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1.
Eur J Public Health ; 34(Supplement_1): i58-i66, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946450

RESUMO

BACKGROUND: Despite concerns about worsening pregnancy outcomes resulting from healthcare restrictions, economic difficulties and increased stress during the COVID-19 pandemic, preterm birth (PTB) rates declined in some countries in 2020, while stillbirth rates appeared stable. Like other shocks, the pandemic may have exacerbated existing socioeconomic disparities in pregnancy, but this remains to be established. Our objective was to investigate changes in PTB and stillbirth by socioeconomic status (SES) in European countries. METHODS: The Euro-Peristat network implemented this study within the Population Health Information Research Infrastructure (PHIRI) project. A common data model was developed to collect aggregated tables from routine birth data for 2015-2020. SES was based on mother's educational level or area-level deprivation/maternal occupation if education was unavailable and harmonized into low, medium and high SES. Country-specific relative risks (RRs) of PTB and stillbirth for March to December 2020, adjusted for linear trends from 2015 to 2019, by SES group were pooled using random effects meta-analysis. RESULTS: Twenty-one countries provided data on perinatal outcomes by SES. PTB declined by an average 4% in 2020 {pooled RR: 0.96 [95% confidence intervals (CIs): 0.94-0.97]} with similar estimates across all SES groups. Stillbirths rose by 5% [RR: 1.05 (95% CI: 0.99-1.10)], with increases of between 3 and 6% across the three SES groups, with overlapping confidence limits. CONCLUSIONS: PTB decreases were similar regardless of SES group, while stillbirth rates rose without marked differences between groups.


Assuntos
COVID-19 , Nascimento Prematuro , SARS-CoV-2 , Natimorto , Humanos , Natimorto/epidemiologia , COVID-19/epidemiologia , Europa (Continente)/epidemiologia , Nascimento Prematuro/epidemiologia , Feminino , Gravidez , Adulto , Fatores Socioeconômicos , Pandemias , Classe Social , Disparidades nos Níveis de Saúde , Recém-Nascido , Resultado da Gravidez/epidemiologia , Disparidades Socioeconômicas em Saúde
2.
Open Res Eur ; 3: 54, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37830050

RESUMO

Context: International comparisons of the health of mothers and babies provide essential benchmarks for guiding health practice and policy, but statistics are not routinely compiled in a comparable way. These data are especially critical during health emergencies, such as the coronavirus disease (COVID-19) pandemic. The Population Health Information Research Infrastructure (PHIRI) project aimed to promote the exchange of population data in Europe and included a Use Case on perinatal health. Objective: To develop and test a protocol for federated analysis of population birth data in Europe. Methods: The Euro-Peristat network with participants from 31 countries developed a Common Data Model (CDM) and R scripts to exchange and analyse aggregated data on perinatal indicators. Building on recommended Euro-Peristat indicators, complemented by a three-round consensus process, the network specified variables for a CDM and common outputs. The protocol was tested using routine birth data for 2015 to 2020; a survey was conducted assessing data provider experiences and opinions. Results: The CDM included 17 core data items for the testing phase and 18 for a future expanded phase. 28 countries and the four UK nations created individual person-level databases and ran R scripts to produce anonymous aggregate tables. Seven had all core items, 17 had 13-16, while eight had ≤12. Limitations were not having all items in the same database, required for this protocol. Infant death and mode of birth were most frequently missing. Countries took from under a day to several weeks to set up the CDM, after which the protocol was easy and quick to use. Conclusion: This open-source protocol enables rapid production and analysis of perinatal indicators and constitutes a roadmap for a sustainable European information system. It also provides minimum standards for improving national data systems and can be used in other countries to facilitate comparison of perinatal indicators.

