Endocrine Abstracts

Introduction: Chronic endogenous hypercortisolism in Cushing’s syndrome imposes a great clinical burden of comorbidities, some of which might persist even after disease remission. Our aim was to analyze factors that predict long-term comorbidities after surgical remission of Cushing’s disease (CD).

Subjects and methods: We retrospectively analyzed 37 patents (91.9% females) aged 39.5±13.9 years (10-70) with diagnosed CD, treated in our institutions, and followed up during 15 years. Each patient was evaluated for presence of comorbidities [overweight/obesity, impaired glucose metabolism (impaired fasting glucose, IFG/impaired glucose tolerance, IGT/diabetes, DM), hypertension (HTA), dyslipidemia, osteoporosis, depression], at the time of diagnosis and during follow up of clinical remission. Spearman’s rank correlation coefficient was used to test associations between comorbidities and age, BMI, biochemical parameters and hormonal levels (basal cortisol and ACTH level, midnight cortisol level). Multiple regression analysis was used to test predictors of long-term comorbidities after CD remission. Statistical analysis was performed by SPSS software.

Results: At diagnosis, dyslipidemia, HTA, overweight/obesity, osteopenia/osteoporosis, IFG/IGT/DM and depression were present in these patients with frequences of 86.5%, 73.0%, 64.9%, 59.5%, 51.4% and 21.6%, respectively. Aside of 4 patients (10.8%), all the other had 2 or more comorbidities. The number of comorbidities positively correlated with age (P=0.009), BMI (P=0.003), glycemia (P=0.018), and triglyceride levels (P=0.032), and negatively with HDL (P=0.009); there were no significant correlations wih hormonal levels (P>0.05). Majority of patients (81.8%) had pituitary microadenoma. Transsphenoidal surgery (TS) was performed in 34 patients (91.9%), with median of 3±4 months after diagnosis. After initial surgical success rate of 82.4% (28 patients), 20 patients (58.8%) kept long-term remission. Remission was achieved by bilateral adrenalectomy in 2 additional patients (22 overall, 59.5%), with follow up of 76.9±60.6 months (1-192). Clinical remission was associated with significant decrease in frequency of overweight/obesity (P=0.006), depression (P=0.004), and HTA (P=0.051) while no significant decrease in frequency of dyslipidemia, IFG/IGT/DM and osteoporosis (P>0.05) was observed. A number of comorbidites remained positively associated with age (P=0.016), BMI (P=0.042), glycemia (P=0.048), and level of triglycerides (P=0.048), and negatively with HDL (P=0.019). In sepwise linear regression analysis the strongest predictors of long-term morbidity were age (B=0.068, P=0.019, 95% CI 0.013-0.124) and HDL level (B=-1.218, P=0.005, 95% CI -2.434--0.001) at diagnosis of CD.

Conclusion: Cushing’s disease is the most prevalent cause of endogenous hypercortisolism, causing significant morbidity in these patients that remains so even after long-term remission. Life-long follow up of cardiovascular outcomes is needed in these patients.