Glucocorticoids (GCS) are known to modulate cardiovascular response during stress conditions. The present study was aimed to test the hypothesis that permissive and/or stimulating effect of GCs is essential for the maintenance of peripheral vascular resistance and for the adequate response of cardiovascular system to stressor exposure. The effects of acute pharmacological adrenalectomy (PhADX) on humoral and cardiovascular parameters were studied in adult Wistar rats under the basal conditions and during the acute restraint stress. Acute PhADX was performed by the administration of metyrapone and aminoglutethimide (100 mg/kg s.c. of each drug) resulting in a suppression of endogenous glucocorticoid synthesis. Blood pressure (BP), heart rate (HR) and core body temperature were measured using radiotelemetry. BP responses to administration of vasoactive agents were determined in pentobarbital-anesthetized animals. PhADX considerably attenuated stress-induced increase of BP, HR and core body temperature. PhADX did not abolish BP and HR lowering effects of ganglionic blocker pentolinium indicating preserved sympathetic function in PhADX rats. BP response to exogenous norepinephrine administration was attenuated in PhADX rats, suggesting reduced sensitivity of cardiovascular system. Suppression of corticosterone synthesis by PhADX increased basal plasma levels of ACTH, aldosterone and plasma renin activity in unstressed animals but there was no further increase of these hormones following stressor exposure. In conclusion, PhADX attenuated stress-induced rise of blood pressure, heart rate and core body temperature indicating an important permissive and/or stimulating role of glucocorticoids in the maintenance of the adequate response of cardiovascular system and thermoregulation to several stimuli including acute exposure to stressor.

• MeSH
• Adrenalectomy MeSH
• Aminoglutethimide pharmacology   MeSH
• Antimetabolites pharmacology   MeSH
• Vascular Resistance drug effects   MeSH
• Restraint, Physical physiology   MeSH
• Glucocorticoids antagonists & inhibitors   biosynthesis   MeSH
• Aromatase Inhibitors pharmacology   MeSH
• Blood Pressure drug effects   MeSH
• Rats MeSH
• Metyrapone pharmacology   MeSH
• Disease Models, Animal MeSH
• Rats, Wistar MeSH
• Heart Rate drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. OBJECTIVE: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). PATIENTS AND METHODS: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). RESULTS: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. CONCLUSIONS: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results.

• MeSH
• Cushing Syndrome drug therapy   physiopathology   surgery   MeSH
• Databases, Factual MeSH
• Adult MeSH
• Pituitary Gland physiopathology   MeSH
• Ketoconazole therapeutic use   MeSH
• Quality of Life MeSH
• Middle Aged MeSH
• Humans MeSH
• Metyrapone therapeutic use   MeSH
• Adrenal Glands physiopathology   MeSH
• Paraneoplastic Endocrine Syndromes MeSH
• Postoperative Period MeSH
• Postoperative Care MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

Hypofyzární adenomy jsou nejčastější tumory selární oblasti. V jejich terapii se kombinují postupy neurochirurgické, radiační a medikamentózní. Ve vybraných případech je možným přístupem i observace pacienta. U akromegalie, Cushingovy choroby a TSH produkujících adenomů je metodou volby neurochirurgický výkon. V léčbě rezidua adenomu se uplatňuje ozáření Leksellovým gama nožem, do nástupu účinku gama nože je podávána medikamentózní léčba. Velké a progredující afunkční adenomy necháváme operovat; pokud jsou dostatečně vzdálené od optických struktur, je možné jejich ozáření. U prolaktinomů je primární léčbou medikamentózní léčba dopaminergními agonisty. Při léčbě hypofyzárních adenomů je nezbytná mezioborová spolupráce endokrinologa, neurochirurga a radiochirurga.

Pituitary adenomas are the most common tumours of the sellar region. A combination of neurosurgery, radiation and pharmacological approaches are applied for the treatment of pituitary adenomas. In certain cases, patient observation is another option. Neurosurgery is the first-choice treatment for acromegaly, Cushing´s disease and TSH secreting adenomas. Leksell gamma knife irradiation is used in the treatment of tumour residues. Until the effect of the irradiation is evident, pharmacological treatment must be administered. Large and/or growing non-functioning pituitary adenomas are operated. Irradiation is possible if there is sufficient distance between the margin of the adenoma and the optic pathway. The primary therapy for prolactinomas is pharmacological treatment with dopamine agonists. Multidisciplinary collaboration among endocrinologists, neurosurgeons and radiosurgeons is necessary in the treatment of pituitary adenomas.

