Article

Genetics of Cushing's syndrome.

Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria.
Neuroendocrinology (Impact Factor: 4.93). 01/2010; 92 Suppl 1:6-10. DOI: 10.1159/000314215
Source: PubMed

ABSTRACT Cushing's syndrome (CS) is characterized by pathologically elevated free glucocorticoid levels. Endogenous hypercortisolism is usually due to ACTH-secreting pituitary corticotropic adenomas and less often due to ectopic ACTH-secreting neuroendocrine neoplasms or ACTH-independent adrenal cortisol hypersecretion. CS is a serious chronic disease leading to a several-fold increase in cardiovascular morbidity and mortality. Multiple genetic alterations have been described in the setting of sporadic corticotropinoma formation. Changes in the expression profiles have been demonstrated in growth factors and their receptors, cell-cycle regulators and in various genes related to hormonal gene transcription, synthesis and secretion. Sporadic adrenal adenomas and carcinomas may demonstrate dysfunction in genes such as TP53 among others. Cushing's disease can be an inherited condition also. Multiple endocrine neoplasia type 1 (MEN1) and familial isolated pituitary adenomas (FIPA) together account for 5% of pituitary adenomas. Cushing's disease occurs infrequently in an inherited setting in both of these conditions. To date only 2 cases of Cushing's disease have been described in association with mutations in AIP. One case of Cushing's disease has been reported as part of MEN4, a rare MEN1-like syndrome due to mutation in the CDKN1B gene. Carney complex (CNC) due to PRKAR1A mutations in most cases is associated with CS, mainly as a cause of bilateral adrenal hyperplasia. The cAMP signaling pathway is affected in this setting. In recent times the involvement of genes such as PDE11A, PDE8B and others have expanded the spectrum of the genetic pathophysiology of CS.

0 Bookmarks
 · 
126 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bilateral adrenal tumors are very uncommon in clinical practice and all originate from the same histology. We presented here a case report and literature review of bilateral adrenal tumors from different histology: pheochromocytoma in one side and adrenocortical adenoma in the other side. The patient was a 37 years old female suffered from Cushing's syndrome form 3 years. One year ago she was diagnosed as ACTH-independent Cushing's syndrome and received Laparoscopic adrenalectomy for right adrenal tumor which diagnosed as a pheochromocytoma by the pathological reports. After the operation, patient's clinical manifestation was not change, then half-year later the lab test showed no improvement in the blood biochemical parameters. Finally, CT detected a mass in left adrenal gland. Thereafter, this patient received Laparoscopic adrenalectomy for left adrenal tumor. The tumor was diagnosed as adrenocortical adenoma by the pathologists. One week after operation, the blood biochemical parameters became normal. In conclusion, bilateral adrenal tumors from different histology are very rare, adrenalectomy for both side tumors and preserving the normal adrenal glands is necessary.
    Cell Biochemistry and Biophysics 08/2014; 71(1). DOI:10.1007/s12013-014-0216-x · 2.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A gain-of-function point mutation in the gene that encodes one of the catalytic subunits of protein kinase A (PRKACA) in cortisol-producing adrenocortical adenomas has been independently reported by three groups. This hotspot point mutation (c.617T>G PRKACA) drives increased cAMP signalling and expands the pathogenic role of protein kinase A in benign lesions of the adrenal cortex.
    Nature Reviews Endocrinology 06/2014; 10(8). DOI:10.1038/nrendo.2014.89 · 11.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The long-term outcomes of the DIGAMI 1 study indicate that intensive glucose lowering could be beneficial after an acute myocardial infarction in patients with type 2 diabetes mellitus. However, questions have been raised about whether it is acute or long-term glycaemic control or insulin that is beneficial.
    Nature Reviews Endocrinology 07/2014; 10(8). DOI:10.1038/nrendo.2014.101 · 12.96 Impact Factor