Introduction: Hypercortisolism in Cushings syndrome (CS) determines increased mortality and morbidity. Hypercortisolism is also present in chronic depressive disorders and stress, where telomere length (TL) is shorter than in controls. We hypothesized that telomere shortening may occur and contribute to premature morbidity in CS.
Aim: Investigate TL in CS compared to matched controls, and longitudinally in a subset of CS patients evaluated both with active disease and after endocrine cure.
Methods: Seventy-seven CS patients (14 males, 59 of pituitary and 17 of adrenal origin; 21 with active disease) and 77 matched controls (for age, gender, smoking) were compared. Mean age was 48±12 in CS vs 48±12 years in controls. In 15 active patients, a second analysis was also performed once they were in remission (mean age 43±12 vs 46±11 years, respectively, P<0.05). Leukocyte TL was measured by TRF-Southern technique (kit-telo TTAGGG Telomere length Assay, Roche).
Results: A negative correlation between TL and age was found (r −0.341, P<0.001). CS patients had more hypertension, diabetes, dyslipidemia, osteoporosis, a greater BMI and total leukocyte count in CS than controls (P<0.05). Globally, mean TL did not differ in CS and controls (7667 vs 7483 base pairs-bp-). TL shortening was observed in both CS and controls with dyslipidemia (controls 7213 vs 7700 bp and CS 7328 vs 7957, P<0.05). After adjustment for age, TL was shorter in active disease than in remission (7271 vs 7870, P<0.05).
Conclusions: As previously described, aging and dyslipidemia were associated with TL shortening in both CS and controls, but did not differ globally. However, we show for the first time that when patients are followed longitudinally, active CS is associated to TL shortening compared to remission, suggesting a negative impact of hypercortisolism on the telomere maintenance system.