RESUMO
PURPOSE: Pituitary macroadenomas (MACs) represent 10-30 % of Cushing's disease (CD) cases. The aim of this study was to report the clinical, laboratorial and imaging features and postsurgical outcomes of microadenoma (MIC) and MAC patients. METHODS: Retrospective study with 317 CD patients (median 32 years old, range 9-71 years) admitted between 1990 and 2014, 74 (23.3 %) of whom had MAC. RESULTS: Hirsutism, plethora facial, muscular weakness and muscular atrophy were more frequent in the MIC patients. Nephrolithiasis, osteopenia, hyperprolactinaemia and galactorrhoea were more prevalent in MAC patients. The morning serum cortisol (Fs), nocturnal salivary cortisol (NSC), nocturnal Fs (Fs 2400 h), low- and high-dose dexamethasone suppression test results and CRH and desmopressin test results were similar between the subgroups. MIC patients showed higher urinary cortisol at 24 h (UC), and MAC patients presented higher ACTH levels but lower Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. There were negative correlations of tumour size with Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. Overall, the postsurgical remission and recurrence rates were similar between MIC and MAC. However, patients in remission (MIC + MAC) showed smaller tumour diameters and a lower prevalence of invasion and extension on MRI. CONCLUSIONS: Despite exhibiting higher plasma ACTH levels, CD patients with MAC presented lower cortisol/ACTH ratios than did patients with MIC, with a negative correlation between tumour size and cortisol/ACTH ratios. The overall postsurgical remission and recurrence rates were similar between MIC and MAC patients, with those with larger and/or invasive tumours showing a lower remission rate.
Assuntos
Adenoma/sangue , Hormônio Adrenocorticotrópico/sangue , Hidrocortisona/sangue , Hipersecreção Hipofisária de ACTH/complicações , Neoplasias Hipofisárias/sangue , Adenoma/etiologia , Adenoma/patologia , Adolescente , Adulto , Idoso , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Hipersecreção Hipofisária de ACTH/fisiopatologia , Neoplasias Hipofisárias/etiologia , Neoplasias Hipofisárias/patologia , Estudos Retrospectivos , Adulto JovemRESUMO
Since the inception of its proficiency test program to evaluate radionuclide measurement in hospitals and clinics, the National Metrology Laboratory of Ionizing Radiation-LNMRI, that represents Brazilian National Metrology Institute (NMI) for ionizing radiation has expanded its measurement and calibration capability. Requirements from the National Health Surveillance Agency from Ministry of Health (ANVISA), to producers of radiopharmaceuticals provided an opportunity to improve the full traceability chain to the highest level. Fluorodeoxyglucose (FDG-(18)F) is the only radiopharmaceutical simultaneously produced by all Brazilian radiopharmaceutical production centers (RPCs). By running this proficiency test, LNMRI began to provide them with the required traceability. For evaluation, the ratio of RPC to reference value results and ISO/IEC17043:2010 criteria were used. The reference value established as calibration factor on the secondary standard ionization chamber was obtained from three absolute measurements systems, and routinely confirmed in each round of proficiency test by CIEMAT/NIST liquid scintillation counting. The γ-emitting impurities were checked using a High-Purity Germanium (HPGe) detector. The results show that Brazilian RPCs are in accordance with (accuracy within ±10%) the Brazilian standard for evaluation of measurements with radionuclide calibrators (CNEN NN 3.05., 2013). Nevertheless, the RPCs should improve the methodology of uncertainty estimates, essential when using the statistical criteria of ISO/IEC 17043 standard, in addition to improving accuracy to levels consistent with their position in the national traceability chain.
