Rare adrenal tumor producing CRH and ACTH seen to cause Cushing’s

Woman responds well after surgery to remove the pheochromocytoma

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A woman seated on an examining table takes an oral medication as a doctor hands her a glass of water.

A report detailed the rare case of a woman whose Cushing’s syndrome quickly developed as a result of a silent pheochromocytoma — a rare adrenal gland tumor — that produced and released both corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH).

The report, “Cushing Syndrome due to a CRH- and ACTH-secreting silent pheochromocytoma,” was published in the journal AACE Clinical Case Reports.

Cushing’s syndrome occurs due to excessive cortisol levels. Cushing’s disease, one of its most common forms, is caused by a tumor in the pituitary gland that produces too much ACTH. This hormone drives the adrenal glands, located atop the kidneys, to release cortisol into the bloodstream.

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Silent pheochromocytoma tied to Cushing’s found on right adrenal gland

Tumors outside the pituitary gland can produce and release ACTH as well, causing a form of Cushing’s called ectopic Cushing’s syndrome. In very rare cases, such tumors also produce and release CRH, another hormone that stimulates ACTH production and release.

Physicians at Johns Hopkins University described the case of a woman with a pheochromocytoma producing both ACTH and CRH.

The woman, 57, had gained weight over the previous two months, and at the hospital showed evidence of muscle weakness, easy bruising, and a round face — all key features of Cushing’s syndrome — along with acne and swelling in her feet. She had a history of well-controlled high blood pressure, but her pressure worsened as she was failing to respond to medications.

She also had hypokalemia, or extremely low blood potassium levels, despite treatment. Given her symptoms, the woman was admitted to the emergency department.

Lab tests revealed abnormally high cortisol and ACTH levels in the bloodstream, as well as high cortisol levels in the urine.

A PET scan showed a mass in her right adrenal gland, which physicians considered to be a silent pheochromocytoma. The term silent means that the tumor did not produce catecholamines, hormones typically associated with pheochromocytomas.

No tumor was detected in the pituitary gland on MRI scans, leading physicians to suspect ectopic ACTH-syndrome.

The patient received treatment with metyrapone, a cortisol-lowering medication marketed under the brand name Metopirone. She also was started on ketoconazole, but the therapy was discontinued due to potential liver damage.

After two months of treatment with metyrapone and once her blood cortisol levels normalized, she underwent surgery to remove the right adrenal gland, where the tumor was residing. Tumor tissue analysis revealed it to be a pheochromocytoma that was positive for both ACTH and CRH.

Her recovery after surgery was reported to be uneventful.  She completed a short course of hydrocortisone treatment and its use stopped one week after her surgery. Of note, hydrocortisone is often administered following adrenal surgery to prevent adrenal insufficiency, which occurs when the adrenal glands are unable to produce sufficient amounts of certain hormones.

Her urine cortisol levels normalized after one month and her high blood pressure again was being kept under control with medications.

A “pheochromocytoma should be considered in patients with [ectopic ACTH syndrome] who have an adrenal mass even in the absence of excessive catecholamine secretion,” the scientists concluded.