3.
Vnitr Lek ; 69(2): 128-131, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37072271

RESUMO

Levothyroxine therapy in management of diferentiated thyroid carcinoma (DTC) has been common practice for decades. Levothyroxine is being administered to patiens with DTC after total thyreoidectomy (with or without postopreative radioiodine treatment) not only to restore euthyroidism but to suppress the production of thyroid-stimulating hormone (TSH) as well because TSH is considered as a growth factor for thyroid follicular cells. However there has been a downside to this threatment recently. The main concerns are the known risks related to iatrogenic subclinical or even mild but clinicaly overt iatrogenic hyperthyroidism. Therefore individualized treatment approach aiming to balance between the risk of tumor recurence and the risks related to hypertyhroidism in view of pateints age, risk factors and comorbidities is essential. Close folow-up is therefore necessary with frequent dose adjustments according to target TSH values published in American Thyroid Association guidelines.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Tiroxina/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Tireotropina/uso terapêutico
4.
Acta Medica (Hradec Kralove) ; 64(1): 50-54, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33855960

RESUMO

Insulin autoimmune syndrome or Hirata's disease is an extremely rare condition leading to hypoglycaemia of variable severity due to autoantibodies against insulin. We present the first case documented in the Czech Republic.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Hipoglicemia/tratamento farmacológico , Hipoglicemia/imunologia , Fatores Imunológicos/uso terapêutico , Adulto , Autoanticorpos/imunologia , Biomarcadores/análise , República Tcheca , Quimioterapia Combinada , Humanos , Masculino , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Síndrome
5.
Histopathology ; 79(3): 406-415, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33738859

RESUMO

AIMS: In somatotroph pituitary neuroendocrine tumours (adenomas), a pattern of cytokeratin (CK) 18 expression is used for tumour subclassification, with possible clinical implications. Rare somatotroph tumours do not express CK 18. We aimed to characterise this subset clinically and histologically. METHODS AND RESULTS: Clinical and pathological data for the study were derived from a previously published data set of a cohort of 110 patients with acromegaly. Data included serum levels of insulin-like growth factor 1 (IGF1), growth hormone (GH), prolactin and thyroid-stimulating hormone (TSH), tumour diameter, tumour invasion defined by Knosp grade and immunohistochemical data concerning the expression of Ki67, p53, E-cadherin, somatostatin receptor (SSTR)1, SSTR2A, SSTR3, SSTR5 and D2 dopamine receptor. Additional immunohistochemical analysis (AE1/3, CK 8/18, vimentin, neurofilament light chain, internexin-α) was performed. CK 18 was negative in 10 of 110 (9.1%) tumours. One of these tumours was immunoreactive with CK 8/18 antibody, while the remainder expressed only internexin-α intermediate filament in patterns similar to CK 18 (perinuclear fibrous bodies). CK-negative tumours showed no significant differences with respect to biochemical, radiological or pathological features. They showed significantly higher expression of SSTR2A compared to the sparsely granulated subtype and significantly lower expression of E-cadherin compared to the non-sparsely granulated subtypes of tumours. The tumours showed divergent morphology and hormonal expression: two corresponded to densely granulated tumours and three showed co-expression of prolactin and morphology of either mammosomatotroph or somatotroph-lactotroph tumours. Four tumours showed morphology and immunoprofile compatible with plurihormonal Pit1-positive tumours. CONCLUSIONS: CK-negative somatotroph tumours do not represent a distinct subtype of somatotroph tumours, and can be further subdivided according to their morphology and immunoprofile.


Assuntos
Queratina-8/análise , Tumores Neuroendócrinos , Neoplasias Hipofisárias , Biomarcadores Tumorais/análise , Tumores Neuroendócrinos/classificação , Tumores Neuroendócrinos/patologia , Hipófise/patologia , Neoplasias Hipofisárias/classificação , Neoplasias Hipofisárias/patologia
6.
J Cell Mol Med ; 25(5): 2484-2492, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33491286

RESUMO

In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1-5, dopamine D2 receptor, E-cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E-cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E-cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E-cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.


Assuntos
Acromegalia/complicações , Acromegalia/genética , Caderinas/genética , Regulação da Expressão Gênica , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/etiologia , Receptores de Somatostatina/genética , Acromegalia/metabolismo , Adulto , Biomarcadores , Tomada de Decisão Clínica , Terapia Combinada , Gerenciamento Clínico , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/terapia , Prognóstico , Isoformas de Proteínas , Curva ROC , Receptores de Somatostatina/metabolismo , Resultado do Tratamento , Adulto Jovem
7.
Endocr Pathol ; 31(4): 337-347, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32632839

