"Nonfunctional" adrenal tumors tied to increased diabetes risk

By Marilynn Larkin

NEW YORK (Reuters Health) - Benign, so-called "nonfunctional" adrenal tumors may increase the risk of type 2 diabetes, researchers report.

Dr. Anand Vaidya of Brigham and Women's Hospital in Boston told Reuters Health by email that benign adrenal tumors are common and "are almost always discovered incidentally when a CAT scan or MRI of the abdomen is performed to investigate another symptom."

"The high prevalence of adrenal tumors is relevant," he said, "since even benign adrenal tumors can oversecrete the hormone cortisol, leading to a higher risk of developing diabetes and cardiovascular disease. Therefore, it is currently recommended that all benign adrenal tumors be evaluated for cortisol excess to determine if the tumor overtly oversecretes cortisol (Cushing syndrome), or oversecretes mild cortisol (considered 'subclinical' Cushing syndrome), or produces cortisol levels so low that the tumor is considered to be 'nonfunctional.'"

"Most benign tumors are ultimately deemed to be 'nonfunctional' and these nonfunctional adrenal tumors are currently considered to pose no health risk," he explained.

However, as he and his colleagues reported in Annals of Internal Medicine, online August 2, "even nonfunctional adrenal tumors double the risk of developing future diabetes," Dr. Vaidya said.

The team reviewed medical records of 166 patients with nonfunctional adrenal tumors and 740 patients with no adrenal tumors from the time of abdominal imaging for conditions such as hypertension, diabetes or cardiovascular disease through a mean 7.7 years of followup.

Those with nonfunctional adrenal tumors had a significantly higher risk for incident composite diabetes (prediabetes or type-2 diabetes) compared with those without adrenal tumors. Specifically, 27.3% of individuals with the tumors had prediabetes or diabetes versus 11.7% of those without (adjusted risk ratio, 1.87).

There were no significant associations between nonfunctional adrenal tumors and other cardiometabolic outcomes.

Dr. Vaidya observed, "Even though we consider these tumors to be 'nonfunctional,' the miniscule amounts of cortisol that they secrete correlated with the prevalence of diabetes (higher cortisol levels in the 'normal' range associated with more diabetes) and with their size (bigger tumors made more cortisol)."

"This research suggests that the term 'nonfunctional' may be a misnomer when referring to adrenal tumors; rather, there may be a continuum or spectrum of cardiometabolic risk associated with the degree of cortisol secretion that extends all the way down to very low cortisol levels that we have previously considered to be safe," he continued.

That said, Dr. Vaidya noted there is no evidence to suggest that clinicians should try to proactively detect these tumors. "This study only suggests that the risk is higher - there will need to be an intervention study to act on them to prove that one can mitigate that risk by doing something about it," he said.

Commenting on the findings, Dr. Divya Yogi-Morren, an endocrinologist at Cleveland Clinic, told Reuters Health by email, "This study supports many endocrinologists' clinical opinion that there is a continuum of metabolic risk associated with increasing endogenous glucocorticoid levels even if these levels fall within the accepted normal range. This is demonstrated by the finding that the subjects in the study with larger nonfunctional adrenal tumors had higher post-dexamethasone cortisol levels and 24-hour urine cortisol levels and had a higher prevalence of diabetes."

"When these biochemical indicators of hypercortisolemia fall within the accepted normal range, clinicians should still remain cognizant of the possibility that those with values on the higher end of normal may still be at increased risk for prediabetes and diabetes, especially when they have other metabolic risk factors such as increased BMI, as the participants did in this study," she said.

"It would be interesting to extend the followup of these patients with nonfunctioning adrenal tumors to further disclose the natural history of these presumed innocent tumors," Dr. Yogi-Morren concluded.

Dr. Wenyu Huang, an endocrinologist at Northwestern Memorial Hospital in Chicago who also was not involved in the study, pointed out that "even if you see a patient with a nonfunctional tumor, it doesn't mean the tumor will be nonfunctional for their entire life. Guidelines recommend following up with endocrine tests at least yearly to make sure it's truly nonfunctional," whereas the study looked only at a single time point.

In addition, "if you have a patient over age 50 with an incidentaloma and your tests show it's nonfunctional, it still doesn't hurt to screen for diabetes anyway, especially if they have additional risk factors such as high BMI," Dr. Huang told Reuters Health.

SOURCE: http://bit.ly/2aMwlYs

Ann Intern Med 2016.

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