1,721,054 research outputs found
G-protein and signalling in pituitary tumours
No full textThe genesis of pituitary tumours is still under debate. Although these neoplasias are monoclonal in origin, mutations of GNAS1, the gene encoding the α subunit of the stimulatory G-protein, Gs, are the only mutational changes unequivocally associated with growth hormone (GH)-secreting adenomas. However, despite the growth advantage that this oncogene has been demonstrated to confer in vitro, patients carrying this mutation have a similar clinical and biochemical phenotype to those who do not carry it. This discrepancy is due to the occurrence of events able to counteract the biological effect of the mutation. Consistent with a potential role of the cyclic adenosine monophosphate pathway in the proliferation of somatotrophs, germline mutations of the gene encoding the type 1α regulatory subunit of protein kinase A (PRKAR1A) have been found in patients with the Carney complex, a syndrome including GH-secreting adenomas, whereas alterations in the expression levels of this subunit are frequently observed in sporadic adenomas
Pituitary incidentalomas
No full textThe widespread use of sensitive neuroradiological imaging studies (i.e. computed tomography scan and magnetic resonance imaging) over the last years lead to the diagnosis of an increased number of asymptomatic pituitary lesions. The management of these so-called "pituitary incidentalomas" is still controversial, due to the limited data so far available on both the clinical relevance and the natural history of such incidentally discovered pituitary masses. Most pituitary incidentalomas are less than 1 cm in diameter (microincidentalomas) and are pituitary adenomas. Although these tumours are in general hormonally inactive, all the patients with incidentalomas should be screened for pituitary hypo- or hyper-function. Macroincidentalomas have greater growth potential and, when associated with hypopituitarism and/or visual disturbances, should be surgically removed. Conversely, incidentalomas not associated with hormonal alterations and dimensionally stable could be managed conservatively. This review will focus on the last data on the natural history and clinical management of pituitary incidentalomas
Central hypothyroidism
No full textCentral hypothyroidism (CH) is a rare cause of hypothyroidism due to an insufficient stimulation of an otherwise normal thyroid gland and it is caused by either pituitary (secondary hypothyroidism) or hypothalamic (tertiary hypothyroidism) defects. The diagnosis of CH is usually suggested by the finding of lowered thyroid hormone concentrations, associated with inappropriately low/normal TSH levels. Restoration and maintenance of euthyroidism represent the therapeutic goals in all forms of CH. On these basis, the vast majority of patients with CH is treated with standard levo-thyroxine (L-T4) therapy which is tailored according to FT4 circulating levels that should be maintained in the normal range
cAMP pathway and pituitary tumorigenesis
No full textThe pituitary is the target of different neurohormones that have a crucial role in the control of cell differentiation, cell proliferation and hormone secretion by recognizing specific receptors belonging to the G Protein-Coupled Receptor super-family (GPCR). Evidence from in vitro studies and naturally occurring human diseases indicate that several endocrine cells, and particularly somatotrophs, recognize cAMP as a growth factor. Accordingly, mutations of the alpha subunit of the stimulatory G protein gene (. GNAS) leading to the constitutive activation of adenylyl cyclase (i.e. gsp oncogene) have been recognized in a significant proportion of GH-secreting pituitary adenomas. The role of cAMP in the control of cell proliferation in selected cell types and in particular in somatotroph cells has been further confirmed by identification of genetics defect affecting the regulatory subunit IA of PKA. The role of cAMP in the control of cell proliferation as well as the crosstalk with different intracellular signalling pathways will be discussed
Hormonal signaling and pituitary adenomas
No full textIn recent years the demonstration that human pituitary adenomas are monoclonal in origin provides further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. Mutations in common oncogenes and tumor suppressor genes are only exceptionally involved in pituitary tumors. Since pituicytes may proliferate in response to hypothalamic neurohormones, locally produced growth factors and peripheral hormones, it has been speculated that dysregulation of the signaling molecules that constitute these pathways may confer growth advantage to the target cell, finally resulting in tumor formation. The only mutational change so far recognized to be unequivocally associated with pituitary tumors occur in the Gsα gene (GNAS1) and cause constitutive activation of the cAMP-dependent pathway. However, other components of pituitary-specific pathways are frequently altered in their expression and activity. This review will focus on the possible impact of G proteins and other components of hormone signaling on pituitary tumorigenesis. Copyrigh
Analysis of N-ras Gene-mutations In Medulloblastomas By Polymerase Chain-reaction and Oligonucleotide Probes In Formalin-fixed, Paraffin-embedded Tissues
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Central hypothyroidism and growth hormone treatment : clinical care
No full textCentral hypothyroidism (CH) is a rare cause of hypothyroidism characterized by a defect of thyroid hormone production due to an insufficient TSH stimulation. CH can be congenital in the case of genetic defects or acquired in the case of lesions affecting either pituitary or hypothalamus. Diagnosis is usually made on a biochemical basis showing defective thyroid hormone circulating levels associated to inappropriately low TSH levels. Treatment of CH takes advantage of thyroid hormone replacement even though treatment cannot be tuned as easily as in primary hypothyroidism because the evaluation of circulating TSH has a very limited value in central defects. Interestingly, GH deficiency may mask subclinical forms of CH that reach a biochemical evidence only after institution of GH replacement therapy
- …