RESUMO

Sox2 is one of the transcription factors responsible for the maintenance of stem cell phenotype. It has been implicated as a marker of stem cells in normal pituitaries and pituitary neuroendocrine tumours. To explore the clinical significance of Sox2 expression in histological sections, we performed immunohistochemical detection of Sox2 in 113 pituitary neuroendocrine tumours from 109 patients with acromegaly. In 11 tumours, we performed double immunostaining for Sox2, annexin A1 and S100 protein. Tumours were characterised using the WHO classification system. Proliferative activity and invasion were assessed. The amount of immunoreactive cells was evaluated and correlated with tumour size and biochemical features (levels of IGF1, GH, prolactin, ßTSH). Sox2+ cells were identified in 35/38 normal pituitaries adjacent to the tumours. In 36 tumours (33%), ≥ 1% of the cells expressed Sox2, in 24 cases (22%), Sox2+ cells comprised < 1% and 49 cases (45%) were negative. We found no significant differences between Sox2+ and Sox2- groups with respect to the age, initial levels of GH, IGF1, prolactin, ßTSH, tumour size, invasion, proliferative activity or histological features. We observed a positive correlation between Sox2+ cell count and ßTSH immunoreactive cells (r = 0.459, p < 0.001) that was further verified by multivariate analysis. Using double stain, the majority of Sox2+ cells coexpressed annexin A1 (average 89%) and S100 protein (average 76.2%) and showed morphological features of folliculo-stellate cells. Sox2+ cells are thus commonly present in growth hormone-producing tumours and normal pituitaries, and their amount does not have any prognostic significance. Most of these cells represent a subpopulation of folliculo-stellate cells, pointing out to their role as a possible stem cell population.


Assuntos
Tumores Neuroendócrinos/patologia , Neoplasias Hipofisárias/patologia , Fatores de Transcrição SOXB1/metabolismo , Acromegalia/etiologia , Acromegalia/metabolismo , Adulto , Biomarcadores Tumorais/metabolismo , Feminino , Hormônio do Crescimento Humano/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/complicações , Neoplasias Hipofisárias/complicações , Células-Tronco/metabolismo
8.
J Pediatr Endocrinol Metab ; 32(5): 479-488, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31075085

RESUMO

Background Females with Turner syndrome (TS) are prone to develop autoimmune diseases (AIDs). The X chromosome contains several immune-related genes. Growth hormone (GH) and estrogens modulate the immune system. We aimed to clarify whether the loss of a specific X chromosome gene locus and the administration of GH and estradiol facilitate the development of AIDs in TS females. Methods Retrospective data on clinical course, AIDs, karyotype and treatment were analyzed from a cohort of 286 Czech females with TS (current age 2.8-43.3 years; median age 18.7 years). The karyotypes were sorted using two different classification systems: a mosaicism-focused and an isochromosome (isoXq)-focused approach. Karyotype subgroups with a significantly higher prevalence of AIDs were further evaluated. Data of common therapies were correlated with the prevalence of AIDs. Results The most frequent AIDs were autoimmune thyroid disease (AITD; 37.4%; n = 107) and celiac disease (CD; 8.7%; n = 25). All karyotype subgroups were prone to develop AIDs. Females with an isolated Xp deletion had a significantly higher prevalence of AITD and CD compared to all other individuals with TS (AITD: 66.0% vs. 31.5%, p < 0.0001; CD: 17.4% vs. 7.2%; p = 0.04, respectively). We observed no link between the mean age at initiation as well as the duration of GH and/or estrogen administration and the occurrence of AIDs. Conclusions Isolated Xp deletion contributes to the development of AIDs in TS patients. The haploinsufficiency of genes located in Xpter-p11.2 may explain this observation. Common therapies used in TS do not modify the risk of AIDs.


Assuntos
Doenças Autoimunes/etiologia , Deleção Cromossômica , Cromossomos Humanos X/genética , Síndrome de Turner/genética , Adolescente , Adulto , Doenças Autoimunes/epidemiologia , Criança , Pré-Escolar , República Tcheca/epidemiologia , Feminino , Seguimentos , Humanos , Cariotipagem , Prevalência , Prognóstico , Estudos Retrospectivos , Síndrome de Turner/complicações , Adulto Jovem
9.
Vnitr Lek ; 63(9): 561-565, 2017.
Artigo em Tcheco | MEDLINE | ID: mdl-29120651

RESUMO

Adverse effect of dopamine agonists on the heart valves aroused much attention some time ago. Gradually, as data accumulated, the approach to the problem was rationalised and further examinations were only recommended in indicated cases. The paper reviews the current knowledge about the treatment of hyperprolactinemia with dopamine agonists and the risk of valvular disease.Key words: dopamine agonists - ergolines/adverse effects - heart valve diseases - hyperprolactinemia - pituitary neoplasms - prolactinoma.


