“Nonfunctional” Adrenal Tumors and the Risk for Incident Diabetes and Cardiovascular Outcomes

Abstract

Background Adrenal tumors are commonly discovered on abdominal imaging. The majority of adrenal tumors are classified as “non-functional” and considered to pose no health risk, whereas a minority will be considered “functional” because they secrete hormones that increase risk for metabolic and cardiovascular diseases. Objective To evaluate the hypothesis that “non-functional” adrenal tumors (NFAT) increase risk for developing cardiometabolic outcomes when compared with having no adrenal tumor. Design Cohort study. Setting Integrated hospital system. Participants Exposed participants with benign NFAT (n=242) and unexposed participants with no adrenal tumor (n=1237). Measurements Medical records were reviewed from the time of abdominal imaging for development of incident outcomes (hypertension, composite diabetes [pre-diabetes or type 2 diabetes], hyperlipidemia, cardiovascular events, chronic kidney disease) (mean 7.7 years). Primary analyses evaluated independent associations between exposure status and incident outcomes using adjusted generalized linear models. Secondary analyses evaluated relationships between NFAT and cortisol physiology. Results NFAT were associated with significantly higher risk for incident composite diabetes when compared with no adrenal tumor (adjusted RR=1.87, 95% CI: 1.17, 2.98; absolute risk: 30/110 vs. 72/615, 15.6%). No significant associations between NFAT and other outcomes were observed. Higher “normal” post-dexamethasone cortisol levels (<1.8 mcg/dL) associated with larger NFAT size and a higher prevalence of type 2 diabetes. Limitations Potential bias in the selection of participants and ascertainment of outcomes. Conclusions Participants with NFAT had a significantly higher risk of developing diabetes when compared to participants without adrenal tumors. These results prompt a re-assessment of whether the classification of benign adrenal tumors as “non-functional” adequately reflects the continuum of hormone secretion and metabolic risk they may harbor.

Nonfunctioning adrenal incidentaloma: A novel predictive factor for metabolic syndrome

“…Some studies have also demonstrated higher frequencies of metabolic syndrome components in NFAI patients . In this context, our results are in line with previous reports, which have demonstrated increased frequency of glucose and lipid disturbances and arterial hypertension.…”

“…In the present study, patients with NFAI presented a higher frequency of all criteria for metabolic syndrome (hypertension, hyperglycaemia, dyslipidaemia, increased waist circumference) and a greater metabolic syndrome frequency by four different classifications compared to controls. Despite the growing number of studies evidencing a higher frequency of these isolated components of metabolic syndrome in the NFAI population, it has been assumed this is the first clinical study to evaluate and classify patients with NFAI by different metabolic syndrome criteria defined by globally recognized institutions, and to compare them to controls with normal adrenal imaging.…”

Clinical utility of late-night and post-overnight dexamethasone suppression salivary cortisone for the investigation of Cushing’s syndrome

“…20,21 In this study, we adopted a double cut-off as proposed by the European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors 15 ; the rationale being that a more sensitive cut-off should be employed in those with a higher pretest probability of Cushing's syndrome, such as the presence of an adrenal adenoma on imaging studies. 22 A more specific cut-off can be employed in general to avoid overdiagnosis.…”

Nonfunctional Adrenal Adenomas: Truth or Myth? Presentation and Treatment of 2 Patients

“…Despite the frequency of mild cortisol-secreting adenomas (1,5) and their association with cardiovascular risk and metabolic derangements (3), there remains a lack of consensus regarding formal diagnostic criteria and treatment recommendations for this condition. Furthermore, recent studies showed that patients with "nonfunctional" (post-DST cortisol ≤1.8 µg/dL) adrenal adenomas present with insulin resistance, increased carotid intima medial thickness, and impaired vascular flow, and are at increased risk of developing diabetes (6,7). This raises the question of whether "nonfunctional" adrenal adenomas are truly nonfunctional.…”

“…Post-dexamethasone suppression test (DST) serum cortisol values >1.8 µg/dL are considered "possible" autonomous cortisol secretion, and additional testing, including adrenocorticotropic hormone (ACTH), may be indicated to confirm hypercortisolism (5). While cortisol values ≤1.8 µg/dL are thought to exclude autonomous cortisol secretion (5), a growing number of studies have demonstrated increased cardiovascular risk, impaired glucose tolerance, diabetes, and hypertension in patients with "nonfunctional" adrenal adenomas based on this cutoff (6,7). Presented here are two patients with adrenal adenomas whose cases further question the definition of clinically relevant cortisol secretory activity.…”