Reference intervals of thyroid hormones during pregnancy in Korea, an iodine-replete area

BACKGROUND/AIMS: Maternal thyroid dysfunction has been associated with adverse pregnancy outcomes. The purpose of our study was to establish trimester-specific reference intervals for thyroid hormones in pregnant women in Korea, where iodine intake is more than adequate and to examine pregnancy and perinatal outcomes in their offspring. METHODS: Among 459 healthy pregnant women who were screened, we enrolled 417 subjects who had negative results for thyroid autoantibodies. Serum thyroid stimulating hormone (TSH) and free thyroxine were measured using an immunoradiometric assay. Urine iodine concentration was measured using inductively coupled plasma-mass spectrometry in 275 women. Reference ranges of thyroid hormones were determined according to the guidelines of the National Academy of Clinical Biochemistry. Pregnancy and perinatal outcomes were compared according to maternal thyroid function. RESULTS: The reference ranges of serum TSH were 0.03 to 4.24 mIU/L in the first trimester, 0.13 to 4.84 mIU/L in the second trimester, and 0.30 to 5.57 mIU/L in the third trimester. Pregnancy and perinatal outcomes did not vary in mothers with subtle changes in thyroid function. CONCLUSIONS: Trimester-specific thyroid hormone reference intervals in Korean pregnant women differ from those of other countries with different iodine nutrition status and ethnicity. The establishment of population-based, reliable trimester-specific reference intervals is critical for the interpretation of thyroid function in pregnant women to avoid unnecessary tests and treatments.

Survey Result of the Counting Efficiency of Gamma Counter by Certified Reference Materials / 대한핵의학회잡지

PURPOSE: In radioimmunoassay (RIA), the gamma counter is the important instrument for the accurate measurement. To manage quality assurance of RIA, the counting efficiency of gamma counter is one of the important parameters. The aimof this study was to evaluate the counting efficiency of gamma counters in multiple institutes on the base of traceability by using the certified reference materials (CRMs).METHODS: Twenty-three institutes that perform RIA were enrolled in this study. I-125 CRMs that were certified by National Institute of Standards and Technology (NIST) were used. Each institute was asked to count the activity of I-125 CRMs at most twice on all gamma counters in use. The counting efficiency of each well of counter was calculated on the base of NIST-certified information, corrected for I-125 decay for date of testing.RESULTS: From 23 institutes, 44 gamma counters were evaluated. The average counting efficiency of all wells was 85.9% and the standard deviation was 13.5%. As a mean value of each gamma counter, three gamma counters showed poor counting efficiency (less than 70%). The poorest counting efficiency was 7%. The counting efficiency of seven gamma counters was between 70 and 75%. Eight counters had the counting efficiency between 75 and 90%. More than half of counter (26 gamma counters) showed excellent counting efficiency (more than 90%). The standard deviation variation range of inter-well efficiency was from 0 to 11.2.CONCLUSION: The first survey on the counting efficiency of gamma counter was performed in South Korea. Most of the RIA laboratories have well managed the quality assurance of gamma counter.

Prevalence and Relationships of Iron Deficiency Anemia with Blood Cadmium and Vitamin D Levels in Korean Women

Anemia, iron deficiency (ID), and iron deficiency anemia (IDA) are common disorders. This study was undertaken to determine the prevalence of anemia, ID, and IDA in Korean females. We examined the associations between IDA, heavy metals in blood, vitamin D level and nutritional intakes. The study was performed using on data collected from 10,169 women (aged > or =10 yr), including 1,232 with anemia, 2,030 with ID, and 690 with IDA during the fifth Korea National Health and Nutrition Examination Survey (KNHANES V; 2010-2012). Prevalence and 95% confidence intervals were calculated, and path analysis was performed to identify a multivariate regression model incorporating IDA, heavy metals in blood, vitamin D level, and nutritional intakes. The overall prevalence of anemia, ID and IDA was 12.4%, 23.11%, and 7.7%, respectively. ID and IDA were more prevalent among adolescents (aged 15-18 yr; 36.5% for ID; 10.7% for IDA) and women aged 19-49 yr (32.7% for ID; 11.3% for IDA). The proposed path model showed that IDA was associated with an elevated cadmium level after adjusting for age and body mass index (beta=0.46, P<0.001). Vitamin D levels were found to affect IDA negatively (beta=-0.002, P<0.001). This study shows that the prevalence of anemia, ID, and IDA are relatively high in late adolescents and women of reproductive age. Path analysis showed that depressed vitamin D levels increase the risk of IDA, and that IDA increases cadmium concentrations in blood. Our findings indicate that systematic health surveillance systems including educational campaigns and well-balanced nutrition are needed to control anemia, ID, and IDA.

