Endocrine Abstracts

Introduction: Cushing’s disease (CD) is associated with significant morbidity and mortality due to cerebro-cardiovascular, thrombotic or infectious complications. However, there is significant variation in the clinical presentation and consequences of hypercortisolism, resulting in a wide clinical spectrum, ranging from mild to severe or even life-threatening disease requiring immediate treatment.

Aim: The description of patients with severe CD in comparison with milder forms, with regards to their clinical characteristics and outcome.

Patients and Methods: 171 patients with CD (144 females), mean age 45 ± 14 years who were admitted in our Department. We defined biochemically severe CD (BCD, n = 19) by serum cortisol more than 36 µg/dl at any time or a 24-h urinary free cortisol > 4 × ULN and/or severe hypokalaemia (<3.0 mmol/l), and as clinically severe CD (CCD, n = 15) the presence of one or more of the following: sepsis, opportunistic infection, uncontrolled hypertension, heart failure, acute psychosis, progressive debilitating myopathy, thromboembolism or uncontrolled hyperglycaemia. Patients fulfilling both criteria were defined as severe CD (SCD, n = 21). The remaining patients were defined as non-severe CD (NSCD, n = 116).

Results: There were no differences in age and mean adenoma size among groups; the prevalence of macroadenomas was 27% in NSCD patients, 16% in BCD, 27% in CCD and 14% in SCD. Baseline ACTH levels were higher in BCD and SCD groups compared to CCD and NSCD groups and the ACTH-to-cortisol ratio was similar among groups. Early, 90-days-mortality from sepsis/opportunistic infections was observed in 3 (20%) patients with CCD and 2 (9.5%) patients with SCD, despite medical aggressive management with ketoconazole and metyrapone. When only patients with long-term follow-up (>2 years, mean follow- up time 4.7 ± 2.8 years) were considered (n = 120), bilateral adrenalectomy to control hypercortisolism was performed in 27% of BCD, 38% of CCD and 31% of SCD, compared to only 8.6% of NSCD patients. Long-term mortality (mean time to death after diagnosis 10.9 ± 5.8 years) was higher in SCD (19%) and BCD (13%) vs 2.5% in NSCD.

Conclusions: Cushing’s disease remains a detrimental disease with significant early and late mortality, especially in patients presenting with severe biochemical and/or clinical hypercortisolism.