Assuntos
Radioisótopos de Flúor/análise , Radioisótopos de Flúor/normas , Setor Público/normas , Radiometria/métodos , Radiometria/normas , Brasil , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Incidentally discovered adrenal masses are common and the clinical evaluation and surveillance aims to diagnose hormone excess and malignancy. Adrenocortical cancer (ACC) is a very rare malignancy. This study aims to define the imaging characteristics of adrenal tumors preceding the diagnosis of ACC. Patients with prior (>5 months) adrenal tumors (<6 cm) subsequently diagnosed with ACC were identified in a large registry at a tertiary referral center. Retrospective chart and image review for patient characteristics and initial, interval, and diagnostic imaging characteristics (size, homogeneity, borders, density, growth rate, etc.) was conducted. Twenty patients with a diagnosis of ACC and a prior adrenal tumor were identified among 422 patients with ACC. Of these, 17 patients were initially imaged with CT and 3 with MR. Only 2 of the 20 patients had initial imaging characteristics suggestive of a benign lesion. Of initial tumors, 25% were <2 cm in size. Surveillance led to the diagnosis of ACC within 24 months in 50% of patients. The growth pattern was variable with some lesions showing long-term stability (up to 8 years) in size. In conclusion, antecedent lesions in patients with a diagnosis of ACC are often indeterminate by imaging criteria and can be small. Surveillance over 2 years detected only 50% of ACCs. Current practice and guidelines are insufficient in diagnosing ACCs. Given the rarity of ACC, the increased risk and health care costs of additional evaluation may not be warranted.
Assuntos
Neoplasias do Córtex Suprarrenal/diagnóstico , Glândulas Suprarrenais/patologia , Neoplasias do Córtex Suprarrenal/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
DAX1 transcription factor is a key determinant of adrenogonadal development, acting as a repressor of SF1 targets in steroidogenesis. It was recently demonstrated that DAX1 regulates pluripotency and differentiation in murine embryonic stem cells. In this study, we investigated DAX1 expression in adrenocortical tumors (ACTs) and correlated it with SF1 expression and clinical parameters. DAX1 and SF1 protein expression were assessed in 104 ACTs from 34 children (25 clinically benign and 9 malignant) and 70 adults (40 adenomas and 30 carcinomas). DAX1 gene expression was studied in 49 ACTs by quantitative real-time PCR. A strong DAX1 protein expression was demonstrated in 74% (25 out of 34) and 24% (17 out of 70) of pediatric and adult ACTs, respectively (χ(2)=10.1, p=0.002). In the pediatric group, ACTs with a strong DAX1 expression were diagnosed at earlier ages than ACTs with weak expression [median 1.2 (range, 0.5-4.5) vs. 2.2 (0.9-9.4), p=0.038]. DAX1 expression was not associated with functional status in ACTs. Interestingly, a positive correlation was observed between DAX1 and SF1 protein expression in both pediatric and adult ACTs (r=0.55 for each group separately; p<0.0001). In addition, DAX1 gene expression was significantly correlated with SF1 gene expression (p<0.0001, r=0.54). In conclusion, DAX1 strong protein expression was more frequent in pediatric than in adult ACTs. Additionally, DAX1 and SF1 expression positively correlated in ACTs, suggesting that these transcription factors might cooperate in adrenocortical tumorigenesis.
Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Carcinogênese/metabolismo , Receptor Nuclear Órfão DAX-1/metabolismo , Fator Esteroidogênico 1/metabolismo , Neoplasias do Córtex Suprarrenal/genética , Adenoma Adrenocortical/genética , Adenoma Adrenocortical/metabolismo , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/metabolismo , Adulto , Carcinogênese/genética , Criança , Pré-Escolar , Receptor Nuclear Órfão DAX-1/genética , Feminino , Expressão Gênica , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fator Esteroidogênico 1/genéticaRESUMO
Progress in the diagnosis and treatment of endocrine diseases has turned pregnancy into a possibility for women with such medical disorders, including Cushing's syndrome (CS). Nevertheless, despite its rarity, pregnancy in patients with CS can be troublesome because of the risk of maternal-fetal complications. Therefore, hypercortisolism, if present, should be surgically or medically controlled in most cases. Moreover, changes in the hypothalamic-pituitary-adrenal axis during normal pregnancy may mislead the diagnosis of CS during this period, because many laboratory assessments suggestive of CS may be present in normal pregnancy, with clinical features mimicking those seen in patients with CS. The aim of the present review is to update the diagnostic approach to this medical condition, mainly for pregnant women without previous diagnosis of CS, and to describe the therapeutic strategies for CS during pregnancy in order to minimize complications for both mother and fetus.
