Differentiated thyroid carcinomas from children and adolescents express IGF-I and the IGF-I receptor (IGF-I-R). Cancers with the most intense IGF-I-R expression may be more aggressive

Adult thyroid cancers express IGF and IGF-I receptor (IGF-I-R), but the clinical impact is not clear. No previous study examined any childhood thyroid cancers that are well-differentiated and have a favorable prognosis. We used immunohistochemistry to determine IGF-I and IGF-I-R in 23 papillary thyroid cancers (PTC) and 6 follicular thyroid cancers (FTC) from children and adolescents. IGF-I was detected in 45% and IGF-I-R in 43% of cancers. IGF-I and IGF-I-R were found more often in PTC (IGF-I = 9/23, IGF-I-R = 8/19) than normal surrounding thyroid (IGF-I = 0/10, p = 0.032 and IGF-I-R = 0/10, p = 0.030). There were too few FTC to support independent statistical analysis, but IGF-I was found in 4 of 6 FTC (0/10 normal), and IGF-I-R was found in 2 of 4 FTC (0/10 normal). IGF-I-R staining was more intense in aggressive (invasive, metastatic, recurrent, or persistent) than indolent tumors (confined to the gland, p = 0.029). Over time, six tumors recurred, five of which expressed IGF-I-R. Overall recurrence risk was significantly greater for tumors that expressed IGF-I-R (p = 0.05) but only approached statistical significance (p = 0.08) when disease-free survival was determined. We conclude that differentiated thyroid cancers of children and adolescents express IGF-I and IGF-I-R. Tumors that express IGF-I-R are more likely to show aggressive clinical features (invasion beyond the capsule, metastasis, or recurrence) and persistence despite treatment.     

Tumor size and extent of disease at diagnosis predict the response to initial therapy for papillary thyroid carcinoma in children and adolescents

Treatment of papillary thyroid carcinoma (PTC) in children and adolescents is controversial. We previously showed that large tumor size, multifocal disease, and extensive disease at diagnosis predict recurrence. We examined 47 patients with PTC to determine whether these features predict response to treatment. Overall, 70% of the patients (33/47) remitted with initial treatment. 79% (15/19), of Class I, 86% (12/14) of Class II, and 100% (6/6) of Class III, but none of Class IV patients (n = 8) (p < 0.001) achieved remission. Tumor size for patients who entered remission (2.0 +/- 0.2 cm) was less than for patients with persistent disease (4.2 +/- 0.4) (p < 0.0005). Extent of disease at diagnosis correlated with the number of radioactive iodine (RAI) treatments (p = 0.022) and dose (p = 0.002) required to achieve first remission. We conclude that extensive disease at diagnosis and larger tumor size predict failure to remit after initial treatment of PTC in children and adolescents.     

The MACIS score predicts the clinical course of papillary thyroid carcinoma in children and adolescents

MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) scores are employed to predict mortality for papillary thyroid carcinoma (PTC) in adults. However, this system has not been validated in children and adolescents. We hypothesized that MACIS scores would correlate with recurrent and persistent disease in children. Patients with PTC (n = 48) were divided into those with aggressive (invasive, metastasic, recurrent or persistent disease) or indolent (lacking these features) disease. Those with aggressive PTC (n = 11) had average MACIS score = 5.2 +/- 1.3, compared to 3.7 +/- 0.4 in patients with indolent disease (n = 37, p < 0.0005). A cutoff score of 4.0 provides a PPV of 29% and NPV of 94% in predicting recurrence, and a PPV of 43% and NPV of 91% in predicting persistent disease. MACIS scores may be useful in predicting outcome in the pediatric population.     

