Cortisol drops trigger ITP relapses in woman treated for Cushing’s: Report
Reducing levels can potentially unmask, worsen autoimmune conditions
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A 67-year-old woman in Japan experienced repeated relapses of immune thrombocytopenia (ITP) after treatment for her Cushing’s syndrome sharply lowered her hormone cortisol levels, a case report shows.
Cushing’s syndrome is a condition marked by excessive cortisol levels. The woman experienced two ITP relapses — the first after starting medication to lower her cortisol levels and the second after surgery to removea a cortisol-producing tumor.
Because cortisol naturally suppresses immune activity, rapidly reducing cortisol levels during treatment for Cushing’s may boost immune responses, potentially unmasking or worsening autoimmune conditions such as ITP, researchers noted.
“This case highlights … the need for careful monitoring in patients with coexisting autoimmune disorders undergoing treatment for [Cushing’s syndrome],” the researchers wrote.
The case study, “A case of immune thrombocytopenia aggravated by therapy for hypercortisolism in adrenocortical carcinoma,” was published in Therapeutic Advances in Endocrinology and Metabolism.
Cushing’s develops due to prolonged exposure to high cortisol levels
ITP occurs when the immune system mistakenly attacks platelets, the blood fragments that help the blood clot and stop bleeding after injury. As a result, people with ITP commonly experience easy bruising or excessive bleeding.
Cushing’s syndrome develops due to prolonged exposure to high levels of cortisol, a condition known as hypercortisolism. It is most commonly caused by long-term, high-dose use of corticosteroids (or simply steroids), which are immunosuppressive medications that mimic cortisol.
However, in certain cases, tumors directly or indirectly increase cortisol production in the body. Here, the most common cause is a tumor in the pituitary gland in the brain, which is known as Cushing’s disease. A tumor in the adrenal glands, which sit atop the kidneys and produce cortisol, is also a frequent cause.
Because cortisol suppresses immune activity, persistently high levels can dampen autoimmune responses. Although treatment of Cushing’s syndrome has been linked to worsening of certain autoimmune disorders, whether lowering excess cortisol could trigger an ITP relapse has not previously been documented.
Woman showed classic Cushing’s features
In this report, researchers in Japan detailed the case of a 67-year-old woman who received treatment for Cushing’s syndrome that caused her ITP to relapse.
She was diagnosed with ITP five years before hospital admission, and was initially treated with corticosteroids. The steroids were gradually tapered and discontinued three years before, after which she was given the ITP-approved therapy eltrombopag, sold as Promacta (with generics available) and Alvaiz. This treatment stabilized her platelet count.
Four months before hospitalization, the woman developed walking difficulties and swelling of her face and legs. In the one to two weeks leading up to admission, her blood pressure rose, requiring medication. An abdominal ultrasound detected a mass in her right adrenal gland, prompting further evaluation.
On physical examination, doctors observed classic features of Cushing’s, including a rounded or “moon” face, a buildup of fat on the upper back known as a “buffalo hump,” abdominal weight gain, and thin, fragile skin.
Hormone testing confirmed markedly elevated cortisol levels in both her blood and urine, as well as high levels of other hormones produced by the adrenal glands. Imaging revealed a roughly 5-centimeter tumor in her right adrenal gland.
Doctors suspected adrenocortical carcinoma, a rare and aggressive adrenal cancer, as the cause of her Cushing’s syndrome. Adrenalectomy, or surgery to remove the adrenal gland, was planned.
Rapid drop in cortisol likely triggered a relapse of woman’s ITP
Upon admission, the woman received supportive medications and Metopirone (metyrapone), a cortisol-lowering medication. Within days, her urinary cortisol levels dropped sharply, but soon afterward, she developed purplish skin bruising, known as purpura, and her platelet count fell dramatically.
Additional testing ruled out other causes of low platelet counts, and doctors concluded that the rapid drop in cortisol likely triggered a relapse of her ITP.
Surgery was postponed while she was given a platelet transfusion, high-dose corticosteroids, and intravenous immunoglobulin therapy to help neutralize the abnormal antibodies that drive autoimmune disease. Once her platelet count recovered, she underwent right adrenalectomy about a month after her admission.
Following surgery, she received steroid replacement therapy, which was gradually tapered. As the dose was reduced, her platelet count declined again. Doctors attributed this second ITP relapse to both the loss of tumor-driven cortisol production and the rapid tapering of post-surgery steroids.
Eltrombopag and corticosteroid therapy were restarted, resulting in a steady recovery of her platelet counts. She was discharged about a month after surgery. Tumor analysis under the microscope confirmed adrenocortical carcinoma.
Despite additional post-surgery treatment with Lysodren (mitotane), a medication approved for adrenocortical carcinoma, her hypercortisolism returned within one month. Imaging confirmed tumor recurrence, and her condition worsened. She died six months after her initial hospital admission.
“Treatment of hypercortisolism in [Cushing’s syndrome] can lead to unexpected complications. In patients with ITP previously responsive to steroid therapy, suppression of [body-produced] cortisol may precipitate relapse, potentially affecting the treatment strategy,” the researchers wrote. “Therefore, careful monitoring is essential during therapeutic interventions to suppress cortisol levels.”
