How Glucose May Lead to Better Outcomes for Cushing’s Disease Surgery

If you or someone you love has Cushing Disease (often confused with the umbrella term, Cushing Syndrome), you’ve probably heard about microadenas. Microadenas are the tiny, benign tumors that develop in the pituitary gland.

Though they’re usually not more than 10 mm, they have a big impact. These tumors are where the whole disease starts. They cause the pituitary gland to create too much adrenocorticotropic hormone (ACTH). In turn, the ACTH leads to overproduction of a hormone called cortisol.

Cortisol is often called the “stress hormone,” because for most people, it only comes into play when the body is in a stressful situation. At healthy levels, it does a great job at controlling the body’s stress reaction, by raising blood pressure and controlling cell metabolism.

The problem for people with Cushing disease is that, because of the tumor, their cortisol levels are too high, even when they aren’t under stress. This leads to mysterious weight gain, mood changes, high blood pressure, hormonal irregularities, and trouble fighting off infection. To read more about Cushing disease, click here.

Many people with Cushing disease decide to undergo surgery to remove the microadena. If the surgeon is able to detect where the tumor is before surgery begins, the odds of a successful surgery skyrocket up. The problem is, current imaging methods like MRIs and PET scans often can’t find the tumor.

Researchers have proposed solutions. They tried using corticotropin-releasing hormone (CRH), because it would increase glucose uptake in the microadena. Then, they could detect the tumor with 18F-FDG, a tracer that would show up in a PET scan. Since 18F-FDG acts like glucose, it would lead them right to the tumor.

This seemed like a promising idea, but studies exploring it showed disappointing results. The researchers started to wonder if they had missed a factor. The idea was solid, but if there was a delay in the way pituitary tumor took up glucose, then it wouldn’t have shown up in the research.

The researchers examined some clinical data for a new study. They found that CRH behaved differently in healthy cells and cells from this type of tumor. While CRH made mouse and human tumor cells take up more glucose, it didn’t have that effect in healthy cells. CRH had its strongest effect on mouse cells after 4 hours. GLUT-1, a glucose transporter, increased after two hours. The researchers believe there’s a link between CRH, GLUT-1, and glucose uptake. When fasentin stopped GLUT-1, it also stopped glucose transport, and glucose uptake.

Throughout the study, the researchers found that the cells in the microadena tumors behaved differently to healthy cells. They processed much more glucose, which means they might be relying on it for energy in a way that other cells don’t.

Essentially, the study confirmed that while CRH does, indeed, lead to glucose uptake in the tumor, the glucose uptake is specific and delayed.

With this knew knowledge about how CRH, glucose, and pituitary tumors interact, researcher have a promising lead to move forward on. They can revamp their efforts to improve tumor imaging prior to surgery, ultimately improving the healths of many people.

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