Genetics of Cushing’s Syndrome

Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria.
Neuroendocrinology (Impact Factor: 4.37). 09/2010; 92 Suppl 1(1):6-10. DOI: 10.1159/000314215
Source: PubMed


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.

8 Reads
  • Source
    • "En la última categoría está el pseudo-Cushing, donde se encuentra la depresión 1% y el alcoholismo crónico 1%. (Chalem, Campos, Esguerra y Chalem, 2005; Yaneva, Vandeva, Zacharieva, Daly y Beckers, 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: El objetivo de este estudio exploratorio es analizar la relación entre el bienestar psicológico y las condiciones médicas y terapéuticas de personas con diagnóstico de síndrome de Cushing. Los instrumentos utilizados fueron el Índice de Bienestar subjetivo (The Psychological Well-Being Index; Dupuy, 1984) y el Cushing’s Syndrome Severity Index (CSI). La selección de la muestra se realizó por conveniencia; considerando que es un síndrome de muy baja incidencia, se estableció contacto con cinco pacientes. Se utilizaron estadísticos descriptivos que facilitaron la obtención de información sobre la muestra. Los resulatdos per- miten concluir que la severidad de los síntomas asociados al síndorme, evaluados a través del CSI, implican malestar moderado en el bienestar psicológico, corroborando lo señalado por la literatura, así como que las alteraciones de orden psicológico influyen en el proceso de enfermedad o recuperación.Palabras clave: síndrome de Cushing (SC 5117073), bienestar psicológico (SC56603), psicología de la salud (SC22398).
    Preview · Article · Jun 2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The pathogenesis of tumour formation in the anterior pituitary including adrenocorticotropic hormone (ACTH)-secreting tumours has been intensively studied, but the causative mechanisms involved in pituitary cell transformation and tumourigenesis remain unclear. We searched PubMed on any paper related with molecular pathology of pituitary corticotroph adenomas and have included to this review all relevant references published up to June 2011. Current studies increased our knowledge on the genetic basis of McCune-Albright syndrome (MAS), multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), pituitary adenoma predisposition syndromes and tuberous sclerosis, but they have performed little to elucidate the causes of sporadic pituitary tumours including Cushing disease. The aim of this review was to focus on the most recently published advances in the molecular pathology of corticotroph adenomas, which are presented in the context of changes seen in all types of pituitary adenomas, as well as in terms of corticotrophin-releasing hormone/ACTH/cortisol-specific pathways. We would expect that over the next 5 years, more detailed analysis of inter-cellular communication pathways between pituitary cells, including the cadherins and integrins, and their interactions with other signalling pathways such as the β-catenin cascade will help elucidate what exactly goes awry in the formation of a benign corticotroph adenoma. This should in turn predict novel forms of pharmacological tumour control.
    Full-text · Article · Oct 2011 · European Journal of Clinical Investigation
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cushing's disease, or pituitary ACTH dependent Cushing's syndrome, is a rare disease responsible for increased morbidity and mortality. Signs and symptoms of hypercortisolism are usually non specific: obesity, signs of protein wasting, increased blood pressure, variable levels of hirsutism. Diagnosis is frequently difficult, and requires a strict algorithm. First-line treatment is based on transsphenoidal surgery, which cures 80% of ACTH-secreting microadenomas. The rate of remission is lower in macroadenomas. Other therapeutic modalities including anticortisolic drugs, radiation techniques or bilateral adrenalectomy will thus be necessary to avoid long-term risks (metabolic syndrome, osteoporosis, cardiovascular disease) of hypercortisolism. This review summarizes potential pathophysiological mechanisms, diagnostic approaches, and therapies.
    Full-text · Article · Jun 2012 · Orphanet Journal of Rare Diseases
Show more