'Bomb fuse' DNA linked to health problems in Cushing's

Each year, two out of every million adults is diagnosed with Cushing's syndrome. The rare disease is caused by a tumor in the pituitary or the adrenal glands that produces too much of the stress hormone cortisol. High levels of cortisol can lead to health problems such as premature aging, diabetes, osteoporosis and cognitive difficulties. The condition can be managed by reducing cortisol levels through surgery, medication, or radiotherapy. In spite of this, most health complications of Cushing's syndrome are not completely reversible even when cortisol levels are managed.

Patients with chronic stress or depression exhibit high levels of cortisol and are known to have shortened DNA sequences on the ends of their chromosomes. These sequences, known as telomeres, are like a bomb fuse -- they become shorter every time a cell divides. Eventually they become so short that the cell is unable to divide and subsequently dies. This shortening process is associated with aging.

In this study, researchers from the Hospital Sant Pau and CIBERER Unit 747 of the Universitat Autònoma de Barcelona compared the telomere length of 77 Cushing's patients with 77 healthy individuals. As expected, the researchers found that older patients had shorter telomeres. No differences were observed between both Cushing's syndrome and control patients. However, three years after being cured, researchers noticed that in a small group of Cushing's syndrome patients telomere length had actually increased, even though they normally get shorter with time.

The findings open up an exciting new avenue for research. "We've seen that the cells of Cushing's patients struggle to maintain their DNA stability," said Dr Anna Aulinas, endocrinologist and lead author of the study. "We don't know why this happens, but this DNA instability could be implicated in the health complications suffered by Cushing's patients after treatment. We believe that telomere biology might play a role in the origin of these complications. This study is an important step in helping us identify new therapeutic targets."

The researchers now plan on recruiting more patients to test whether their findings are also observed in larger groups. They will also look more closely at the role of the enzymes responsible for maintaining telomeres in Cushing's patients, which could also have wider significance. "Telomere biology is a really exciting area of research as it affects so many fundamental biological processes. In other diseases, such as certain cancers and cardiovascular disease, research is devoted to look for new drugs and therapies to maintain and repair the telomere machinery and dynamics. Our work could therefore be an additional piece of the puzzle."