Horvath et al. (2006) identified 10 individuals with Cushing syndrome and adrenocortical hyperplasia who did not have PRKAR1A mutations. In most of these individuals, the adrenal glands had an overall normal size and weight and featured multiple small ... Horvath et al. (2006) identified 10 individuals with Cushing syndrome and adrenocortical hyperplasia who did not have PRKAR1A mutations. In most of these individuals, the adrenal glands had an overall normal size and weight and featured multiple small yellow-to-dark brown nodules surrounded by a cortex with a uniform appearance. Microscopically, there was moderate diffuse cortical hyperplasia with mostly nonpigmented nodules, multiple capsular deficits, and massive circumscribed and infiltrating extraadrenal cortical excrescences with micronodules. Although overall there was no pigmentation by regular microscopy, electron microscopy showed granules of lipofuscin and features of a cortisol-producing adrenocortical hyperplasia.
In affected members of 2 unrelated families with adrenal Cushing syndrome due to PPNAD2, Horvath et al. (2006) identified 2 different heterozygous mutations in the PDE11A gene (604961.0001; 604961.0002). Adrenal tumor tissues showed loss of heterozygosity (LOH) for ... In affected members of 2 unrelated families with adrenal Cushing syndrome due to PPNAD2, Horvath et al. (2006) identified 2 different heterozygous mutations in the PDE11A gene (604961.0001; 604961.0002). Adrenal tumor tissues showed loss of heterozygosity (LOH) for 2q31-q35, decreased protein expression, and high cyclic nucleotide levels and cAMP-responsive element-binding protein (CREB; 123810) phosphorylation. Horvath et al. (2006) concluded that the pathophysiologic mechanism is linked to increased cAMP levels, as seen in patients with McCune-Albright syndrome (MAS; 174800) and PPNAD1.