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Molecular biology investigation of somatostatin receptors in diagnostics of pituitary tumors
Drastíková, Monika ; Beránek, Martin (advisor) ; Fryšák, Zdeněk (referee) ; Patočka, Jiří (referee)
Molecular biology investigation of somatostatin receptors in diagnostics of pituitary tumors The overwhelming majority of pituitary tumors are benign, with 25-30% of them representing clinically non-functioning pituitary adenomas (NFA). The treatment of choice for NFA is transsphenoidal neurosurgery. However, the procedure is often not completely successful and frequently tumor remnants remain, resulting in regrow over the long-term follow-up period. This fact has led to the development of new therapy strategies using pharmacological treatment: somatostatin analogs (SA) and estrogen receptor modulators. SA are effectively used in the treatment of acromegaly, neuroendocrine tumors and Cushing's disease. In contrast, pharmacological treatment of NFA has for the most part been unsuccessful. Low SA effectiveness could be associated with the variable expression of target receptors on the adenomas. The aim of the study was to determine the somatostatin (SSTR subtypes 1-5) and estrogen receptor 1 (ER1) expression profile. To obtain more complex receptor profile expression in the pituitary, we also investigated dopamin receptor 2 (D2R). Methods The group of patients was made up of 105 men and 101 women (20-87 years old; median 61). 144 samples were NFA, 44 growth hormone secreting (GHomas), 9 corticotrophin...
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Impairment of hypothalamo-pituitary function and its evaluation in various pathologic situations.
Kosák, Mikuláš ; Hána, Václav (advisor) ; Čáp, Jan (referee) ; Fryšák, Zdeněk (referee)
Traumatic brain injury represents serious medical problem. Besides various types of complications, endocrine dysfunction of hypothalmo-pituitary units can occur. Aim of our work was to determine whether chronic subdural haematoma, as specific type of traumatic brain injury, is associated with a risk of developing hypopituitarism as well. In a prospective study, pituitary functions in a cohort of 49 patients after surgery for chronic subdural haematoma, were evaluated. Patients were tested for hormonal deficits including dynamic tests, soon after surgery, in 3 and 12 months thereafter. 10 patients were tested retrospectively 12 months after surgery. Gonadotropic axis was impaired in 9 patients (25,7 %) in acute phase and reamained impaired in 3 (12 %) after 12 months. Growth hormone deficiency was present in 23 (46,9 %) patients during the acute phase and in 15 (46,9 %) patients in evaluation 12 months after the surgery. Serious hormonal deficiencies due to impairment of the most important axes (HPA a thyrotropic) were not proved in our patients. The second part of this work is devoted to the novel methods in diagnostic assesement of hypothalamo-pituitary-adrenocortical axis. Aim of our work was to evaluate and compare reliability of cortisol measurements in serum and saliva simultaneously during the...
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Quantitative analysis of D2 dopamine receptors in clinically non-functioning pituitary adenomas
Gabalec, Filip ; Čáp, Jan (advisor) ; Fryšák, Zdeněk (referee) ; Hána, Václav (referee)
Quantitative analysis of D2 dopamine receptors in clinically non-functioning pituitary adenomas Introduction Clinically non-functioning pituitary adenomas account for about one-third of pituitary tumors. The majority of them are pathologically classified as gonadotropinomas or null-cell adenomas without hormonal expression. The rest represent silent corticotroph adenomas and plurihormonal tumors. Conservative therapy with dopamine agonists is effective in some cases only depending on the expression of dopamine 2 receptors (D2R). Objective The aim of this study was to quantitatively estimate D2R expression in clinically nonfunctioning pituitary adenomas and correlate the results with adenoma type according to pathological classification. Methods and results Out of the 87 adenomas investigated, 63 expressed gonadotropins, 7 were silent corticotroph adenomas, 7 were plurihormonal tumors, and only 6 did not express any pituitary hormone on immunohistochemical investigation. With the use of the reverse transcriptase real-time PCR technique, D2R mRNA was expressed in all adenomas with very heterogeneous quantity. The expression was very low in corticotroph adenomas (relative median quantity after normalization to housekeeping gene 0.01) and lower in plurihormonal tumors (median 0.4) than in gonadotroph...
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