Assuntos
Síndrome de Cushing/metabolismo , Síndrome de Cushing/terapia , Gerenciamento Clínico , Complicações na Gravidez/metabolismo , Complicações na Gravidez/terapia , Síndrome de Cushing/diagnóstico , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Complicações na Gravidez/diagnósticoRESUMO
La enfermedad de Lhermitte-Duclos o gangliocitoma displásico cerebeloso es una entidad infrecuente que se presenta como un proceso expansivo de la fosa posterior, de lento crecimiento y patogenia desconocida. Puede estar asociada a otras anomalías congénitas. Presentamos el caso de un gangliocitoma displásico de cerebelo en un paciente de sexo masculino, de 77 años de edad, con antecedentes de adenocarcinoma prostático, que fue estudiado por tomografía computada (TC) y resonancia magnética (RM). Los hallazgos característicos, junto con una evaluación neuroquirúrgica y un manejo apropiados, permitieron efectuar el diagnóstico preoperatorio sin necesidad de recurrir a exámenes histopatológicos...
The Lhermitte-Duclos disease or dysplastic cerebellar gangliocytoma is an uncommon disorder that presents as an expansive, slow growing process of the posterior fossa, of unknown pathogenesis, that may be associated with other congenital anomalies.A case is presented of a dysplastic cerebellar gangliocytoma in a 77 year-old male patient, with a history of prostatic adenocarcinoma. A study was made using Computed Tomography (CT) and Magnetic Resonance (MRI), where the characteristic findings enabled a preoperative diagnosis to be made without need for histopathological examination, in addition to a neurosurgical evaluation and appropriate management...
Assuntos
Humanos , Masculino , Idoso , Neoplasias Cerebelares , Ganglioneuroma , Imageamento por Ressonância MagnéticaRESUMO
La enfermedad de Lhermitte-Duclos o gangliocitoma displásico cerebeloso es una entidad infrecuente que se presenta como un proceso expansivo de la fosa posterior, de lento crecimiento y patogenia desconocida. Puede estar asociada a otras anomalías congénitas. Presentamos el caso de un gangliocitoma displásico de cerebelo en un paciente de sexo mascu lino, de 77 años de edad, con antecedentes de adenocarcinoma prostático, que fue estudiado por tomografía computada (TC) y resonancia magnética (RM). Los hallazgos característicos, junto con una evaluación neuroquirúrgica y un manejo apropiados, permitieron efectuar el diagnóstico preoperatorio sin necesidad de recurrir a exámenes histopatológicos.(AU)
The Lhermitte-Duclos disease or dysplastic cerebellar gangliocytoma is an uncommon disorder that presents as an expansive, slow growing process of the posterior fossa, of unknown pathogenesis, that may be associated with other congenital anomalies. A case is presented of a dysplastic cerebellar gangliocytoma in a 77 year-old male patient, with a history of prostatic adenocarcinoma. A study was made using Computed Tomography (CT) and Magnetic Resonance (MRI), where the characteristic findings enabled a preoperative diagnosis to be made without need for histopathological examination, in addition to a neurosurgical evaluation and appropriate management.(AU)
RESUMO
The MSH2 c.388_389del mutation has occasionally been described in Lynch families worldwide. At the Portuguese Oncology Institute in Porto, Portugal, we have identified 16 seemingly unrelated families with this germline mutation. To evaluate if this alteration is a founder or a recurrent mutation we performed haplotype analysis in the 16 Portuguese index cases and 55 relatives, as well as in four index cases and 13 relatives reported from Germany, Scotland, England, and Argentina. In the Portuguese families we observed a shared haplotype of approximately 10 Mb and all were originated from the north of Portugal. These results suggest that this alteration is a founder mutation in Portugal with a relatively recent origin. In the reported families outside Portugal with this mutation different haplotype backgrounds were observed, supporting the hypothesis that it occurred de novo on multiple occasions. We also conclude that the high proportion of families with the MSH2 c.388_389del mutation indicates that screening for this alteration as a first step may be cost-effective in the genetic testing of Lynch syndrome suspects of Portuguese ancestry, especially those originating from the north of Portugal.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Efeito Fundador , Proteína 2 Homóloga a MutS/genética , Deleção de Sequência , Argentina , Sequência de Bases , Inglaterra , Mutação em Linhagem Germinativa , Alemanha , Haplótipos , Humanos , Repetições de Microssatélites , Motivos de Nucleotídeos , Polimorfismo de Nucleotídeo Único , PortugalRESUMO
