Invasive tumor in thymus causes difficult case of ectopic Cushing’s
ACTH-producing tumor led to metastatic cancer in 31-year-old woman
An invasive tumor in the thymus turned out to be the cause of a 31-year-old woman’s severe ectopic, adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome, according to a case recently reported in Poland.
As initial imaging scans failed to detect the thymus lesion, a tumor in the left adrenal gland was suspected as the primary cause of the disease. However, the ACTH-producing thymus tumor continued to grow and caused multiple cancerous tumors that spread and eventually led to the patient’s death.
“The presented case highlights that the diagnosis and management of [ectopic ACTH-dependent Cushing’s syndrome] remain challenging,” researchers wrote.
The patient was described in “Case report: A challenging case of severe Cushing’s syndrome in the course of metastatic thymic neuroendocrine carcinoma with a synchronous adrenal tumor,” which was published in Frontiers in Endocrinology.
Cushing’s syndrome refers to any health issue caused by high cortisol levels. One of its most common forms, Cushing’s disease, is caused by a tumor in the brain’s pituitary gland that produces high amounts of the ACTH hormone, increasing the production of cortisol by the adrenal glands.
Ectopic tumors tend to be more aggressive and metastasize
In rare cases, however, excess ACTH can come from a tumor elsewhere in the body, in which case patients are said to have ectopic Cushing’s syndrome. While pituitary tumors are generally benign, these ectopic tumors tend to be much more aggressive and invade nearby and distant tissues to form metastases.
In the report, researchers in Poland described the case of a 31-year-old woman whose Cushing’s syndrome was caused by a metastatic ACTH-producing carcinoma in the thymus, a small gland located in the chest between the lungs.
The tumor, however, was not detected in initial assessments, and the diagnosis was further complicated by the presence of a tumor in the left adrenal gland that was suspected to be the primary cause of Cushing’s.
The woman was initially admitted to an emergency department with a three-week history of progressing fatigue, muscle weakness, headaches, high blood pressure (hypertension), and generalized swelling. She also reported increased thirst and frequent urination, including at night, which are common signs of diabetes.
Physical examination revealed pitting edema, which is when a swollen part of the body has a dimple (or pit) after applied pressure, hypertension, elevated heart rate, and acne. The patient also had low potassium and chloride levels, and high blood sugar levels consistent with diabetes. She started treatment with insulin to regulate blood sugar, as well as potassium supplementation, and antihypertensive and preventive anticoagulant medications.
However, the patient’s body did not respond to these treatments and her overall clinical condition led researchers to suspect Cushing’s syndrome. Further analyses revealed she had elevated blood cortisol levels in the morning and at midnight, and results of her 24-hour urinary free cortisol test exceeded 65 times the upper reference value. She also had elevated levels of ACTH, confirming a diagnosis of ACTH-dependent Cushing’s.
The patient initially received a continuous etomidate infusion, which significantly eased her symptoms. Etomidate is an anesthetic agent, marketed as Amidate, that can rapidly lower cortisol levels.
CT scan reveals large mass on left adrenal gland
An MRI scan of her brain’s pituitary gland revealed no lesion which, together with the rapid progression of symptoms, was highly suggestive of ectopic Cushing’s. A CT scan revealed a large solid mass in the left adrenal gland, suspected to be a malignant ACTH-producing tumor, and metastatic bone lesions. No other potential cancer origin was found.
Surgery to remove the woman’s left adrenal gland normalized her cortisol levels and reduced ACTH levels although they still remained above reference values. The patient was discharged five weeks after first being admitted to hospital, but pathology results again suggested a different ectopic tumor was causing her symptoms.
Indeed, follow-up imaging studies after eight weeks revealed a previously undetected lesion in the thymus, consistent with an invasive thymus cancer. Only partial surgical removal of the tumor was possible because of its local invasion and rapid progression.
After the surgery, the patient received radiotherapy, but her ACTH levels increased, indicating disease progression. Follow-up imaging revealed the presence of metastatic lesions in the pancreas and brain, and she started chemotherapy.
The treatment led to partial disease remission and a further reduction of ACTH levels. The patient also underwent surgery to remove the brain tumor, and the disease remained stable for 10 months.
However, further imaging scans showed the disease had spread to the lungs, breast, and muscle. Despite chemotherapy leading to a short-term partial response, the woman died about 3.5 years after she was first hospitalized.
“Malignant [thymus ACTH-producing tumors] with ectopic [Cushing’s syndrome] are extremely rare, and their management has to be individualized in every case, requiring a multidisciplinary approach,” the researchers wrote. “Regardless, the prognosis remains poor due to the aggressiveness of the disease.”
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