Isturisa exposure early in pregnancy may be less risky than thought
Woman with Cushing’s delivers healthy baby girl despite use of medication
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Despite taking Isturisa (osilodrostat), a medication not recommended during pregnancy, a 38-year-old woman in Japan with recurrent Cushing’s disease carried a healthy baby through the first trimester, according to a newly published case report.
After the pregnancy was discovered at 16 weeks, doctors immediately discontinued Isturisa. The woman’s cortisol levels were successfully managed with Signifor (pasireotide) and metyrapone.
Though the baby girl was born prematurely, she showed no congenital abnormalities or adrenal insufficiency, a condition where adrenal glands fail to produce enough cortisol. This positive outcome led researchers to suggest that the caution against using Isturisa in pregnancy may warrant reevaluation.
The study, “A Case of Adrenocorticotropin-dependent Cushing Syndrome with Osilodrostat Exposure in Early Pregnancy,” was published in JCEM Case Reports.
What is Cushing’s disease?
Cushing’s disease occurs when a tumor in the brain’s pituitary gland releases excessive adrenocorticotropic hormone (ACTH), driving the adrenal glands on top of the kidneys to overproduce the hormone cortisol. As a result, patients develop a range of Cushing’s symptoms, including unusual fat accumulation around the abdomen, muscle weakness, and menstrual cycle irregularities.
The first-line treatment is usually surgery to remove the pituitary tumor. When surgery isn’t an option or hasn’t been effective, several medications can be used to lower cortisol.
However, it remains challenging to manage Cushing’s disease during pregnancy “because of limited treatment options and fetal safety concerns,” the researchers wrote, adding that no standardized guidelines exist in part because of the condition’s rarity during pregnancy.
Isturisa, which blocks an enzyme in the adrenal gland needed for cortisol production, is one treatment option. However, it is “contraindicated in pregnancy because of its proven [toxic effects for the fetus] in animal studies,” the team wrote. As a result, “data on its use in human pregnancy are lacking.”
In this report, researchers detail the case of a patient with recurrent Cushing’s disease who became pregnant unknowingly while being treated with Isturisa, providing a rare and important source of clinical insight into early pregnancy exposure.
The woman developed symptoms of Cushing’s disease when she was 30. After a Cushing’s disease diagnosis was confirmed, she underwent pituitary surgery at age 31 to remove a 6 mm tumor. While her symptoms initially improved, blood tests four years later revealed that her disease had returned, even though MRI scans showed no visible tumor.
She was then started on Metopirone (metyrapone), a drug used off-label to lower excess cortisol in people with Cushing’s.
Because she experienced significant nausea, she was switched to Isturisa along with low-dose hydrocortisone, a steroid used to replace cortisol as part of a strategy that suppresses cortisol production while safely supplying the body with the hormone it needs.
This combination successfully normalized her cortisol levels. Despite this, her menstrual cycles remained irregular, but she did not suspect she was pregnant.
At age 38, she went to the hospital with persistent nausea. Gastrointestinal testing found no cause. Only after continued symptoms did a pregnancy test reveal she was 16 weeks pregnant. Isturisa was immediately stopped.
Delivery and outcome
To control her cortisol levels, doctors started her on Signifor, an ACTH-lowering therapy given every four weeks by an injection under the skin. Metopirone was later added again when her cortisol levels began to rise.
At about 26 weeks of pregnancy, her water broke early, and because the baby was in a breech position, she underwent an emergency cesarean section. During this time, she tested positive for COVID-19 but developed no symptoms.
Before delivery, the patient was given hydrocortisone to prevent adrenal crisis, which is a dangerous drop in cortisol that can occur when cortisol production is blocked or when the body undergoes a significant stress such as childbirth or surgery.
The baby girl, born weighing 871 grams (1.9 pounds), required temporary ventilation due to respiratory distress syndrome, a common condition in premature babies. Her cortisol level was low, but she showed no signs of adrenal insufficiency, a significant concern given the mother’s exposure to a cortisol-blocking drug in early pregnancy.
The researchers suggested that in early pregnancy, the fetal adrenal glands are still immature and depend on maternal hormones, meaning the effects of drugs that block adrenal cortisol production, such as Isturisa, may be relatively limited.
The baby developed normally during her stay in the neonatal intensive care unit and after her discharge. After delivery, the mother resumed Isturisa, and her cortisol levels remained stable.
“Although preterm birth in this case may have resulted from various factors — including limited clinical data on [Isturisa] and [Signifor] — [the fact] that the neonate showed no congenital abnormalities or adrenal problems indicates that the current caution against using [Isturisa] in pregnancy might need to be reconsidered,” the researchers concluded.
