Shorter telomeres associated with high doses of glucocorticoids: the link to increased mortality?

Abstract

ObjectivePatients with non-functioning pituitary adenomas exhibit high morbidity and mortality rates. Growth hormone deficiency and high doses of glucocorticoid substitution therapy have been identified as corresponding risk factors. Interestingly, high levels of endogenous cortisol in, e.g., patients with post-traumatic stress disorder or patients with Cushing’s disease have been linked to shorter telomere length. Telomeres are noncoding DNA regions located at the end of chromosomes consisting of repetitive DNA sequences which shorten with aging and hereby determine cell survival. Therefore, telomere length can serve as a predictor for the onset of disease and mortality in some endocrine disorders (e.g., Cushing’s disease).Design/methodsHere, we examine telomere length from blood in patients (n = 115) with non-functioning pituitary adenomas (NFPA) in a cross-sectional case–control (n = 106, age-, gender-matched) study using qPCR. Linear regression models were used to identify independent predictors of telomere length.ResultsWe show that patients with NFPA exhibited shorter telomeres than controls. No significant association of indices of growth hormone deficiency (IGF-1-level-SDS, years of unsubstituted growth hormone deficiency etc.) with telomere length was detected. Interestingly, linear regression analysis showed that hydrocortisone replacement dosage in patients with adrenal insufficiency (n = 52) was a significant predictor for shorter telomere length (β = 0.377; P = 0.018) independent of potential confounders (gender, age, BMI, arterial hypertension, systolic blood pressure, number of antihypertensive drugs, total leukocyte count, waist-to-hip ratio, waist circumference, diabetes mellitus type 2, HbA1c, current statin use). Median split analysis revealed that higher hydrocortisone intake (>20 mg) was associated with significantly shorter telomeres.ConclusionThese observations strengthen the importance of adjusted glucocorticoid treatment in NFPA patients with respect to morbidity and mortality rates.

Stress reactivity elicits a tissue-specific reduction in telomere length in aging zebrafish (Danio rerio)

“…Importantly, increased levels of stress hormone, such as cortisol and glucocorticoids, have been previously reported to have a negative effect on telomere length in peripheral tissues [63][64][65] . Furthermore, the expression of telomerase, the enzyme with the ability to counteract telomere erosion, is susceptible to modulation by different hormones 39,[65][66][67] , including glucocorticoids 68 , thus providing further support for such a molecular mechanism. Interestingly, the balance of cardiomyocyte mr and gr has been shown to be paramount for cardiovascular health in mice 69 , which is consistent with the higher MR:GR ratio found here in aging zebrafish with shorter telomeres.…”

Leukocyte Telomere Length Is Not Reduced in Children and Adults with Cystic Fibrosis but Associates with Clinical Characteristics—A Cross-Sectional Study

“…Although no RTL difference between CF and HS was identified herein, inhaled corticosteroids associated with shorter RTL. Athanasoulia-Kaspar et al reported that patients with nonfunctioning pituitary adenomas and higher daily cortisol doses had shorter telomeres [29]. Furthermore, an in vitro study showed a considerable reduction (50%) in telomerase activity in T-lymphocytes after exposure to high cortisol levels [30].…”

Can telomere length predict bone health? A review of current evidence

“…Additionally, Verde et al identified that tobacco consumption caused a reduction in leukocyte telomere length [33]. Furthermore, the use of medications, for instance, glucocorticoids [34] and proton pump inhibitors (PPIs) [35], has been previously shown to induce telomere shortening. Patients with non-functioning pituitary adenomas displaying adrenal insufficiency receiving hydrocortisone replacement have also been shown to have shorter telomeres [34].…”

“…Furthermore, the use of medications, for instance, glucocorticoids [34] and proton pump inhibitors (PPIs) [35], has been previously shown to induce telomere shortening. Patients with non-functioning pituitary adenomas displaying adrenal insufficiency receiving hydrocortisone replacement have also been shown to have shorter telomeres [34]. Moreover, chronic exposure to esomeprazole impaired endothelial function and accelerated endothelial senescence by reducing telomere length [35].…”