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1.
Orv Hetil ; 156(16): 626-35, 2015 Apr 19.
Artigo em Húngaro | MEDLINE | ID: mdl-25864138

RESUMO

INTRODUCTION: Laboratory diagnosis of pheochromocytoma-paraganglioma syndrome has been markedly improved during the past two decades. AIM: Retrospective assessment of diagnostic utility of urinary catecholamines and their metabolites as well as serum chromogranin A in 155 patients diagnosed at the 2nd Department of Medicine, Semmelweis University. METHOD: Urinary catecholamines and metabolites were measured using high-performance liquid chromatography with electrochemical detection in 155 patients with pheochromocytoma-paraganglioma (of whom 28.4% had hereditary background) and in 170 non-pheochromocytoma patients used as controls. Serum chromogranin A was measured by immunoradiometry. RESULTS: Sensitivity (93.2%) and specificity (87.0%) of urinary fractionated metanephrines were higher than those of urinary catecholamines (90.9% vs. 85.7%, respectively) and serum chromogranin A (88.7% and 77.5%, respectively). Urinary normetanephrine and serum chromogranin A correlated positively with tumor size (r = 0.552, p<0.0001 and r = 0.618, p<0.0001, respectively). CONCLUSIONS: These data confirm the diagnostic utility of urinary catecholamines and their metabolites. Urinary normetanephrine and serum chromogranin A may help to estimate tumour mass and probably tumour progression.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/metabolismo , Catecolaminas/urina , Cromogranina A/sangue , Feocromocitoma/diagnóstico , Feocromocitoma/metabolismo , Adolescente , Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/urina , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Criança , Cromatografia Líquida de Alta Pressão , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Hungria , Ensaio Imunorradiométrico , Masculino , Metanefrina/urina , Pessoa de Meia-Idade , Normetanefrina/urina , Feocromocitoma/sangue , Feocromocitoma/urina , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
2.
Orv Hetil ; 150(31): 1457-62, 2009 Aug 02.
Artigo em Húngaro | MEDLINE | ID: mdl-19617182

RESUMO

UNLABELLED: During the past decade the importance of medical therapy, especially treatment with somatostatin analogues has increased significantly in patients with active acromegaly. AIMS: Authors analyzed the outcome of somatostatin analogue treatment in acromegalic patients evaluated and followed up at the 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, during the past 10 years. PATIENTS AND METHODS: Changes in serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentration, as well as morphologic changes of pituitary adenomas followed by MRI scans were evaluated and compared in 32 acromegalic patients (26 women, 6 men) during long-term somatostatin analogue treatment (mean+/-SE, 3.1+/-0.3 years, range, 1-7 years). Primary somatostatin analogue treatment was applied in 10 patients (7 women and 3 men), whereas 15 patients (14 women and 1 man) had pituitary surgery and 7 patients (5 women and 2 men) underwent both pituitary surgery and irradiation therapy prior to somatostatin analogue treatment. RESULTS: After a 3-month treatment with somatostatin analogues, both serum GH and IGF-1 levels decreased significantly and they remained around the same decreased levels throughout the treatment period. Serum GH decreased from 15.7+/-4.9 to 5.5+/-1.4 ng/ml, and serum IGF-1, expressed as a percentage of the upper limit of age- and sex-adjusted reference value, decreased from 204+/-14% to 135+/-12% at the end of treatment. The efficacy of somatostatin analogue treatment was not influenced by surgical or surgical and irradiation therapies which were applied prior to medical treatment. At the end of treatment 36.7% of patients had safe serum GH (<2.5 ng/ml), while serum IGF-1 returned below the upper limit of age- and sex-adjusted reference range in 41.4% of patients. Pituitary MRI showed regression of the adenoma in 46% of patients, and none of the patients had progression of the pituitary adenoma. CONCLUSIONS: Somatostatin analogues are effective therapeutic options for acromegalic patients when primary surgical treatment cannot be performed due to complications and associated disorders, or in patients whose acromegaly remains active after pituitary surgery or after pituitary surgery and irradiation.


Assuntos
Acromegalia/tratamento farmacológico , Acromegalia/etiologia , Adenoma/complicações , Adenoma/terapia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/terapia , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Adenoma/diagnóstico , Adenoma/radioterapia , Adenoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Hipofisectomia , Fator de Crescimento Insulin-Like I/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/cirurgia , Radioterapia Adjuvante , Resultado do Tratamento
3.
Orv Hetil ; 148(5): 195-202, 2007 Feb 04.
Artigo em Húngaro | MEDLINE | ID: mdl-17344139

