Tumor in woman’s rare Cushing’s case not found by MRI, 2 surgeries

Report details successful treatment of ectopic tumor in case

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by Andrea Lobo |

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A technician stands over a person who is lying down, about to have a MRI scan.

A 48-year-old woman in Belgium was found to have a hormone-producing tumor located in the sphenoid sinus, a hollow space behind the nose and between the eyes, in a rare case of Cushing’s syndrome.

The tumor perfectly mimicked the biological characteristics of a classical pituitary adrenocorticotropic hormone (ACTH)-producing tumor on a hormonal evaluation. It also had the characteristics of a benign polyp in the nasal sinus.

“We report a challenging case of severe ACTH-dependent Cushing’s syndrome without any identifiable pituitary tumor despite adequate [MRI] imaging and two exploratory … surgeries,” the researchers wrote, noting that “preoperative hormonal testing and [a type of sinus sampling] were highly consistent with a pituitary origin of ACTH secretion.”

The patient was successfully treated with surgery after the tumor was found, the report noted.

The study, “Ectopic sphenoidal ACTH-secreting adenoma revealed by 11C Methionine PET scan: case report,” was published in the journal BMC Endocrine Disorders.

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Cushing’s syndrome comprises a group of conditions that cause elevated levels of the stress hormone cortisol, or hypercortisolism. Cortisol is produced by the adrenal glands located atop the kidneys.

In Cushing’s disease, a specific form of the syndrome, a tumor in the brain’s pituitary gland releases excessive amounts of ACTH — a hormone that signals the adrenal glands to produce cortisol.

Ectopic Cushing’s syndrome (ECS) is a rare form of Cushing’s caused by an ACTH-producing tumor found outside the pituitary gland.

In this report, researchers from the Cliniques Universitaires Saint-Luc, in Brussels, described the case of a middle-aged woman thought to have Cushing’s disease. The preliminary diagnosis was based on the patient’s weight gain — 7 kg, or roughly 15 pounds, in one year — face swelling, and frequent bruising. She also reported a recent spontaneous rib fracture and the loss of bone tissue due to poor blood supply in the shoulder.

The initial clinical evaluation revealed fat accumulation in the trunk and a body mass index, a ratio of weight to height, compatible with overweight. The woman also had an accumulation of fat tissue in the back of the neck, skin frailty, hypertension, and peripheral amyotrophy, characterized by pain in the upper extremities.

Blood analysis, liver enzymes, kidney function, and electrolyte levels all were normal, except for elevated levels of lactate dehydrogenase — a protein that plays an important role in energy production— and neutrophils, a type of white blood cell.

Her morning cortisol and ACTH levels were elevated, as were her 24-hour free urinary cortisol levels. Dexamethasone tests were indicative of Cushing’s syndrome.

A corticotrophin release stimulation test induced a 57% elevation in ACTH levels and a 34% elevation in cortisol, which was compatible with Cushing’s disease. Other pituitary hormone levels were normal, whereas dehydroepiandrosterone (DHEA), a hormone produced in the adrenal glands that helps to produce other hormones (such as testosterone and estrogen) were elevated, as were testosterone levels.

A magnetic resonance imaging (MRI) of the pituitary gland did not reveal a tumor, although a sampling from the nasal sinus indicated a pituitary origin of ACTH secretion, particularly on the right side.

In an exploratory transsphenoidal surgery, a minimally invasive surgery used to remove tumors from the pituitary gland, researchers dissected part of the right side of the pituitary gland while maintaining gland function. The analysis revealed normal tissue, and after surgery, cortisol levels remained elevated.

A second surgery targeting the left side of the pituitary gland also failed to decrease cortisol levels.

Due to the lack of disease remission, researchers further explored possible sources of ectopic ACTH secretion. A full-body positron emission tomography (PET)/CT imaging failed to reveal a potential cause.

An 11C-methionine PET scan combined with MRI did not reveal a pituitary tumor but revealed a mass in the posterior wall of the sphenoid sinus. 11C-methionine is an amino acid (the building blocks of proteins) tracer, which has shown a sensitivity of 70-100% in studies with Cushing’s patients.

“Recent studies have shown that nuclear imaging techniques may provide consistent results in localizing pituitary adenomas when MRI alone failed to locate them,” the researchers wrote.

Although this mass was previously detected in the first MRI scan and had features commonly seen in benign mucosal polyps, it was not considered a potential ectopic ACTH-producing tumor.

Studies have shown that nuclear imaging techniques may provide consistent results in localizing pituitary adenomas when MRI alone failed to locate them.

The diagnosis was confirmed by the reduction of cortisol levels after the mass was removed by a third transsphenoidal surgery. The patient started hydrocortisone replacement therapy. During follow-up, the clinical signs of high cortisol levels rapidly improved.

The researchers noted the “key role of 11C Methionine PET co-registered to high-resolution MRI for localizing ectopic [tumors], efficiently guiding surgical removal and leading to complete remission of hypercortisolism.”

“We report a case of ACTH-dependent Cushing’s syndrome, caused by an ectopic corticotroph [tumor] located in the sphenoidal sinus, which perfectly mimicked the biological features of a classical pituitary ACTH [tumor] on a comprehensive hormonal evaluation,” the team concluded.