Assuntos
Agonistas de Dopamina/uso terapêutico , Doenças das Valvas Cardíacas/induzido quimicamente , Hiperprolactinemia/tratamento farmacológico , Ergolinas/uso terapêutico , Humanos
10.
11.
Vnitr Lek ; 62(9 Suppl 3): 45-49, 2016.
Artigo em Tcheco | MEDLINE | ID: mdl-27734691

RESUMO

Treatment with tyrosine kinase inhibitors leads to thyroid dysfunction in up to one half of treated patients, hypothyroidism being the most common. It is caused by destructive thyroiditis, impaired transport of T4 into the cell and deiodinase induction. Bexarotene is a nuclear retinoid X receptor agonist. Its application is accompanied with central hypothyroidism and hypertriglyceriaemia in virtually all patients and it also increases thyroxin metabolism. Autoimmune endocrine side effects are common in cancer immunotherapy. Cytokines (interpheron α and interleukin 2) cause autoimmune thyroiditis in 2-10 % of treated patients. Therapy with immune checkpoints inhibitors is connected with a variety of immune-related adverse events (irAE). Endocrine irAE include hypophysitis and thyroiditis during treatment with monoclonal antibodies against CTLA4 and thyroid dysfunction during therapy with antibody against CD1 receptor and its ligand. Knowledge, early recognition and management of these side effects is crucial.Key words: bexarotene - endocrine complication - hypophysitis - immune checkpoint inhibitors - immunotherapy.


Assuntos
Anticarcinógenos/efeitos adversos , Antineoplásicos/efeitos adversos , Hipofisite/induzido quimicamente , Hipotireoidismo/induzido quimicamente , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Tetra-Hidronaftalenos/efeitos adversos , Tireoidite Autoimune/induzido quimicamente , Anticorpos Monoclonais/efeitos adversos , Bexaroteno , Antígeno CTLA-4/antagonistas & inibidores , Humanos , Imunoterapia , Ipilimumab , Doenças da Glândula Tireoide/induzido quimicamente , Tiroxina/metabolismo
12.
Endokrynol Pol ; 67(1): 48-53, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26884115

RESUMO

INTRODUCTION: The relationship between Hashimoto's thyroiditis (HT) and thyroid cancer (TC) is controversial. While most surgical studies report a high incidence of malignancy among patients with HT, cytological studies do not. The role of autoantibodies in the incidence of malignancy is unclear. MATERIAL AND METHODS: A single-centre retrospective observational study was conducted in patients evaluated for thyroid nodules by US-guided fine-needle aspiration cytology (FNAC) and, if indicated, by surgery. The levels of thyroid-stimulating hormone (TSH) and anti-thyroid antibodies were measured at the time of FNAC. RESULTS: Of 4947 patients, 599 (12.1%) were diagnosed with HT. A malignant/suspicious cytological result was found in 14.2% of the patients with HT and in 15.2% of the others. The odds ratio (OR) for malignancy in HT was 0.921 (0.716-1.183, p = 0.51). Of 1603 patients who underwent surgery, differentiated thyroid carcinoma was found in 29.5% of the HT patients and in 15.2% of the others (OR 2.33, 95% confidence interval CI, 1.403-3.854, p < 0,001). Low TSH (< 0.4 mIU/L) decreased the malignancy rate in the entire patient population, both when considering the cytological results and the surgical results. This was not confirmed in the subgroup diagnosed with HT. No relationship was observed between autoantibodies against thyroid peroxidase (ATP) or thyroglobulin (ATG) and malignancy rate. CONCLUSIONS: No association between HT and thyroid cancer was observed cytologically; a positive relationship in histological series was caused by selection bias. Low TSH levels decreased the risk of TC in patients with nodular goitre, but this has not been proven in patients with HT.


