Signifor Controlled Patient’s Cortisol Fluctuations

Cortisol fluctuations in a woman with Cushing’s disease were controlled successfully with Signifor (pasireotide LAR), possibly for the first time, according to a recent case report.

The report, “Resolution of cyclicity after pasireotide LAR in a patient with Cushing’s disease,” was published in the journal AACE Clinical Case Reports.

Cortisol fluctuations — alternating periods of normal and low cortisol levels, also known as cyclicity of cortisol secretion, or CIC — occur in a minority of Cushing’s disease patients.

Exactly how CIC happens remains unknown and the intensity, duration, and number of cycles a patient might experience vary widely, further complicating diagnosis and treatment.

Signifor is a lab-made version of somatostatin, a hormone naturally produced in the body. The medication is used to lower cortisol levels in Cushing’s disease patients who fail or are ineligible for brain surgery. It has not, however, been described in the treatment of CIC.

In people with Cushing’s disease, excessively high cortisol levels (hypercortisolism) are triggered by a tumor in the brain’s pituitary gland that releases high amounts of adrenocorticotropic hormone (ACTH). Brain surgery to remove these tumors is the standard treatment for the condition.

The current report details the case of 43-year-old woman who was admitted to a hospital in Brazil in July 2013 with a “full picture of Cushing’s syndrome” lasting several months.

Symptoms included weight gain, especially around the torso, facial swelling (“moon face”), easy bruising, muscle wasting and weakness, headache, menstrual irregularity, depression, acne, excessive hair growth (hirsutism), and brittle bones (osteopenia).

Her high blood cortisol levels fell to a normal range following treatment with high dose dexamethasone (8 mg overnight). This led to an improvement in her symptoms and caused her treatment team to decide to cancel the patient’s brain surgery.

Her symptoms and hypercortisolism returned in February 2014 and she underwent brain surgery in June. Yet, doctors found no evidence of tumor growth in the tissue removed.

Her cortisol levels remained high, prompting her doctors to schedule an invasive procedure called bilateral and simultaneous petrosal sinus sampling, in which ACTH levels are sampled from within the veins that drain the pituitary gland.

Although this procedure was canceled when the woman’s symptoms and cortisol levels again resolved spontaneously, it eventually was performed in July 2015, after the patient experienced several CIC episodes.

After that, and still in the absence of any detectable tumor, the patient began receiving cabergoline and ketoconazole to control her CIC. This proved unable to change the frequency and extreme hormonal variations of her episodes, which varied in duration from a few days up to several months.

She started treatment with Signifor in late 2019, at an initial dose of 20 mg monthly, injected into a muscle. Because she initially experienced low blood pressure, weakness, and dizziness, oral hydrocortisone given at a daily dose of 20 mg was added to her regimen.

The patient continued treatment with Signifor for about two years, during which her urinary cortisol levels normalized and no new CIC episodes occurred. Throughout this time, she tolerated the treatment well, experiencing only a slight increase in blood sugar levels. At the same time, her overall health progressively improved.

“In conclusion,” the researchers wrote, “we herein present a patient with [Cushing’s disease] with well-documented cyclicity in challenging diagnostic and therapeutic management who demonstrated an effective clinical and laboratory response to [Signifor], with a resolution of hormonal variation.”

“To our knowledge, this is the first case to use this medication to control cyclicity in a [Cushing’s disease] patient,” they wrote.