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Benign adrenal tumors often overproduce cortisol, may raise hypertension, diabetes risks

Annals of Internal Medicine
Reuters Health - 03/01/2022 - Mild autonomous cortisol secretion (MACS) occurred in nearly half of patients, mainly women, with benign adrenal tumors, and was associated with higher prevalence of hypertension and type 2 diabetes in a cross-sectional study.

"Adrenal tumors affect 3-5% of the population and are mostly detected incidentally," Dr. Wiebke Arlt of the University of Birmingham told Reuters Health by email. "Radiologists often don't mention the adrenal nodule in their reports, and if they (do), in many patients this does not prompt a referral to an endocrinologist."

"However, nearly half of the people with benign adrenal tumors we investigated showed evidence of cortisol overproduction, which was a surprising finding," she said. "We also found that increasing cortisol excess comes with an increasing risk of developing type 2 diabetes and high blood pressure."

"Another surprising finding was that the majority of affected individuals were women and with increasing cortisol excess the percentage of women increased further," she added. "Thus, adrenal tumor-related MACS appears to be a previously under-recognized health condition primarily affecting women of post-menopausal age."

As reported in Annals of Internal Medicine, Dr. Arlt and colleagues studied 1,305 patients with benign adrenal tumors recruited from 14 endocrine centers in 11 countries from 2011-2016.

Cortisol excess was defined by clinical assessment and the 1-mg overnight dexamethasone-suppression test: serum cortisol: <50 nmol/L, nonfunctioning adrenal tumor (NFAT); 50 to 138 nmol/L, possible MACS (MACS-1); >138 nmol/L and absence of typical clinical Cushing syndrome (CS) features, definitive MACS (MACS-2).

Net steroid production was assessed by multisteroid profiling of 24-hour urine by tandem mass spectrometry.

About half (49.7%) of participants had NFAT (64.1% women); 34.6% had MACS-1 (67.2% women); 10.7% had MACS-2 (73.6% women); and 5% had CS (86.2% women).

Hypertension prevalence and severity were higher in MACS-2 and CS than in NFAT. Adjusted prevalence ratios for hypertension were: MACS-2, 1.15 and CS, 1.37; aPRs for use of at least three antihypertensives: MACS-2, 1.31 and CS, 2.22.

Type 2 diabetes was more prevalent in CS than in NFAT (aPR, 1.62), and was more likely to require insulin in MACS-2 (aPR, 1.89) and CS (aPR, 3.06).

Urinary multisteroid profiling showed an increase in glucocorticoid excretion from NFAT over MACS-1, and from MACS-2 to CS, whereas androgen excretion decreased.

Dr. Arlt said, "Patients with adrenal tumors should be assessed for MACS and if MACS is present, they should be regularly screened for type 2 diabetes and hypertension and offered appropriate treatment."

Dr. Andre Lacroix of the University of Montreal, author of a related editorial, commented in an email to Reuters Health, "This largest-to-date study on adrenal incidentalomas is very important as it now clearly demonstrates that the higher amount of cortisol excess is associated with increased prevalence of more severe high blood pressure and diabetes. Thus, clinicians should determine the cardiometabolic consequences and the degree of cortisol secretion as precisely as possible in patients with adrenal lesions."

However, he noted, "Relying on a single total serum cortisol value after the 1-mg dexamethasone test has potential pitfalls. It would be preferable to have longitudinal data of cortisol levels over time to better examine the correlations between cortisol excess and its consequences."

He also questioned whether the cortisol cut-off values used in the study are the most appropriate, and noted that future studies could include examining the effects of moderate cortisol excess on mortality and on morbidities such as osteoporosis, infections, muscle strength, and neurocognitive/psychiatric health.

"Clinicians should refer patients with bilateral adrenal nodules and probable primary bilateral macronodular adrenal hyperplasia with any cortisol excess for genetic analysis, and family members carrying the same gene mutation should be screened for early diagnosis and prevention of cortisol excess," he added. "Progression to higher levels of cortisol excess should be verified regularly in PBMAH patients in order to decide when a specific therapy is required."

SOURCES: https://bit.ly/3sUK8DV and https://bit.ly/3HxVIZT Annals of Internal Medicine, online January 3, 2022.

By Marilynn Larkin

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