Assuntos
Autoanticorpos/sangue , Doença de Hashimoto , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/epidemiologia , Tireotropina/sangue , Autoantígenos/imunologia , Feminino , Humanos , Incidência , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Masculino , Estudos Retrospectivos , Tireoglobulina/imunologia , Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/sangue
13.
Artigo em Inglês | MEDLINE | ID: mdl-26607296

RESUMO

AIMS: Pituitary adenomas (PA) are non-invasive benign tumors with a high autopsy prevalence. They are classified according to the type of hormone secreted (prolactin, growth hormone, adrenocorticotropin, thyrotropin, folitropin, or luteinizing hormone). Clinically non-functioning adenomas (CNFA) lacking the typical hypersecretion of hormones make up a significant portion of PA. The aim of the study was to determine the complete expression profiles of somatostatin receptors (SSTR1-SSTR5), dopamine receptors type 2 (D2R), and estrogen receptors (ER1) in various types of PA. METHODS: Adenoma specimens were obtained from 206 patients during transsphenoidal resection. For quantitative analysis, reverse transcription and consequent real-time PCR with synthetic multilocus calibrators (SMC) were used. The obtained data were normalized to the number of transcripts of the beta-glucuronidase gene. RESULTS: The use of SMC enabled the alignment of individual calibration functions for all the receptors. No relationships between the expression of the receptors and the tumor size, site of extension, gender or age at diagnosis were significant. In growth hormone-secreting adenomas, D2R and SSTR2 transcripts were extensively expressed, followed by ER1, SSTR5, SSTR3, and SSTR1. In patients with macroprolactinomas, transsphenoidal resection was indicated because dopamine agonists did not normalize prolactin levels. D2R, ER1 and SSTR1 transcripts were significantly transcribed. Corticotroph adenomas showed high levels of D2R and ER1 transcripts and lower amounts of SSTR2 and SSTR1 transcripts. SSTR5 transcripts were very low. Subjects with CNFA dominantly expressed D2R and ER1, followed by SSTR2 and SSTR3 mRNA. CONCLUSION: We evaluated SSTR1-SSTR5, D2R, and ER1 expressions in a large group of pituitary adenomas and we found that determining their individual expression profiles could help when choosing the optimal postoperative treatment.


Assuntos
Adenoma/metabolismo , Neoplasias Hipofisárias/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Somatostatina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
14.
Vnitr Lek ; 61(10): 852-7, 2015 Oct.
Artigo em Tcheco | MEDLINE | ID: mdl-26486476

RESUMO

Incidentaloma is an adrenal mass discovered serendipitously. Because of increasing use of imaging techniques it is a common finding, being present in more than 1 % of adults. During work-up malignancy has to be ruled out. Classically imaging using CT or MRI is used. Recently PET-CT with FDG has been used more often as its sensitivity for diagnosis of malignancy is about 97 % and specificity 91 %. Hormonal evaluation should diagnose subclinical hypercortisolism. (Dexamethasone Suppression Test is the method of choice). Aldosterone and Renin should be measured only in patients with hypertension and catecholamines in tumours with higher native density than 10 HU. During follow-up repeated CT scan are needed only in selected patients and the need of routine biochemical follow-up has been questioned as well.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Aldosterona/sangue , Diagnóstico por Imagem , Hidrocortisona/sangue , Renina/sangue , Neoplasias das Glândulas Suprarrenais/sangue , Catecolaminas , Diagnóstico Diferencial , Humanos , Feocromocitoma/sangue , Feocromocitoma/diagnóstico , Sensibilidade e Especificidade
15.
Vnitr Lek ; 61(10): 858-61, 2015 Oct.
Artigo em Tcheco | MEDLINE | ID: mdl-26486477

RESUMO

Adrenal insufficiency is a potentially life threatening condition. The paper deals with differential diagnostics and limits of dynamic testing, possibilities of de-escalation of corticosteroid therapy and substitution therapy with glucocorticoids, mineralocorticoids and androgens. New replacement possibilities are mentioned including those in development.


