Genetic causes of familial pituitary adenomas

peer reviewe

Genetic Factors in the Development of Pituitary Adenomas.

Pituitary adenomas are one of the most frequent intracranial tumors. Usually, they are benign but are of great clinical significance because of tumor compression syndrome and hormone overproduction. The interest in this pathology is increasing, particularly after some recent reports on their prevalence that proved to be 3-5 times more than previously estimated. Pituitary tumors arise in a sporadic setting and rarely as part of hereditary genetic syndromes. Such rare hereditary conditions like MEN1, Carney complex and McCune-Albright syndrome give significant insight into pituitary tumorigenesis. Newer genes associated pituitary tumor development include CDKN1B (MEN4) and AIP, the latter of which is involved in the pathophysiology of 15% of FIPA kindreds. The number of genes involved in pituitary tumorigenesis is progressively increasing and the possible mechanisms of action include signal transduction pathways, cell cycle regulators, growth factors, chromosome instability and others. Nevertheless, in the majority of sporadic adenomas, the primary genetic defect remains unknown. Furthermore, there is not a well established relationship between the genotype and its influence on the protein expression, ligand-receptor interaction, tumor growth or hormone hyperproduction. Further studies should evaluate the clinical significance of genetic alterations and their implications for existing and new therapeutic options

Paraneoplastic endocrine syndromes: diagnosis and management

Paraneoplastic endocrine syndromes define a group of secondary signs and symptoms associated to a neoplasia, independently from the location of the primary tumor or its metastases. Paraneoplastic or ectopic endocrine syndromes usually result from aberrant hormone precursors or hormone-like substances by tumours. Knowledge of paraneoplastic endocrine complications is important both for the early diagnosis of neoplasia and the prognosis of the patient. In this review we discuss almost all reported paraneoplastic endocrine syndromes. We analyze their prevalence, etiology, laboratory diagnosis and treatment

Genetics of Cushing's Syndrome

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

Learning from recombinant GH treatment in obesity

peer reviewedObese and untreated growth hormone deficiency (GHD) patients have a number of similar clinical and biological abnormalities. Treatment with recombinant human growth hormone (rhGH) in GHD patients has proven effective in beneficially modulating body composition and certain cardiovascular risk factors, thus leading to the hypothesis that administration of rhGH in obese patients could show similar beneficial results. Hyperinsulinism and increased free fatty acid levels are the main factors causing reduced GH release in the setting of obesity. We reviewed the outcomes of 25 adult and paediatric clinical studies carried out in 1987-2009 that examined the effects of rhGH administration in the obese state. Body composition showed mainly a reduction in visceral abdominal fat, whereas total bodyweight increased or remained unchanged. Effects of rhGH on lipid and carbohydrate metabolic profiles in obese patients were heterogeneous. The increasing burden of obesity on one hand, the absence of definitive medical treatment on the other, give rise to grounds for considering rhGH as a possible therapeutic option if not in the general obese population, at least in patients with higher risk of cardiovascular morbidity and mortality