En la Jurisdicción Sanitaria Ecatepec, se realizó un taller de Riesgos y Daños para la salud con el propósito de priorizar el daño a la salud susceptible a ser intervenido a través de la aplicación del método de Hanlón, por los estudiantes de posgrado de Enfermería en salud pública y el equipo multidisciplinario de la jurisdicción. Participaron 48 personas con cargos normativos y operativos de los Centros Municipales de Salud (COMUSA), DIF, CONALEP, y Salud Municipal a quienes se les capacitó sobre la utilidad y aplicación del Método de Hanlón, proporcionándoles la información estadística para hacer los cálculos respectivos. Los resultados de la priorización de mayor a menor puntuación fueron: Diabetes Mellitus tipo 2, Neumonía e Influenza, Enfermedades del corazón, Tumores malignos, Accidentes, agresiones y suicidios, Enfermedades del hígado, SIDA, e insuficiencia renal. Tomando en cuenta que en las primeras cuatro causas ya han sido trabajadas por generaciones previas de estudiantes de la Especialidad, se determinó que la causa a ser intervenida es: accidente, agresiones y suicidios.
In the Health Jurisdiction Ecatepec, a risk and darrage workshop health was carried out which used the Hanlon method in order to prioritize the possible damage and give the attention through the multidisciplinary staff and the Public Health Nursing speciality students. The number of participants in the workshop were 48 from health Municipality Centers, DIF, CONALEP, whom were trained about the features and how to use Hanlon method. The statistical information was given to do the respective calculation. The results of prioritize were ordered from the highest to the lowest score: diabetes mellitus type 2, Pneumania and influenza, heart illness, malign tumors, accidents, agrressions and suicides, liver sickeness, AIDS, renal insufficiency. Because the first 4 causes had been studied before, it was determined that the causes to be intervened will be accidents, agrressions and suicides.
Assuntos
Humanos , Masculino , Feminino , Saúde , Enfermagem em Saúde Pública , Risco à Saúde HumanaRESUMO
Mutations of the p53 tumor suppressor gene are the single most common genetic alterations in human cancers. Recently, a distinct nucleotide substitution was identified in exon 10 of the p53 gene, leading to an Arg337His mutation in 97% of children with adrenocortical tumors from Southern Brazil. In the present study, we investigated the presence of this mutation in a larger series of 55 patients (37 adults and 18 children) with benign and malignant sporadic adrenocortical tumors. None of the patients had family cancer histories that conformed to the criteria for Li-Fraumeni syndrome. Twenty-one asymptomatic close relatives of patients with p53 mutations and 60 normal unrelated individuals were also studied. The missense Arg337His mutation was identified in 19 patients (14 children and 5 adults), and 8 of 11 cases studied had LOH. Among the 19 patients with the Arg337His mutation, only one boy and three adults showed fatal evolution or recurrent metastases. This mutation was also identified in heterozygous state in asymptomatic first-degree relatives of the patients, indicating that Arg337His mutation was inherited in most cases. In contrast, this mutation was not found in 120 alleles of normal unrelated controls. In conclusion, the germ line Arg337His mutation of p53 protein is present at a high frequency (77.7%) in children with benign or malignant sporadic adrenocortical tumors, but it is not restricted to the pediatric group, since 13.5% of adults with adrenocortical tumors also had this mutation. The presence of this mutation was related to unfavorable prognosis in most of the adults, but not in the children with adrenocortical tumors.