Assuntos
Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/tratamento farmacológico , Androgênios/uso terapêutico , Glucocorticoides/uso terapêutico , Mineralocorticoides/uso terapêutico , Insuficiência Adrenal/etiologia , Diagnóstico Diferencial , Terapia de Reposição Hormonal , Humanos , Hidrocortisona/sangue
16.
Pituitary ; 15(2): 222-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21597974

RESUMO

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). The aim of this study was to quantitatively estimate D2R expression in clinically non-functioning pituitary adenomas and correlate the results with adenoma type according to pathological classification. 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 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 (median 1.3) and null-cell adenomas (median 1.9). The difference between corticotroph adenomas and plurihormonal tumors in comparison with other pathological types was statistically significant. The expression of D2R did not depend on the presence or absence of gonadotropins. We conclude that D2R expression is very low in corticotroph adenomas and significantly lower in plurihormonal tumors. The positivity of gonadotropins does not predict the D2R quantity.


Assuntos
Adenoma/metabolismo , Neoplasias Hipofisárias/metabolismo , Receptores de Dopamina D2/metabolismo , Adenoma/patologia , Humanos , Imuno-Histoquímica , Neoplasias Hipofisárias/patologia , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Dopamina D2/genética
17.
Eur J Endocrinol ; 164(3): 325-33, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21148630

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of coadministered lanreotide Autogel (LA; 120  mg/month) and pegvisomant (40-120  mg/week) in acromegaly. DESIGN: This is a 28-week, multicenter, open-label, single-arm sequential study. METHODS: Patients (n=92) biochemically uncontrolled, on somatostatin analogs (SSAs) or using pegvisomant monotherapy entered a 4-month run-in taking LA (120  mg/month). Patients uncontrolled after the run-in period (n=57) entered a 28-week coadministration period, receiving LA 120  mg/month plus pegvisomant (60  mg once weekly, adapted every 8 weeks based on IGF1 levels to 40-80  mg once weekly or 40 or 60  mg twice weekly). RESULTS: In total, 33 (57.9%) patients had normalized IGF1 following coadministration (P<0.0001 versus 30% minimum clinically relevant); median pegvisomant dose in normalized patients was 60  mg/week. IGF1 normalized at any time during coadministration in 45 (78.9%) patients (P<0.0001) with median pegvisomant dose at 60  mg/week. Being nondiabetic (odds ratio (OR): 4.65) and older (OR, upper versus lower quartile: 3.40) showed increased likelihood of normalization. Symptom reduction was greatest for arthralgia (-0.6 ± 1.6) and soft tissue swelling (-0.6 ± 1.8). Five patients reported treatment-emergent adverse events causing treatment withdrawal: three serious (treatment related - thrombocytopenia, urticaria; not treatment related - abdominal pain/vomiting) and two nonserious (hepatotoxicity and cytolytic hepatitis, both elevating alanine aminotransferase to >5 × upper limit of normal with normalization after withdrawal). CONCLUSIONS: In patients partially controlled by SSAs, LA (120  mg/month) plus pegvisomant normalized IGF1 in 57.9% of patients after 7 months, at a median effective pegvisomant dose of 60  mg/week, and 78.9% at any time. In these patients, results suggest a pegvisomant-sparing effect versus daily pegvisomant monotherapy.


Assuntos
Acromegalia/sangue , Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Fator de Crescimento Insulin-Like I/metabolismo , Peptídeos Cíclicos/uso terapêutico , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Acromegalia/metabolismo , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Criança , Hormônios/uso terapêutico , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Pessoa de Meia-Idade , Adulto Jovem
18.
Acta Medica (Hradec Kralove) ; 54(3): 127-30, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22250484

RESUMO

Only a few cases of pneumocystis pneumonia (PCP) in Cushing's syndrome have been published in the literature so far. In the majority of these patients, the pneumonia occurred after reduction of the hypercortisolism with medicamentous treatment. We report two cases of PCP during conservative treatment of hypercortisolism. We describe clinical, imaging and laboratory findings in two patients and review published cases of pneumocystits pneumonia in Cushing's syndrome. A 60-year-old woman and 20-year-old man with Cushing's syndrome due to ectopic ACTH syndrome were treated at our department. Both developed pneumocystis pneumonia early after treatment with ketoconazole and ethomidate bromide had been introduced and the levels of cortisol rapidly decreased. PCP prophylaxis in patients with high cortisolemia should be started before treatment of hypercortisolism in current practice. Gradual lowering of plasma cortisol should also reduce the risk of infection by Pneumocystis jiroveci.