Sensitivity of iodine deficiency indicators and iodine status in Turkey

BACKGROUND: Iodine deficiency is a major health problem worldwide. Goiter prevalence and the median urinary iodine concentration in a population usually define endemic iodine deficiency. In addition to goiter prevalence and median urinary concentration, thyroid stimulating hormone (TSH) and thyroxine have been used as iodine deficiency indicators. OBJECTIVE: To evaluate endemic goiter prevalence in Western Anatolia, Turkey, and to evaluate the sensitivity of thyroglobulin and height percentile as iodine deficiency indicators. SUBJECTS: We examined 727 school-children (378 girls, 349 boys) in two cities (Bolu and Düzce) and six mountainous rural areas, in West Anatolia. Of the 727 children, 234 were from four urban schools, and 493 were from eight rural schools. METHODS: Clinical examination and ultrasonography were used to evaluate goiter prevalence. Iodine in spot urine, serum total thyroxine (T4), serum free thyroxine (FT4), thyroid stimulating hormone (TSH), and thyroglobulin (Tg) were measured. Iodine deficiency severity was classified based on thyroid volume measurements by ultrasonography and urinary iodine excretion. RESULTS: The degree of iodine deficiency according to concentration of urinary iodine was severe in 276 children (38%), moderate in 151 (20.8%), mild in 114 (15.7%), and within normal levels in 186 (25.4%). Although urban areas showed normal or mild urinary iodine excretion, four rural areas showed from mild to severe iodine deficiency (p < 0.001). Thyroid volumes of the severe iodine deficiency group were significantly higher than those of moderate and mild iodine deficiency groups (p < 0.001). There was no significant difference between thyroid volumes in moderate and mild iodine deficiency groups. FT4 levels of the severe iodine deficiency group were significantly lower than in moderate and mild iodine deficiency groups (p < 0.001). There was no significant correlation between TSH and iodine excretion (r = 0.01, p > 0.05). Thyroglobulin (Tg) levels were significantly different between all groups (p < 0.001). There was a significant negative correlation between Tg and urinary iodine excretion (r = -0.27, p < 0.001). CONCLUSIONS: Severe and moderate iodine deficiency areas are more prevalent in Turkey than mild and normal iodine concentration areas. In addition to urinary iodine concentration and thyroid volume, height percentile and Tg are also sensitive markers for endemic iodine deficiency. TSH screening should be performed nationwide in Turkey. We recommend compulsory iodination of table and industrial salt.     

Effect of vaginal douching with povidone-iodine during early pregnancy on the iodine supply to mother and fetus

Vaginal douching with polyvinylpyrrolidone iodine (PVP-I) during pregnancy results in maternal iodine overload and increases the iodine content of amniotic fluid. We evaluated the possible effects of this therapy on the thyroid of the fetus by investigating 62 women with a mean duration of amenorrhea of 20 weeks who solicited controlled abortion. Nineteen of them douched daily with PVP-I for 7 consecutive days before abortion (treated group). The other 43 women were not treated (control group). In both groups the iodine content was determined in the fetal thyroid and in amniotic fluid and maternal urine at the time of abortion. In addition, in the treated group the concentrations of iodine were also determined in amniotic fluid and urine before therapy and in urine after 4 days of therapy. There were no differences in the concentrations of iodine in urine and amniotic fluid in the control group and in the treated group before therapy. In the treated group urinary iodine increased from 6.1 +/- (SEM) 0.8 micrograms/dl before therapy to 91 +/- 20 micrograms/dl after 4 days and to 153 +/- 60 micrograms/dl after 7 days of therapy (p less than 0.001). In parallel, iodine in amniotic fluid increased from 1.2 +/- 0.2 micrograms/dl before therapy to 3.7 +/- 1.3 micrograms/dl after 7 days (p less than 0.05). In both groups the iodine content of the fetal thyroid increased with gestational age. However, it increased more rapidly in the treated group (from 1 to 7.7 micrograms) than in the control group (from 1 to 2.5 micrograms), p less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)     

Therapeutic use of 131I-metaiodobenzylguanidine (MIBG) in neuroblastoma: a phase II study in nine patients

Effects of high activities of I 131 meta-iodobenzylguanidine (mIBG) were evaluated in nine children with advanced neuroblastoma. All patients had been previously heavily treated and had either primarily refractory disease or resistant relapse. Twenty-two doses of mIBG labeled with 1.3 to 4 GBq (35-108 mCi) of iodine 131 were administered. Three subjective effects, especially relief of pain, and two objective effects were observed. Transient blood pressure increase was observed once and did not recur after prolongation of the infusion time to 6 hours. A major side effect was bone marrow toxicity, essentially marked by thrombopenia, particularly severe in previously bone-marrow-transplanted patients.     

Assessment of bone quality by quantitative ultrasound of proximal phalanges of the hand and fracture rate in children and adolescents with bone and mineral disorders

