Mild Autonomous Cortisol Secretion Linked to Increased Hypertension, Requiring Insulin Therapy

Alessandro Prete, MD

New research suggests patients with adrenal masses could be at an increased risk of severe hypertension and requiring insulin therapy if they had type 2 diabetes.

In what investigators are calling the largest study of its kind, results suggest patients with adrenal incidentalomas with mild autonomous cortisol secretion (MACS) were more likely to be diagnosed with hypertension and to require 3 or more medications to achieve adequate blood pressure control. Results also indicate patients with type 2 diabetes and MACS were nearly twice as likely as their counterparts without MACS to require insulin therapy.

“Our study found that MACS is very frequent and is an important risk condition for high blood pressure and type 2 diabetes, especially in older women, and the impact of MACS on high blood pressure and type 2 diabetes risk has been underestimated until now,” said study investigator Alessandro Prete, MD, MBBS, of the University of Birmingham’s Institute of Metabolism and Systems Research, in a statement.

With funding from Diabetes UK, the European Commission, the Medical Research Council, and the Claire Khan Trust Fund at University Hospitals Birmingham Charity, the current study was designed by Prete and a team of colleagues from the University of Birmingham and other institutions with an interest of describing the effect of mild autonomous cortisol secretion on cardiometabolic disease among patients with benign adrenal tumors. With this in mind, the study was designed as a cross-sectional analysis of data from 14 endocrine secondary and tertiary care centers, with recruitment performed from 2011-2016.

From these care centers, investigators identified 1305 patients with benign adrenal tumors for inclusion in the study. For the purpose of analysis, cortisol excess was defined by clinical assessment and the 1 mg overnight dexamethasone-suppression test. Serum cortisol levels below 50 nmol/L was considered a nonfunctioning adrenal tumor, 50-138 nmol/L was considered possible MACS, and greater than 138 nmol/L with an absence of typical clinical Cushing’s syndrome features was considered definitive MACS. Investigators assessed net steroid production using multisteroid profiling of 24-hour urine by tandem mass spectrometry. Outcomes of interest for the investigators’ analyses included incidence and severity of hypertension as well as need for insulin therapy among patients with type 2 diabetes.

Of the 1305 patients included in the study, 49.7% (n=649) had a nonfunctioning adrenal tumor, 34.6% (n=451) had possible MACS, 10.7% (n=140) had definitive MACS, and 5.0% (n=65) had Cushing’s syndrome. These groups were 64.1%, 67.2%, 73.6%, and 86.2% women, respectively. Initial analyses suggested the prevalence and severity of hypertension were greater among those with definitive MACS and Cushing’s syndrome than nonfunctioning adrenal tumors (aPRs for hypertension: definitive MACS, 1.15 [95% CI, 1.04-1.27], and Cushing’s syndrome, 1.37 [95% CI, 1.16-1.62]; aPRs for use of 3 or more antihypertensives: definitive MACS, 1.31 [95% CI, 1.02-1.68], and Cushing’s syndrome, 2.22 [95% CI, 1.62-3.05]).

Further analysis indicated diagnoses of type 2 diabetes were more prevalent among those with Cushing’s syndrome than those with nonfunctioning adrenal tumors (aPR, 1.62 [95% CI, 1.08-2.42]). Additionally, patients with type 2 diabetes were more likely to require insulin therapy if they had definitive MACS (aPR, 1.89 [95% CI, 1.01-3.52]) and Cushing’s syndrome than if they had a nonfunctioning adrenal tumor. Investigators pointed out urinary multisteroid profiling indicated an increase in glucocorticoid exertion from nonfunctioning adrenal tumor over possible MACS and definitive MACS to Cushing’s syndrome, whereas androgen excretion decreased.

“Previous studies suggested that MACS is associated with poor health. However, our study is the largest ever study to establish conclusively the extent of the risk and severity of high blood pressure and type 2 diabetes in patients with MACS,” said Wiebke Arlt, MD, DSc, director of the University of Birmingham’s Institute of Metabolism and Systems Research. “Our hope is that this research will put a spotlight on this condition and increase awareness of its impact on health. We advocate that all patients who are found to carry an adrenal incidentaloma are tested for MACS and have their blood pressure and glucose levels measured regularly.”

This study, “Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors,” was published in the Annals of Internal Medicine.