Cardiovascular features of possible autonomous cortisol secretion in patients with adrenal incidentalomas

Sbardella, Emilia; Minnetti, Marianna; D’Aluisio, Denise; Rizzà, Laura; Giorgio, Maria Rosaria Di; Vinci, Fabio; Pofi, Riccardo; Giannetta, Elisa; Venneri, Mary Anna; Vestri, Annarita; Morelli, Sergio; Lenzi, Andrea; Isidori, Andrea M.

doi:10.1530/eje-17-0986

Cited by 60 publications

(48 citation statements)

References 34 publications

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“…The present data provide strong evidence to support the view that patients with adrenal incidentalomas have a worse metabolic profile, which is associated with increased cardiovascular risk (13)(14)(15)(16)18). The observation that diabetes was an independent predictor of the presence of adrenal tumors points to the relationship with insulin resistance, which may be bidirectional, as recently argued by Sydney et al (30).…”

Section: Discussionsupporting

confidence: 86%

“…Autonomous cortisol secretion has been defined as subclinical Cushing's syndrome or subclinical hypercortisolism, and represents the lower end of the Cushing's syndrome spectrum. An increasing body of evidence suggests that is associated with metabolic and cardiovascular diseases that may eventually result in excess mortality (13)(14)(15)(16)(17)(18)(19).…”

Section: Most Adrenal Incidentalomas Are Benign Cortical Adenomas Thamentioning

confidence: 99%

“…The possibility that even non-functioning adrenal incidentalomas may predict an increased risk of diabetes has been proposed by Lopez et al (36), who demonstrated in a longitudinal retrospective study how the frequency of incident diabetes found during the follow-up was higher for patients with non-secretory tumors than for those without. More recent studies have suggested that the lack of autonomous cortisol secretion does not exclude an adverse metabolic and cardiovascular profile (13,30,37). A recent meta-analysis assessing morbidity and mortality in patients with adrenal incidentalomas found that diabetes was twice as frequent in patients with autonomous cortisol excess than in patients with non-secretory tumors, although the latter still had a frequency of diabetes higher than the general population (38).…”

Section: Accepted Manuscript 13mentioning

confidence: 99%

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

Reimondo

Castellano

Grosso

et al. 2020

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context The frequency of adrenal incidentalomas and their association with comorbid conditions have been assessed mostly in retrospective studies that may be prone to ascertainment bias. Objective The objective of this work is to evaluate the frequency of adrenal incidentalomas and their associated comorbid conditions. Design A prospective cohort study was conducted. Setting This study took place at a radiology department at a public hospital. Participants Unselected outpatients who underwent an abdominal computed tomography (CT) from January 2017 to June 2018. Patients with known or suspected adrenal disease or malignancy were excluded. Exposure All abdominal CT scans were evaluated by an experienced radiologist. Hormonal workup including a 1-mg dexamethasone suppression test was performed in patients bearing adrenal incidentalomas. Main Outcome and Measure Frequency of adrenal incidentalomas in abdominal CT of unselected patients; frequency of comorbid conditions, and hormonal workup in patients bearing adrenal incidentalomas. Results We recruited 601 patients, and in 7.3% of them an adrenal tumor was found serendipitously. The patients bearing an adrenal incidentaloma had higher body mass index (P = .009) and waist circumference (P = .004) and were more frequently diabetic (P = .0038). At multivariable regression analysis, diabetes was significantly associated with the presence of adrenal incidentalomas (P = .003). Autonomous cortisol secretion was observed in 50% of patients who did not suppress cortisol less than 50 nmol/L after 1 mg dexamethasone. Conclusions The frequency of adrenal incidentalomas is higher than previously reported. Moreover, adrenal incidentalomas are tied to increased risk of type 2 diabetes. This finding is free from ascertainment bias because patients with adrenal incidentalomas were drawn from a prospective cohort with the same risk of diabetes as the background population.