RESUMO

Iatrogenic Cushing's syndrome is the most common form of hypercortisolism. Glucocorticoids are widely used for the treatment of various diseases, often in high doses that may lead to the development of severe hypercortisolism. Iatrogenic hypercortisolism is unique, as the application of exogenous glucocorticoids leads to the simultaneous presence of symptoms specific for hypercortisolism and the suppression of the endogenous hypothalamic-pituitary-adrenal axis. The principal question of its therapy is related to the problem of glucocorticoid withdrawal. There is considerable interindividual variability in the suppression and recovery of the hypothalamic-pituitary-adrenal axis, therefore, glucocorticoid withdrawal and substitution can only be conducted in a stepwise manner with careful clinical follow-up and regular laboratory examinations regarding endogenous hypothalamic-pituitary-adrenal axis activity. Three major complications which can be associated with glucocorticoid withdrawal are: i. reactivation of the underlying disease, ii. secondary adrenal insufficiency, iii. steroid withdrawal syndrome. Here, the authors summarize the most important aspects of this area based on their clinical experience and the available literature data.


Assuntos
Síndrome de Cushing/metabolismo , Síndrome de Cushing/terapia , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Doença Iatrogênica , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Síndrome de Cushing/induzido quimicamente , Humanos
4.
Orv Hetil ; 148(18): 843-7, 2007 May 06.
Artigo em Húngaro | MEDLINE | ID: mdl-17468067

RESUMO

The differentiation of adrenocorticotropic hormone producing pituitary adenoma (Cushing's disease) from the ectopic ACTH syndrome is always a complex and difficult task, and in rare cases it is not possible to differentiate between the two disorders, even with the use of dynamic endocrine tests and the most advanced imaging techniques. Inferior petrosal sinus sampling (IPSS) with subsequent ACTH measurements became the gold-standard method of the differential diagnostic process. 34 patients with ACTH dependent Cushing's syndrome in whom the source of ACTH secretion couldn't be identified unambiguously with imaging techniques and/or dynamic endocrine tests underwent altogether 41 IPSS between 1999 and 2005. The sensitivity of the method was calculated on the basis of 31 samplings of 25 patients who had definite endocrinological diagnosis confirmed by the recovery from Cushing's syndrome after surgical intervention and/or by histological examinations (22 patients with ACTH-producing pituitary adenoma and 3 patients with ectopic ACTH syndrome). As a result of IPSS, pituitary-dependent Cushing's disease was diagnosed with a baseline central to peripheral ACTH ratio of >2.0 or with a ratio of >3.0 after corticotropin releasing hormone (CRH) administration. IPSS correctly identified ACTH-producing pituitary adenoma in 20 of 28 sampling procedures, with a sensitivity of 71.4%. Three patients had true negative and 8 had false negative results. There was no false positive result. Four of the 8 patients with false negative first sampling had a repeat sampling procedure leading to true positive result in each patient. In patients with Cushing's disease having true positive interventions, the basal and 5 minutes post-CRH ACTH concentrations were diagnostic in 14 and 19 cases, respectively. The sensitivity of IPSS within this series, reported for the first time from Hungary, was lower than it was found in much larger series published in international literature. In addition to technical difficulties, the lower sensitivity can be accounted also for the highly selected nature of the patient group.


Assuntos
Síndrome de ACTH Ectópico/diagnóstico , Adenoma/diagnóstico , Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing/sangue , Síndrome de Cushing/diagnóstico , Amostragem do Seio Petroso , Neoplasias Hipofisárias/diagnóstico , Síndrome de ACTH Ectópico/complicações , Adenoma/complicações , Adenoma/metabolismo , Adulto , Idoso , Síndrome de Cushing/etiologia , Diagnóstico Diferencial , Reações Falso-Negativas , Feminino , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/metabolismo , Valor Preditivo dos Testes , Sensibilidade e Especificidade
5.
Eur J Hum Genet ; 25(6): 702-710, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28401898

RESUMO

There is a difficulty in the molecular diagnosis of congenital adrenal hyperplasia (CAH) due to the c.955C>T (p.(Q319*), formerly Q318X, rs7755898) variant of the CYP21A2 gene. Therefore, a systematic assessment of the genetic and evolutionary relationships between c.955C>T, CYP21A2 haplotypes and the RCCX copy number variation (CNV) structures, which harbor CYP21A2, was performed. In total, 389 unrelated Hungarian individuals with European ancestry (164 healthy subjects, 125 patients with non-functioning adrenal incidentaloma and 100 patients with classical CAH) as well as 34 adrenocortical tumor specimens were studied using a set of experimental and bioinformatic methods. A unique, moderately frequent (2%) haplotypic RCCX CNV structure with three repeated segments, abbreviated to LBSASB, harboring a CYP21A2 with a c.955C>T variant in the 3'-segment, and a second CYP21A2 with a specific c.*12C>T (rs150697472) variant in the middle segment occurred in all c.955C>T carriers with normal steroid levels. The second CYP21A2 was free of CAH-causing mutations and produced mRNA in the adrenal gland, confirming its functionality and ability to rescue the carriers from CAH. Neither LBSASB nor c.*12C>T occurred in classical CAH patients. However, CAH-causing CYP21A2 haplotypes with c.955C>T could be derived from the 3'-segment of LBSASB after the loss of functional CYP21A2 from the middle segment. The c.*12C>T indicated a functional CYP21A2 and could distinguish between non-pathogenic and pathogenic genomic contexts of the c.955C>T variant in the studied European population. Therefore, c.*12C>T may be suitable as a marker to avoid this genetic confound and improve the diagnosis of CAH.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Variações do Número de Cópias de DNA , Esteroide 21-Hidroxilase/genética , Glândulas Suprarrenais/metabolismo , Hiperplasia Suprarrenal Congênita/patologia , Evolução Molecular , Feminino , Haplótipos , Humanos , Masculino , Esteroide 21-Hidroxilase/metabolismo
6.
Orv Hetil ; 147(32): 1497-503, 2006 Aug 13.
Artigo em Húngaro | MEDLINE | ID: mdl-16981423