Performance Evaluation of the Serum Thyroglobulin Assays With Immunochemiluminometric Assay and Immunoradiometric Assay for Differentiated Thyroid Cancer

BACKGROUND: Measurement of postoperative serum thyroglobulin (Tg) is important for detecting persistent or recurrent differentiated thyroid cancer. We evaluated the analytic performance of the DxI 800 assay (Beckman Coulter, USA) for serum Tg and anti-thyroglobulin antibodies (TgAbs) in comparison with that of the GAMMA-10 assay (Shinjin Medics Inc., Korea) for serum Tg and RIA-MAT 280 assay (Stratec, Germany) for TgAb. METHODS: We prospectively collected blood samples from 99 patients thyroidectomized for thyroid cancer. The functional sensitivity was investigated in standards and human serum. Precision and linearity were evaluated according to the guidelines of the Clinical and Laboratory Standards Institute. The correlation between the two assays was assessed in samples with different Tg ranges. RESULTS: The functional sensitivity of the DxI 800 assay for serum Tg was between 0.0313 and 0.0625 ng/mL. The total CV was 3.9-5.6% for serum Tg and 5.3-6.9% for serum TgAb. The coefficient of determination (R2) was 1.0 and 0.99 for serum Tg and TgAb, respectively. The cut-offs for serum TgAb were 4.0 IU/mL (DxI 800) and 60.0 IU/mL (RIA-MAT 280), and the overall agreement was 68.7%. The correlation between the two assays was excellent; the correlation coefficient was 0.99 and 0.88 for serum Tg and TgAb, respectively. CONCLUSIONS: The DxI 800 is a sensitive assay for serum Tg and TgAb, and the results correlated well with those from the immunoradiometric assays (IRMA). This assay has several advantages over the IRMA and could be considered an alternative test for Tg measurement.

Hepatitis B Surface Antigen Quantification across Different Phases of Chronic Hepatitis B Virus Infection Using an Immunoradiometric Assay

BACKGROUND/AIMS: Quantification of hepatitis B surface antigen (HBsAg) is an emerging serologic test and may be useful for identifying treatment strategies for chronic hepatitis B (CHB). This study aimed to evaluate HBsAg titers during the natural course of CHB and identify correlations between HBsAg titers and hepatitis B virus (HBV) DNA concentrations across different CHB phases measured using an immunoradiometric assay (IRMA). METHODS: CHB phases were defined on the basis of HBV DNA concentrations, the presence of hepatitis B e antigen/antibody (HBeAg/Ab) and serum alanine aminotransferase levels. Serum HBsAg titers and paired HBV DNA concentrations in the different phases of CHB were compared using 627 serum samples. RESULTS: Mean HBsAg titers were significantly higher in the immunotolerant (IT) phase and immunoreactive (IR) HBeAg-positive phase than in the low-replicative (LR) and HBeAg-negative CHB (ENH) states. The correlation between HBsAg titers and HBV DNA concentrations was modest in the IT (n=36, r=0.804, p<0.001) and IR (n=48, r=0.773, p<0.001) phases, and it was poor in the LR state (n=116, r=0.289, p=0.002); however, no significant correlation was observed in the ENH state (n=67, r=0.146, p=0.237) or in the oral nucleos(t)ide analogue-treated group (n=267). CONCLUSIONS: HBsAg quantification using IRMA might be useful for discriminating different CHB phases and different stages of chronic liver disease.

Usefulness of Serum IGF-I and IGFBP-3 Levels in Children with Short Stature / 임상검사와정도관리

BACKGROUND: Serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels are known markers of growth hormone (GH) secretion. The clinical utility of serum IGF-I and IGFBP-3 testing, however, remains controversial. The aims of this study were to evaluate the usefulness of IGF-I and IGFBP-3 as indicators of GH secretion through the GH stimulation test and to investigate whether a decrease in serum IGF-I levels in children with short stature, regardless of the cause, can be used as a screening test for short stature. METHODS: A total of 262 children presented with short stature, precocious puberty, or premature thelarche and were grouped into 7 tiers based on the 2007 growth chart. Serum IGF-I and IGFBP-3 levels and GH stimulation were analyzed using an immunoradiometric assay, and the data from 68 children who were below the 3rd percentile for height were used to evaluate the usefulness of IGF-I and IGFBP-3 as markers of GH status. RESULTS: GH deficiency was confirmed by the GH stimulation test in 25 of the 68 children, and 15 (15/25, 60%) and 4 (4/25, 16%) of them showed a decrease in IGF-I and IGFBP-3 levels, respectively. The sensitivity and specificity for predicting GH secretion were 60% and 16%, respectively, for IGF-1 and 41.9% and 97.7%, respectively, for IGFBP-3. Decreased serum IGF-I levels were more frequently observed in children below the 25th percentile than in those in the 25th to 95th percentiles. CONCLUSIONS: IGF-I and IGFBP-3 levels have been used as a screening tool for GH secretion in children with short stature, but based on the results of the GH stimulation test in the current study, the levels of IGF-I and IGFBP-3 might not be useful as markers of GH secretion. Evaluating serum IGF-I levels alone is not a sufficient screening test for children with a short stature.

