Scientists Urge Close Monitoring of Cushing’s Patients on Isturisa
Approved therapy found to cause adrenal insufficiency in woman, 41
Treatment with Isturisa (osilodrostat) caused adrenal insufficiency — a condition in which the adrenal glands are unable to produce enough of certain hormones — in a 41-year-old woman with Cushing’s disease, a case report showed.
While the researchers noted that “monitoring for side effects and biochemical and clinical efficacy of therapy is incredibly challenging for both physicians and patients,” they urged that individuals on such treatment be closely followed by clinicians.
“Close monitoring is crucial to avoid adrenal insufficiency, the life-threatening potential complication of therapy,” the team wrote.
Here, the patient, a nurse, was found to have “inappropriately increased” her dose of the approved Cushing’s therapy.
The study detailing her case, titled “Osilodrostat-induced adrenal insufficiency in a patient with Cushing’s disease,” was published in the journal Clinical Case Reports.
Case highlights need for patient monitoring
Cushing’s disease occurs when benign tumors called adenomas form in the brain’s pituitary gland, leading to an excessive production of adrenocorticotropic hormone (ACTH). This triggers the overproduction of the stress hormone cortisol by the adrenal glands, causing a wide range of physical, hormonal, and psychological symptoms.
Surgical removal of the pituitary tumor is the first choice of treatment for Cushing’s disease. Other options include removing the adrenal glands, radiation therapy, and using medications to lower cortisol levels.
Medications — such as Isturisa, in this case — also may be used as a first-line treatment when patients are ineligible for either surgery or radiation therapy.
This treatment can cause several side effects, including nausea, vomiting, lack of energy, and adrenal insufficiency. A potentially life-threatening condition, adrenal insufficiency occurs when the adrenal glands are not able to produce enough cortisol.
This study described a case of Isturisa-induced adrenal insufficiency in a U.S. patient with Cushing’s disease caused by a recurrent pituitary tumor.
The woman was admitted to the emergency department after her oxygen levels dropped to 80%. This was accompanied by worsening fatigue, shortness of breath, extreme tiredness, nausea, vomiting, and dizziness.
A decade earlier, she had been diagnosed with Cushing’s disease and had undergone surgery to remove the pituitary tumor. Symptoms returned a few years later and the woman underwent a second surgery. She also had radiation therapy, as the second surgery failed to completely remove the tumor.
To ease her Cushing’s symptoms, she was given Aldactone (spironolactone) and ketoconazole. She also was taking levothyroxine to treat hypothyroidism, or low thyroid hormone levels, which she developed after surgery. Other medications were given, but the patient had to stop them due to side effects.
The woman was then started on Isturisa, one year before she was admitted to the hospital. At admission, she had normal values of blood pressure, oxygen saturation, body temperature, and pulse. No issues were found in her breathing or heart rate.
Lab tests indicated her cortisol levels were low, at 5.7 micrograms per deciliter (mcg/dL; morning normal range: 6.7–22.6 mcg/dL). Thyroid hormone levels were normal.
A few hours later, her blood pressure dropped and she was given a saline solution, but only a slight response was observed. A better response was achieved after a single dose of into-the-vein (intravenous) hydrocortisone, a steroid medication.
The next day, her morning cortisol levels were at 7.9 mcg/dL and ACTH levels were at 62 picograms per milliliter (pg/ml; normal range: 6–50 pg/mL).
Although she had been prescribed Isturisa at 10 mg twice daily, the patient had increased the dose to 15 mg twice daily. This resulted in a drop in urine cortisol levels to less than 1.0 mcg/L, suggesting treatment-induced adrenal insufficiency.
Risks of side effects with treatment
According to researchers, the difference between cortisol levels in the urine and blood “reflects the variability in testing and reiterates the challenge in assessing adequacy of therapy.”
Lab tests such as morning serum cortisol, late-night salivary cortisol, and 24-hour urine-free cortisol “are essential to ensure eucortisolism [normal cortisol values] despite test-to-test and same-test variability,” they wrote.
“Monitoring treatment efficacy in Cushing’s disease is essential, as patients undergoing treatment are at an increased risk of having a complete block of adrenal steroidogenesis [cortisol production],” the researchers wrote.
Over the next two days, the patient’s blood pressure normalized and her Isturisa dose returned to the original prescribed dose of 10 mg twice daily.
She continued treatment with ketoconazole and her symptoms eased significantly. She also was prescribed oral hydrocortisone to reduce major stress caused by chronic treatment-induced adrenal insufficiency.
According to the team, rapid treatment adjustment before a life-threatening event was possible because the patient recognized the symptoms of adrenal insufficiency and went to hospital in time.
This highlights the “paramount importance that physicians educate patients about the symptoms of adrenal insufficiency … and inform patients when it is necessary to present to the emergency department and/or contact their endocrinologist.”
Patients also should know that “adrenal insufficiency can occur any time after treatment initiation or dose adjustment, or even at a stable dose,” they wrote.
Additional studies are needed to develop “treatment guidelines to provide to physicians treating this disease and patients under their care,” the team concluded.