Study Links Pituitary Gland Changes in PWS to Behavioral Symptoms

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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People with Prader-Willi syndrome (PWS) have smaller pituitary glands than their typically-developing peers, according to data from a small study.

The findings also suggest that altered pituitary size is associated with behavioral abnormalities in PWS.

Results were published in the journal Biomarkers in Neuropsychiatry, in the study “Reduced pituitary volume with relative T1 shortening correlates with behavior in Prader-Willi syndrome.”

PWS is caused by known genetic alterations, but the exact biological mechanisms of how the body is affected by PWS are still being worked out. It is thought that one of the biological drivers of PWS symptoms is dysfunction of the hypothalamus-pituitary axis (HPA).

The HPA is a complex set of hormonal interactions between the pituitary gland — a small, bean-shaped gland located in the base of the brain — as well as the hypothalamus and the adrenal glands. The HPA helps to regulate a wide array of bodily processes, from digestion, to the activity of the immune system, to emotional responses.

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Although the HPA is thought to be dysregulated in PWS, data on how reported structural pituitary alterations correlate with disease symptoms is still needed.

Now, researchers at the University of Niigata in Japan used MRI to assess the size of the pituitary gland in 21 people with PWS (median age 25 years, 14 were male). These were compared with the pituitary glands of 31 typically-developing people, who were similar in age and sex. All of the study participants were Japanese.

“We hypothesized that individuals with PWS have developmental abnormalities in the pituitary glands, and this study aimed to determine whether such alterations are associated with Prader-Willi syndrome-associated behavioral characteristics,” the scientists wrote.

Results showed that, compared to the typically-developing controls, people with PWS had significantly smaller pituitary glands, for both the anterior (292.7 vs. 486 cubic milimeters or mm3) and posterior lobes (72.3 vs. 104.2 mm3).

PWS patients also had significant reductions in signal intensity (SI) in the pituitary gland, which the researchers said may be reflective of differences in certain signaling molecules made by the pituitary.

This finding “unequivocally demonstrated significant volume differences with altered SI in the pituitary structures in individuals with PWS,” the researchers wrote.

The team then used statistical tests to check for significant associations between MRI measurements of the pituitary and various behavioral abnormalities associated with PWS, assessed with standardized questionnaires. Results showed that a smaller pituitary was significantly associated with more severe hyperphagia (abnormal hunger) and autism behaviors, but with lower scores in a scale of obsessive behaviors.

“Altered [pituitary] structures have significant correlations with individual behavioral characteristics,” the scientists wrote.

The findings overall add to the body of research about how the HPA is affected in this rare disease. A noted limitation of the study is the small size, and since all participants were Japanese, the results might not be reflective of other racial groups.

“Further analyses with a larger number of participants balanced for genetic subtypes are highly warranted” to advance the understanding of neurodevelopmental processes of PWS, according to the investigators.