Valores de referência para níveis séricos do fator de crescimento semelhante à insulina tipo I (IGF-I) numa população adulta do Estado do Rio de Janeiro, Brasil / Reference ranges for serum levels of insulin-like growth Factor I (IGF-I) in an adult population of Rio de Janeiro State, Brazil

O nível sérico do Fator de crescimento semelhante à insulina tipo I (IGF-I) é fundamental para auxiliar no dignóstico e controle terapêutico dos transtornos relacionados à secreção do Hormônio de Crescimento (GH), bem como no diagnóstico e seguimento de outras doenças. Estabelecer valores de referência para as dosagens séricas de IGF-I por um ensaio imunoquimioluminométrico (ICMA), utilizando o sistema automatizado Immulite 2000/Diagnostic Products Corporation (DPC), e por um ensaio imunoradiométrico (IRMA), utilizando o kit comercial ACTIVE IGF-I/Diagnostic System Laboratories (DSL)-5600, numa população brasileira adulta da cidade do Rio de Janeiro. Este estudo, aprovado pelo Comitê de Ética do Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, Brasil, incluiu amostras de 484 indivíduos saudáveis (251 homens e 233 mulheres) com idades entre 18 e 70 anos. As amostras foram estudadas por ICMA- Immulite 2000/DPC and IRMA- ACTIVE IGF-I/DSL-5600. Para análise dos dados foram utilizados modelos específicos para idade e sexo, após transformação dos dados de IGF-I. Foi observada uma lenta diminuição dos níveis de IGF-I com a idade usando ambos os ensaios. Os níveis de IGF-I foram signicativamente (p=0,0181) mais elevados em mulheres do que em homens, quando as amostras foram analisadas usando ICMA. Não houve diferença significativa dos níveis de IGF-I entre homens e mulheres quando as amostras foram analisadas usando IRMA. Este estudo estabeleceu valores de referência de IGF-I específicos para idade e sexo, determinados com o sistema automatizado ICMA-Immulite 2000/DPC, e valores de referência de IGF-I específicos para idade, determinados com o kit comercial IRMA- ACTIVE IGF-I/DSL-5600, em uma população adulta brasileira, da cidade do Rio de Janeiro

Serum level of insulin-like growth factor I (IGF-I) is fundamental in order to aid in the diagnosis and follow-up of growth hormone (GH)-related disorders, as well as in the diagnosis and follow-up of other diseases. The aim of this investigation was to determine reference values for IGF-I using an automated immunochemiluminometric assay (ICMA) system Immulite 2000/Diagnostic Products Corporation (DPC); and an immunoradiometric assay (IRMA), using the commercial kit ACTIVE IGF-I/Diagnostic System Laboratories (DSL)-5600, in an adult Brazilian population of Rio de Janeiro city. The study, approved by the Ethical Committee of the Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, Brazil, included samples of blood taken from 484 healthy subjects (251men, 233 women) aged from 18 up to 70. The samples were analyzed by ICMA- Immulite 2000/DPC and IRMA- ACTIVE IGF-I/DSL-5600. For statistical analysis, age and sex-specific models were fitted after transformation of IGF-I values. In adulthood, a slow age-dependent decrease was found, using both assays. IGF-I in women were significantly (p=0,0181) higher than in men when samples were analayzed using ICMA.There was no significant difference between men and women IGF-I values when samples were analayzed using IRMA. The present study established age- and sex specific IGF-I reference values, determined with the automated system: ICMA-Immulite 2000/DPC and age-specific IGF-I reference values determined with the IRMA- ACTIVE IGF-I/DSL-5600, in an adult Brazilian population of Rio de Janeiro city

Efficacy of a Single Luteinizing Hormone Measurement after GnRH Agonist Administration for Therapeutic Monitoring of Girls with Central Precocious Puberty

PURPOSE: The effectiveness of gonadotropin releasing hormone (GnRH) agonist therapy in central precocious puberty (CPP) depends on the suppression of luteinizing hormone (LH) secretion. The purpose of this study was to determine the utility of a single luteinizing hormone measurement after GnRH agonist injection for the therapeutic monitoring of CPP. METHODS: The study included 148 females with CPP who had been treated with GnRH agonist. During the therapy, suppression of their pubertal development was assessed based on their height standard deviation score (SDS), bone age, and pubertal stage. Every six months, their serum LH and follicular stimulating hormone (FSH) levels were measured using immunoradiometric assays. Their estradiol levels were also assayed using radioimmunoassay two hours following GnRH agonist administration. RESULTS: The means of the onset age, bone age, and chronological age were 7.2 +/- 0.93, 10.1 +/- 1.1, and 8.2 +/- 0.94 years, respectively. Eight patients had pathologic intracranial lesions including harmatoma, hydrocephalus, meningitis, astrocytoma, and Rathke's cleft cyst. The basal and peak LH levels were 1.56 +/- 1.1 and 18.2 +/- 12.1 IU/L, respectively. In 39 females with CPP, pubertal development was not sufficiently suppressed even after one year of therapy. The receiver operating characteristic (ROC) curve showed a cutoff value of LH for pubertal suppression of less than 2.5 IU/L. The area under the curve (AUC) was 0.674. CONCLUSION: The cutoff value of 2.5 IU/L for a LH measurement, taken two hours following subcutaneous GnRH agonist injection, is adequate for therapeutic monitoring of females with CPP. This method is both convenient and cost effective.

