ACTH-producing advanced adrenal cancer is Cushing’s cause in woman
Study details 'exceedingly rare' case of patient, 26, in Portugal
In what researchers describe as an “exceedingly rare” case, adrenocorticotropic hormone (ACTH)-producing advanced adrenal gland cancer was determined to be the cause of Cushing’s syndrome in a 26-year-old woman in Portugal.
Adrenocortical carcinoma is typically associated with ACTH-independent Cushing’s — forms of the syndrome in which excessive cortisol production is not driven by ACTH. However, according to the researchers, in rare instances like this one, this type of malignant cancer may be linked to ACTH-dependent forms of Cushing’s.
“[This type of cancer] may exceedingly rarely produce ACTH and thus may be associated with an ACTH-dependent Cushing’s syndrome and not with the classical ACTH-independent Cushing’s syndrome that typically arises from cortisol-producing adrenal [tumors],” the researchers wrote.
The case was described in a study titled “ACTH-producing adrenocortical carcinoma: an exceedingly rare diagnosis,” published in the Journal of the Egyptian National Cancer Institute.
Researchers urge ‘broad-minded approach’ in looking for Cushing’s cause
Cushing’s syndrome is characterized by hypercortisolism, or the presence of high levels of the stress hormone cortisol, which is produced by the adrenal glands located atop the kidneys. Cushing’s disease is one of the most common forms of the syndrome. It is caused by a tumor in the brain’s pituitary gland, which produces excessive amounts of ACTH, a hormone that triggers cortisol production.
Less frequently, tumors in the adrenal glands themselves can increase cortisol production and cause Cushing’s. In very rare cases, these tumors are malignant. Their presence is usually associated with ACTH-independent Cushing’s.
In this study, the researchers described the case of a young woman who was found to have adrenocortical carcinoma associated with ACTH-dependent Cushing’s.
The woman was referred to a hospital in Porto due to weight gain, swelling of the extremities, hair loss, excessive body hair growth, and acne that had been evolving over the prior eight months. A previous CT scan detected the presence of a tumor in her right adrenal gland that had invaded the kidney and liver.
A physical examination revealed she had high blood pressure, facial swelling, fat accumulation between the shoulder blades — known as a buffalo hump, it’s a hallmark disease symptom — stretch marks in the abdomen and thighs, armpit skin darkening, and muscle wasting. All of these are signs and symptoms of Cushing’s.
Laboratory tests revealed cortisol levels were elevated in the urine, as well as in the saliva.
Her blood cortisol levels also failed to drop after an overnight low-dose dexamethasone test, which is usually performed to confirm the presence of hypercortisolism.
The woman’s ACTH levels also were elevated, as were the levels of male sex hormones — a condition called hyperandrogenism.
Further PET/CT imaging studies indicated she had adrenal cancer that had invaded the right portion of the liver and the right kidney. Lesions consistent with cancer metastasis, which occurs when cancer spreads into other organs, were also found in the liver.
Given these observations, the researchers concluded that adrenal cancer was the likely cause of the patient’s hypercortisolism and hyperandrogenism.
However, they could not explain her high ACTH levels, as there were no signs of other tumors associated with ectopic ACTH production, or that taking place outside the pituitary gland.
This case emphasizes that physicians should have a broad-minded approach when evaluating cases of rare endocrine malignancies.
The woman was referred for surgery to remove as much of the tumor as possible. However, during the procedure, clinicians concluded the tumor was impossible to remove. During surgery, a biopsy from one of the liver nodules was obtained, and its microscopic analysis was consistent with the diagnosis of adrenocortical carcinoma that had spread to the liver. Tumor cells were also found to be positive for ACTH, indicating the tumor had the ability to produce ACTH.
The patient then started treatment with metyrapone and spironolactone to control hypercortisolism and hyperandrogenism symptoms. She also was slated to start a palliative chemotherapy combined regimen. However, less than a month after her first chemotherapy treatment, the woman suddenly died, and the family refused an autopsy to confirm the cause of death.
“This case emphasizes that physicians should have a broad-minded approach when evaluating cases of rare endocrine malignancies,” the researchers wrote.
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