HELENA PANTELIOU LIMA VALASSI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
conferenceObject ACTH but Not HDL-Cholesterol or Salivary Cortisol Was a Predictor of Adrenal Insufficiency in Patients with Septic Shock(2014) FESTTI, Josiane; GRION, Cintia M. C.; FESTTI, Luciana; MAZZUCO, Tania; VALASSI, Helena Panteliou Lima; BRITO, Vinicius N.; BARBOSA, Decio Sabbatini; CARRILHO, Alexandre Jose Faria- Post-receptor IGF1 insensitivity restricted to the MAPK pathway in a Silver-Russell syndrome patient with hypomethylation at the imprinting control region on chromosome 11(2012) MONTENEGRO, Luciana R.; LEAL, Andrea C.; COUTINHO, Debora C.; VALASSI, Helena P. L.; NISHI, Mirian Y.; PARNHOLD, Ivo J.; MENDONCA, Berenice B.; JORGE, Alexander A. L.Background: Hypomethylation of the paternal imprinting center region 1 (ICR1) is the most frequent molecular cause of Silver-Russell syndrome (SRS). Clinical evidence suggests that patients with this epimutation have mild IGF1 insensitivity. Objective: To assess in vitro IGF1 action in fibroblast culture from a patient with SRS and IGF1 insensitivity. Methods: Fibroblast cultures from one patient with SRS due to ICR1 demethylation and controls were established. The SRS patient has severe growth failure, elevated IGF1 level, and poor growth rate during human recombinant GH treatment. IGF1 action was assessed by cell proliferation, AKT, and p42/44-MAPK phosphorylation. Gene expression was determined by real-time PCR. Results: Despite normal IGF1R sequence and expression, fibroblast proliferation induced by IGF1 was 50% lower in SRS fibroblasts in comparison with controls. IGF1 and insulin promoted a p42/44-MAPK activation in SRS fibroblasts 40 and 36%, respectively, lower than that in control fibroblasts. On the other hand, p42/44-MAPK activation induced by EGF stimulation was only slightly reduced (75% in SRS fibroblasts in comparison with control), suggesting a general impairment in MAPK pathway with a greater impairment of the stimulation induced by insulin and IGF1 than by EGF. A PCR array analysis disclosed a defect in MAPK pathway characterized by an increase in DUSP4 and MEF2C gene expressions in patient fibroblasts. Conclusion: A post-receptor IGF1 insensitivity was characterized in one patient with SRS and ICR1 hypomethylation. Although based on one unique severely affected patient, these results raise an intriguing mechanism to explain the postnatal growth impairment observed in SRS patients that needs confirmation in larger cohorts.
conferenceObject Validation of Reference Range of Prolactin after Precipitation with Polyethyleneglycol (PEG) for Hyperprolactinemia Evaluation(2014) BRITO, Luciana Pinto; VALASSI, Helena Panteliou Lima; MAZI, Cassia; MENDONCA, Berenice B.; BATISTA, Marcelo Cidade- Steroid Screening Tools Differentiating Nonclassical Congenital Adrenal Hyperplasia and Polycystic Ovary Syndrome(2020) MAFFAZIOLI, Giovana D. N.; BACHEGA, Tania A. S. S.; HAYASHIDA, Sylvia A. Y.; GOMES, Larissa G.; VALASSI, Helena P. L.; MARCONDES, Jose A. M.; MENDONCA, Berenice B.; BARACAT, Edmund C.; MACIEL, Gustavo A. R.Purpose: To analyze the performance of basal 17OH-progesterone (17OHP) levels versus the basal 17OHP/cortisol ratio in nonclassical congenital adrenal hyperplasia (NCAH) and polycystic ovary syndrome (PCOS) differential diagnosis. Basal 17OHP levels >10 ng/mL have been used to confirm NCAH diagnosis without the adrenocorticotropic hormone (ACTH) test; however, the optimal cutoff value is a matter of debate. Methods: A cross-sectional study was performed at the endocrinology and gynecological endocrinology outpatient clinics of a tertiary hospital. A total of 361 patients with PCOS (age 25.0 +/- 5.3 years) and 113 (age 19.0 +/- 13.6 years) patients with NCAH were enrolled. Basal and ACTH-17OHP levels were measured by radioimmunoassay, and CYP21A2 molecular analysis was performed to confirm hormonal NCAH diagnosis. Receiver operating characteristic curve analysis compared basal 17OHP levels and the 17OHP/cortisol ratio between NCAH and PCOS patients. Results: Basal 17OHP levels were higher in NCAH patients than in those with PCOS (8.85 [4.20-17.30] vs 1.00 [0.70-1.50] ng/mL; P < 0.0001), along with 17OHP/cortisol ratio (0.86 [0.47-1.5]) vs 0.12 [0.07-0.19]; P < 0.0001, respectively). Basal 17OHP levels and the 170HP/cortisol ratio were strongly correlated in both groups (rho = 0.82; P < 0.0001). Areas under the curves for basal 17OHP levels (0.9528) and the 17OHP/cortisol ratio (0.9455) were not different to discriminate NCAH and PCOS (P > 0.05). Basal 17OHP level >5.4 ng/mL and 17OHP/cortisol ratio >2.90 had 100% specificity to identify NCAH. Main Conclusions: Basal 17OHP levels >5.4 ng/mL can be used to perform differential diagnoses between NCAH and PCOS, dismissing the ACTH test. The basal 17OHP/cortisol ratio was not superior to basal 17OHP levels in this scenario.
