Removing Adrenal Glands May Help with Cortisol Control in Difficult-to-treat Patients, Study Reports

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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surgery and Cushing's

Surgically removing both adrenal glands is a safe and effective way to control excessive cortisol levels in people with Cushing’s disease who fail to improve after pituitary surgery or through medication, a study suggests.

Findings also showed that levels of adrenocorticotropic hormone (ACTH) and cortisol, as well as excess cortisol levels (hypercortisolism) for more than six months predicted the need for such surgery, called synchronous bilateral adrenalectomy (SBA).

The research, “Synchronous bilateral adrenalectomy in ACTH-dependent hypercortisolism: predictors, biomarkers and outcomes,” was published in the journal Endocrine.

Cushing’s disease results from production of high levels of ACTH in pituitary tumors, which lead to excessive cortisol being released by the adrenal glands. In patients with ACTH-dependent Cushing’s, complete tumor removal may not be possible and medicines inefficient. SBA is an option in such cases, as it is after long periods of uncontrolled Cushing’s disease.

Though traditionally used only in emergency situations, this surgery has shown an ability to control hypercortisolism, and is associated with low morbidity and mortality. In line with reports showing its increased use, a large study found it to be the treatment-of-choice in 18% of Cushing’s patients. However, specific guidelines for this procedure’s use are lacking.

Researchers at Università Cattolica del Sacro Cuore, in Italy, evaluated outcomes in Cushing’s patients who underwent SBA and aimed to identify biomarkers that help to predict when this surgery is required.

Nineteen patients were analyzed, 11 with Cushing’s disease and eight with ACTH-dependent Cushing’s syndrome. All underwent surgery between December 2003 and December 2017 after failing to control excessive cortisol levels by surgical removal of the pituitary tumor, medication, or other strategies. Following surgery, all were treated with glucocorticoid replacement therapy.

Over a follow-up period ranging from 72 months in Cushing’s patients to 156 months (about 13 years) in those with ACTH-dependent Cushing’s syndrome, no surgery-related complications were reported and no recurrences of hypercortisolism.

One woman developed Nelson’s syndrome, which is characterized by an enlarged pituitary gland and large tumors known as adenomas. She underwent a second pituitary surgery, resulting in stabilization of the residual pituitary adenoma.

Compared to a group of 44 Cushing’s disease patients cured by removing the pituitary tumor, the 11 who underwent SBA were younger at diagnosis (26.5 vs. 42 years), had active disease for a longer time (9 vs. 3 months), and their ACTH and cortisol levels were higher.

ACTH levels above 40 ng/mL, cortisol levels higher than 190 ng/mL in the blood and more than 40 micrograms per 24 hours (mcg/24 h) in urine, and active hypercortisolism for more than six months were found to predict a need for SBA.

Among patients with a pituitary adenoma, having a higher percentage of a marker of cell proliferation (called Ki67) in tumors predicted the need for surgery with a sensitivity of 100%.

Compared to eight patients with ACTH-dependent Cushing’s syndrome who were cured by medication or resection of a lobe from one lung, the eight who underwent SBA had a significantly higher drop in cortisol levels following treatment with dexamethasone at 8 mg. Particularly, a reduction in cortisol higher than 73% with dexamethasone indicated the need for SBA to control cortisol levels in ACTH-dependent Cushing’s syndrome.

“Our data confirm that an SBA is effective both for an immediate control of hypercortisolism and for the improvement of hypercortisolism-related symptoms,” the investigators wrote.

“A multidisciplinary team in a referral centre with a high volume of patients is strongly recommended for the management of these patients and the identification of patients, for better surgical timing,” they added.