Rare Bone Tumor Led to Cushing’s Syndrome in Child

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by Patricia Inacio PhD |

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A recent report described the rare case of 9-year old girl who developed Cushing’s syndrome due to a hormone-producing Ewing sarcoma, a rare type of tumor that arises in bones or in its surrounding soft tissues.

This case, according to the report’s authors, highlights the diagnostic challenges in identifying and managing such rare cases.

The case report, “Rapidly fatal ectopic ACTH syndrome in a nine-year-old girl with Ewing Sarcoma,” was published in the journal AACE Clinical Case Reports.

The most common cause of Cushing’s syndrome is a tumor in the brain’s pituitary gland — a specific form of the condition known as Cushing’s disease — where tumor cells release too much adrenocorticotropic hormone (ACTH). This hormone then stimulates the adrenal glands sitting atop the kidneys to produce large amounts of cortisol, which leads to the typical symptoms of Cushing’s.

However, tumors outside the pituitary gland that release ACTH (ectopic ACTH tumors) also can be a cause of Cushing’s syndrome, despite being much rarer. These cases are estimated to account for less than 1% of all adolescents with Cushing’s syndrome. The majority of these tumors arise in cells of the nervous system or in hormone-producing cells.

In this report, authors described the first case of ectopic ACTH production due to a Ewing sarcoma in a 9-year old girl. The tumor arose in the humerus, which is the long bone in the arm that runs from the shoulder to the elbow.

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The girl from Nepal presented to the hospital with a puffy face and a flushed appearance. Her abdomen had been enlarged for five months.

She complained of progressing difficulties for the past two months of standing after being seated. A week before admission, she began experiencing low backache and became bedridden.

A general examination revealed she was obese for her age and had high blood pressure. She also had a “moon face” — fat buildup on the sides of the face, which is seen often in patients with Cushing’s — flushing, and acne across her forehead, cheeks, and shoulder blades.

Muscle weakness was more evident in her legs, and her spine also showed signs of tenderness. No bone deformities were seen.

Her blood cortisol levels were abnormally high and did not drop after an overnight dexamethasone suppression test (ODST). This test is commonly used to confirm the presence of hypercortisolism (excessive cortisol levels). It measures the levels of cortisol in the blood in the morning after patients take a tablet of dexamethasone, a corticosteroid that normally blocks its production.

Her ACTH levels also were abnormally high.

Brain MRI scans showed no signs of a tumor in the pituitary gland, which had a normal shape and size. However, a chest X-ray — and later MRI and 3D CT scans — revealed she had a lesion on her left humerus.

More tests confirmed cells in the lesion were actively dividing — a hallmark feature of cancer — and led to a diagnosis of Ewing sarcoma. Bone scans raveled no signs of metastasis (cancer spreading).

She received treatment for high blood pressure and low potassium levels, as well as insulin because her blood sugar levels were out of control.

Ketoconazole, sold as Nizoral among other brand names, also was used to manage her Cushing’s syndrome. Ketoconazole is an anti-fungal medication that can lower cortisol levels. In the U.S., the therapy is sometimes used off-label to treat the condition, while in Europe it is approved specifically for that indication.

She also underwent chemotherapy, plus a treatment for osteoporosis. However, within seven days after starting chemotherapy, she died.

“This case highlights an atypical presentation of ectopic ACTH caused by [Ewing sarcoma] arising from the humerus,” the authors wrote.

“Managing the dual [conditions] with advanced disease is complex and further research into such rare presentations will help in prompt identification of the disease and administration of appropriate therapy resulting in the best possible outcomes,” they wrote.