Assuntos
Neoplasias do Córtex Suprarrenal/genética , DNA/metabolismo , Genes p53 , Mutação , Adolescente , Adulto , Sítios de Ligação , Criança , Pré-Escolar , Sequência Conservada , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Proteína Supressora de Tumor p53/químicaRESUMO
OBJECTIVE: To measure the accessibility to health services and determine a model to explain this accessibility. MATERIALS AND METHODS: All states of the Mexican Republic were included. The measurement of accessibility considers the availability of resources and the perception of barriers. Place of residence, education, participation in the work forces and household conditions were included in the model. RESULTS: The average of availability resources was 64.59% sd 15.68 (range 42 to 100) and the average corresponding to perception of barriers, 87.61% SD 4.04 (range 79.23 to 95.65). Accessibility was 71.50% SD 10.74 (range 56 to 96). The states with highest accessibility were the Federal District and Baja California Sur and the lowest, Chiapas and Oaxaca. The model included education and labor participation (R2 = 0.67, p < 0.05). CONCLUSIONS: Accessibility was determined by socioeconomic factors.
Assuntos
Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , MéxicoRESUMO
Ovarian steroid cell tumors are rare neoplasms composed of typical steroid hormone-secreting cells. Most ovarian steroid cell tumors, however, cannot be appropriately classified on a morphological basis, because the neoplastic cells closely resemble adrenal cortical cells. Nevertheless, the true adrenal origin of such tumors has been difficult to demonstrate. Here we report a 3-yr-old girl with isosexual pseudoprecocious puberty due to an ovarian steroid tumor whose adrenal cell origin was determined by the presence of messenger ribonucleic acid (mRNA) of adrenal-specific steroidogenic P450 enzymes (P450c11 and P450c21) and ACTH receptor (ACTHR). Her height was +2.3 SD, and she had Tanner stage III breast development, Tanner stage II pubic hair, and a normal clitoris. Bone age was 5 yr. Basal gonadotropin levels were undetectable (<0.6 U/L for LH and <1.0 U/L for FSH) and remained undetectable after stimulation with 100 microg GnRH, i.v. Basal serum testosterone and 17-hydroxyprogesterone levels were slightly elevated, whereas basal serum androstenedione, estradiol, and dehydroepiandrosterone sulfate levels were clearly elevated. Pelvic ultrasound disclosed an enlarged uterus and an adnexal multicystic mass in the right ovary, and pathological studies disclosed an ovarian steroid cell tumor. To establish the cellular origin of the tumor we determined the presence of mRNA for P450c11, P450c21, and ACTHR in tumor tissue and normal adrenal and ovarian tissue. Detection of ACTHR, P450c21, and P450c11 mRNAs isoforms was achieved in tumoral and adrenal control tissue, but not in the ovary control tissue. The RT-PCR products of P450c11 from adrenal control tissue were composed by both BglI-sensitive and -resistant complementary DNAs, indicating the presence of both P450c11AS and P450c11beta, whereas RT-PCR product from the tumor was resistant to BglI digestion, indicating only the presence of P450c11beta. We conclude that the histological origin of so-called adrenal rest tumor could be reliably determined by assessing the expression of specific genes in the tumor as P450c11beta and P450c21. The use ofthese molecular tools will allow a more precise classification of an important subset of the ovarian steroid cell tumors and can help to identify ectopic adrenal tissue in ovary and testis.
Assuntos
Glândulas Suprarrenais/metabolismo , Neoplasias Ovarianas/patologia , Puberdade Precoce/etiologia , Receptores da Corticotropina/metabolismo , Esteroides/biossíntese , Glândulas Suprarrenais/enzimologia , Pré-Escolar , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/enzimologia , Puberdade Precoce/enzimologia , RNA Mensageiro/análise , RNA Neoplásico/análise , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: To search for germline activating mutations of the FSH receptor in girls with gonadotropin-independent precocious puberty. DESIGN: Molecular studies in human tissue. SETTING: Four girls with polycystic ovaries and gonadotropin-independent isosexual precocious puberty without clinical and molecular features of McCune-Albright syndrome. INTERVENTION(S): Peripheral blood was used for DNA extraction. The alpha-subunit of the Gs gene and the entire exon 10 of FSH receptor gene were amplified by polymerase chain reaction (PCR). Gs-alpha mutations characteristic of McCune-Albright syndrome were excluded by denaturating gradient gel electrophoresis (DGGE) and allele-specific PCR. Exon 10 of the FSH receptor gene was analyzed by DGGE and direct sequencing. MAIN OUTCOME MEASURE(S): Results of DGGE and direct sequencing. RESULT(S): No germline activating mutations were detected in exon 10 of our patients. Instead, two previously described polymorphisms were found, leading to the substitution of alanine for threonine at position 307 and of serine for asparagine at position 680 of the FSH receptor molecule. CONCLUSION(S): Germline activating mutations were not found in exon 10 of the FSHR gene in any of our patients. Further studies, preferably in ovarian tissue, will be required to exclude the presence of somatic activating mutations of the FSH receptor in these patients.
