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An increased risk of death was seen with higher levels of autonomous cortisol secretion (ACS), a new study found.

In a retrospective cohort of patients with adrenal incidentalomas, plasma cortisol level after a 1-mg dexamethasone suppression test (DST) had a linear relationship with mortality risk, reported Henrik Olsen, MD, of Skåne University Hospital in Sweden, and colleagues.

Specifically, patients with a cortisol DST of 5 µg/dL or higher had the highest risk of death -- over three-fold higher -- compared with those with a cortisol DST less than 1.8 µg/dL (HR 3.04, 95% CI 1.86-4.98), they noted in the .

Those with a cortisol DST of 3 µg/dL to 5 µg/dL had a more than two-fold higher risk for mortality versus those with a level under 1.8 µg/dL (HR 2.30, 95% CI 1.52-3.49).

However, those with just slightly elevated levels of ACS -- a cortisol DST of 1.8 µg/dL to 3 µg/dL -- did not see a significantly higher risk for death compared with those who had levels under 1.8 µg/dL.

Over the median 6.4-year follow-up period, a total of 170 of 1,048 patients with adrenal incidentalomas died.

"Adrenal incidentalomas are frequently detected at cross-sectional imaging," Olsen explained to 乌鸦传媒, adding that these tumors are present in about 6% to 10% of people ages 60 to 80.

While these tumors can secrete cortisol and cause ACS, Olsen noted that ACS itself encompasses a wide spectrum, ranging from discretely elevated cortisol after dexamethasone, to very high levels comparable to those seen in clinical Cushing syndrome.

"Thus, the risk associated with ACS may theoretically vary with the grade of ACS," he noted. "It is important to know the risk associated to a specific grade of ACS to be able to incorporate this in the decision to operate or not."

Based on these findings, Olsen pointed out that the threshold of "clinical importance" was a cortisol level after dexamethasone of 3 µg/dL or higher.

"Approximately 20% of patients with adrenal incidentalomas have ACS with cortisol DST 83 nmol/L or higher [3 µg/dL]," he explained. "This is linked to a two- to three-fold increase in mortality depending on the cortisol DST level."

Overall, the most common causes of mortality among those with a cortisol DST above 3 µg/dL were cardiovascular diseases, followed by cancer, infectious diseases, and other diseases.

"Until studies have demonstrated beneficial effect of surgery on mortality, some clinicians may consider this finding when deciding which patients to recommend for surgery," Olsen suggested.

This analysis included adult patients at the endocrinology units of Helsingborg Hospital and Skåne University Hospital in Sweden from 2005 to 2015. Some exclusion criteria included metastatic cancer, a tumor smaller than 1 cm, non-adenoma lesions, pheochromocytomas, primary aldosteronism or clinical Cushing syndrome, oral glucocorticoid treatment or use of inhaled steroids, or systemic estrogen treatment.

All patients had a DST with 1 mg of dexamethasone taken at 11 p.m. followed by a blood sample to measure cortisol, which was collected at 8 a.m. the next morning.

Among the 1,048 patients included, the majority had a cortisol DST below 1.8 µg/dL (n=575), followed by 1.8-3 µg/dL (n=272), 3-5 µg/dL (n=119), and 5 µg/dL or greater (n=82).

Rates of hypertension increased according to cortisol level grouping, with 73% of those with a cortisol DST of 5 µg/dL or greater having hypertension. Average adenoma size also increased according to cortisol DST. Additionally, higher cortisol levels were more common for those with bilateral adenomas.

Not surprisingly, patients with a cortisol DST of 5 µg/dL or higher also saw a significantly higher risk for a major cardiovascular event (HR 2.41, 95% CI 1.45-4.02).

About a quarter of patients falling into the highest degree of cortisol DST underwent surgery, whereas only 2.4% of those with the lowest DST had surgery.

One limitation to the study was an inability to quantify the mortality risk among those with a cortisol DST of 7.25 µg/dL or higher due to the small number of patients with this level.

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