<unk> , the endocrine manifestation that comes from Carney Complex (CNC), can be syndromic or isolated. The main cause of isolated<unk>  is a mutation of PRKAR1α, located at 17q22-24, which is the gene encoding the regulatory R1α subunit of protein kinase A. Germline heterozygous PRKAR1α inactivation mutations are present in 80% of CNC patients affected by Cushing's syndrome. There are over 117 mutations of the PRKAR1α gene that can cause CNC, with many of these mutations producing premature stop codons, thus resulting in the complete loss of PRKAR1α protein. CNC patients have also been discovered with an unusually shortened PRKAR1α protein, detected in tumours and leukocytes, following a splice-site mutation, which causes exon-6 skipping. Therefore, both haploinsufficiency and the complete loss of PRKAR1α can lead to the increased PKA activity observed in<unk>  patients, due to the disruption of the cAMP signalling pathway. Sahut-Barnola et al. used a mouse model to cre-lox knockout the Prkar1a gene specifically from cells of the adrenal cortex and observed that the mice subsequently developed Cushing syndrome that is independent of the pituitary. They also observed that the mutation caused increased PKA activity. The R1α loss caused the adult adrenal gland became hyperactive and hyperplastic on both sides, as seemingly the foetal adrenal cells within it were not maintained and thus expanded. This established tumoral growths. This mouse KO model phenocopies what happens in human cases of<unk> . Inactivation of PDE11A4, located at 2q31-5, has also been identified in<unk>  patients without PRKAR1α mutations. PDE11A4 is the gene encoding phosphodiesterase 11A4, another participant of the cAMP signalling pathway.
Primary pigmented nodular adrenocortical disease
Lipoid congenital adrenal hyperplasia
Late onset congenital adrenal hyperplasia
Multiple endocrine neoplasia
Multiple endocrine neoplasia type 1
Adrenocortical adenoma
Multiple endocrine neoplasia type 2
Congenital adrenal hyperplasia