Assuntos
Mutação em Linhagem Germinativa , Cistos Ovarianos/genética , Puberdade Precoce/genética , Receptores do FSH/genética , Substituição de Aminoácidos , Criança , Pré-Escolar , Eletroforese/métodos , Feminino , Heterozigoto , HumanosRESUMO
The gonadotropin releasing hormone (GnRH) secreting hypothalamic hamartoma (HH) is a congenital malformation consisting of a heterotopic mass of nervous tissue that contains GnRH neurosecretory neurons attached to the tuber cinereum or the floor of the third ventricle. HH is a well recognised cause of gonadotropin dependent precocious puberty (GDPP). Long term data are presented on eight children (five boys and three girls) with GDPP due to HH. Physical signs of puberty were observed before 2 years of age in all patients. At presentation with sexual precocity, the mean height standard deviation (SD) for chronological age was +1.60 (1.27) and the mean height SD for bone age was -0.92 (1.77). Neurological symptoms were absent at presentation and follow up. The hamartoma diameter ranged from 5 to 18 mm and did not change in six patients who had magnetic resonance imaging follow up. All patients were treated clinically with GnRH agonists (GnRH-a). The duration of treatment varied from 2.66 to 8.41 years. Seven of the eight children had satisfactory responses to treatment, shown by regression of pubertal signs, suppression of hormonal levels, and improvement of height SD for bone age and predicted height. One patient had a severe local reaction to GnRH-a with failure of hormonal suppression and progression of pubertal signs. It seems that HH is benign and that GnRH-a treatment provides satisfactory and safe control for most children with GDPP due to HH.
Assuntos
Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/metabolismo , Hamartoma/complicações , Doenças Hipotalâmicas/complicações , Puberdade Precoce/etiologia , Antineoplásicos Hormonais/uso terapêutico , Criança , Pré-Escolar , Feminino , Seguimentos , Gosserrelina/uso terapêutico , Hamartoma/sangue , Hamartoma/tratamento farmacológico , Humanos , Doenças Hipotalâmicas/sangue , Doenças Hipotalâmicas/tratamento farmacológico , Leuprolida/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Puberdade Precoce/tratamento farmacológicoRESUMO
Activating mutations of the G protein genes have been associated with the development of several endocrine neoplasms. Such activating mutations, gip2, affecting the alpha-subunit of the G alpha i2 protein were previously described by a single group in 30% of ovarian sex cord stromal tumors. Other activating mutations of the alpha-subunit of the Gs (gsp) have been identified in GH-secreting and nonfunctioning pituitary tumors, autonomous thyroid adenomas, and all affected McCune-Albright tissues, but not in sex cord stromal tumors. In the present study, we investigated the presence of gip2 and gsp mutations in 14 human sex cord stromal tumors. Six Leydig cell tumors (4 ovaries and 2 testes), 2 thecomas, 2 granulosa cell tumors, 3 androblastomas, and 1 gonadoblastoma (sex cord and germ cell) were included in this study. Genomic DNA was obtained from either fresh-frozen tumor tissues or paraffin-embedded sections and in some cases from blood samples. Using PCR, denaturing gradient gel electrophoresis, and direct sequencing, we detected 4 tumors (66.6%) with the gsp mutation (R201C) in our series of ovarian and testicular Leydig cell tumors. In contrast, no gip2 mutations were found in any of the sex cord stromal tumors studied. In conclusion, our findings suggest that the putative oncogene gsp may play a significant role in the molecular mechanism of these tumors.
