Chromogranin A levels set Cushing’s disease, ectopic Cushing’s apart
Protein's levels higher in people with ACTH-dependent ectopic Cushing's
A protein found in tissues that produce and release hormones may be a biomarker to help distinguish Cushing’s disease from adrenocorticotropic hormone (ACTH)-dependent ectopic Cushing’s.
That’s according to a recent study in Japan that also reported that chromogranin A was higher in people with ACTH-dependent ectopic Cushing’s than those with Cushing’s disease.
The research was prompted by a case of cyclic ectopic Cushing’s syndrome, with elevated chromogranin A during periods of disease activity, when ACTH and cortisol were high, and when the disease was inactive.
“Investigating a noninvasive and simple procedure test for diagnosing cyclic Cushing’s syndrome is crucial and plasma chromogranin A measurement shows promise for aiding in the … diagnosis,” the researchers wrote in “Evaluating the usefulness of plasma chromogranin A measurement in cyclic ACTH-dependent Cushing’s syndrome,” in the Endocrine Journal.
Cushing’s syndrome comprises conditions driven by high cortisol levels. One of its common forms, Cushing’s disease, is caused by tumors in the pituitary gland that produce high amounts of ACTH, leading to high levels of cortisol being produced by the adrenal glands atop the kidneys. In rare cases, Cushing’s syndrome is caused by ACTH-producing tumors in other parts of the body, often called ectopic Cushing’s.
Chromogranin A levels stay elevated
Here, researchers described the case of a 72-year-old woman with cyclic ectopic Cushing’s caused by an ACTH-producing carcinoid tumor in her lungs.
The woman was seen at a hospital for a routine follow-up, during which she expressed a general feeling of weakness or discomfort. Blood tests revealed elevated ACTH and cortisol. A CT scan revealed two lung nodules and enlarged adrenal gland, while an MRI scan detected a pituitary microadenoma, a small benign tumor in the pituitary gland.
The woman was referred to a university hospital to be evaluated and, when she was admitted, her ACTH and cortisol levels were within the normal range and she had no symptoms of Cushing’s, but they progressively increased during her hospitalization.
Her ACTH levels didn’t respond to corticotropin-releasing hormone (CRH) stimulation or desmopressin tests, which normally stimulate the release of ACTH in people with pituitary adenomas. This led clinicians to suspect ectopic Cushing’s.
Additional tests failed to confirm excessive production and release of ACTH, leaving the responsible lesion unidentified. The woman was discharged after her ACTH and cortisol spontaneously normalized.
Following several episodes of disease worsening, a CT scan performed during the woman’s fourth hospitalization showed that one lung nodule had grown and was producing ACTH, causing Cushing’s. After it was surgically removed, the woman’s ACTH normalized and the disease showed no signs of reoccurring.
The researchers found it interesting that the woman’s blood chromogranin A levels were elevated, particularly in periods where the disease was active, prompting them to investigate whether chromogranin A could be used as a diagnostic marker for ACTH-dependent Cushing’s
They analyzed the woman’s blood samples as well as samples from two people with noncyclic ectopic Cushing’s caused by pancreatic tumors and six people with Cushing’s disease.
Chromogranin A levels were found to be significantly higher in people with ectopic Cushing’s than in those with Cushing’s disease (734.8 vs. 371.7 nanograms per milliliter). They were also higher in both disease groups compared with the reference mean levels of the protein in human samples.
The findings indicate that measuring “plasma chromogranin A levels could aid in differentiating [ectopic Cushing’s] from [Cushing’s disease],” the researchers said.
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