Efficacy of a Single Luteinizing Hormone Measurement after GnRH Agonist Administration for Therapeutic Monitoring of Girls with Central Precocious Puberty

PURPOSE: The effectiveness of gonadotropin releasing hormone (GnRH) agonist therapy in central precocious puberty (CPP) depends on the suppression of luteinizing hormone (LH) secretion. The purpose of this study was to determine the utility of a single luteinizing hormone measurement after GnRH agonist injection for the therapeutic monitoring of CPP. METHODS: The study included 148 females with CPP who had been treated with GnRH agonist. During the therapy, suppression of their pubertal development was assessed based on their height standard deviation score (SDS), bone age, and pubertal stage. Every six months, their serum LH and follicular stimulating hormone (FSH) levels were measured using immunoradiometric assays. Their estradiol levels were also assayed using radioimmunoassay two hours following GnRH agonist administration. RESULTS: The means of the onset age, bone age, and chronological age were 7.2 +/- 0.93, 10.1 +/- 1.1, and 8.2 +/- 0.94 years, respectively. Eight patients had pathologic intracranial lesions including harmatoma, hydrocephalus, meningitis, astrocytoma, and Rathke's cleft cyst. The basal and peak LH levels were 1.56 +/- 1.1 and 18.2 +/- 12.1 IU/L, respectively. In 39 females with CPP, pubertal development was not sufficiently suppressed even after one year of therapy. The receiver operating characteristic (ROC) curve showed a cutoff value of LH for pubertal suppression of less than 2.5 IU/L. The area under the curve (AUC) was 0.674. CONCLUSION: The cutoff value of 2.5 IU/L for a LH measurement, taken two hours following subcutaneous GnRH agonist injection, is adequate for therapeutic monitoring of females with CPP. This method is both convenient and cost effective.

Regulation of IGF System in Rats after Experimental Myocardial Infarction / 체질인류학회지

Insulin-like growth factor system (IGF system) has been reported to be associated with the variety of disorders of myocardial function. However, the effect of myocardial infarction (MI) on the IGF system has not been fully described. Thus, the present study was to investigate in more detail the changes of IGF system in the male rat following myocardial infarction (MI). Ligation of the left coronary artery was performed in male Sprague-Dawley male rats at 60 days of age. Control rats were obtained sham-operated animals. MI rats were sacrificed at 1, 3, 7, 14, and 30 day after ligation of left anterior descending coronary artery. Control rats were sacrificed on 30 day after thoracotomy. Myocardial infarct size was assessed by planimetry and perimetry. Serum and heart concentrations of IGF-I and -II were determined by radioimmunoassay. Serum levels of IGF-binding protein (IGFBP)-1 and IGFBP-3 were analyzed with a two-site immunoradiometric assay. Mean infarct size was 35.2~42.3% of the left ventricle after coronary occlusion in experimental groups. Serum levels of IGF-I were markedly reduced, but the levels of IGF-II were not altered in MI rats compared with shamligated controls. Serum IGFBP-I levels in MI rats were significantly increased at 1 and 3 day compared with sham rats. The levels of serum IGFBP-3 were significantly higher in the ligated rats. IGF-I levels of the infarct/periinfarct area of the left ventricle were significantly decreased in rats with myocardial infarction, whereas the levels of IGF-II remained unchanged. These results demonstrate that the IGF system is altered in the myocardial infarction and suggest that the IGF system plays an important role in the response of the heart to myocardial infarction.

Influence of Gender on Serum Growth Hormone, Insulin-Like Growth Factor-I and Its Binding Protein-3 during Aging

PURPOSE: The serum concentrations of insulin-like growth factors-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and growth hormone (GH) are related to body composition, function and metabolism, and are influenced by the aging process. This study was to investigate the influence of gender on serum concentrations of IGF-I, IGFBP-3 and GH in middle and old age subjects. MATERIALS AND METHODS: Sixty healthy volunteers (male 35, female 25, 36-70 years) were divided into 50 years groups, based on gender. Women > 50 years were post-menopause. IGF-I, IGFBP-3, and GH were determined by immunoradiometric assay. RESULTS: IGF-I was shown to be negatively correlated with age (women r = -0.62, p 50 years showed a significant reduction in IGF-I values than women 50 years showed smaller IGF-I/IGFBP-3 molar ratios (0.177998 +/- 0.039404) than men of same age group (0.228326 +/- 0.050979, p < 0.01) and women < or = 50 years (0.247667 +/- 0.069411, p < 0.01). Age was shown to positively correlate with GH/IGF-I (r = 0.49, p < 0.05) and GH/IGFBP-3 ratios (r = 0.40, p < 0.05) in women. CONCLUSIONS: The influence of aging on serum concentrations of IGF-I is more remarkable in women than in men. Menopause causes reduction of IGF-I/IGFBP-3 molar ratio. Women have the trend of progressive hypoactivity of GH to stimulate IGF-I and IGFBP-3 secretions with age.

