Isturisa resolves ectopic Cushing’s due to lung cancer in man, 68

Report stresses importance of monitoring adrenal size, ACTH, cortisol levels

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by Andrea Lobo |

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Isturisa (osilodrostat) was able to successfully treat ectopic Cushing’s syndrome due to a lung tumor in a 68-year-old man with lung cancer, according to a recent case report.

Treatment led to a reduction in the patient’s blood cortisol levels, which were elevated as a result of the lung tumor producing high levels of adrenocorticotropic hormone (ACTH). Treatment also simultaneously reduced the size of his adrenal glands, which were found to be enlarged at the time of diagnosis.

“We found that [Isturisa] was able to fully control the blood cortisol levels, and the dose … could be reduced after the patient’s blood cortisol level was controlled,” researchers wrote.

Moreover, this case shows “it is important to follow-up not only ACTH and cortisol levels but also adrenal size on imaging studies in patients treated with [Isturisa]. Evaluation of the adrenal [disease] in these patients is also needed,” they wrote.

The report, “A Case of an Ectopic ACTH-Producing Tumor With Adrenal Shrinkage During Osilodrostat Administration,” was published in the journal JCEM Case Reports.

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In ectopic Cushing’s syndrome, tumors outside pituitary release excessive ACTH

Cushing’s syndrome comprises a group of disorders marked by high cortisol levels, or hypercortisolism. One of its most common forms, Cushing’s disease, is caused by a tumor in the brain’s pituitary gland that produces excessive amounts of ACTH, a hormone that prompts the adrenal glands, sitting atop the kidneys, to produce cortisol.

Less frequently, ACTH is released by tumors found outside the pituitary gland, which is referred to as ectopic Cushing’s syndrome.

Here, a team of researchers in Japan described the case of a 68-year-old man with ectopic Cushing’s caused by a lung tumor that was releasing ACTH.

The man was admitted to the hospital with enlarged lymph nodes in the chest, and was experiencing fever, back pain, dizziness, and diarrhea. A physical examination also showed he had high blood pressure.

His blood tests revealed he had severely low potassium and high blood sugar levels. Also, a CT scan revealed the presence of a tumor in his right lung, with swelling of nearby lymph nodes, and enlargement of both adrenal glands.

Biopsy confirms small cell lung cancer diagnosis

Considering certain tumor markers, including neuron-specific enolase and pro-gastrin-releasing peptide, were also elevated, the researchers suspected the patient had small cell lung cancer. This was confirmed with a biopsy.

Although he had no Cushing’s features, biopsy results indicated the tumor was positive for an ACTH precursor, so it had the potential to produce ACTH.

Consistent with the researchers’ suspicions, the man’s blood ACTH and cortisol levels were elevated. This, together with the fact that a MRI scan could not detect obvious tumors in the pituitary gland, indicated the patient had ectopic ACTH-producing small cell lung cancer.

The patient was initially treated with metyrapone, starting at a daily dose of 500 mg, which was gradually increased to 2,000 mg. This failed to sufficiently reduce the patient’s blood cortisol levels. The man also started chemotherapy with etoposide and carboplatin.

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Isturisa helped to normalize patient’s cortisol levels

Isturisa was introduced at a daily dose of 1 mg, which was gradually increased to 20 mg per day, with a simultaneous decrease of metyrapone. This resulted in the normalization of the patient’s cortisol levels, and he was able to discontinue metyrapone.

Subsequently, the dose of Isturisa was reduced to a daily dosage of 1 mg, without any increase in cortisol levels. Despite treatment, high levels of active ACTH levels were still present in the patient’s blood.

On day 128, a CT scan revealed a marked reduction in size of his adrenal glands, and treatment was discontinued without leading to an increase in the patient’s cortisol levels. However, the patient died due to lung cancer, about five months after his diagnosis.

“In our case, we observed 2 significant aspects. First, the patient’s adrenal glands exhibited shrinkage despite the [blood] ACTH levels not decreasing. Second, the [Isturisa] dose was reduced while the adrenal glands shrank,” the researchers wrote.

“Through an unknown mechanism,” they added, Isturisa “decreases the size of adrenal glands; this effect enabled us to reduce the dosage.”