Assuntos
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/genética , Tumor de Células de Leydig/genética , Mutação , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas/genética , Adolescente , Adulto , Criança , DNA de Neoplasias/análise , Eletroforese em Gel de Ágar , Éxons , Feminino , Subunidade alfa Gi2 de Proteína de Ligação ao GTP , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Células EstromaisRESUMO
The pituitary-adrenal responsiveness to desmopressin of women with depressive illness was compared with that of patients with Cushing's disease, who are known to be highly responsive, and to that of normal controls, who are known to be poorly responsive to the peptide. Although 100% of the patients in the group with Cushing's disease met the response criterion with cortisol increases of 632 +/- 80 nmol/L above baseline (mean +/- SE), the prevalence of responders was 36% in the depressive group and 10% in normal controls, with cortisol changes from baseline of 154 +/- 28 and 79 +/- 15 nmol/L, respectively. All response parameters were significantly higher in the patients with Cushing's disease and did not differ between depressive patients and normal controls, who exhibited the same general pattern of cortisol and ACTH responses. It is concluded that the desmopressin test can be used in the differentiation between depression and Cushing's disease, and that the hypothalamic-pituitary-adrenal regulation is distinct in these two conditions.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing/tratamento farmacológico , Desamino Arginina Vasopressina/uso terapêutico , Depressão/tratamento farmacológico , Hidrocortisona/sangue , Adolescente , Adulto , Síndrome de Cushing/sangue , Depressão/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
OBJECTIVE: We assessed the ability of desmopressin to stimulate the pituitary-adrenal axis in patients with Cushing's syndrome. DESIGN AND SUBJECTS: The cortisol response to 5 ot 10 micrograms of intravenous desmopressin was evaluated in 31 patients with Cushing's syndrome of several aetiologies and in 15 normal subjects. RESULTS: Cortisol responses were observed in 15 out of 16 patients with pituitary dependence and in two patients with adrenal nodular hyperplasia, the increase above baseline ranging from 61 to 379% in the responders. Eight patients with adrenal tumours and one with the ectopic ACTH syndrome did not respond to desmopressin, having shown changes in their cortisol levels from -5 to 42% above baseline. Responses occurred in two out of the 15 normal individuals, whose cortisol increased 58 and 69% above baseline, respectively. Stimulation tests with standard agents as lysine vasopressin or ovine corticotrophin-releasing hormone were performed in the same patients and there was a high degree of concordance. No serious adverse reactions were observed in the tests with desmopressin. CONCLUSIONS: Desmopressin was able to stimulate the pituitary-adrenal axis in patients with Cushing's disease and, like corticotrophin releasing hormone, it may prove useful in the differential diagnosis of Cushing's syndrome.
Assuntos
Síndrome de Cushing/diagnóstico , Desamino Arginina Vasopressina , Síndrome de ACTH Ectópico/diagnóstico , Adolescente , Neoplasias do Córtex Suprarrenal/diagnóstico , Adulto , Criança , Síndrome de Cushing/sangue , Diagnóstico Diferencial , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Testes de Função Adreno-Hipofisária/métodos , Estimulação QuímicaRESUMO
La caracterizacion de 60 casos de 24 familias mexicanas con enfermedad de Von Willebrand (EvW) revelo su distribucion en el centro y el norte del pais, con predominio en pacientes del sexo femenino (78 por ciento) y con ancestros europeos. En la mayor parte de la forma de herencia fue autosomica. Hubo seis enfermos con EvW grave segun los valores de VIII: C y la agregacion plaquetaria con ristocetina menores de 10 por ciento. Once (22 por ciento) tuvieron EvW tipo I o clasica, y 43 (72 por ciento) la variedades II.Se comenta la necesidad de las determinaciones de TTPa, VIII:C, VIII R:Ag, factor de von Willebrand y agrecion plaquetaria inducida por ristocetina para su correcta caracterizacion, y tambien como prueba aislada VIII R:Ag es 100 por ciento util. Por ultimo, se hacen consideracones acerca de las variaciones moleculares que afectan al patron evolutivo de la EvW en cada paciente