conferenceObject Efficacy of liquid-chromatography and radioimmunoassay in false-positives' drop-off in CAH newborn screening(2022) CARVALHO, Daniel; LIMA-VALASSI, Helena; ALVES, Atecla; MIRANDA, Mirela; RODRIGUES, Andressa; HAYASHI, Giselle; MADUREIRA, Guiomar; STEINMETZ, Leandra; DAMIANI, Durval; MENDONCA, Berenice; BACHEGA, Tania- ADRENOCORTICOTROPIC HORMONE BUT NOT HIGH-DENSITY LIPOPROTEIN CHOLESTEROL OR SALIVARY CORTISOL WAS A PREDICTOR OF ADRENAL INSUFFICIENCY IN PATIENTS WITH SEPTIC SHOCK(2014) FESTTI, Josiane; GRION, Cintia Magalhaes Carvalho; FESTTI, Luciana; MAZZUCO, Tania Longo; LIMA-VALASSI, Helena Pantelion; BRITO, Vinicius Nahime; BARBOSA, Decio Sabbatini; CARRILHO, Alexandre Jose FariaRelative adrenal insufficiency in sepsis has been extensively debated on; however, accurate diagnosis and therapeutic intervention remain controversial. The authors aimed to evaluate adrenocorticotropic hormone (ACTH), salivary cortisol, total cortisol and estimated plasma-free cortisol, cholesterol, and lipoproteins as predictors of adrenal insufficiency in patients within 24 h of septic shock diagnosis. This prospective study evaluated all hospitalized patients older than 18 years who developed septic shock and were using vasoactive drugs within 24 h of diagnosis. Blood and saliva samples were drawn at baseline and 60 min (T60) after 250 g tetracosactide intravenous injection. Patients were divided into two groups: responders ( [T60 minus baseline] total cortisol >9 g/dL) and nonresponders ( total cortisol 9 g/dL or baseline total cortisol <10 g/dL). The latter group was considered to have adrenal insufficiency. A total of 7,324 hospitalized patients were monitored, and 34 subjects with septic shock were included in the analysis. Adrenal insufficiency was found in 32.4%. Total cholesterol, high-density lipoprotein cholesterol, triglycerides, and salivary cortisol did not differ between groups. Estimated plasma-free cortisol was not better than total plasma cortisol in estimating adrenal function. Baseline endogenous ACTH was higher in nonresponders than responders (55.5 pg/mL vs. 18.3 pg/mL, respectively; P = 0.01). The cutoff ACTH value that discriminated patients with adrenal insufficiency was 31.5 pg/mL. Thus, endogenous ACTH measured within 24 h of septic shock diagnosis could predict adrenal response to tetracosactide.
- Analysis of an iodide radioimmunoassay for 11-deoxicortisol measurement(2014) MADEIRA, Joao Luiz de Oliveira; BUSSMANN, Luciane Zgoda; LIMA-VALASSI, Helena Panteliou; MENDONCA, Berenice Bilharinho deObjective: Our aim was to correlate 11-deoxycortisol levels obtained by two currently available techniques for 11-deoxycortisol measurement: radioimmunoassay, and high performance liquid chromatography followed by tandem mass spectrometry (MS/MS). The latter is the gold standard method for steroid hormone measurement. Materials and methods: We selected 88 samples and the results of these two methods were compared by Deming regression. Results: The analytical sensitivity of the RIA was 0.30 ng/mL, with inadequate linearity and inadequate precision profile (34% of the samples had a CV >= 20%). From the selected samples, 54 had measurable levels of 11-deoxycortisol in both methods and were used in the comparison. The comparison of RIA with LC-MS/MS showed an overestimation of the results by RIA. The correlation coefficient was 0.610; linear regression slope was 3.751; and the intercept was 0.145, indicating a poor correlation between the two methods. Conclusion: We concluded that 11-deoxycortisol measured by radioimmunoassay, despite a good analytical sensitivity, showed very low specificity, precluding its use as a reliable method for 11-deoxycortisol measurement.