RESUMO

In this article, the role of conventional radiotherapy and radiosurgery in the management of pituitary tumors is discussed. After a brief review about the mechanism of action and different techniques of irradiation therapy, the therapeutic effectiveness and side effects are analysed in the various types of pituitary tumors. Conventional fractionated radiotherapy has long been used to control growth and/or hormonal secretion of residual or recurrent pituitary tumors. Nevertheless, there is still a controversy concerning patient selection for radiotherapy, because several potentially significant side effects including hypopituitarism may develop. Stereotactic radiosurgical methods may have several advantages over conventional radiotherapy; they can be applied, for example, in patients with residual or recurrent pituitary tumors who had previously received conventional radiotherapy. However, long-term follow-up data with these relatively new techniques are still limited.


Assuntos
Neoplasias Hipofisárias/radioterapia , Radiocirurgia , Acromegalia/radioterapia , Encéfalo/patologia , Encéfalo/efeitos da radiação , Síndrome de Cushing/radioterapia , Fracionamento da Dose de Radiação , Raios gama/uso terapêutico , Humanos , Hipopituitarismo/etiologia , Necrose/etiologia , Recidiva Local de Neoplasia/radioterapia , Neoplasia Residual/radioterapia , Segunda Neoplasia Primária/etiologia , Quiasma Óptico/efeitos da radiação , Seleção de Pacientes , Prolactinoma/radioterapia , Radioterapia/efeitos adversos
7.
Orv Hetil ; 147(2): 51-9, 2006 Jan 15.
Artigo em Húngaro | MEDLINE | ID: mdl-16509213

RESUMO

INTRODUCTION: Primary aldosteronism is the most common form of mineralocorticoid hypertension. The disease has been described by Jerome W. Conn in 1955; since that time there has been a great progress in the knowledge concerning the prevalence, diagnostics and treatment of the disease. AIMS: The authors retrospectively analyzed the efficacy of diagnostic procedures and the outcome of treatment by the analysis of data of 187 patients with primary aldosteronism examined between 1958 and 2004 at the 2nd Department of Medicine of Semmelweis University. METHODS: The efficacy of different methods used for the diagnosis, the frequency of the different subtypes of primary aldosteronism, as well as the surgical outcomes in patients with surgically treated subtypes of primary aldosteronism were studied. RESULTS: Aldosterone-producing adenoma was detected in more than two thirds of patients (n = 135), whereas idiopathic hyperaldosteronism was found in 46 patients. Other subtypes of primary hyperaldosteronism occurred less frequently (unilateral primary adrenocortical hyperplasia in 5 patients and adrenocortical carcinoma in one patient). For the diagnosis of familial hyperaldosteronism type I, molecular biological studies of the aldosterone-synthase/11beta-hydroxylase gene chimera were carried out in 30 patients but none of them showed the presence of the chimeric gene. When comparing the clinical parameters of patients with aldosterone-producing adenoma and idiopathic hyperaldosteronism, no significant differences were found in the time period between the diagnosis of hypertension and the diagnosis of primary aldosteronism, or in the systolic and diastolic blood pressure values. The mean of the lowest documented serum potassium concentration was slightly lower in patients with aldosterone-producing adenoma (2.8 +/- 0.1 mmol/l) compared to those with idiopathic hyperaldosteronism (3.1 +/- 0.2 mmol/l), but the difference was not significant. Normokalemic primary hyperaldosteronism was found in 7 cases. The ratio of plasma aldosterone concentration (ng/dl) to plasma renin activity (ng/ml/h) was above 20 in all patients with aldosterone-producing adenoma and in all but 5 cases with idiopathic hyperaldosteronism. To confirm the diagnosis and to differentiate the subtypes of primary aldosteronism, the postural test combined with furosemide administration was performed in the majority of patients. When cases showing an elevation of plasma cortisol level during the test were excluded, this test differentiated patients with aldosterone-producing adenoma from those with idiopathic hyperaldosteronism with a sensitivity of 69% and a specificity of 92%. In cases of adrenocortical adenomas not or not clearly detectable by radiological imaging techniques, as well as in cases with bilateral adrenocortical adenomas, selective adrenal vein sampling was performed (n = 55). All but 4 patients with aldosterone-producing adenoma underwent adrenalectomy. Histology and postoperative hormone results confirmed the preoperative diagnosis in all operated patients. After surgery serum potassium concentration returned to normal in all patients showing low serum potassium levels before surgery. Also, the moderate to severe preoperative hypertension disappeared or improved after surgery. CONCLUSIONS: These observations are in contrast with the results of international studies which showed a high frequency of normokalemic primary aldosteronism and a more frequent occurrence of idiopathic hyperaldosteronism well treatable with aldosterone-antagonists. Therefore, it can be presumed that a significant number of primary aldosteronism cases that are not accompanied with severe hypokalemia remain undetected in Hungary.


