Adrenal gland abnormalities found to be common in Cushing’s disease
Small growths in tissue occur 10 times more often in patients, per new study
About half of people with Cushing’s disease have abnormalities in their adrenal glands, the small organs above the kidneys that make cortisol, a new study from Israel has found.
Further, small growths in the adrenal tissue — called adrenal nodules — occurred about 10 times more often in these patients than in the general population, data showed.
In Cushing’s disease, excess cortisol is produced because a tumor in the brain releases high levels of adrenocorticotropic hormone (ACTH), which overstimulates the adrenal glands.
Thus, these findings suggest “that chronic ACTH secretion in [Cushing’s disease] is associated with adrenal nodules appearance,” the researchers wrote.
The team added that, because some nodules may begin producing cortisol on their own, it would be important to monitor adrenal function and structure in people with Cushing’s.
The study, “High prevalence of adrenal imaging abnormalities in Cushing’s disease,” was published in the journal Endocrine.
Cushing’s syndrome occurs when the body is exposed to high levels of cortisol, commonly called the stress hormone, for long periods. In Cushing’s disease, this is caused by a tumor in the brain’s pituitary gland that makes the pituitary produce unusually high levels of ACTH. This then stimulates the adrenal glands to release excessive cortisol, causing typical Cushing’s symptoms. Less commonly, excessive ACTH can be produced by a tumor elsewhere in the body, a condition known as ectopic Cushing’s syndrome.
Over time, such chronic ACTH exposure causes the adrenal glands to undergo hyperplasia, or general enlargement of the adrenal tissue. It may also lead to focal lesions within the tissue, called adrenal nodules.
Using adrenal imaging to look for abnormalities
While the occurrence of adrenal hyperplasia is well documented in ACTH-dependent Cushing’s, the presence and characteristics of adrenal nodules in Cushing’s disease remain poorly understood, according to the researchers, who noted that small sample sizes have often limited previous studies.
To learn more, the team, from Tel Aviv University, analyzed data from 68 people with Cushing’s disease who underwent adrenal imaging over a period of about 30 years. These individuals had the imaging done during the course of their disease, spanning from March 1995 to December 2024.
The patients had a mean age of 44.6, and were primarily women (75%). The median size of the pituitary tumor was 6 mm, or about 0.24 inches, and the median ACTH levels in their blood were 1.2 times the normal upper limit.
Almost all of the patients (95.6%) underwent transsphenoidal surgery, a procedure in which the tumor is removed through the nose. Data showed that 67.7% had an ACTH-producing tumor, and 70.8% saw their hormone levels return to normal after the procedure. During follow-up, 26.2% required additional pituitary surgery due to persistent or recurrent disease.
Additionally, 22.1% underwent radiation therapy, and 57.4% received Cushing’s disease medications, mainly after surgery.
In total, 63 patients underwent abdominal CT scans, and five additional individuals had abdominal MRI scans.
Findings highlight importance of ‘thorough’ lab and imaging diagnosis
A total of 33 patients with Cushing’s disease were found to have normal adrenal glands, per scan data.
However, 16 patients (23.5%) had one adrenal nodule of 10 mm (0.4 inches) or larger, with a median size of 27.5 mm (1.1 inches). Five patients had nodules in the right adrenal gland, six in the left, and five in both glands. All nodules had features consistent with benign tumors, known as adrenal adenomas.
Nine patients (13.2%) had nodules of 20 mm (0.8 inches) or larger, while 19 (27.9%) had adrenal hyperplasia and/or nodules smaller than 10 mm.
Patients with adrenal nodules of 10 mm or larger, as well as those with adrenal hyperplasia or smaller nodules, were significantly older than those with normal adrenal glands. Overall, the number of adrenal nodules tended to increase with age, from 16.7% in patients ages 26-35 to 30.8% in those ages 46-55.
Adrenal nodules in patients with [Cushing’s disease] appear to be a relatively common finding, highlighting the importance of thorough laboratory and imaging diagnosis to identify the cause [of high cortisol levels in patients].
Importantly, lower levels of ACTH were detected in patients with adrenal nodules relative to those without any abnormality in their adrenal glands, which may reflect partial autonomous cortisol secretion by some of the nodules, the researchers wrote.
Patients with adrenal nodules of 10 mm or larger had larger pituitary tumors compared with those who had normal adrenal glands. Rates of remission after surgery were similar across groups, the data showed.
In two of four patients, removing one adrenal gland due to high cortisol levels after pituitary surgery resulted in disease remission. According to the researchers, this suggests that this approach may be effective in managing persistent high cortisol levels after pituitary surgery, especially in those with a large adrenal nodule.
“Our study found that abnormal adrenal imaging was present in 51.5% of patients with [Cushing’s disease],” the researchers wrote, noting also that “the prevalence of adrenal nodules in our [patient group] is 10 times higher than in the general population across all age groups.”
Overall, the scientists concluded that “adrenal nodules in patients with [Cushing’s disease] appear to be a relatively common finding, highlighting the importance of thorough laboratory and imaging diagnosis to identify the cause” of high cortisol levels in patients.
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