Crooke cell adenoma tied to worse outcomes in Cushing’s in study

More targeted treatment needed to improve outcomes after surgery

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Cushing’s disease caused by Crooke cell adenoma — a rare but typically more aggressive pituitary tumor — is less likely than forms of the disease associated with other types of pituitary tumors to go into remission in the months following surgery.

This is true despite the fact that surgery usually is successful at removing these tumors, called CCAs for short.

That’s according to a new study titled, “Crooke Cell Adenoma Confers Poorer Endocrinological Outcomes Compared with Corticotroph Adenoma: Results of a Multicenter, International Analysis,” that was published in the journal World Neurosurgery.

“Our novel insight is that global outcomes continue to remain poor for [Crooke cell adenoma] despite modern improvements in surgical technique,” the researchers wrote.

“Further work is necessary to better understand the pathophysiology [or disordered physiological processes] of CCA to devise more targeted treatment approaches,” the team concluded.

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Investigating outcomes of Crooke cell adenoma vs. other tumor types

Cushing’s disease is caused by a tumor in the pituitary gland, a small gland located in the brain. The tumor causes the pituitary gland to release high levels of signaling molecules that spur the production of the stress hormone cortisol elsewhere in the body; high cortisol levels ultimately cause most Cushing’s symptoms.

A Crooke cell adenoma, or CCA, is part of a specific subset of pituitary tumors that is marked by certain characteristic changes in the appearance of the cells that compose them. CCAs are rare — typically found in 5% to 10% of people with Cushing’s disease — and are generally considered to be more aggressive and associated with poorer clinical outcomes.

“Because of the rarity of CCA, most studies are small, involve a single-center cohort [group], and have variability in diagnostic criteria; thus, understanding of outcomes remains limited,” the scientists wrote.

Now, researchers sought to learn more. To that end, an international team conducted an analysis comparing the outcomes of people with Cushing’s disease caused by Crooke cell adenoma and other types of pituitary tumors.

The team pooled data collected from a dozen specialty centers across North and South America, Europe, and Asia. The final analysis included data on 500 people with Cushing’s disease who underwent surgery to remove the disease-driving pituitary tumor.

“We aimed to evaluate outcomes in patients with CCA and compare them with those of patients with [non-CCA pituitary tumors] by using a large, multicenter, international dataset from high-volume skull base centers,” the researchers wrote.

Among the patients, 20 had CCA, and the other 480 had other types of pituitary tumors. The two groups were generally comparable in terms of demographic and clinical factors like age, sex, tumor size, and prior treatment use. The specific surgical approaches that were used also were similar in both groups, as were the rates of surgery-related complications.

Following surgery, all 20 patients with CCAs achieved gross total resection, meaning that analyses suggested that the entire tumor was removed during surgery and there wasn’t any detectable tumor left on medical tests. For people with non-CCA pituitary tumors, most but not all (83%), achieved gross total resection.

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Lower rates of disease remission seen for Cooke cell adenoma patients

Researchers subsequently compared individuals in both groups who achieved gross total resection.

Patients with CCAs were found to have significantly lower rates of normal pituitary function following surgery (50% vs. 77.8%).

CCA patients also had lower rates of disease remission — specifically cortisol normalization, or a return to normal cortisol levels — in the months following surgery (75% vs. 84.3%). These lower rates occurred despite these patients having higher rates of local disease control (100% vs. 96%) and lower rates of residual tumor on imaging scans (0% vs. 7.2%).

The findings demonstrate that overall outcomes for CCA patients were poor despite surgery, the researchers noted.

These results suggest that CCA may be more aggressive or invasive, so tumor cells are more able to insidiously survive following surgery, according to the team. Theoretically, this might mean that patients with CCA would be more likely to benefit from other treatments like chemotherapy or radiation.

The team stressed, however, that further research is needed to understand why outcomes tend to be poorer in patients with Cooke cell adenoma and how this could be addressed by treatment.

“The location of [CCA] tumors, medial cavernous invasion, persistence of residual disease despite resection, or molecular differences with other pituitary tumors remain to be explored as potentials reasons for such poor outcomes,” they wrote.