Progressively increased patterns of subclinical cortisol hypersecretion in adrenal incidentalomas differently predict major metabolic and cardiovascular outcomes: a large cross-sectional study

Abstract

Background: Subclinical Cushing's syndrome (SCS) is defined as alterations in hypothalamic-pituitaryadrenal axis without classic signs/symptoms of glucocorticoid excess. Whether SCS leads to metabolic and cardiovascular diseases is still controversial. Aim: To evaluate the prevalence of hypertension, type 2 diabetes (T2D), coronary heart disease (CHD), ischemic stroke, osteoporosis, and fractures, and their relationship to increasing patterns of subclinical hypercortisolism, in patients with nonsecreting adrenal adenomas (NSA) and SCS. Methods: Using the 1 mg dexamethasone suppression test (DST), 348 patients were classified as follows: 203 were defined as NSA and 19 SCS, using the most stringent cutoff values (!50 and O138 nmol/l respectively). Patients with cortisol post-DST (50-138 nmol/l) were considered as intermediate phenotypes and classified as minor (nZ71) and major (nZ55) using plasma ACTH and/or urinary free cortisol as additional diagnostic tools. Results: SCS patients showed higher prevalence of T2D, CHD, osteoporosis, and fractures with respect to NSA. Intermediate phenotypes also showed higher prevalence of CHD and T2D with respect to NSA. The prevalence of all clinical outcomes was not different between intermediate phenotype patients, which were therefore considered as a single group (IP) for multivariate logistic regression analysis: both IP and SCS-secreting patterns showed a significant association with CHD (odds ratio (OR), 4.09; 95% confidence interval (CI), 1.47-11.38 and OR, 6.10; 95% CI, 1.41-26.49 respectively), independently of other potential risk factors. SCS was also independently associated with osteoporosis (OR, 5.94; 95% CI, 1.79-19.68). Conclusions: Patterns of increasing subclinical hypercortisolism in adrenal adenomas are associated with increased prevalence of adverse metabolic and cardiovascular outcomes, independently of other potential risk factors.

Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses

“…For instance, increased total plasma cortisol is a typical finding in people with Cushing's Disease68, 69 but is not commonly observed in horses and ponies with PPID 2. Further, atherosclerosis and related cardiovascular disease (ie, stroke, myocardial infarction) are a key aspect of Metabolic Syndrome in people and are associated with increases in total and free cortisol,34, 70 but these clinical abnormalities are not appreciated in EMS 1, 31. In EMS, cardiovascular pathology resulting from vascular endothelial dysfunction might manifest as laminitis,71 but other mechanisms, such as insulin‐mediated overstimulation of the insulin‐like growth factor 1 receptor leading to lamellar hypertrophy and weakening, might also contribute to the development of laminitis in EMS 72.…”

Bilateral and unilateral adrenal incidentalomas: biochemical and clinical characteristics

“…SH has been associated with an increased prevalence of arterial hypertension (AH) and metabolic alterations such as dyslipidaemia (DL) and type 2 diabetes mellitus (T2DM) (12), and with an increased risk of osteoporosis and vertebral fractures (FX) (13).…”

cAMP signaling in cortisol-producing adrenal adenoma

“…Several cross-sectional studies have highlighted that glucocorticoid-induced osteoporosis (GIO) and its related complications indeed occur also in patients with subclinical hypercortisolism (24, 25,26,27,28,29). Moreover, three recent retrospective studies showed a role for mild cortisol hypersecretion in the development of cardiovascular diseases in patients with subclinical hypercortisolism (30,31).…”