Bone quality by quantitative ultrasound and fracture rate were assessed in 135 (64 males) children and adolescents aged 3-21 y with bone and mineral disorders such as chronic anticonvulsants or glucocorticoids treatment, juvenile rheumatoid arthritis, celiac disease, paucity of intrahepatic bile ducts, autoimmune hepatitis, genetic diseases, idiopathic juvenile osteoporosis, disuse osteoporosis, beta-thalassemia major, survivors of acute lymphoblastic leukemia, liver transplantation, calcium deficiency, and nutritional or X-linked hypophosphatemic rickets. Amplitude-dependent speed of sound through the distal end of the first phalangeal diaphysis of the last four fingers of the hand was measured by an ultrasound device. In the majority of patients cortical area to total area ratio by metacarpal radiogrammetry (n = 120) and lumbar bone mineral density (BMD) by dual-energy x-ray absorptiometry (n = 99) were also assessed. In patients with X-linked hypophosphatemic rickets radial BMD by single-photon absorptiometry instead of lumbar BMD was measured. Mean values of amplitude-dependent speed of sound, cortical area to total area ratio, lumbar BMDarea, or lumbar BMD corrected for bone sizes estimated by a mathematical model (BMDvolume), as well as mean values of radial BMD in patients with X-linked hypophosphatemic rickets, expressed as z score, were significantly reduced (p < 0.0001) in comparison with their reference values (-1.7 +/- 1.0, -2.0 +/- 0.9, -3.0 +/- 1.3, -1.9 +/- 1.0, -2.7 +/- 0.7, respectively). A positive relationship was found between amplitude-dependent speed of sound and cortical area to total area ratio (r = 0.90, p < 0.0001), lumbar BMDarea (r = 0.62, p < 0.0001), or lumbar BMDvolume (r = 0.66, p < 0.0001). Fifty-two patients (38.5%) had suffered fractures in the 6 mo preceding the bone measurements, the radial distal metaphysis being the most frequent fracture site (28.8%). Mean values of amplitude-dependent speed of sound, cortical area to total area ratio, lumbar BMDarea, or lumbar BMDvolume, expressed as z score, of fractured patients were significantly lower (p < 0.0001) than those of fracture-free patients (-2.2 +/- 1.0 and -1.4 +/- 0.8, -2.6 +/- 0.9 and -1.7 +/- 0.7, -3.5 +/- 1.2 and -2.5 +/- 1.0, -2.5 +/- 1.0 and -1.3 +/- 0.7, respectively). Phalangeal quantitative ultrasound may be a useful method to assess bone quality and fracture risk in children and adolescents with bone and mineral disorders.     

Clinical course of pediatric and adolescent Graves' disease treated with radioactive iodine

The use of radioactive iodine (RAI) therapy in children and adolescents with Graves' disease is increasing; however, few data exist to guide dosing in this population. We aimed to determine the clinical course, failure rate and factors associated with failure of RAI for pediatric Graves' disease. A retrospective chart review from a tertiary care pediatric endocrinology clinic (1990-2003) identified 22 patients (12.7 +/- 4.0 years at diagnosis) with Graves' disease treated with RAI after initial pharmacological therapy. Patients received a calculated dose of RAI (0.1 mCi/g thyroid tissue, adjusted for 6-h radio-iodine uptake). Twenty-seven percent (95% CI 11-50%) remained hyperthyroid and required a second dose. If the first RAI was successful, the average time to hypothyroidism was 2.96 +/- 1.05 months. There were no statistically significant differences between those successfully treated with one dose and those requiring re-treatment. This high failure rate indicates a need to examine dosing of RAI in this age group.     

Iodine and selenium deficiency in school-children in an endemic goiter area in Turkey

Endemic goiter is one of the most important health problems in Turkey. However, there are not enough studies associated with iodine and selenium status. This study was carried out to establish the effects of iodine and selenium levels on thyroid gland size and thyroid functions in 73 healthy school-children, 7-12 years old (mean 9.56 +/- 1.77 years), 38 girls (52%) and 35 boys (48%), living in an endemic goiter area. Goiter was found in 32 of the children (43.8%) by palpation, and 56 of the children (76.7%) by ultrasonography. Mean serum T3 and TSH levels were in the upper limit of normal, and mean serum T4 levels were within the normal limits, but mean serum thyroglobulin levels were higher than the normal limits. Mean serum selenium level was 30.84 +/- 23.04 microg/l, and mean urinary iodine level was 3.91 +/- 3.77 microg/dl, appropriate for moderate iodine and selenium deficiency. Thyroid volumes of the children were negatively correlated with serum selenium levels, but there was no correlation with urinary iodine levels and thyroid hormones. In conclusion, school-children in this area had significant goiter problems, probably due to the iodine and selenium deficiencies.     

Thyroidal uptake and radiation dose after repetitive I-131-MIBG treatments: influence of potassium iodide for thyroid blocking

