Signifor Controls Ectopic Cushing’s Symptoms in Woman for 5 Years

Cause was likely tumors later found and removed from her lungs

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Signifor (pasireotide) treatment was able to control symptoms of ectopic Cushing’s syndrome in a woman for years, according to a case report.

The report, “Complete and sustained remission of hypercortisolism with pasireotide treatment of an adrenocorticotropic hormone (ACTH)-secreting thoracic neuroendocrine tumour: an n-of-1 trial,” was published in the Endocrine Journal.

Cushing’s syndrome is characterized by abnormally high levels of the stress hormone cortisol, which leads to symptoms like weight gain and mood changes. Cushing’s disease is a specific form of Cushing’s syndrome caused by a tumor in the brain’s pituitary gland, which prompts it to produce and release large amounts of a signaling molecule called adrenocorticotropic hormone (ACTH). High levels of ACTH trigger the adrenal glands sitting atop the kidneys to produce more cortisol.

Ectopic Cushing’s syndrome, or ECS, is a rare form of Cushing’s caused by an ACTH-producing tumor found outside the pituitary gland.

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Woman experienced weight gain, facial swelling and redness, high blood pressure

In this report, scientists in Greece described the case of a 50-year-old woman who went to their clinic with symptoms of weight gain, facial swelling and redness, and high blood pressure, which had been ongoing for two years.

Tests indicated she had high levels of both cortisol and ACTH, which usually indicates the presence of Cushing’s disease. However, additional tests, including imaging scans of the pituitary gland, found no signs of any disease-driving tumor.

This suggested that the woman might have ECS, though in the initial evaluation, clinicians were not able to identify a potential disease-driving tumor. Some slight abnormalities were noted on imaging scans of her lungs, though this was ascribed to lung inflammation.

To manage her symptoms, she was started on Signifor, which is approved in the U.S. to treat Cushing’s disease in patients for whom surgery is ineffective or not an option. The therapy lowers cortisol levels by inhibiting the effects of excessive ACTH; it is sold by Recordati Rare Diseases, which was not involved in the present study.

Signifor was initially administered at a dose of 300 micrograms (mcg) twice daily, given via an under-the-skin injection. Soon after starting treatment, the patient’s cortisol and ACTH levels dropped to within the normal range, and her symptoms eased considerably.

The dose was reduced to 300 mcg once daily, and the patient continued on treatment for five years. The therapy was well tolerated in general. There were some abnormalities in the patient’s blood sugar, a well-known side effect of Signifor, but these were “easily managed” with blood sugar medicines, according to the researchers.

“By minimizing the drug quantity and reducing the dosing frequency, we managed to keep the patient perfectly biochemically and clinically controlled, avoiding, at the same time, drug related adverse events,” the scientists wrote.

Symptoms flared when patient tried to stop treatment

In the years she was on Signifor, the patient tentatively tried stopping the treatment twice. Both times, her symptoms flared shortly after, but were then controlled again when treatment was restarted.

Two years after her initial lung scan, new imaging technologies became available and another lung scan was conducted. This scan showed some cancer-like abnormalities in the lower part of her left lung, and a decision was made to surgically remove this portion of the lung.

Surgery was completed without complications, and examination of the removed tissue confirmed the presence of an ACTH-producing tumor, which was presumably the cause of her ECS.

“To our knowledge, this is the first report of ECS clinical and biochemical remission with [Signifor], as first line treatment for a low-grade lung carcinoid, for a prolonged period of 5 years,” the researchers wrote.