Rare Case of Cushing’s Disease Due to ‘Collision’ Brain Tumor Reported

Rare Case of Cushing’s Disease Due to ‘Collision’ Brain Tumor Reported
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Researchers report a very rare case of Cushing’s disease in a 34-year-old woman caused by a “collision” brain tumor, a tumor simultaneously consisting of a meningioma and a pituitary adenoma.

Meningioma, the most common type of brain tumor, arises from the meninges — the protective layers of tissue around the brain. A pituitary adenoma is a tumor in the pituitary gland.

While the woman’s history, lab results, and the detection of a meningioma (but not of a standard pituitary tumor) suggested endogenous Cushing’s syndrome — rather than the disease — close analysis of the surgically removed meningioma revealed its mixed nature and confirmed a Cushing’s disease diagnosis.

Endogenous Cushing’s syndrome occurs when the body produces abnormally high levels of the hormone cortisol due to a tumor in the pituitary gland (the specific cause of Cushing’s disease) or elsewhere in the body.

The case report highlighted the importance of considering meningiomas close to the pituitary as potential mixed tumors (known as collision tumors), comprising pituitary adenomas in patients whose clinical and lab data suggest Cushing’s syndrome other than Cushing’s disease.

The case study, “Cushing’s disease due to a pituitary adenoma as a component of collision tumor: A case report and review of the literature,” was published in the Journal of Medical Case Reports.

A tumor in the pituitary gland that secretes higher-than-normal amounts of the adrenocorticotrophic hormone (ACTH) — which stimulates cortisol production by the adrenal glands — is the most common cause of endogenous Cushing’s syndrome.

However, other tumors can cause the body to produce abnormally high levels of cortisol, including those outside the pituitary and wrongly producing ACTH, and adrenal tumors secreting too much cortisol.

The high-dose dexamethasone suppression test is often used to assess whether the disease-causing tumor is in the pituitary gland. It involves the analysis of a patient’s blood cortisol levels after administration of a high-dose of dexamethasone (a steroid that mimics cortisol).

A greater than 50% drop in cortisol levels after dexamethasone treatment indicates the presence of a pituitary tumor, which lowered ACTH secretion in a natural response to higher levels of cortisol. A lesser drop in cortisol levels suggests the presence of a tumor elsewhere.

Physicians then use imaging tests to confirm the location of these disease-causing tumors.

Researchers in Turkey reported, presumably for the first time, a case of Cushing’s disease caused by a collision tumor containing a pituitary adenoma and a meningioma.

The woman was admitted to the hospital with menstrual irregularity, severe weakness of the upper arm and upper leg muscles, and a 10–15 kg (22–33.1 lbs) weight gain within a year.

Further examination revealed other common signs of Cushing’s syndrome, such as excessive fat around the torso, a moon face with red cheeks, and excessive hair growth on her chest and belly. She also had high blood pressure (hypertension), a less common Cushing’s symptom.

She reported no history of smoking, alcohol consumption, chemical or radiation exposure, or hormone-related diseases in the family, and showed no signs of neuromuscular, respiratory, or cardiovascular problems.

Lab work showed that blood cortisol levels were abnormally high throughout the day, and those of ACTH slightly higher than normal.

Both low- and high-dose dexamethasone suppression tests failed to promote a profound (more than 50%) drop in blood cortisol levels, which combined with the absence of a pituitary tumor in a magnetic resonance imaging scan, suggested Cushing’s syndrome other than Cushing’s disease.

However, the scan showed a meningioma near the pituitary gland. Additional tests found no other tumors, suggesting that this tumor could be abnormally producing ACTH or the corticotropin-releasing hormone (that stimulates ACTH production by the pituitary gland) and causing Cushing’s in this patient.

The meningioma was removed through a minimally invasive endoscopic endonasal surgery, and tissue analyses showed that the tumor generally consisted of an ACTH-secreting pituitary adenoma infiltrated by meningioma.

Pituitary adenoma-meningioma collision tumors have been described in only four cases to date, none resulting in Cushing’s disease, the researchers noted.

After the surgery, the woman showed adrenal insufficiency with abnormally low cortisol levels, for which she was prescribed steroid replacement therapy while waiting for her adrenal glands to regain normal function and cortisol production.

At her latest visit, she had lost 12 kg (26.5 lbs), no longer showed signs of hypertension, menstrual irregularity, or muscle weakness, and her lab test results were within normal ranges. Her mental and physical well-being were restored.

“Even if a high-dose dexamethasone suppression test fails to suppress basal cortisol level, the importance of considering a … meningioma as a possible component of a collision tumor presenting as ACTH-dependent Cushing’s syndrome is highlighted here,” the researchers wrote.

They also noted that further research is needed to better understand the underlying mechanisms of this particular type of collision tumor.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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