Rare case of ectopic Cushing’s syndrome reported in infant girl
Case 'noteworthy,' in part, for effective multidisciplinary management
The rare case of a 6-month-old girl in India who developed ectopic Cushing’s syndrome due to a cancerous tumor in her right hip was described in a new study.
After completing two rounds of chemotherapy and undergoing surgery, the girl recovered normal functioning in her hypothalamic-pituitary-adrenal axis, which controls cortisol levels in the body, at the age of 2.5 years.
“The case is noteworthy for its rarity, the atypical age at presentation, and successful multidisciplinary management,” the researchers wrote.
The case study was published as a letter to the editor, titled “Cushing Syndrome in an Infant Due to Paraneoplastic Syndrome Associated with Ewing Sarcoma,” in the Indian Journal of Pediatrics.
This type of ectopic Cushing’s syndrome ‘extremely rare’ in infants
Cushing’s syndrome is a broad umbrella term that encompasses several conditions marked by unusually high levels of the hormone cortisol.
Endogenous Cushing’s syndrome occurs when excess cortisol levels are caused by problems within the body itself, most commonly a pituitary tumor that produces and releases adrenocorticotropic hormone, known as ACTH. High levels of ACTH, in turn, cause the adrenal glands atop the kidneys to overproduce cortisol, leading to Cushing’s. This specific form of the syndrome is known as Cushing’s disease.
In about 10%-15% of cases, however, an ACTH-producing tumor found outside the brain’s pituitary gland triggers the overproduction of cortisol. This is known as ectopic Cushing’s syndrome.
In very rare cases, tumors can also produce and release corticotropin-releasing hormone, or CRH, another hormone that stimulates ACTH production and release, leading to the excessive production of cortisol.
Ectopic Cushing’s syndrome due to excessive ACTH or CRH is “extremely rare in infants.”
In this study, the researchers described the case of a very young girl, not even age 1, who developed ectopic Cushing’s syndrome. She was referred to the clinic after two weeks of rapid weight gain, diarrhea, and urinary dribbling.
The baby had some of the typical symptoms of Cushing’s, including darkened skin, high blood pressure, and obesity. She also had an ill-defined mass in the right portion of her lower abdomen.
Bloodwork revealed the girl had unusually high levels of cortisol and ACTH, and low levels of potassium, consistent with the presence of Cushing’s. However, an MRI scan showed the pituitary gland was normal with no tumors present, excluding the possibility of Cushing’s disease.
Instead, imaging tests revealed the presence of a large mass in the girl’s abdomen, specifically arising from the right iliac wing — the right upper portion of the hip bone.
A biopsy revealed the tumor was an Ewing sarcoma, a rare, malignant type of tumor that primarily affects children and young adults. Further analysis did not show evidence that the tumor was producing and releasing ACTH.
“Possible reasons could be tumor heterogeneity [variability] with biopsy not capturing ACTH positive regions, antibodies not identifying ACTH precursors/ degradation products; or CRH secreting [producing] tumor,” the researchers wrote.
Child reported as in remission, with normal growth, after surgery
The infant underwent surgery to have part of her pelvis removed to eliminate the tumor. She also completed two courses of chemotherapy, which lasted a total of 34 weeks, or about eight months.
After three weeks of chemotherapy, she no longer required treatment for high blood pressure and actually developed hypocortisolemia, or unusually low levels of cortisol in the blood.
The researchers reported that treating the patient was particularly challenging.
Some issues included adjusting the dose of chemotherapy and recurrent febrile neutropenia, or repeated high fevers with low levels of immune cells in the blood. The patient required “meticulous” adjustments of her dose of hydrocortisone, a steroid that’s commonly administered to treat hypocortisolemia, the team noted.
The girl completed treatment at 1.5 years of age. A year later, when the patient was 2.5 years old, the hypothalamic-pituitary-adrenal axis, which controls cortisol levels in the body, was normal.
At her last follow-up, at the age of 2.7 years, she was in remission. Her growth had normalized and she was developing normally, with no neurological issues or motor disability, the team reported.
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