Correlation between the cord blood concentarion of leptin and maternal, placental, fetal factors in uncomplicated singleton pregnancy / 대한산부인과학회지

OBJECTIVE: Umbilical leptin concentrations have been associated with whole-body mineral content, fetal bone growth stimulation, pulmonary development in utero, nutritional intake, energy metabolism, and adiposity in children and adults. In this study, we investigated the effect of maternal factor, placental factor and fetal factor on cord blood leptin concentrations. METHODS: We measured leptin concentration in umbilical cord blood using immunoradiometric assay in 50 women with uncomplicated singleton term pregnancies. we analyzed the correlation of leptin level with maternal age, sex, gestational age, smoking, placental weight, neonatal body mass index, maternal body mass index, head circumference, and chest circumference by simple linear regression. RESULTS: There were significant correlation between leptin and gestational age, fetal BMI, head circumference, and chest circumference with correlation coefficient 0.244 (P=0.010), 0.182 (P=0.030), 0.243 (P=0.011), and 0.228 (P=0.014), respectively in the male neonates. There were significant correlation between leptin and fetal BMI with correlation coefficient 0.341 (P=0.003) in the female neonates. No statistically significant correlation between the concentration of leptin and neonatal gender was observed, in spite of higher mean value of female leptin concentration level. Also no statistically significant correlation between the concentration of leptin and smoking and drinking of mother was observed. CONCLUSION: In this study, leptin is significantly correlated with maternal age, maternal BMI, gestational age, fetal BMI, and chest circumference. It was suggested that leptin level was more associated with maternal factor and fetal factor than placental factor.

Study on the diagnostic utility of serum levels of insulin-like growth Factor-I and insulin-like growth factor binding protein-3 in growth hormone deficiency / 소아과

PURPOSE: This study aimed to determine the best cutoff line for insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 to discriminate between growth hormone deficiency (GHD) patients and the control group. METHODS: Two hundred thirty subjects with normal controls (129 boys and 101 girls, aged 7-15 years), 14 patients with complete GHD (12 boys and 2 girls), and 17 patients with partial GHD (9 boys and 8 girls) were studied. IGF-I serum concentrations were measured by radioimmunoassay (RI), and IGFBP-3 concentrations were measured by immunoradiometric assay (IRMA). RESULTS: The receiver operating characteristic (ROC) plot analysis showed that the best IGF-I and IGFBP-3 cutoff line was at -1 standard deviation (SD). By comparing IGF-I serum levels of GHD children within 1 SD of normal control, we determined the sensitivity (S) (87.5-100%) and specificity (Sp) (80-84.6%) according to the age group. For IGFBP-3 , we determined the following values: S (58.7-85.7%) and Sp (79.2-85.5%). Eleven of 1 4 patients with complete GHD (78.5%) and 16 of 17 patients with partial GHD (94.1%) had IGF-I concentrations equal to or below -1 SD of the control group mean. Ten of 12 complete GHD children (83.3%) and 13 of 17 partial GHD children (76.5%) had IGFBP-3 concentrations equal or below -1 SD of the control group mean. CONCLUSION: We conclude that the measurement of IGF-I and IGFBP-3 concentrations might provide essential supplementary data in the diagnostic evaluation of patients with GHD. Our results support the need to use cutoff lines based on below -1 SD of the control.

The effect of sun exposure on 25-hydroxyvitamin D concentrations in young healthy subjects living in the city of São Paulo, Brazil

The range of 25-hydroxyvitamin D (25OHD) concentration was determined in a young healthy population based on bone metabolism parameters and environmental and behavioral aspects. We studied 121 healthy young volunteers (49 men, 72 women) living in São Paulo (23º 34' south latitude) belonging to three occupational categories: indoor workers (N = 28), medical school students (N = 44), and resident physicians (N = 49). Fasting morning blood samples were collected once from each volunteer from August 2002 to February 2004, and 25OHD, total calcium, albumin, alkaline phosphatase, phosphorus, creatinine, intact parathyroid hormone, osteocalcin, and type I collagen carboxyterminal telopeptide were measured. Data are reported as means ± SD. Mean subject age was 24.7 ± 2.68 years and mean 25OHD level for the entire group was 78.7 ± 33.1 nM. 25OHD levels were lower (P < 0.05) among resident physicians (67.1 ± 27.0 nM) than among students (81.5 ± 35.8 nM) and workers (94.0 ± 32.6 nM), with the last two categories displaying no difference. Parathyroid hormone was higher (P < 0.05) and osteocalcin was lower (P < 0.05) among resident physicians compared to non-physicians. Solar exposure and frequency of beach outings showed a positive association with 25OHD (P < 0.001), and summer samples presented higher results than winter ones (97.8 ± 33.5 and 62.9 ± 23.5 nM, respectively). To define normal levels, parameters such as occupational activity, seasonality and habits related to solar exposure should be taken into account. Based on these data, we considered concentrations above 74.5 nM to be desired optimal 25OHD levels, which were obtained during the summer for 75 percent of the non-physicians.