Assuntos
Adenoma/cirurgia , Neoplasias do Córtex Suprarrenal/cirurgia , Aldosterona/metabolismo , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Adenoma/metabolismo , Neoplasias do Córtex Suprarrenal/metabolismo , Adrenalectomia , Adulto , Idoso , Citocromo P-450 CYP11B2/genética , Feminino , Humanos , Hungria/epidemiologia , Hiperaldosteronismo/sangue , Hiperaldosteronismo/complicações , Hiperaldosteronismo/epidemiologia , Hiperaldosteronismo/genética , Hiperpotassemia/etiologia , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Proteínas Mutantes Quiméricas/genética , Estudos Retrospectivos , Esteroide 11-beta-Hidroxilase/genética
8.
Orv Hetil ; 147(44): 2107-15, 2006 Nov 05.
Artigo em Húngaro | MEDLINE | ID: mdl-17209299

RESUMO

Nucleotide sequence variants of the glucocorticoid receptor gene and their significance in determining glucocorticoid sensitivity. The physiologic response and sensitivity to glucocorticoids may significantly differ among species, individuals, tissues and cell types. The variability of the effect of endogenous and exogenous glucocorticoids is largely determined by genetic components, of which the authors review the knowledge on the glucocorticoid receptor gene. The authors describe the genomic and non-genomic pathways of receptor function, the significance of isoforms produced during receptor protein formation, the pathomechanism of glucocorticoid resistance syndrome and the results of clinical investigations related to receptor gene polymorphisms. Through subtle alteration of receptor function, the gene polymorphisms may increase or diminish sensitivity to glucocorticoids and may play a role in the pathogenesis of metabolic disorders. In their own studies the authors found, that the N363S polymorphism, which increases glucocorticoid sensitivity, may play a role in the pathogenesis of bilateral adrenal adenomas, it may modify the clinical phenotype of patients with congenital adrenal hyperplasia, and may have an impact on steroid-induced ocular hypertension. It is presumed that further research in other diseases will continue to complete our knowledge on the pathophysiology of glucocorticoid receptor gene polymorphisms.


Assuntos
Glucocorticoides/metabolismo , Mutação , Polimorfismo Genético , Receptores de Glucocorticoides/genética , Adenoma/genética , Neoplasias das Glândulas Suprarrenais/genética , Hiperplasia Suprarrenal Congênita/genética , Asparagina , Sequência de Bases , Feminino , Humanos , Lasers de Excimer , Masculino , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/genética , Hipertensão Ocular/metabolismo , Hipertensão Ocular/cirurgia , Fenótipo , Ceratectomia Fotorrefrativa , Isoformas de Proteínas , Estudos Retrospectivos , Serina
9.
J Steroid Biochem Mol Biol ; 97(3): 257-65, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16176874

