Cushing disease. TL of total lymphocytes and their subtypes (Naïve T-cells, Memory T-cells, B-cells and NK-cells) were measured before and 1 year after treatment. TL was compared to age-matched control samples (6-8 per age group) and was correlated with clinical and biochemical characteristics. Paired or two-sample parametric or non-parametric statistical tests were performed, as appropriate.Lymphocyte TL of patients with active CS did not differ from controls (p=.43). B-cell and NK-cell TLs were shorter after cure compared to active CS [mean B-cell TL difference: -1.44 Kb (-15%), p=.001; mean NK-cell difference: -0.51 Kb (-7%), p=.10] and controls [mean B-cell TL difference: -0.98 (-11%), p=.039; mean NK-cell difference: -1.3 Kb (-16%), p=.005]. Lymphocyte TL in active CS and the change of TL before and after cure did not correlate with measured markers of hypercortisolemia (morning and midnight cortisol, urinary free cortisol or ACTH levels). However, there was a strong inverse correlation between the difference of TL in active disease compared to controls and triglyceride level for all lymphocyte subtypes (range r= -0.74 to -0.86, range p= .003 to p=.022), suggesting that the higher the triglyceride levels, the shorter the TL in patients with CS. Additionally, inverse correlation was observed for weight and BMI SDS and B-cell TL, specifically (r= -0.76, p= .019 and r= -0.76, p= .018, respectively). Furthermore, there appeared to be an implication for shorter TL in CS patients with dyslipidemia compared to those without (mean TL difference from controls: -1.1 Kb in patients with dyslipidemia vs 0.53 Kb in those without, p= .067).We conclude that although TL in active CS does not seem to differ from controls, B-cell and NK-cell TLs are affected after cure, and this may be related to acute changes that occur in the immune system peri- and post-operatively. Interestingly, the level of TL shortening correlates strongly with several complications of CS, including weight, BMI and dyslipidemia. This suggests that TL may be used as a surrogate prognostic marker of hypercortisolemia-related complications.