Autonomous hypercortisolism: definition and clinical implications

Abstract

In current practice, an adrenal adenoma usually comes as an unexpected byproduct of an imaging study performed for unrelated reasons, without any prior suspect of adrenal disease. Therefore, these tumors currently represent a public health challenge because they are increasingly recognized due to the widespread use of high-resolution cross-sectional imaging for diagnostic purposes. In radiology series, the prevalence of adrenal adenomas increases steeply with age, from around 3% below the age of 50 years up to 10% in the ageing population. These tumors may have clinical relevance because they are able to secrete cortisol autonomously, independently from the pituitary control, in up to 20%-30% of patients. In most of the cases the resulting cortisol excess is insufficient to produce a typical Cushing phenotype but may have clinical consequences, such as hypertension, diabetes, obesity, dyslipidemia and osteoporosis. Despite some controversy on the most effective diagnostic algorithm to define this subtle hypercortisolism, there is mounting evidence that a simple approach by using the 1-mg overnight dexamethasone suppression test (DST) may stratify patients for their cardiovascular risk. Crosssectional, retrospective studies showed that patients with increasingly higher cortisol following DST have an adverse cardiovascular risk profile and are at increased risk of death. Therefore, also a subtle autonomous cortisol excess is associated with increased morbidity and mortality, mainly of cardiovascular origin.

Adrenal Incidentalomas are Tied to Increased Risk of Diabetes: Findings from a Prospective Study

“…patients do not present the classic stigmata of adrenal steroid excess. In 20-30% of adrenal incidentalomas, an autonomous cortisol secretion is found that may have clinical consequences (9)(10)(11)(12). To standardize and simplify heterogeneous clinical practice, the European Society of Endocrinology and the European Network for the Study of Adrenal Tumors (ESE/ENSAT) guidelines recommended a 1 mg overnight dexamethasone suppression test (DST) to exclude cortisol excess (10).…”

Is Follow-up of Adrenal Incidentalomas Always Mandatory?

“…Nevertheless, it has been shown that low-grade autonomous cortisol excess might be associated with comorbidities (hyper-tension, glucose intolerance/type 2 diabetes mellitus, obesity, dyslipidemia, osteoporosis) [2,40], without being a preliminary stage of overt Cushing syndrome [26].…”

Targeting Nrf2-Mediated Oxidative Stress Response Signaling Pathways as New Therapeutic Strategy for Pituitary Adenomas

“…NFPAs are nonhormone-secreting PAs (Qian et al, 2018). The main clinical symptoms of PAs include inappropriate hormone secretion syndrome, and compression of the neighboring tissues and structures such as headache, visual field defect, and increased intracranial pressure (Reimondo et al, 2019). PA is a multifactor, multi-process, and multi-consequence complex disease, which is involved in a series of molecular alterations at the levels of genome, transcriptome, proteome, peptidome, metabolome, and radiome; and these molecules mutually associate and function in a molecular network system (Zhan and Desiderio, 2010b;Hu et al, 2013;Grech et al, 2015;Cheng and Zhan, 2017;Lu and Zhan, 2018).…”