Hidden hypercortisolism: a too frequently neglected clinical condition

When to Suspect Hidden Hypercortisolism in Type 2 Diabetes: A Meta-Analysis

“…Importantly, at variance with clinically overt Cushing's syndrome, which is considered a rare disease (1) the HidHyCo has not a negligible prevalence, being estimated to be present in 0.8-2% of the adult population (2). In particular in T2D, the prevalence of hypercortisolism has been estimated to be as low as 2-3% and as high as 60%, depending on the severity of T2D, insulin requirements and comorbidity burden, in patients with severe insulin resistance (4,46). In addition, a recent meta-analysis suggest that among T2D patients, the prevalence of a confirmed HidHyCo may be estimated to be about 3.6% (7).…”

“…This is of utmost importance in T2D patients, in whom, an activated hypothalamicpituitary-adrenal axis has been described (48), which may render the diagnosis of autonomous cortisol secretion even more difficult (47). To date, the best screening test for diagnosing HidHyCo is still a matter of debate (4,13,47) and, therefore, no widely accepted indications are available for which T2D patient should be screened for HidHyCo and with what test. While awaiting larger studies to fill the current lack of indications on this matter, the present meta-analysis may give some useful guidance for clinicians regarding when to consider the possibility of HidHyCo in patients with T2D, and thus, when it may be more appropriate to screen such patients.…”

“…Since less severe hypercortisolism is clearly not "subclinical," hidden hypercortisolism (HidHyCo) is a better term, appearing in current literature, describing this condition. Underlying HidHyCo in patients with T2D, hypertension, or osteoporosis may remain occult until its presence is suspected because of the progression and/or severity of the associated chronic diseases (4).…”

Grand Challenge in Adrenal Endocrinology: Is the Legacy of the Past a Challenge for the Future of Precision Medicine?

“…In recent years, more and more evidence has emerged on the deleterious systemic effects arising from adrenal hormone alterations, even if mild and/or asymptomatic. On the other hand, an increased prevalence of adrenal diseases has been reported in patients without signs and symptoms specific of adrenal disorders but affected by chronic diseases or conditions (ie diabetes, hypertension, osteoporosis, depression, fibromyalgia, hypotension) that are often misdiagnosed as 'idiopathic' but which should instead be attributed to observed alterations in adrenal function (1)(2)(3)(4)(5)(6)(7). Such an expansion in knowledge of the role of adrenal hormones in the pathophysiology of common human diseases is in accordance with well-known evidence arising from studies in mammals that adrenal hormones influence several functions, including different metabolic pathways, immune responses, cognition, circadian rhythms, saline homeostasis, blood pressure control and stress response (8).…”

“…Therefore, since occult adrenal hormone dysfunction can occur in some categories of patients, recent research has focused on the screening of adrenal disorders among subjects affected by bone fragility, hypertension, and type 2 diabetes (2,4). However, the aftermath of a wide screening is the finding of false positive results, with potential economic and psychological consequences for health care systems and the patients, respectively (19).…”