Patients with Subclinical Cushing’s Syndrome due to Adrenal Adenoma Have Increased Cardiovascular Risk

Abstract

Subclinical Cushing's syndrome (SCS) is increasingly being reported in incidentally discovered adrenal adenomas; its hallmark is mild autonomous cortisol hyperproduction without specific clinical signs of cortisol excess. Increased prevalence of hypertension, obesity, and impaired glucose tolerance have been described in SCS, but there is no specific study of the risk factors for cardiovascular diseases. In this cross-sectional study we assessed the cardiovascular profile in 28 consecutive SCS patients (19 women and 9 men; aged 56 +/- 10.6 yr) compared with 100 controls matched for age, gender, and body mass index. Systolic (P < 0.001) and diastolic (P < 0.005) blood pressures were higher in patients, as were fasting glucose, insulin, total cholesterol, triglycerides (all P < 0.001), and fibrinogen (P < 0.05). Moreover, the insulin resistance index was increased in patients as was the waist to hip ratio and mean carotid artery intima-media thickness (all P < 0.001). Of the patients, 60.7% had arterial hypertension, 71.4% had lipid abnormalities, 28.6% had impaired glucose tolerance, 35.7% type 2 diabetes mellitus, and 53.6% had abnormalities in hemostatic parameters. Atherosclerotic plaques were more frequent in patients (P < 0.0001). Only 4 (14.3%) patients did not have multiple risk factors for cardiovascular events. Six (21.3%) had clinical evidence of cardiovascular disease; another 11 (39.3%) had cardiovascular abnormalities as revealed by ultrasound scanning of carotid arteries and/or electrocardiogram records. These results strongly suggest that an increased cardiovascular risk profile, similar to that described in overt Cushing's syndrome, is present in SCS subjects. This finding supports the concept that chronic mild endogenous cortisol excess may have important systemic effects on the human body.

Subclinical Cushing's Syndrome

“…These data support the view that clinically inapparent adrenal adenomas may be associated with an increased risk of metabolic and cardiovascular diseases (27), and extend the results previously obtained by Tauchmanova et al (33). They found that 28 of 126 subjects with adrenal incidentaloma, who qualified for subclinical Cushing's syndrome, showed an adverse risk profile compared with matched controls; these patients also showed a significant increment in the carotid intimalmedial thickness (31).…”

“…Preliminary results suggest that adrenalectomy may benefit patients who have subclinical Cushing's syndrome, but these data should be confirmed in large prospective trials (3,31). At the present time, there is insufficient evidence to recommend adrenalectomy to any patient who qualifies for subclinical Cushing's syndrome (3,28,46).…”

Circulating E-selectin levels and insulin resistance are associated with early stages of atherosclerosis in nonfunctional adrenal incidentaloma

“…Some authors suggested an association between NFA and mild cortisol overproduction secondary to diseases such as subclinical hypercortisolism or subclinical Cushing syndrome (SCS) (6,7). On the other hand, hyperinsulinemia mediated pathogenesis has been considered by other authors who observed a proliferative effect of insulin on adrenal cancer cells without effect on cortisol synthesis (8).…”

The Frequency of Type 2 Diabetic Patients who Meet the Endocrinological Screening Criteria of Subclinical Cushing's Disease

“…SubCS, as well as overt Cushing's syndrome, is also associated with glucose intolerance and cardiovascular disease [5]. The prevalence of subCS (8/10,000) [7], which exceeds that of overt Cushing's syndrome, gives an additional significance to aggressive exploration of subCS.…”

“…versed by surgical treatment of subCS [5,6]. This warrants screening for insidious hypercortisolism in metabolic disorders.…”