RESUMO

The CYP17 gene, located on chromosome 10q24-q25, encodes the cytochrome P450c17 enzyme. Mutations of this gene cause the 17alpha-hydroxylase/17,20-lyase deficiency, which is a rare, autosomal recessive form of congenital adrenal hyperplasia. Approximately 50 different mutations of the CYP17 gene have been described, of which some mutations have been identified in certain ethnic groups. In this study, we present the clinical history, hormonal findings and mutational analysis of two patients from unrelated families, who were evaluated for hypertension, hypokalemia and sexual infantilism. In the first patient, who was a 37-year-old female, additional studies showed a large myelolipoma in the left adrenal gland, and a smaller tumor in the right adrenal gland. In the second patient, who was a 31-year-old phenotypic female, clinical work-up revealed a 46,XY kariotype, absence of ovaries and presence of testes located in the inner opening of both inguinal canals. Analysis of the CYP17 gene by polymerase chain reaction amplification and direct sequencing demonstrated a novel homozygous mutation of codon 440 from CGC (Arg) to TGC (Cys) in both patients. The effect of this novel mutation on 17alpha-hydroxylase/17,20-lyase activity was assessed by in vitro studies on the mutant and wild-type P450c17 generated by site-directed mutagenesis and transfected in nonsteroidogenic COS-1 cells. These studies showed that the mutant P450c17 protein was produced in transfected COS-1 cells, but it had negligible 17alpha-hydroxylase and 17,20-lyase activities. In addition, three-dimensional computerized modeling of the heme-binding site of the P450c17 enzyme indicated that replacement of Arg by Cys at amino acid position 440 predicts a loss of the catalytic activity of the enzyme, as the mutant enzyme containing Cys440 fails to form a hydrogen bond with the propionate group of heme, which renders the mutant enzyme unable to stabilize the proper position of heme. Based on these findings we conclude that expressing the CYP17 gene with functional analysis, combined with three-dimensional computerized modeling of the heme-binding site of the protein provide feasible tools for molecular characterizing of functional consequences of the novel CYP17 mutation on enzyme function.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Modelos Moleculares , Mutação , Esteroide 17-alfa-Hidroxilase/química , Esteroide 17-alfa-Hidroxilase/genética , Hiperplasia Suprarrenal Congênita/enzimologia , Adulto , Substituição de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Células COS , Chlorocebus aethiops , Feminino , Heme/metabolismo , Hormônios/sangue , Humanos , Dados de Sequência Molecular , Estrutura Secundária de Proteína , Esteroide 17-alfa-Hidroxilase/metabolismo
10.
Orv Hetil ; 146(27): 1453-8, 2005 Jul 03.
Artigo em Húngaro | MEDLINE | ID: mdl-16089107

RESUMO

Oncocytic tumor of the adrenal gland. The authors describe a case of a rare tumor arising in the adrenal gland. The tumor 6 cm in diameter, connected to the right adrenal gland, was found incidentally in a healthy young man of 34 years of age, who suffered an accident and had a rib fracture. No pathological hormone production was detected on laboratory tests. The right adrenal gland with the tumor was removed by laparoscopic surgery. Histopathological examination revealed an oncocytic adenoma of the adrenal cortex. The authors describe the morphology and the differential diagnosis of this rare tumor of the adrenal gland.


Assuntos
Adenoma Oxífilo/diagnóstico , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adenoma Oxífilo/patologia , Adenoma Oxífilo/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Diagnóstico Diferencial , Humanos , Achados Incidentais , Masculino
11.
Orv Hetil ; 146(43): 2191-7, 2005 Oct 23.
Artigo em Húngaro | MEDLINE | ID: mdl-16323565

RESUMO

Multiple endocrine neoplasia type 1 syndrome is an autosomal dominant disorder characterized by endocrinopathies involving the parathyroid glands, anterior pituitary gland, and pancreas. Also, it may be associated with foregut carcinoid, adrenocortical tumors and non-endocrine tumors. After reviewing the prevalence, genetic background, clinical symptoms, diagnosis and treatment of the disorder, the authors present their genetic screening method used for the detection of mutations of the MEN1 gene (prescreening of polymerase chain reaction amplified exons using temporal temperature gradient gel electrophoresis followed by direct DNA sequencing). Using this method, the authors identified disease-causing MEN1 gene mutations in 9 probands (small deletions in 2 cases, insertion in 2 cases, nonsense mutations in 2 cases and missense mutations in 3 cases). Of the 9 mutations, 4 proved to be novel mutation not reported in the literature. Family screening indicated de novo mutations in 2 probands. In addition to mutations, several sequence polymorphisms were also detected. The authors conclude that one of the major advantages of genetic screening in families with MEN1 syndrome was the identification of family members carrying the mutation who should be regularly screened for disease manifestations and those not carrying the mutation in whom clinical screening is unnecessary. Also, genetic screening may be useful in cases when MEN1 syndrome is suspected, but the clinical manifestations do not fully establish the diagnosis of MEN1 syndrome.


Assuntos
Testes Genéticos , Neoplasia Endócrina Múltipla Tipo 1 , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/terapia , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/genética , Tumor Carcinoide/terapia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/terapia , Testes Genéticos/métodos , Humanos , Hungria/epidemiologia , Hiperparatireoidismo/diagnóstico , Hiperparatireoidismo/genética , Hiperparatireoidismo/terapia , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/terapia , Mutação , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Linhagem , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/terapia , Polimorfismo Genético
12.
Eur J Endocrinol ; 147(3): 349-55, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12213672

