Researchers at the National Institutes of Health and nine European research institutions have discovered a genetic mutation that appears to contribute to a severe form of Cushing’s syndrome. The findings were published online February 26 in the New England Journal of Medicine.

In the study, tissue samples from nearly 200 patients having a subtype of Cushing’s syndrome where noncancerous tumors in one adrenal gland produced excess cortisol were removed and analyzed.  Thirty seven percent of the tumors contained a mutation in the PRKACA gene, but other cells in the body did not have this gene mutation. The PRKACA gene contains the necessary information to make a subunit of the PKA (protein kinase A) enzyme that is involved in a variety of chemical reactions in the cell.

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In examining tissue from patients with noncancerous tumors on both adrenal glands, an extra copy of the PRKACA gene was found in all the cells of the body. This suggests that it was hereditary, unlike the spontaneous gene mutation in tumors on only one adrenal gland. For both types of tumors, the mutation increased the overproduction of cortisol.

The researchers also identified a patient with Carney Complex with a pituitary gland tumor and elevated growth hormone as having an extra copy of the PRKACB gene, which is likely to cause an increase in PKA and hormone production. The team hopes that these discoveries will lead to medications to block the excess cortisol production.

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