Seguimento de pacientes de alto risco com carcinoma diferenciado de tireóide sem doença persistente após a terapia inicial / Follow-up of high-risk patients with differentiated thyroid cancer without persistent disease after initial therapy / Follow-up of high-risk patients with differentiated thyroid cancer without persistent disease after initial therapy

Este estudo avaliou o seguimento de pacientes com câncer de tireóide de alto risco, após a terapia inicial. Foram selecionados 125 pacientes de alto risco (tumor >4 cm e/ou invasão extra-tireoidiana e/ou metástases linfonodais e idade >45 anos), com ressecção tumoral completa. Todos foram tratados com tireoidectomia total e ablação com 131I [3,7­5,5 GBq (100­150 mCi)] e foram excluídos 18 casos (14,8 por cento) com metástases na PCI pós-dose (t-PCI). O valor preditivo negativo da Tg estimulada <1 ng/ml combinada ao US cervical na primeira avaliação (6­12 meses após a terapia ablativa) foi de 96,2 por cento para ausência de recidivas em até 5 anos. Este valor aumentou para 98,7 por cento quando acrescentamos a PCI com 185 MBq (5 mCi) 131I (d-PCI). O valor preditivo positivo (VPP) da Tg estimulada >1 ng/ml foi de 52 por cento para presença de metástases detectadas até 5 anos depois, mas considerando apenas pacientes que apresentaram d-PCI e US negativos inicialmente, o VPP foi 19 por cento (9 por cento se Tg 1­10 ng/ml vs. 40 por cento se Tg >10 ng/ml). Tg reduziu espontaneamente nos pacientes com Tg estimulada >1 ng/ml na primeira avaliação, US e d-PCI negativos e sem recidiva no seguimento, sendo indetectável em metade destes ao final de 5 anos. No primeiro ano após a terapia ablativa, 20 pacientes tiveram captação em leito tireoidiano na d-PCI com Tg estimulada e US negativos e não foram tratados com 131I; estes evoluíram sem recidiva e 60 por cento apresentavam uma d-PCI sem nenhuma captação após 5 anos. Em pacientes sem doença aparente (no US e d-PCI) e Tg estimulada <1 ng/ml, a recidiva em 5 anos foi de apenas 1,3 por cento. Um algoritmo para o seguimento de pacientes de alto risco após a terapia inicial é apresentado por este estudo.

This study evaluated the follow-up of high-risk patients with thyroid cancer after initial therapy. A total of 125 high-risk patients (tumor >4 cm and/or extrathyroid invasion and/or lymph node metastases, and age >45 years), with complete resection of the tumor, were selected. All patients underwent total thyroidectomy and ablation with 131I [3.7­5.5 GBq (100-150 mCi)]. Eighteen patients (14.8 percent) presenting metastases on post-dose whole-body scan (RxWBS) were excluded. The negative predictive value of stimulated Tg <1 ng/ml in combination with neck US during first assessment (6­12 mo. after ablative therapy) was 96.2 percent for the absence of recurrence up to 5 years. This value increased to 98.7 percent when adding WBS performed with 185 MBq (5 mCi) 131I (DxWBS). The positive predictive value (PPV) of stimulated Tg >1 ng/ml was 52 percent for the detection of the presence of metastases up to 5 years; however, considering only patients with initially negative DxWBS and US, the PPV was 19 percent (9 percent if Tg of 1­10 ng/ml vs. 40 percent if Tg >10 ng/ml). Tg levels decreased spontaneously in patients with stimulated Tg >1 ng/ml during first assessment, negative US and DxWBS, and no recurrence during follow-up, with Tg being undetectable in half these patients at the end of 5 years. Twenty patients presented uptake in the thyroid bed upon DxWBS during the first year after ablative therapy, with stimulated Tg and US being negative, and were not treated with 131I; these patients did not relapse and no uptake on DxWBS was observed in 60 percent after 5 years. Recurrence after 5 years was only 1.3 percent in patients without apparent disease (negative US and DxWBS) and stimulated Tg <1 ng/ml. An algorithm for the follow-up of high-risk patients after initial therapy is presented in this study.

