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Cushing’s Patients with USP8-mutant Tumors Have More Frequent Relapses Sooner After Surgery, Study Shows

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Friday, July 20, 2018

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MUNICH, Germany - Patients with Cushing’s disease whose pituitary tumors bear mutations in the USP8 gene are more likely to experience recurrence, and develop them sooner after surgery, a new study shows.

The study, “The USP8 mutational status may predict long-term remission in patients with Cushing’s disease,” was published in the journal Clinical Endocrinology.

Cushing’s disease develops due to pituitary tumors secreting high levels of the adrenocorticotropic hormone (ACTH), which stimulate the adrenal glands to produce excess cortisol.

Surgical removal of the tumor using transsphenoidal (TSS) surgery usually is the treatment of choice in these patients. In TSS, an endoscope is inserted into the brain through the nose.

Almost half the patients with Cushing’s disease have mutations in the USP8 gene. Interestingly, high levels of the USP8 mutant protein have been associated with increased production of ACTH.

Nonetheless, current data on the clinical features, surgical outcomes, and long-term remission in Cushing’s disease patients with USP8 mutations are limited.

Some studies have shown that, after surgery, patients with USP8 mutant tumors still tend to have high cortisol and ACTH levels, suggesting higher rates of tumor recurrence. But the effect of USP8 mutational status on long-term recurrence in adult Cushing’s patients is inconclusive.

So, researchers analyzed the differences in the rates of recurrence between patients with either a normal or mutant USP8 gene who have undergone TSS.

Prior to TSS, baseline results indicated that patients with USP8 mutant tumors were diagnosed significantly earlier (at an average age of 46) compared to patients with normal UPS8 gene (average age of 53).

Additionally, patients with UPS8 mutations also had significantly higher cortisol levels at baseline compared to patients with normal USP8 genes.

And while only 18% of patients with a normal UPS8 gene experienced a recurrence, 58% of those with UPS8 mutations saw their disease return.

Recurrence also occurred significantly earlier in patients with the USP8 mutation (an average of 70 months) compared to patients without USP8 mutations (average of 102 months).

This suggests that recurrence is more frequent and occurs sooner after TSS in patients with USP8 mutant tumors.

“Our study suggests that this molecular alteration, which occurs in around 40% of cases, may be useful to foretell post-operative outcome in patients with [Cushing’s disease],” investigators wrote.

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Author: Iqra Mumal
Source: Cushings Disease News
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