RESUMO

OBJECTIVE: The aims of the present study were (a) to examine the occurrence of 21-hydroxylase gene (CYP21) mutations in patients with unilateral and bilateral adrenal incidentalomas and (b) to correlate the results of mutation screening with hormonal parameters of 21-hydroxylase deficiency. DESIGN: The frequency of the eight commonly occurring CYP21 mutations in blood DNA samples of 19 patients with bilateral, as well as in blood and tumoral tissue DNA samples of 31 patients with unilateral adrenal incidentalomas, was determined. In all patients, hormonal evaluation for 21-hydroxylase deficiency was performed using measurements of basal and ACTH-stimulated plasma 17-hydroxyprogesterone (17-OHP) concentrations. METHODS: Blood and tumoral DNA samples were analyzed by allele-specific PCR for the detection of the eight commonly occurring CYP21 mutations (deletion/large gene conversion, intron 2 splicing, Ile172Asn, exon 6 cluster, Val281Leu, Leu307insT, Gln318Stop and Arg356Trp mutations). Plasma 17-OHP concentrations were measured by radioimmunoassay. RESULTS: Of the 19 patients with bilateral adrenal incidentalomas, one patient had homozygous (Val281Leu) and three patients had heterozygous germline CYP21 mutations (Val281Leu in two cases and Arg356Trp in one case). Heterozygous germline CYP21 mutations were also detected in five of the 31 patients with unilateral adrenal incidentalomas (Ile172Asn in three cases and Val281Leu in two cases). Mutation screening of tumoral DNA in unilateral incidentalomas showed the presence of corresponding germline mutations but no additional somatic mutations were found. ACTH-stimulated plasma 17-OHP concentrations were above 1500 ng/dl in all patients with bilateral incidentalomas who had homozygous and heterozygous CYP21 mutations, but heterozygous carriers with unilateral incidentalomas had highly variable ACTH-stimulated plasma 17-OHP levels (between 111 and 1705 ng/dl). CONCLUSIONS: These results suggest a similar frequency of germline CYP21 mutations in patients with bilateral and unilateral adrenal incidentalomas (21.1% and 16.1% respectively). Therefore, it cannot be ruled out that, in at least some patients, CYP21 mutations may play a role in the pathomechanism of bilateral and unilateral adrenal incidentalomas. However, the lack of clear association of CYP21 mutations with increased ACTH-stimulated plasma l7-OHP response, especially in patients with unilateral incidentalomas, suggests that the effect of CYP21 mutations on adrenocortical tumor formation may also involve mechanism(s) independent of ACTH-induced changes in 17-OHP secretion.


Assuntos
Adenoma/genética , Neoplasias das Glândulas Suprarrenais/genética , Hiperplasia Suprarrenal Congênita , Hormônios/sangue , Esteroide 21-Hidroxilase/genética , 17-alfa-Hidroxiprogesterona/sangue , Adenoma/sangue , Neoplasias das Glândulas Suprarrenais/sangue , Hormônio Adrenocorticotrópico , Alelos , DNA/análise , DNA/sangue , Análise Mutacional de DNA , Feminino , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Splicing de RNA
13.
Steroids ; 68(5): 477-82, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12798499

RESUMO

Although 6beta-hydroxycortisol (6betaOHF) is usually considered a cortisol metabolite produced by the liver, a few reports suggest that it may also originate from extrahepatic sources. To examine whether human adrenal cells are capable of 6beta-hydroxylating cortisol, we measured 6betaOHF secretion with a radioimmunoassay method in isolated human adrenal cell systems obtained from three normal adrenals, four nonhyperfunctioning adrenocortical adenomas, two adrenal adenomas causing Cushing's syndrome, and five aldosterone (Aldo)-producing adenomas. Cells were examined both under basal conditions and after stimulation with adrenocorticotrophic hormone (ACTH). In addition, 6betaOHF concentrations were determined in inferior vena cava and suprarenal vein plasma samples obtained from the side of nonhyperfunctioning adrenal adenomas (five patients) and aldosterone-producing adenomas (five patients). Under basal incubation conditions, 6betaOHF secretion, expressed as a percent of cortisol secretion, was between 0.5 and 2.0% in normal adrenal cells, between 1.0 and 7% in cells from nonhyperfunctioning adenomas, 12 and 15% in cells from Cushing's syndrome patients, and between 2.6 and 3.9% in cells from aldosterone-producing adenomas. In these cells, increasing doses of ACTH produced a dose-dependent stimulation of both 6betaOHF and cortisol secretion. The 6betaOHF concentration in suprarenal vein samples obtained from the side of adenomas was markedly increased; the suprarenal vein/inferior vena cava 6betaOHF ratios were 13.1+/-2.1 (mean+/-S.E.) in the case of nonhyperfunctioning adenomas and 17.8+/-4.5 in the case of aldosterone-producing adenomas. These results firmly suggest that 6betaOHF is not only a hepatic metabolite, but also a secretory product of human adrenals and that similarly to cortisol, its secretion may be controlled by ACTH.


Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Córtex Suprarrenal/metabolismo , Hidrocortisona/análogos & derivados , Hidrocortisona/metabolismo , Córtex Suprarrenal/citologia , Córtex Suprarrenal/efeitos dos fármacos , Neoplasias do Córtex Suprarrenal/patologia , Hormônio Adrenocorticotrópico/farmacologia , Aldosterona/biossíntese , Relação Dose-Resposta a Droga , Humanos
14.
Orv Hetil ; 143(19 Suppl): 1066-70, 2002 May 12.
Artigo em Húngaro | MEDLINE | ID: mdl-12063862

RESUMO

The authors report clinical observations in 12 acromegalic patients treated with long-acting octreotide (Sandostatin LAR, Novartis, 20 mg intramuscular injection per 28 days administered for 6-36 months). Clinically and hormonally active acromegaly was evidenced in all patients by the presence of typical clinical symptoms, increased serum growth hormone and insulin-like growth factor I concentrations, and by non-suppressible serum growth hormone levels after oral glucose administration. In all patients previous treatments (transsphenoidal surgery, pituitary irradiation and bromocriptine therapy) were uneffective or contraindicated, or they were refused by the patients. Octreotide test (Sandostatin, Novartis, 100 g subcutaneously) performed in all patients before treatment precisely predicted the hormonal effectiveness of long-acting octreotide treatment. Three-six months after therapy serum growth hormone levels decreased from 13.6 +/- 3.9 ng/ml (mean +/- SD) to 3.4 +/- 1.7 ng/ml, while insulin-like growth factor I concentrations decreased from 483 +/- 127 ng/ml to 248 +/- ng/ml. Of the 12 patients 7 (58%) had serum growth hormone levels considered as safe values (< 2.5 ng/ml), whereas in 9 patients (75%) serum insulin-like growth factor I concentrations returned to age- and sex-matched normals. Repeat pituitary magnetic resonance imaging performed in 8 patients treated longer than 1 year revealed a decrease of tumor size in 3 patients (37%). There was a considerable clinical improvement during treatment: severe headache, which was present in most patients, as well as perspiration, joint pain, swelling of extremities, and weakness markedly decreased or disappeared. These results indicate that long-acting octreotide offers a very effective treatment of choice in acromegalic patients in whom other previous therapies were ineffective, contraindicated, or refused.


Assuntos
Acromegalia/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Octreotida/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Acromegalia/sangue , Acromegalia/etiologia , Idoso , Antineoplásicos Hormonais/administração & dosagem , Preparações de Ação Retardada , Esquema de Medicação , Feminino , Hormônios/uso terapêutico , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Octreotida/administração & dosagem , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/complicações , Estudos Retrospectivos , Resultado do Tratamento
15.
PLoS One ; 9(9): e107244, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25210767

RESUMO

PURPOSE: Systematic evaluation of the potential relationship between the common genetic variants of CYP21A2 and hormone levels. METHODS: The relationships of CYP21A2 intron 2 polymorphisms and haplotypes with diverse baseline and stimulated blood hormone levels were studied in 106 subjects with non-functioning adrenal incidentaloma (NFAI). The rationale for using NFAI subjects is dual: i) their baseline hormone profiles do not differ from those of healthy subjects and ii) hormone levels after stimulation tests are available. RESULTS: The carriers (N = 27) of a well-defined CYP21A2 haplotype cluster (c5) had significantly elevated levels of cortisol (p = 0.0110), and 17-hydroxyprogesterone (p = 0.0001) after ACTH stimulation, and 11-deoxycortisol after metyrapone administration (p = 0.0017), but the hormone values were in normal ranges. In addition, the carriers (N = 33) of the C allele of the rs6462 polymorphism had a higher baseline aldosterone level (p = 0.0006). The prevalence of these genetic variants of CYP21A2 did not differ between NFAI and healthy subjects. CONCLUSIONS: The common CYP21A2 variants presumably exert the same effect on hormone levels in the healthy and disease-affected populations. Therefore, they may contribute to complex diseases such as some cardiovascular diseases, and may influence the genotype-phenotype correlation in patients with congenital adrenal hyperplasia (CAH) including the individual need for hormone substitution.


Assuntos
17-alfa-Hidroxiprogesterona/sangue , Hidrocortisona/sangue , Esteroide 21-Hidroxilase/genética , Adenoma/sangue , Adenoma/genética , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/metabolismo , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Haplótipos , Heterozigoto , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Ranitidina , Estudos Retrospectivos
16.
Steroids ; 76(1-2): 38-42, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20813120