Avaliação plasmática de igf-1 no prolactinoma / IGF-1 plasma levels evaluation in prolactinoma

Prolactinomas são os tumores hipofisários mais comuns, podendo co-secretar GH (hormônio do crescimento). IGF-1 (fator de crescimento insulina-símile-1) é o principal responsável pelas ações do GH e parâmetro diagnóstico de acromegalia. Objetivando determinar por uma dosagem de IGF-1, na avaliação inicial de pacientes com prolactinoma, ocorrência de tumores mistos [GH e prolactina (PRL)], estudamos 7 homens e 27 mulheres, entre 19 e 72 anos, confrontando-os aos resultados de GH basal e durante teste oral de tolerância à glicose, quando GH basal >0,4 ng/mL ou níveis de IGF-1 alterados. A proporção de pacientes com GH >0,4 ng/mL e IGF-1 elevada foi alta; mas, após administração de 75g de glicose por via oral, nenhum paciente foi diagnosticado como acromegálico. Sugerimos, porém que a dosagem de IGF-1 seja realizada pelo risco de co-secreção de GH nos prolactinomas. Atenção especial para pacientes que apresentem significativa diminuição dos níveis de PRL, sem correspondente regressão do tamanho do adenoma.

Prolactinomas are the most frequent pituitary tumors and may co-secrete GH (growth hormone). IGF-1 (insulin-like growth factor-1) is the main responsible for GH actions and a parameter for the diagnosis of acromegaly. With the objective of identifying through a IGF-1 levels analysis, in the initial evaluation of prolactinoma patients, the existence of mixed tumors [GH and prolactin (PRL)], we studied 7 men and 27 women, aged between 19 and 72 years, confronting them with the results of basal and glucose stimulated (glucose tolerance test - GTT) GH levels, indicated when GH >0.4 ng/mL or IGF-1 levels were elevated. The prevalence of patients with GH >0.4 ng/mL and elevated IGF-1 was higher than expected; however, after GTT, no patient fulfilled the diagnostic criteria for acromegaly. However, we suggest that, they should be submitted to IGF-1 evaluation, due to the risk of GH co-secretion in prolactinomas. Special attention should be paid to those who present a significant decrease of PRL levels without concomitant tumor size reduction.

Positive correlation between serum and peritoneal fluid CA-125 levels in women with pelvic endometriosis / Correlação positiva entre os níveis séricos e no fluido peritonial de CA-125 em mulheres com endometriose pélvica

CONTEXT AND OBJECTIVE: One of the diagnostic markers of endometriosis is CA-125, and elevated levels of this are caused by high concentrations in the ectopic endometrium. The objective of this study was to correlate CA-125 levels in serum and peritoneal fluid from women with and without pelvic endometriosis. DESIGN AND SETTING: This was a prospective, cross-sectional, controlled study of consecutive pa-tients undergoing laparoscopy for infertility, pelvic pain or tubal ligation, during early follicular phase, at the university hospital of Faculdade de Medicina de Ribeirão Preto. METHODS: Fifty-two patients were divided into two groups: endometriosis group, consisting of 35 patients with biopsy-confirmed pelvic endometriosis, and control group, consisting of 17 patients without endometriosis. CA-125 levels in serum samples and peritoneal fluid were determined by chemiluminescence. RESULTS: CA-125 levels in serum and peritoneal fluid were higher in patients with advanced pelvic endometriosis (means of 39.1 ± 45.8 U/ml versus 10.5 ± 5.9 U/ml in serum, p < 0.005; 1,469.4 ± 1,350.4 U/ml versus 888.7 ± 784.3 U/ml in peritoneal fluid, p < 0.05), and showed a positive correlation between each other (correlation coefficient (r) = 0.4880). Women with more advanced degrees of endometriosis showed higher CA-125 levels in both serum and peritoneal fluid (p = 0.0001). CONCLUSION: There is a positive correlation between serum and peritoneal fluid values of CA-125 in women with and without endometriosis, and their levels are higher in peritoneal fluid. Advanced endometriosis is related to higher levels in both serum and peritoneal fluid.

CONTEXTO E OBJETIVO: Um dos marcadores diagnósticos de endometriose é o CA-125, e seus níveis elevados são devidos à alta concentração no endométrio ectópico. O objetivo deste estudo foi correlacionar os níveis de CA-125 no soro e fluido peritonial de mulheres com e sem endometriose pélvica. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, longitudinal, controlado, de pacientes consecutivas submetidas a laparoscopia por infertilidade, dor pélvica ou laqueadura tubária, durante a fase folicular precoce no Hospital Universitário da Faculdade de Medicina de Ribeirão Preto. MÉTODOS: Cinqüenta e duas pacientes foram divididas em dois grupos: grupo endometriose, com 35 pacientes com biópsia confirmada de endometriose pélvica, e grupo controle, com 17 pacientes sem endometriose. Níveis de CA-125 em amostras no soro e fluido peritonial foram determinadas por quimiluminescência. RESULTADOS: Os níveis de CA-125 no soro e fluido peritonial foram mais altos nas pacientes com endometriose pélvica avançada (média 39,1 ± 45,8 U/ml versus 10,5 ± 5,9 U/ml no soro, p < 0,005, 1469,4 ± 1350,4 U/ml versus 888,7 ± 784,3 U/ml no fluido peritonial, p < 0,05), e o estudo mostrou uma correlação positiva entre eles (coeficiente de correlação = 0,4880). Mulheres com estágios mais avançados de endometriose mostraram níveis de CA-125 maiores em ambos soro e fluido peritonial (p = 0,0001). CONCLUSÃO: Há uma correlação positiva entre os valores de CA-125 no soro e no fluido peritonial em pacientes com e sem endometriose e seus níveis são maiores no fluido peritonial. Endometriose avançada é relacionada com níveis mais altos de CA-125 em ambos soro e fluido peritonial.

