Endocrine Abstracts

The molecular mechanisms underlying adrenal adenomas have not yet been elucidated. Many groups have sought mutations within the ACTH receptor as well as its downstream signalling pathway, although none have yet been identified. However, mutations in the alpha regulatory subunit of the cAMP dependant Protein Kinase A (PRKAR1A) have recently been described in more than 50% of patients with Carney complex. This syndrome is characterised by nodular adrenocortical hyperplasia as well as spotty skin pigmentation, myxomas and various other endocrine tumours. We have therefore sought similar mutations in 20 hyperfuntioning adrenocortical tumours taken from patients presenting with ACTH independent Cushing's syndrome (15 female, 5 male, mean age 54.2 years). All tumours were confirmed as adrenocortical adenomas, with surrounding adrenal atrophy on histological examination.

Messenger RNA was first isolated from the tumours and complementary DNA produced by reverse transcription. Intron spanning primers specific to PRKAR1A were then designed and PRKAR1A amplified by polymerase chain reaction. Direct sequencing of all samples was then performed. No mutations or polymorphisms have been identified in any of the adenomas studied.

This suggests that in contrast to the ACTH independent adrenocortical hyperplasia of Carney complex, isolated adrenal adenomas are not commonly caused by mutation of the PRKAR1A.