Rare ACTH-producing Prostate Tumor Leads to Cushing’s Diagnosis

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by Margarida Maia PhD |

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A man developed Cushing’s syndrome that was caused by a tumor in his prostate gland, according to a report from Singapore.

He did not present the usual symptoms of Cushing’s, but instead appeared to have a severe excess of cortisol, the body’s main stress hormone. His symptoms included lower-than-normal potassium levels in the blood (hypokalemia), swelling, and weakness in the lower limbs. This resulted in a delay in being diagnosed and treated.

“The diagnosis can be missed due to atypical clinical presentations,” but “prompt initiation of treatment is important, as it is a rapidly progressive and aggressive disease,” the researchers wrote.

The report, “Challenging case of ectopic ACTH secretion from prostate adenocarcinoma,” was published in Case Reports in Endocrinology.

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Cushing’s syndrome occurs when there is an excess of cortisol in the body. It’s sometimes caused by the brain’s pituitary gland producing too much adrenocorticotropic hormone (ACTH), which drives the adrenal glands on top of the kidneys to produce and release cortisol.

There may be other sources of ACTH, including certain tumors in other parts of the body. When this occurs, the source is said to be ectopic. Carcinomas — tumors that begin in the tissues that line or cover internal organs — are some of the most common sources of ectopic ACTH production.

However, “ectopic ACTH production from prostate carcinoma is rare, and there are less than 50 cases published to date,” the researchers wrote. “The diagnosis can be challenging due to atypical and variable clinical presentations of this uncommon source of ectopic ACTH secretion.”

Researchers reported the case of a 61-year-old man who developed Cushing’s resulting from a prostate carcinoma.

The man visited the Changi General Hospital in Singapore with hypokalemia, and swelling and weakness in the lower limbs. He also had poorly controlled diabetes and a one-year history of high blood pressure. He was being treated for his prostate carcinoma and was also taking complementary medicines.

His hypokalemia was being treated with a potassium supplement and by stopping complementary medicines. But he returned to the hospital with a new episode of hypokalemia a month later.

A physical examination revealed none of the usual symptoms of Cushing’s, such as a round face, increased fat accumulation around the neck, and stretch marks.

Lab tests showed he had a high pH in the blood (alkalosis), high levels of potassium in the urine, and high morning cortisol levels in the blood, causing clinicians to suspect hypercortisolism, or exposure to excessive levels of cortisol.

The man’s ACTH levels neared the upper normal limit. Moreover, his cortisol levels remained higher than normal after low- and high-dose dexamethasone suppression tests, indicating an ACTH-dependent form of Cushing’s. Dexamethasone is a lab-made version of cortisol that shuts off ACTH production in healthy people, leading to cortisol decreases. A low-dose test can tell whether the body is making more cortisol than normal, and a high-dose test can tell whether the excess cortisol is dependent or independent of ACTH.

To determine the source of the extra ACTH, doctors first performed a gallium PET/CT scan. Gallium is radioactive. After it’s injected into the bloodstream, it travels through the body and builds up in cells that are actively dividing, such as tumor cells. Doctors observed a buildup of gallium in the prostate gland.

They next removed a piece of tissue from the prostate carcinoma. When they examined it under the microscope, they found that some tumor cells produced ACTH. Based on these findings, they made a diagnosis of ectopic Cushing’s syndrome secondary to the prostate carcinoma.

“The classical symptoms of Cushing’s syndrome are frequently absent due to the rapid clinic onset resulting in diagnostic delay,” the researchers wrote.

The man was started on a potassium supplement and spironolactone, a potassium-sparing medication, to treat his hypokalemia. He was given metformin and sitagliptin to control diabetes, lisinopril and terazosin to lower his blood pressure, and ketoconazole to reduce cortisol production, which was cut by more than half. Doctors also recommended chemotherapy, but it was delayed due to severe bacterial and viral infections.

Ketoconazole can be toxic to the liver, and as the man’s liver function was compromised, ketoconazole was switched to octreotide. However, octreotide failed to lower cortisol levels.

As a result, his condition worsened, and he was considered unfit for adrenal surgery or chemotherapy. He died due to prostate cancer progression occurring within three months of his diagnosis.