Treatment evaluation, follow-up and familial screening of medullary thyroid carcinoma by highly specific calcitonin measurements.

BACKGROUND: Calcitonin is the most sensitive and specific marker for medullary thyroid carcinoma (MTC). AIMS: The aim of this study was to emphasize the role and the limits of plasma basal calcitonin (bCT) measurement in the management of Moroccan MTC patients and their relatives. SETTINGS AND DESIGN: This is a retrospective study on 6 MTC patients referred to our institute from January 1996 to December 2004. MATERIALS AND METHODS: Serum bCT levels were measured in 36 individuals comprising six known MTC cases, 18 relatives and 12 healthy volunteers, using two-sites immunoradiometric assay method. Five of MTC patients have been followed from 12 to 96 months after surgery. STATISTICAL ANALYSIS USED: Calculations were performed using SPSS 10.0 program. Data comparison was done by Student's t -test. RESULTS: The circulating preoperative bCT concentrations were elevated for all MTC patients (range, 44,8 -2055 pg/ml, normal <10). Recent postoperative bCT determinations varied from 24.4 to 1972 pg/ml in four patients. In one patient, the bCT value decreased to an undetectable level during a follow-up of 12 months. The mean bCT level of relatives was 4.90 +/- 3.54 pg/ml; two patients had slightly elevated bCT. Five (42%) healthy volunteers had undetectable bCT levels and all had less than 10 pg/ml; the mean bCT value was 3.06 +/- 2.51 pg/ml. CONCLUSIONS: Routine plasma bCT measurement still has an important place in the preoperative diagnosis and follow-up treatment of MTC.

Managing thyroid cancer without thyroxine withdrawal

A suspensão da tiroxina (T4) ou o TSH recombinante são usados para a estimulação da tireoglobulina (Tg), para o mapeamento de corpo inteiro (MCI) e para o tratamento com 131Iodo em pacientes com carcinoma tireoideano. Esse estudo avaliou um protocolo de redução de dose do T4 como alternativa para o preparo desses pacientes. Cinquenta e um pacientes submeteram-se à suspensão total de T4 para o MCI e a medida de Tg. Tratamento com T4 foi então reinstituído e mantido até que o TSH atingisse níveis < 0.3 mUI/l. A dose de T4 foi então dominuída para 0,8 µg/kg/dia e o TSH medido semanalmente. A Tg foi analisada quando o TSH estava > 30 mUI/l. Pacientes diagnosticados com a doença na fase inicial da avaliação foram tratados. Nós também avaliamos as alterações clínicas e laboratoriais observadas para ambos os preparos. Usando o protocolo de redução de dose, níveis de TSH > 30 mUI/l foram atingidos em 6 e 8 semanas em 84,6 and 100% dos pacientes, respectivamente. A suspensão do T4 esteve associada com sintomas mais comuns de hipotireoidismo e com elevação da creatino- quinase (CK) e LDL-colesterol. O protocolo de redução da dose de T4 mostrou-se útil para a estimulação da Tg e terapia ablativa, sem apresentar as complicações do hipotireoidismo severo ou chegar ao custo do TSH recombinante.

Sensibilidad a IGF-I en niños pequeños para la edad gestacional / IGF-I sensitivity in small for gestational age children

Background: The lack of catch up growth (CUG) in small for gestational age (SGA) children may be related to a reduced sensitivity to insulin growth factor 1 (IGF-I). Aim: To assess the sensitivity to IGF-I in small for gestational age children, measuring basal and post IGF-I nocturnal profile of growth hormone (GH). Patients and methods: We studied 34 prepubertal SGA children aged 4 to 11 years. Twenty three had CUG and 11 did not have CUG. As an IGF-I sensitivity test, nocturnal GH levels were measured every 20 minutes from 23:00 h to 07:00 h, both under baseline conditions and after the administration of a subcutaneous bolus of 1 mg/kg/body weight of the IGF-I + IGFBP-3 complex (Somatokine®). Results: At the time of the study, the Z scores for height among children with and without CUG were -1.55 ± 0.22 and -3.24 ± 0.28, respectively (p <0.0001). There were no statistical differences between CUG + vs CUG- patients in mean basal GH (6.6 ± 0.5 and 5.6 ± 0.6 ng/ml, respectively). After Somatokine® administration, mean GH, and the mean GH area under the curve (AUC) decreased significantly in both groups. However, mean overnight GH AUC decreased in all SGA children with CUG, after Somatokine® administration, whereas 3 out of 11 SGA children without CUG had an increase in their mean GH AUC in response to Somatokine®. Conclusions: These findings suggest that pituitary sensitivity to IGF-I may be decreased in some SGA children without CUG.