Cardiovascular complications of mild autonomous cortisol secretion

Aresta, Carmen; Favero, V. Del; Morelli, Valentina; Giovanelli, Luca; Parazzoli, Chiara; Falchetti, Alberto; Pugliese, Flavia; Gennari, Luigi; Vescini, Fabio; Salcuni, Antonio Stefano; Scillitani, Alfredo; Persani, Luca; Chiodini, Iacopo

doi:10.1016/j.beem.2021.101494

Cited by 29 publications

(25 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, in eucortisolemic patients with diabetes, modulation of 11bHSD activity was found to improve diabetes control. Finally, a growing body of evidence suggests a positive relationship between physiological, yet higher, urinary cortisol levels and cardiovascular risk (25).…”

Section: Discussionmentioning

confidence: 99%

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

Chiodini

Gennari

2021

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

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

Chiodini

Gennari

2021

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

“…Arterial hypertension is present in over 60% of mHC patients [ 83 ]. At the time of diagnosis, about 58–64% of patients with mHC display hypertension [ 54 ].…”

Section: Pathophysiology Of the Systemic Consequences Of Mild Hypercortisolismmentioning

confidence: 99%

“…Patients with AI and mHC have a higher risk of cardiovascular events (including coronary artery disease, myocardial infarction, stroke, transient ischemic attack and heart failure) and mortality compared to patients with nonsecreting AI and controls [ 83 , 88 ]. Importantly, the increased cardiovascular risk and mortality in mHC is independent of the presence of diabetes and hypertension [ 89 , 90 , 91 , 92 ].…”

Section: Pathophysiology Of the Systemic Consequences Of Mild Hypercortisolismmentioning

confidence: 99%

“…Finally, the possible role of accelerated subclinical atherosclerosis in the determination of cortisol excess-related CV risk should not be overlooked. Several studies reported an increased intima–media thickness, higher prevalence of carotid plaques and lower flow-mediated dilatation in patients with overt Cushing’s syndrome compared to controls [ 83 ]. Interestingly, in a study including 60 normotensive euglycemic patients with AI and 32 healthy controls with normal adrenal imaging, the intima–media thickness correlated with cortisol levels after DST, whose cutoff set at 1.4 μg/dL had higher accuracy (sensitivity 79.2%, specificity 88%) in predicting the cardiovascular risk profile [ 93 ].…”

Section: Pathophysiology Of the Systemic Consequences Of Mild Hypercortisolismmentioning

confidence: 99%

See 1 more Smart Citation

Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside

Favero

Cremaschi

Parazzoli

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

Mild hypercortisolism is defined as biochemical evidence of abnormal cortisol secretion without the classical detectable manifestations of overt Cushing’s syndrome and, above all, lacking catabolic characteristics such as central muscle weakness, adipose tissue redistribution, skin fragility and unusual infections. Mild hypercortisolism is frequently discovered in patients with adrenal incidentalomas, with a prevalence ranging between 5 and 50%. This high variability is mainly due to the different criteria used for defining this condition. This subtle cortisol excess has also been described in patients with incidentally discovered pituitary tumors with an estimated prevalence of 5%. To date, the mechanisms responsible for the pathogenesis of mild hypercortisolism of pituitary origin are still not well clarified. At variance, recent advances have been made in understanding the genetic background of bilateral and unilateral adrenal adenomas causing mild hypercortisolism. Some recent data suggest that the clinical effects of glucocorticoid (GC) exposure on peripheral tissues are determined not only by the amount of the adrenal GC production but also by the peripheral GC metabolism and by the GC sensitivity. Indeed, in subjects with normal cortisol secretion, the combined estimate of cortisol secretion, cortisone-to-cortisol peripheral activation by the 11 beta-hydroxysteroid dehydrogenase enzyme and GC receptor sensitizing variants have been suggested to be associated with the presence of hypertension, diabetes and bone fragility, which are three well-known consequences of hypercortisolism. This review focuses on the pathophysiologic mechanism underlying both the different sources of mild hypercortisolism and their clinical consequences (bone fragility, arterial hypertension, subclinical atherosclerosis, cardiovascular remodeling, dyslipidemia, glucose metabolism impairment, visceral adiposity, infections, muscle damage, mood disorders and coagulation).

show abstract

“…Mild hypercortisolism (mHC), also defined as subclinical hypercortisolism, less severe hypercortisolism or subclinical Cushing syndrome (CS), is a condition of excessive cortisol secretion, without the specific symptoms and manifestations of clinically overt CS (i.e., proximal muscle weakness, facial plethora, easy bruising, purple striae) [ 1 , 2 ]. Despite the lack of typical signs and symptoms and the absence of severe cortisol excess, mHC has been associated with bone fragility, mood alterations, hypertension, alterations in glucose and lipid metabolism, increased cardiovascular risk and mortality [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. At variance, patients with mHC may present with features that are common in the general population and less discriminatory for the presence of a cortisol excess, such as a dorso-cervical fat pad (“buffalo hump”), facial fullness, obesity, supraclavicular fullness, thin skin, peripheral edema, acne, hirsutism and poor skin healing.…”

Section: Introductionmentioning

confidence: 99%

Management and Medical Therapy of Mild Hypercortisolism

Favero

Cremaschi

Falchetti

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Mild hypercortisolism (mHC) is defined as an excessive cortisol secretion, without the classical manifestations of clinically overt Cushing’s syndrome. This condition increases the risk of bone fragility, neuropsychological alterations, hypertension, diabetes, cardiovascular events and mortality. At variance with Cushing’s syndrome, mHC is not rare, with it estimated to be present in up to 2% of individuals older than 60 years, with higher prevalence (up to 10%) in individuals with uncontrolled hypertension and/or diabetes or with unexplainable bone fragility. Measuring cortisol after a 1 mg overnight dexamethasone suppression test is the first-line test for searching for mHC, and the degree of cortisol suppression is associated with the presence of cortisol-related consequences and mortality. Among the additional tests used for diagnosing mHC in doubtful cases, the basal morning plasma adrenocorticotroph hormone, 24-h urinary free cortisol and/or late-night salivary cortisol could be measured, particularly in patients with possible cortisol-related complications, such as hypertension and diabetes. Surgery is considered as a possible therapeutic option in patients with munilateral adrenal incidentalomas and mHC since it improves diabetes and hypertension and reduces the fracture risk. In patients with mHC and bilateral adrenal adenomas, in whom surgery would lead to persistent hypocortisolism, and in patients refusing surgery or in whom surgery is not feasible, medical therapy is needed. Currently, promising though scarce data have been provided on the possible use of pituitary-directed agents, such as the multi-ligand somatostatin analog pasireotide or the dopamine agonist cabergoline for the—nowadays—rare patients with pituitary mHC. In the more frequently adrenal mHC, encouraging data are available for metyrapone, a steroidogenesis inhibitor acting mainly against the adrenal 11-βhydroxylase, while data on osilodrostat and levoketoconazole, other new steroidogenesis inhibitors, are still needed in patients with mHC. Finally, on the basis of promising data with mifepristone, a non-selective glucocorticoid receptor antagonist, in patients with mild cortisol hypersecretion, a randomized placebo-controlled study is ongoing for assessing the efficacy and safety of relacorilant, a selective glucocorticoid receptor antagonist, for patients with mild adrenal hypercortisolism and diabetes mellitus/impaired glucose tolerance and/or uncontrolled systolic hypertension.

show abstract

Cardiovascular complications of mild autonomous cortisol secretion

Cited by 29 publications

References 101 publications

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

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

Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside

Management and Medical Therapy of Mild Hypercortisolism

Contact Info

Product

Resources

About