Assuntos
Síndrome de Cushing/tratamento farmacológico , Pneumonia por Pneumocystis/etiologia , Adulto , Síndrome de Cushing/sangue , Etomidato/uso terapêutico , Feminino , Humanos , Hidrocortisona/sangue , Cetoconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/etiologia , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/prevenção & controle , Adulto Jovem
19.
Cardiovasc Intervent Radiol ; 33(4): 760-5, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19795165

RESUMO

Adrenal venous sampling (AVS) is generally considered to be the gold standard in distinguishing unilateral and bilateral aldosterone hypersecretion in primary hyperaldosteronism. However, during AVS, we noticed a considerable variability in aldosterone concentrations among samples thought to have come from the right adrenal glands. Some aldosterone concentrations in these samples were even lower than in samples from the inferior vena cava. We hypothesized that the samples with low aldosterone levels were unintentionally taken not from the right adrenal gland, but from hepatic veins. Therefore, we sought to analyze the impact of unintentional cannulation of hepatic veins on AVS. Thirty consecutive patients referred for AVS were enrolled. Hepatic vein sampling was implemented in our standardized AVS protocol. The data were collected and analyzed prospectively. AVS was successful in 27 patients (90%), and hepatic vein cannulation was successful in all procedures performed. Cortisol concentrations were not significantly different between the hepatic vein and inferior vena cava samples, but aldosterone concentrations from hepatic venous blood (median, 17 pmol/l; range, 40-860 pmol/l) were markedly lower than in samples from the inferior vena cava (median, 860 pmol/l; range, 460-4510 pmol/l). The observed difference was statistically significant (P < 0.001). Aldosterone concentrations in the hepatic veins are significantly lower than in venous blood taken from the inferior vena cava. This finding is important for AVS because hepatic veins can easily be mistaken for adrenal veins as a result of their close anatomic proximity.


Assuntos
Glândulas Suprarrenais/irrigação sanguínea , Aldosterona/sangue , Veias Hepáticas/metabolismo , Hiperaldosteronismo/sangue , Hiperaldosteronismo/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Veia Cava Inferior/metabolismo
20.
Eur J Endocrinol ; 162(1): 101-7, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19605541

RESUMO

OBJECTIVE: In primary aldosteronism, adrenal venous sampling (AVS) is essential for subtype differentiation as it evaluates aldosterone secretion from both adrenals. Selectivity of adrenal sampling is assessed by the ratio of cortisol concentrations in adrenal venous blood and inferior vena cava blood (C(adrenal)/C(ivc)). Since the criteria for selective adrenal sampling differ among the reported literature, we performed a study to evaluate the influence of different selectivity criteria on AVS results. DESIGN AND METHODS: Reports of AVS were screened retrospectively. All AVS were performed with cosyntrophin infusion. Reports containing samples with C(adrenal)/C(ivc)>or=10 taken from both adrenals and at least one other adrenal sample characterised by C(adrenal)/C(ivc)>or=1.1 were enrolled. For each individual, we chose reference samples that were defined by the highest C(adrenal)/C(ivc) achieved from each adrenal. The significance of the remaining samples with C(adrenal)/C(ivc)>or=1.1 was analysed in regard to their respective reference samples. We assessed the impact of analysed samples on identification of lateralisation of aldosterone secretion that is crucial for decisions concerning adrenalectomy. RESULTS: AVS reports of 87 patients were enrolled. A total of 225 adrenal samples were analysed and divided into five groups according to C(adrenal)/C(ivc):1.1-1.99, 2-2.99, 3-4.99, 5-9.99 and >or=10. By comparing reference with analysed samples, a concordant assessment with respect to lateralisation of aldosterone secretion was observed in 39, 52, 72, 85 and 94% of the respective groups of analysed samples. CONCLUSION: AVS provides consistent information when adrenal samples with high cortisol concentrations are used.


Assuntos
Glândulas Suprarrenais/irrigação sanguínea , Hiperaldosteronismo/sangue , Hiperaldosteronismo/diagnóstico , Flebotomia/métodos , Flebotomia/normas , Adulto , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/normas , Coleta de Amostras Sanguíneas/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Flebotomia/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Tempo , Veias
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