RESUMO

OBJECTIVE: The cut-off value for salivary cortisol measurement for the diagnosis of Cushing's syndrome (CS) may depend both on the severity of the disease and the composition of control group. Therefore, we examined the utility of midnight salivary cortisol measurements in patients who were evaluated for signs and symptoms of CS or because they had adrenal incidentalomas. Because serum osteocalcin (OC) is considered as a sensitive marker of hypercortisolism, we also investigated whether OC could have a role in the diagnosis of CS. PATIENTS AND METHODS: Each of the 151 patients was included into one of the following groups: (A) overt CS (n=23), (B) subclinical CS (n=18), (C) inactive adrenal adenomas (n=40), (D) patients without HPA disturbances (n=70). Patients (C+D) were used as controls. Serum, salivary and urinary cortisol, and OC were measured by electrochemiluminescence immunoassay. RESULTS: Group A had suppressed OC as compared to both group B and group (C+D). Serum and salivary cortisol concentrations showed strong negative correlations with OC in patients with overt CS. The areas under the curves of salivary and serum cortisol at 24:00 h (0.9790 and 0.9940, respectively) serum cortisol after low dose dexamethasone test (0.9930) and OC (0.9220) obtained from ROC analysis for the diagnosis of overt CS were not statistically different. CONCLUSION: This study confirms the usefulness of midnight salivary cortisol measurements in the diagnosis of overt CS in the everyday endocrinological praxis. Our results suggest that OC may have a role in the diagnosis of overt CS.


Assuntos
Síndrome de Cushing/sangue , Síndrome de Cushing/diagnóstico , Hidrocortisona/análise , Osteocalcina/sangue , Saliva/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Clin Chim Acta ; 411(5-6): 364-7, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19968981

RESUMO

BACKGROUND: Midnight salivary cortisol (MSC) concentration has been considered as a sensitive marker of overt hypercortisolism. Because no studies on commercially available automated, non-isotopic MSC assays have been reported, we determined and compared the diagnostic performance of an automated electrochemiluminescent immunoassay (ECLIA, Elecsys E170) and an in-house radioimmunoassay (RIA) for MSC measurement. METHODS: The study involved 126 consecutive patients referred for evaluation because of symptoms of Cushing's syndrome, obesity, or the presence of incidentally discovered adrenal adenoma. Using detailed clinical, hormonal and radiological evaluation overt endogenous hypercortisolism was confirmed in 9 patients and was excluded in 117 patients. RESULTS: ROC analysis indicated that the best performance of MSC was obtained at cutoff value of 0.35 microg/dl using ECLIA (sensitivity, 100%; specificity, 88%) and 0.29 microg/dl (sensitivity, 100%; specificity, 71%) using RIA. When the findings were compared to those obtained from low dose dexamethasone test, both ECLIA and RIA of MSC showed a better diagnostic performance. CONCLUSION: MSC measurement is useful for the diagnosis of overt hypercortisolism but the cutoff value is highly dependent on the method used. We recommend the use of automated ECLIA for MSC assay, and we propose further studies on other automated immunoassay analyzers potentially suitable for MSC measurements.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Adenoma Adrenocortical/diagnóstico , Síndrome de Cushing/diagnóstico , Hidrocortisona/sangue , Obesidade/diagnóstico , Saliva/química , Adulto , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Curva ROC , Radioimunoensaio , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Steroids ; 74(9): 725-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19540999

RESUMO

The 11beta-hydroxysteroid dehydrogenase isoenzymes (11beta-HSD) catalyse the interconversion of cortisol (F) and cortisone (E). Earlier studies demonstrated that growth hormone (GH) and insulin resistance may exert opposite effects on the conversion of E to F by 11beta-HSD type 1. Therefore, in the present study we determined F and E concentrations in 562 plasma samples obtained from acromegalic patients during an active phase (76 patients) and after cure of the disease (68 patients). In addition, we examined whether type 2 diabetes mellitus or impaired glucose tolerance, which are frequently associated with active acromegaly could influence plasma F and E levels in these patients. We found that plasma F concentrations were similar in patients with active acromegaly and in those who were cured with pituitary surgery, irradiation and/or medical therapy (mean+/-S.E., 12.4+/-0.3 and 12.7+/-0.4 microg/dl, respectively). However, plasma E levels were significantly higher in patients with active compared to those with cured acromegaly (2.8+/-0.1 and 2.2+/-0.1 microg/dl, respectively; p<0.001), resulting in a lower F/E ratio in patients with active disease (4.6+/-0.1 vs. 5.9+/-0.2 in the cured group of patients; p<0.001). When the effect of altered carbohydrate homeostasis on plasma F and E was analysed, the results indicated significantly lower plasma E levels and higher F/E ratios in active acromegalic patients with type 2 diabetes mellitus or impaired glucose tolerance compared to those with normal carbohydrate metabolism (E, 2.5+/-0.1 and 3.0+/-0.1 microg/dl, respectively; F/E, 5.1+/-0.2 and 4.4+/-0.1; p<0.001), whereas plasma F concentrations were similar in these two groups (12.1+/-0.4 and 12.6+/-0.3 microg/dl, respectively). These findings indicate that disease activity exerts a significant impact on 11beta-HSD in acromegalic patients, which is further modified with altered carbohydrate homeostasis, frequently present in patients with active disease.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Acromegalia/complicações , Acromegalia/enzimologia , Metabolismo dos Carboidratos , Acromegalia/sangue , Acromegalia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Cortisona/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Intolerância à Glucose/complicações , Intolerância à Glucose/metabolismo , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
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