Imaging Tests Mislead Physicians in Diagnosing Cushing’s Patient

Blood tests should be performed before imaging examinations when Cushing’s syndrome is suspected, to prevent misdiagnosis, a recent case report study suggests.

The report described the case of a 24-year-old woman with elevated cortisol levels and a pituitary tumor, in which an imaging test misled doctors into believing she had Cushing’s disease.

When a high-dose dexamethasone suppression test failed to reduce the patient’s cortisol levels, physicians investigated further and found a thymus tumor that ended up being the true culprit.

Neuroendocrine tumors in the thymus are very rare, with only a few cases previously described in the literature. Yet, according to researchers, this type of tumor should be kept in mind as a possible secondary cause of Cushing’s syndrome.

The case report study, “A rare initial presentation of a thymic neuroendocrine tumor as Cushing’s syndrome,” was published in the journal Clinical Case Reports.

Cushing’s syndrome is characterized by high levels of the hormone cortisol in the body. Cortisol, a steroid hormone, is normally produced by the adrenal glands, which sit on top of each kidney.

Excessive cortisol levels, or hypercortisolism, can be caused by adrenal tumors that produce too much cortisol, or by having high levels of adrenocorticotropic hormone (ACTH) — a hormone that stimulates cortisol production in the adrenal glands.

High ACTH levels, in turn, may be caused by the presence of ACTH-producing tumors, which are typically found in the lungs, pancreas, thyroid, or thymus gland. Such tumors also can be found in the pituitary gland — located at the base of the brain — and are associated with a form of Cushing’s syndrome known as Cushing’s disease.

Now, researchers from Qatar described the case of a Filipina woman, recently diagnosed with hypertension and hypothyroidism, who was treated at their hospital after complaining of fatigue and weakness lasting for the previous three months.

The woman had typical features of Cushing’s, including excess weight in her mid-section, a slightly rounded face (moon face), acne, and fat accumulation in her back. Muscle weakness also was reported, mainly in her lower legs.

The patient had high blood pressure and blood tests showed she also had high levels of cortisol (2,636 nanomoles per liter (nmol/L); normal range: 133–537 nmol/L) and ACTH (114 picograms per milliliter (pg/mL); normal range: 7.2–63.3 pg/mL).

Doctors performed a low-dose (1 mg) dexamethasone suppression test, a standard test to screen for hypercortisolism, to see if her ACTH and cortisol levels could be reduced. However, the woman’s cortisol remained high at 3,572 nmol/L.

A computed tomography (CT) imaging scan then revealed the presence of a small, noncancerous tumor in the patient’s pituitary gland, consistent with the diagnosis of Cushing’s disease.

However, a high-dose (8 mg) dexamethasone suppression test, which is usually performed to help physicians pinpoint the cause of hypercortisolism, failed once again to lower her cortisol levels (2,959 nmol/L).

This failure in reducing cortisol levels suggested she had another form of Cushing’s syndrome. The researchers noted that this test can suppress ACTH-producing tumors in the pituitary gland (Cushing’s disease), but not in ACTH-producing tumors found elsewhere in the body (ectopic Cushing’s syndrome).

These observations encouraged the physicians to search further for the root cause of the woman’s elevated cortisol levels. CT scans of her chest, abdomen, and pelvis were taken, revealing the presence of a small tumor in the thymus, as well as adrenal gland enlargement.

That tumor was surgically removed, and subsequent analyses confirmed it was an ACTH-producing tumor. After surgery, her ACTH levels dropped to 6.1 pg/mL and her cortisol levels to 399 nmol/L. At this point, her symptoms also started to ease and her blood pressure to drop, allowing for a progressive reduction in blood pressure-lowering medicines.

“While evaluating the cause of Cushing’s syndrome, biochemical confirmation should be sought first as imaging studies might misdirect the diagnosis toward the wrong problem,” the researchers wrote.

“One of the rare secondary causes that should be kept in mind while evaluating Cushing’s syndrome is the thymic neuroendocrine tumor,” they concluded.