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Section: Discussionsupporting

confidence: 86%

Section: Most Adrenal Incidentalomas Are Benign Cortical Adenomas Thamentioning

confidence: 99%

Section: Accepted Manuscript 13mentioning

confidence: 99%

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

Reimondo

Castellano

Grosso

et al. 2020

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Therefore, eGFR measured by serum creatinine can be overestimated in patients with hypercortisolism. In a recent study showing association between hypercortisolism and cardiac function [23], serum creatinine levels were not significantly different among NFA with pACS, however, this report did not compare eGFR estimated by multiple parameters including serum creatinine and cystatin. The present study is the first to address this important issue, and found that eGFRcre is overestimated even in the pACS patients without Cushing syndrome.…”

Section: Discussionmentioning

confidence: 61%

Overestimation of glomerular filtration rate calculated from serum creatinine as compared with cystatin C in patients with subclinical hypercortisolism: Hyogo Adrenal Metabolic Registry

et al. 2020

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The skeletal muscle mass are decreased in the patients with hypercortisolism. Glomerular filtration rate (eGFR) is not accurately evaluated by calculation from serum creatinine (eGFRcre) in these patients. However, it is not known whether it applies to patients with subclinical hypercortisolism. We investigated the dissociation between eGFRcre and eGFR calculated from cystatin C (eGFRcys) in patients with subclinical hypercortisolism and its association with the skeletal muscle mass. This cross-sectional study includes 23 patients with overt Cushing's syndrome (CS), 84 patients with possible autonomous cortisol secretion (pACS) and 232 patients with non-functioning adenomas (NFA). eGFRcre, eGFRcys, the ratio of eGFRcre to eGFRcys (eGFRcre/eGFRcys) were calculated. Skeletal muscle index (SMI) was measured by a direct segmental multi-frequency bioelectrical impedance body composition analyzer. eGFRcre/eGFRcys was significantly higher (p < 0.01) in pACS (mean ± standard error: 1.15 ± 0.02) than NFA (1.06 ± 0.01). In multiple linear regression analysis, the presence of pACS (β = 0.162, p < 0.01), and post 1 mg-DST cortisol levels (β = 0.190, p < 0.01) were significantly associated with eGFRcre/eGFRcys independent of age, gender, BMI and diabetes. eGFRcre/eGFRcys was significantly and inversely associated with SMI (r =-0.164, p = 0.02). Furthermore, post 1 mg-DST cortisol levels was significantly associated with SMI in simple (r =-0.177, p = 0.01) and multiple (β =-0.089, p = 0.01) regression analyses. In conclusion, dissociation between eGFRcre and eGFRcys was observed in patients with subclinical hypercortisolism at least partly explained by muscle mass. Our findings raise an important clinical point that eGFRcre value should be carefully evaluated even in the phase of subclinical hypercortisolism.

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“…Recent evidence highlighted that cardiac performance may be al tered in patients with hypercortisolism, adding interesting and novel features to the cardiovascular profile of patients with ACS. A recent crosssectional analysis of a large cohort of patients with in cidentalomas revealed that left ventricular mass index, a marker of cardiac hypertrophy associated with hypertension, and pulse wave velocity, a marker of arterial stiffness, were significantly higher in patients with ACS [17]. Moreover, concentric and eccentric left ven tricular hypertrophy was more prevalent in patients with ACS.…”

Section: Risk Of Cardiovascular Diseasesmentioning

confidence: 99%

Adrenal Incidentaloma: Picking out the High-Risk Patients

Dalmazi

2018

Exp Clin Endocrinol Diabetes

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Patients with adrenal incidentalomas and autonomous cortisol secretion (ACS) have been recognized as a category at risk of developing cardiovascular and metabolic co-morbidities. Considering the increasing number of patients affected by this condition, it is important to perform an accurate subtyping of the patients, in the light of a tailored treatment. This review aims to identify the phenotypic characteristics of patients with adrenal incidentalomas and ACS who are at risk of developing severe cortisol-related co-morbidities. ACS has been associated with severe alteration of the cardiovascular profile, including hypertension, diabetes, and atherosclerosis. Moreover, ACS has been identified as a contributing factor to the development of cardiovascular events and related mortality. Patients with ACS are also at risk of incident bone fractures, which occur in half of the patients independently of the bone mass density, and infectious diseases. Severity and persistence of hypercortisolism are among the main contributing factors for cardiovascular diseases and bone fractures. Moreover, progression of hypercortisolism over time and altered circadian cortisol rhythm seem to be important additional factors. The role of potential novel biomarkers is also discussed in this review.

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Cardiovascular features of possible autonomous cortisol secretion in patients with adrenal incidentalomas

Cited by 60 publications

References 34 publications

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

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

Overestimation of glomerular filtration rate calculated from serum creatinine as compared with cystatin C in patients with subclinical hypercortisolism: Hyogo Adrenal Metabolic Registry

Adrenal Incidentaloma: Picking out the High-Risk Patients

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