• MeSH
• Adrenocorticotropic Hormone MeSH
• Acromegaly diagnosis   surgery   therapy   MeSH
• Pituitary ACTH Hypersecretion diagnosis   therapy   MeSH
• Hypopituitarism MeSH
• Ketoconazole therapeutic use   MeSH
• Humans MeSH
• Metyrapone therapeutic use   MeSH
• Pituitary Neoplasms * diagnosis   classification   therapy   MeSH
• Prolactinoma diagnosis   drug therapy   MeSH
• Radiosurgery instrumentation   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Cushingův syndrom je vzácné onemocnění s variabilní etiologií spojené s významně zvýšenou morbiditou a mortalitou postižených pacientů. Z tohoto důvodu je nezbytné včasné stanovení etiologicky správné dia­gnózy a časná léčba vedoucí ke zmírnění postižení pacientů a snížení jejich morbidity a mortality. Článek představuje shrnutí současných doporučení České endokrinologické společnosti pro léčbu Cushingova syndromu.

Cushing's syndrome is a rare disorder with variable aetiology which is connected with significantly increased morbidity and mortality. Therefore, early determination of correct aetiology and early treatment are essential for a decrease of morbidity and mortality of patients. Present article introduces review and current recommendation of Czech Society of Endocrinology for the treatment of Cushing's syndrome.

• MeSH
• Adrenocortical Carcinoma therapy   MeSH
• Dopamine Agonists MeSH
• Algorithms MeSH
• Cushing Syndrome * diagnosis   etiology   therapy   MeSH
• Diagnosis, Differential MeSH
• ACTH Syndrome, Ectopic therapy   MeSH
• Endocrinology MeSH
• Etomidate MeSH
• Ketoconazole MeSH
• Pregnancy Complications MeSH
• Humans MeSH
• Metyrapone MeSH
• Mitotane MeSH
• Drug Monitoring MeSH
• Neurosurgery MeSH
• Practice Guidelines as Topic * MeSH
• Somatostatin analogs & derivatives   MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Pregnancy MeSH
• Female MeSH

• MeSH
• Adrenocortical Adenoma therapy   MeSH
• Adrenocortical Carcinoma therapy   MeSH
• Dopamine Agonists therapeutic use   MeSH
• Cushing Syndrome * diagnosis   etiology   therapy   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• ACTH Syndrome, Ectopic therapy   MeSH
• Etomidate therapeutic use   MeSH
• Drug Therapy methods   standards   MeSH
• Ketoconazole therapeutic use   MeSH
• Humans MeSH
• Disease Management MeSH
• Metyrapone therapeutic use   MeSH
• Mitotane therapeutic use   MeSH
• Adrenal Gland Neoplasms therapy   MeSH
• Off-Label Use MeSH
• Perioperative Care standards   MeSH
• Somatostatin analogs & derivatives   MeSH
• Sympatholytics therapeutic use   MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Practice Guideline MeSH

• MeSH
• ACTH-Secreting Pituitary Adenoma * surgery   MeSH
• Adrenocortical Hyperfunction * MeSH
• Adrenocorticotropic Hormone * analysis   MeSH
• Dopamine Agonists administration & dosage   therapeutic use   MeSH
• Cushing Syndrome * diagnosis   etiology   drug therapy   surgery   classification   therapy   MeSH
• Diabetes Mellitus MeSH
• Child MeSH
• Hirsutism MeSH
• Hormone Replacement Therapy methods   utilization   MeSH
• Hydrocortisone analysis   blood   urine   MeSH
• Hypertension MeSH
• 14-alpha Demethylase Inhibitors administration & dosage   therapeutic use   MeSH
• Clinical Laboratory Techniques methods   utilization   MeSH
• Humans MeSH
• Metyrapone administration & dosage   therapeutic use   MeSH
• Adolescent MeSH
• Treatment Failure MeSH
• Obesity MeSH
• Osteoporosis MeSH
• Growth Disorders MeSH
• Child, Preschool MeSH
• Radiosurgery MeSH
• Stereotaxic Techniques MeSH
• Steroid 11-beta-Hydroxylase antagonists & inhibitors   administration & dosage   therapeutic use   MeSH
• Striae Distensae MeSH
• Hypothalamo-Hypophyseal System MeSH
• Age Factors MeSH
• Gamma Rays therapeutic use   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH

OBJECTIVES: Of several enzymes metabolizing xenobiotics, cytochrome P450 (CYP) and peroxidase enzymes seem to be most important. One of the major challenges in studies investigating metabolism of xenobiotics is to resolve which of these two groups of enzymes is predominant to metabolize individual xenobiotic compounds. Utilization of selective inhibitors of CYP and peroxidase enzymes might be a useful tool to identify the contribution of these enzymes to metabolism of xenobiotics in samples, where both types of enzymes are present. The aim of this study was to investigate specificities of several known CYP inhibitors to these enzymes; whether they inhibit only the CYP enzymes and do not inhibit peroxidases. METHODS: Since the oxidation of o-anisidine catalyzed by a model peroxidase used, horseradish peroxidase (HRP), is a two-substrate reaction, the inhibition potential of tested chemicals was studied with respect to both peroxidase substrates, o-anisidine and hydrogen peroxide. Initial velocities of o-anisidine oxidation by HRP under various conditions were determined spectrophotometrically. RESULTS: The CYP inhibitors metyrapone, troleandomycine, disulfiram, sulfaphenazole, quinidine and 1-aminobenzotriazole do not inhibit o-anisidine oxidation catalyzed by HRP. In contrast, ketoconazole, diethyldithiocarbamate, ellipticine, α-naphtoflavone, proadifen SKF525A, piperonylbutoxide, were found to inhibit not only the CYPs, but also the HRP-mediated oxidation of o-anisidine. Interestingly, α-naphtoflavone inhibits oxidation of o-anisidine by HRP with respect to H2O2, but not with respect to o-anisidine. Diethyldithiocarbamate is the most potent peroxidase inhibitor of o-anisidine oxidation with Ki with respect to o-anisidine of 10 μM and Ki with respect to H2O2 of 60 μM, being even the better peroxidase inhibitor than the classical "peroxidase inhibitor" - propyl gallate (Ki with respect to o-anisidine of 60 μM and Ki with respect to H2O2 of 750 μM). CONCLUSIONS: The results of the present study demonstrate that 1-aminobenzotriazole, a potent inhibitor of various CYP enzymes, seems to be the best candidate suitable for utilization in studies evaluating participation of CYP enzymes in metabolism of xenobiotics in various complex biological materials containing both CYP and peroxidase enzymes. Moreover, precaution to prevent misinterpretation of results is necessary in cases when proadifen SKF525A, piperonylbutoxide, diethyldithiocarbamate, ketoconazole, α-naphtoflavone and ellipticine are used in similar studies (as CYP inhibitors in various complex biological materials containing both CYP and peroxidase enzymes), since these chemicals can except of CYP enzymes inhibit also peroxidase-mediated reactions.

• MeSH
• Enzyme Activation drug effects   MeSH
• Benzoflavones chemistry   pharmacology   MeSH
• Quinidine chemistry   pharmacology   MeSH
• Disulfiram chemistry   pharmacology   MeSH
• Ditiocarb chemistry   pharmacology   MeSH
• Ellipticines chemistry   pharmacology   MeSH
• Cytochrome P-450 Enzyme Inhibitors MeSH
• Enzyme Inhibitors chemistry   pharmacology   MeSH
• Ketoconazole chemistry   pharmacology   MeSH
• Horseradish Peroxidase antagonists & inhibitors   metabolism   MeSH
• Humans MeSH
• Metyrapone chemistry   pharmacology   MeSH
• Piperonyl Butoxide chemistry   pharmacology   MeSH
• Proadifen chemistry   pharmacology   MeSH
• Substrate Specificity drug effects   MeSH
• Sulfaphenazole chemistry   pharmacology   MeSH
• Cytochrome P-450 Enzyme System MeSH
• Triazoles chemistry   pharmacology   MeSH
• Troleandomycin chemistry   pharmacology   MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH

• MeSH
• Adrenalectomy MeSH
• Adrenal Insufficiency therapy   MeSH
• Adrenocorticotropic Hormone secretion   MeSH
• Cushing Syndrome therapy   MeSH
• ACTH Syndrome, Ectopic therapy   MeSH
• Hypophysectomy MeSH
• Humans MeSH
• Metyrapone therapeutic use   MeSH
• Mitotane therapeutic use   MeSH
• Nelson Syndrome therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Comment MeSH
• Overall MeSH

Vývoj lékařských věd se nemohl vyhnout ani hypofýze. Nových poznatků ve fyziologii, patologii i léčbě hypofyzárních onemocnění je mnoho, vybrali jsme jen některé informace. Přibývají nové regulátory hypofyzární sekrece. Patří mezi ně hypotalamické chemokiny a produkt KISS-1 genu ? kisspeptin. Impulzy, které přicházejí z mozkových center i z periferie do hypofýzy, se musí integrovat. K tomu slouží systém folikulostelárních buněk, parakrinní mechanizmy a hypofyzární mikrocirkulace. Existují v hypofýze též kmenové buňky? Zdá se, že ano. Kandidáty jsou jednak zmíněné buňky folikulostelárního systému, jednak nově objevené buňky SP (side population). Na kritická postižení organizmu jako polytraumata, těžké popáleniny a šokové stavy, reaguje hypofýza dvoufázově. Akutní fáze je charakterizována hypersekrecí většiny hypofyzárních hormonů a současně periferní rezistencí na jejich působení. Při následné chronické fázi dochází naopak ke snížené sekreci všech hypofyzárních hormonů s výjimkou ACTH. Klinicky relevantní hypofyzární adenomy postihují asi 1 ? populace. Dvě třetiny z toho tvoří prolaktinomy. Většinu prolaktinomů léčíme bez větších potíží, komplikovaná může být léčba u prolaktinomů, které jsou rezistentní na medikamentózní léčbu. Zde může sehrát významnou úlohu Leksellův gama nůž. Mnohem obtížnější je léčba akromegalie. Vypracovali jsme vlastní postup při léčbě akromegalií. Adenomy necháváme operovat, případná rezidua u nich ozáříme Leksellovým gama nožem a do účinku ozáření léčíme medikamentózně. Efekt léčby zkoušíme v pořadí podle nákladnosti léčby: kabergolin, somatostatinová analoga, pegvisomant. Podobný postup uplatňujeme i u nemocných s Cushingovým syndromem centrální etiologie pouze s tím rozdílem, že medikamentózní léčba do účinku gama nože se opírá o ketokonazol a metyrapon. Jak u akromegalie, tak u Cushingovy choroby jsou vyvíjeny nové medikamenty, od kterých si slibujeme větší léčebné výhody.

• MeSH
• Acromegaly drug therapy   MeSH
• Adenoma, Basophil drug therapy   radiotherapy   MeSH
• Pituitary Gland physiology   secretion   MeSH
• Ketoconazole therapeutic use   MeSH
• Humans MeSH
• Metyrapone therapeutic use   MeSH
• Pituitary Neoplasms diagnosis   therapy   MeSH
• Prolactinoma drug therapy   radiotherapy   MeSH
• Radiosurgery methods   MeSH
• Receptors, Somatotropin antagonists & inhibitors   therapeutic use   MeSH
• Somatostatin analogs & derivatives   therapeutic use   MeSH
• Check Tag
• Humans MeSH

• MeSH
• Antidepressive Agents classification   adverse effects   therapeutic use   MeSH
• Depression drug therapy   MeSH
• Adult MeSH
• Pharmacologic Actions MeSH
• Data Interpretation, Statistical MeSH
• Humans MeSH
• Metyrapone administration & dosage   adverse effects   therapeutic use   MeSH
• Randomized Controlled Trials as Topic MeSH
• Steroids antagonists & inhibitors   biosynthesis   metabolism   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH