The burden of Cushing's Disease cardiometabolic comorbidities: comparison between surgical remission and long-term eucortisolism with medical treatment

Background and aim: Cushing’s disease (CD) is associated with phenotypic traits and comorbidities that may persist after the normalization of cortisol levels. Medical therapy is used in recurrent or persistent CD after neuro-surgery (TSS). We aimed to investigate the impact of long-term normalization of hypercortisolism (achieved with surgical remission or medical treatment) on clinical picture and cardiometabolic comorbidities.
Methods: Monocentric retrospective study, 2- and 5-years observation. Sixty CD patients, with sustained normal 24-h urinary free cortisol (UFC) levels; 36 in remission after successful TSS (REM) and 24 in long-term medical therapy (LTMT).
Results: Persistence of moon face, dorsocervical fat pad and bruisability is more marked in LTMT than in -REM (p<0.05) at 5 years, but most CD phenotypic traits persist in both groups, especially in those with increased late night salivary cortisol (LNSC). Hypertension in the REM group recovers more than in LTMT at 5 years (-31% vs -5%, p<0.04). Overall, hypertensive patients have impaired salivary cortisol rhythm. At 2 years, diabetes is less prevalent in REM than in LTMT (2/36 vs 9/24; p=0.002) with lower need of glucose-lowering drugs. Overall, diabetic patients have higher salivary cortisol levels (p<0.001). Dyslipidemia is more prevalent in LTMT (p=0.01), but with scarce improvement in both groups (-22% REM, - 6% LTMT).
Conclusions: Surgical remission brings faster improvements in clinical phenotype. However, obesity, arterial hypertension, dyslipidemia, and hypercoagulability do not completely revert in 5 years, especially in LTMT group. Most comorbidities persist despite UFC normalization, probably due to impaired LNSC.