Recently, it was demonstrated that some cases of primary adrenal Cushing's syndrome were secondary to the ectopic expression of non-mutated GIP receptor (GIP-R) in bilateral adrenal hyperplasias or unilateral adrenal adenomas, resulting in food-dependent steroidogenesis.
We identified several mutations in genes of the cAMP/protein kinase A pathway, including three novel mutations in PRKACA, associated with female sex and Cushing's syndrome.
Gastric inhibitory polypeptide (GIP) stimulates cortisol secretion, cAMP production and DNA synthesis in an adrenal adenoma responsible for food-dependent Cushing's syndrome.
Hypersecretion of adrenocorticotropin hormone (ACTH), the key activator of the cAMP pathway in adrenal cortex, is associated with adrenocortical hyperplasia and cortisol oversecretion (Cushing's syndrome).
In this study, polymorphisms in the 11βHSD1 and NR3C1 genes were associated with impaired cognitive function, indicating that GC sensitivity and prereceptor regulation of GC action may play a role in the long-term consequences of CS.
Adrenocorticotropin-independent Cushing's syndrome in pregnancy related to overexpression of adrenal luteinizing hormone/human chorionic gonadotropin receptors.
Therefore, in a patient with CS with equivocal ACTH levels and a pituitary microadenoma, multiple samplings for ACTH and adrenal imaging should be performed to exclude ACTH-independent CS and if required, bilateral inferior petrosal sinus sampling to determine the source of ACTH excess.
Heterozygous inactivating mutations of PRKAR1A have been reported initially in about 45% of the CNC index cases and could be found in about 80% of the CNC families presenting mainly with Cushing's syndrome.
Genetic testing of the 2 sisters and their mother (who also had multiple facial lentigines but did not have Cushing syndrome) revealed a novel mutation in the PRKAR1A gene.
During investigation, an adrenocorticotropic hormone (ACTH) independent CS was identified and the possibility of an adrenocortical tumor was suggested.
Primary macronodular adrenal hyperplasia (PMAH), also known in the past as bilateral macronodular adrenalhyperplasia or adrenocorticotropin (ACTH)-independent macronodular adrenal hyperplasia, is a rare type of Cushing's syndrome (CS) and is associated with bilateralenlargement of the adrenal glands.
Adrenocorticotropic hormone independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is a main characteristic of CNC.
PRKAR1A mutation analysis in two large families with CS and no other CNC manifestations demonstrated a M1V germline mutation; a total of 21 asymptomatic individuals were screened, and mutation carriers were evaluated for CNC.
Lack of mutations in the gene coding for the hGR (NR3C1) in a pediatric patient with ACTH-secreting pituitary adenoma, absence of stigmata of Cushing's syndrome and unusual histologic features.