Study IDs Risk Factors for Kidney Impairment After Adrenal Surgery

Risks include low ACTH levels before surgery or higher steroid doses post-surgery

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Researchers have identified risk factors for kidney impairment in adults with Cushing’s syndrome after they undergo surgery to remove their adrenal glands.

These factors include having low pre-operative adrenocorticotropic hormone (ACTH) levels or taking higher steroid replacement doses after the surgery.

“Disease activity represented by ACTH levels or the steroid replacement dose may be an indicator of postoperative renal function,” researchers wrote in their study, “Predictors of renal function after adrenalectomy in patients with Cushing or subclinical Cushing syndrome,” which was published in the International Journal of Urology.

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Cushing’s syndrome is marked by the chronic excess of the stress hormone cortisol. Cushing’s disease, which accounts for about 70% of all Cushing’s syndrome cases, is caused by non-cancerous tumors in the brain’s pituitary gland that trigger the production of excess ACTH.

Too much ACTH stimulates the adrenal glands, which sit atop the kidneys, to produce too much cortisol, leading to Cushing’s symptoms that include weight gain, high blood pressure, high blood sugar levels, and bone thinning.

Surgery to remove pituitary tumors — called transsphenoidal adenomectomy — is the first line of treatment for Cushing’s disease patients and has been shown to relieve symptoms in up to 90% of cases.

Studies suggest that high levels of cortisol may also impair the kidneys. The estimated glomerular filtration rate (eGFR), a measure of kidney function, is lower in people with Cushing’s disease than in healthy populations.

However, the effects of adrenalectomy — a surgery to remove the adrenal glands, which is the first-line treatment for adrenal Cushing’s — on kidney function in patients remain unclear.

What did the study investigate?

In the new study, scientists at the Keio University School of Medicine, in Japan, examined changes in kidney function in a group of 76 adults with Cushing’s who underwent adrenalectomy. They also sought pre- and post-surgical predictors of kidney impairment.

The study included 62 female and 14 male patients, of whom 17 (22.4%) had subclinical Cushing’s, meaning they had elevated cortisol levels, but were without overt disease symptoms. The mean age at adrenalectomy was 49.0 years, with a mean follow-up of 60.9 months (about five years).

One month after the procedure, kidney function significantly deteriorated, based on lower mean eGFR values and high mean levels of creatinine, a marker of kidney dysfunction, in the bloodstream. At the same time, mean blood cortisol levels significantly decreased.

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In comparison, one year after surgery, kidney function fully recovered to pre-surgical levels, as did the levels of two markers of adrenal gland deficiency. Similar results were seen between patients with signs of Cushing’s and those who did not exhibit symptoms.

In 26 participants (34.2%), however, the kidney impairment seen after one month did not fully resolve after one year. Pre-operative ATCH levels in these patients were significantly lower than in those who did not show signs of kidney impairment one year after surgery.

Overall, lower pre-operative ACTH levels, larger tumor size, and the absence of high blood pressure were predictors of kidney impairment. After statistical adjustments, a low pre-operative ACTH level was the only independent predictor of kidney impairment after one year.

No predictive factors were found for kidney function one month after surgery. Again, no differences were seen between the groups.

Information on steroid replacement following surgery, which allows the body to naturally maintain healthy cortisol levels until recovery, was available for 43 patients. Among them, 18 (41.9%) had kidney impairment after one year. Although steroid doses were similar up to nine months, those with kidney problems required higher doses after one year.

Within this group, pre-operative ACTH levels were lower in patients with impaired kidney function.

In patients without risk factors, one out of 10 (10%) sustained post-surgical kidney impairment. In those with one risk factor — low pre-operative ACTH or sustained steroid replacement after one month — five out of 16 (31.3%) had kidney impairment, as did 12 out of 17 (70.6%) with both of these risk factors.

These findings led researchers to recommend that “urologists need to consider these risk factors before and after adrenalectomy.”