conferenceObject Simple method for Mitotane determination in plasma samples by LC-DAD(2023) MARQUES, Anna Sylvia Ferreira; ALVES, Atecla Nunciata Lopes; MENDONCA, Berenice Bilharinho; LIMA-VALASSI, Helena Pantelilou- Role of the Mevalonate Pathway in Adrenocortical Tumorigenesis(2021) LIMA-VALASSI, Helena Panteliou; LERARIO, Antonio Marcondes; MONTENEGRO, Luciana Ribeiro; FRAGOSO, Maria Candida Barisson Villares; ALMEIDA, Madson Queiroz; MENDONCA, Berenice Bilharinho; LIN, Chin Jia3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is the rate-limiting enzyme of the mevalonate pathway, which generates cholesterol and non-sterol compounds such as isoprenoid, which are involved in key steps of tumorigenesis such as cell growth and proliferation. Our aim was to evaluate the role of the mevalonate pathway in adrenocortical tumors (ACTs). Expression pattern of HMGCR , FDFT1 , LDLR , SCARB1 , StAR , TSPO , CYP11A1 , CYP11B1 , CYP17A1 , CYP21A1 , and HSD3B1 genes , involved in the mevalonate pathway and steroidogenesis, was quantified by real-time RT-PCR in 46 ACT [14 adenomas (ACA) and 11 carcinomas (ACC) from adults and 13 ACA and 8 ACC from pediatric patients]. Effects of the mevalonate pathway inhibition on NCI-H295A cell viability was assessed by colorimetric assay. HMGCR was overexpressed in most adult ACT. The expression of TSPO , STAR , CYP11B1 , CYP21A1 , and HSD3B1 in adult ACC was significantly lower than in ACA (p<0.05). Regarding pediatric ACT, the expression of genes involved in steroidogenesis was not different between ACA and ACC. Inhibition of isoprenoid production significantly decreased the viability of NCI-H295A cells (p<0.05). However, cholesterol synthesis blockage did not show the same effect on cell viability. Low expression of TSPO,StAR , CYP11B1 , CYP21A1 , and HSD3B1 characterized a signature of adult ACCs. Our data suggest that HMGCR overexpression in adult ACC might lead to intracellular isoprenoid accumulation and cell proliferation. Therefore, the mevalonate pathway is a potential target for ACC treatment.
- Validation of an immunoassay for anti-Mullerian hormone measurements and reference intervals in healthy Brazilian subjects(2015) WOLOSZYNEK, Renata Reis; BRITO, Luciana Pinto; BATISTA, Marcelo Cidade; VALASSI, Helena Panteliou Lima; MENDONCA, Berenice Bilharinho; BRITO, Vinicius NahimeBackground Anti-Mullerian hormone is marker of ovarian and testicular reserve. The clinical use of this hormone requires proper standardization of reference intervals. The aims of this study were to validate the Anti-Mullerian hormone Gen II immunoassay, to establish Anti-Mullerian hormone reference intervals in healthy subjects, and to evaluate the influence of hormonal contraceptives, smoking, and body mass index on Anti-Mullerian hormone. Methods The validation of the Anti-Mullerian hormone Gen II assay (Beckman Coulter Company, TX, USA) was performed using a simplified protocol recommended by Clinical Laboratory Standard Institute. One-hundred and thirty-three healthy females and 120 males were prospectively selected for this study. Results The analytical and functional sensitivities of the Anti-Mullerian hormone Gen II immunoassay were 0.02 and 0.2ng/mL, respectively. Intra-assay coefficients ranged from 5.2 to 9.0%, whereas inter-assay precision ranged from 4.6 to 7.8% at different concentrations. In females, Anti-Mullerian hormone showed progressive decline with increasing age (r=-0.4, p<0.001), whereas in males, age showed no influence on Anti-Mullerian hormone concentrations. In females, Anti-Mullerian hormone concentrations did not differ between users and non-users of hormonal contraceptives, smokers, and non-smokers and obese and lean individuals. However, there was a negative and significant correlation between Anti-Mullerian hormone and body mass index in males (r=-0.3, p=0.008). Conclusions Anti-Mullerian hormone Gen II assay was reliable for determining serum Anti-Mullerian hormone concentrations. Anti-Mullerian hormone concentrations declined with aging and presented a wide inter-individual variability. The lack of influence of hormonal contraceptives, smoking, and obesity on Anti-Mullerian hormone in both sexes allowed us to refine the normative concentrations for the Brazilian population.