ACTH-producing thymus tumor is ectopic Cushing’s syndrome’s cause
Researchers: Diagnosing, managing, treating condition held 'unique challenges'
Ectopic Cushing’s syndrome in a 10-year-old girl that was caused by a thymus tumor was effectively managed with ketoconazole and surgery to remove the thymus, according to a case report from the Czech Republic.
“This case presents some unique challenges related to the diagnosis, management, and treatment of thymic neuroendocrine tumor in a child,” the researchers wrote. “Due to the rarity of this disease and the challenging work-up … a multidisciplinary team of experienced physicians in [Cushing’s syndrome] management is highly recommended.”
The case study, “Ectopic adrenocorticotrophic hormone syndrome in a 10-year-old girl with a thymic neuroendocrine tumor: a case report,” was published in BMC Endocrine Disorders.
In Cushing’s syndrome, the adrenal glands produce high levels of the hormone cortisol. Cushing’s disease, one of its most common forms, is caused by a tumor in the pituitary gland that produces excessive amounts of adrenocorticotropic hormone (ACTH), which triggers excessive cortisol production. Less frequently, the syndrome is caused by ACTH-producing tumors in other parts of the body, where it’s called ectopic Cushing’s.
A challenging diagnosis
The girl was admitted to the hospital with facial swelling and blood in the urine. She had gone to the emergency department the day before with frequent and painful urination, nausea, and back pain. Over the year, she’d had excessive weight gain, growth retardation, facial changes, development of public hair, along with increased irritability and mood changes.
When she was admitted, she was found to have a moon face, facial redness, acne, fat accumulation in the abdomen, purple stretch marks in the abdomen and legs, and high blood pressure. She also had low blood potassium and phosphate levels, which were managed with supplements, and a kidney ultrasound revealed kidney stones.
More tests revealed her urine and blood cortisol levels were elevated, confirming hypercortisolism. The girl also had high ACTH levels in the blood. Both low- and high-dose dexamethasone tests failed to reduce her cortisol levels, which suggested she may have an ectopic ACTH-dependent form of Cushing’s.
A corticotropin-releasing hormone (CRH) test, which prompts the pituitary gland to produce ACTH, led to increased cortisol, which suggested a possible pituitary tumor. She started on ketoconazole to ease her hypercortisolism symptoms.
An imaging test revealed a lesion in the pituitary gland, so the girl’s medical team decided on transsphenoidal surgery to remove it. An examination of the removed tissue failed to confirm a diagnosis, however.
Reaching a diagnosis of ectopic Cushing’s syndrome
Considering the variable results in previous tests, the girl underwent bilateral inferior petrosal sinus sampling, an invasive test used to measure ACTH in the veins that drain blood from the pituitary gland. The results were consistent with a diagnosis of ectopic Cushing’s.
“Bilateral inferior petrosal sinus sampling is highly recommended to differentiate between Cushing disease and ectopic ACTH syndrome,” the researchers wrote.
The girl was started on ketoconazole to alleviate her signs and symptoms of hypercortisolism while the medical team looked for the tumor that was causing her condition.
The girl’s urine cortisol levels normalized after three weeks of treatment, but three weeks later, she developed symptoms related to adrenal insufficiency, which is the inability of the adrenal glands to produce enough cortisol and other hormones. The treatment was discontinued and the girl saw her symptoms ease.
Tests revealed a tumor in the thymus, an organ of the immune system. The girl started treatment with hydrocortisone before surgery to maintain normal cortisol levels, which further eased her Cushing’s facial features. The thymus was removed and tested positive for ACTH, indicating it was the source of her condition.
Hydrocortisone treatment was reduced after the surgery and eventually stopped. Blood pressure-lowering medications were also discontinued, as were potassium supplements. The girl lost weight and her mood improved.
“The outline of a good management plan to use all tests appropriately and in the correct sequence, monitoring carefully for any signs or symptoms of adrenal insufficiency, and apply appropriate imaging studies, with experienced radiologists providing accurate readings,” the researchers wrote.
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