BACKGROUND: In I-131-MIBG therapy, I-131-iodide can be released from the I-131-MIBG molecule. Hypothyroidism might result from the undesirable irradiation of the thyroid gland. To prevent this, stable iodide such as potassium iodide (KI) is given to oversaturate the thyroid before I-131-MIBG is administered. PROCEDURE: In the present study, the incidence of hypothyroidism (elevated TSH) was correlated with the thyroidal uptake of I-131 and dose (MIRD dosimetry) after 35 individual treatments in ten patients. Iodine-131-MIBG therapy was performed using a modified dosage of 1.9-11.1 GBq (50-300 mCi) IV. Premedication with KI was done as recommended with a dose of 100 mg KI orally from 2 days before until 4 weeks after I-131-MIBG. RESULTS: The absorbed thyroidal dose amounted to a very variable range of 0.2 (patient # 1) up to 30.0 (patient 3) Gy with 7.1 +/- 7.9 Gy per treatment and 24.1+/- 19.2 Gy per patient (mean+/- SD), despite the same and compliantly taken KI premedication protocol. Up to now, 4/10 or 40% of patients have developed hypothyroidism after a mean follow-up period of 11 months and a mean total administered dose of 18.7 GBq (505 mCi). A trend towards higher thyroidal doses was seen in the hypothyroid patients. CONCLUSIONS: This study observes a general high inter- and intra-individual variability in radio-iodide uptake in the thyroid after I-131-MIBG therapy despite KI premedication, as well as possible occurrence of hypothyroidism. A dose-response relationship needs confirmation on a larger cohort of patients to reach statistical value. An alternative thyroid cytoprotection strategy for possible long-term survivors may be considered.     

Treatment of recurrent papillary thyroid carcinoma in children and adolescents

Mortality for children with papillary thyroid carcinoma (PTC) is low (< or = 10%), but recurrence is frequent (20%). In adults, recurrent PTC has a poor prognosis (50% remission) and a high mortality (16-63%). We hypothesized that treatment of recurrent PTC would be more effective in children than in adults. We reviewed the clinical course of 42 children with PTC in remission. Seven (7/42, 17%) recurred and records were available for six. All six received RAI (median = 130 mCi), and one had a cervical node removed. Five of the six (83%) achieved remission (median duration 67 mo, range 10-99 mo), one had a second recurrence and a third remission, and one patient (17%) had persistent disease. There were no deaths. In conclusion, although we had only one child less than 10 years of age in our study, these and previous data suggest that treatment of recurrent PTC in children is generally effective.     

Thyroid hormone synthesis and storage in the thyroid gland of human neonates

The aim of this study was to evaluate the morphological and biochemical maturation of the thyroid gland in human neonates. The mean iodine concentration in the thyroid gland of very premature infants (less than 32 weeks gestational age, 0-3 days survival, n = 12) was significantly lower than in the older group (34-41 weeks gestational age, 0-30 days survival; n = 15; p < 0.05). For the whole group of neonates there was a statistically significant linear correlation between duration of life, i.e. gestational age and survival, and iodine concentration (r = 0.64, p < 0.01). Although there was wide dispersion of the results the same tendency was seen for thyroglobulin (Tg) concentration in the thyroid gland (r = 0.52, n = 21; p < 0.05). Comparative histological examination of the fetal thyroids gave results in accordance with the biochemical data as intrafollicular colloid appeared to be more abundant in more mature thyroids. The iodine content in Tg was found to be 0.63 +/- 0.22% in very preterm neonates and was slightly but not significantly lower than that found in the thyroids of the older group (0.82 +/- 0.14%; p = 0.055). The content of T4 and T3 per Tg molecule in the neonates was related to the iodine content. The differences in mean values of T4/Tg and T3/Tg molar ratios between the two groups were not significant: T4: 2.8 +/- 1.8 mol/ mol, T3: 0.29 +/- 0.12 mol/mol in very preterm neonates; and T4: 3.5 +/- 0.7 mol/mol, T3: 0.34 +/- 0.09 mol/mol in the older group. These results offer useful information for further analysis of the development of thyroid function in the human neonate.     

Prevalence of 20S proteasome, anti-nuclear and thyroid antibodies in young patients at onset of type 1 diabetes mellitus and the risk of autoimmune thyroiditis

Patients with type 1 diabetes mellitus (DM1) are at high risk to develop further autoimmune disorders, which are mostly characterized by the presence of organ-specific antibodies in serum and a subclinical disease course. Diabetes-related (glutamic acid decarboxylase, tyrosine phosphatase, IA-2) and thyroid-specific (thyroperoxidase, thyroglobulin) as well as antibodies to 20S proteasome, and anti-nuclear antibodies, were measured at DM1 onset in 147 children and adolescents. Patients were followed prospectively for the development of autoimmune thyroiditis (TSH elevation and/or sonographic thyroid gland enlargement in the presence of thyroid antibodies) up to 12 years, median observation time 4.4 years. Eight of 147 (5.4%) patients developed autoimmune thyroiditis. The cumulative incidence (+/-SE) at 5 years was 0.08+/-0.03. The prevalence of thyroid antibodies was 16.7%, of DM-related 88.4%, 20S proteasome 21.9%, and anti-nuclear antibodies 20.0%. There was a positive correlation between thyroid and anti-nuclear antibodies (p <0.001). Clinical course of DM1 and remission duration were not influenced by the presence of autoantibodies. However, in contrast to patients without antibodies, those with positive antibodies had significantly (p <0.001) elevated cumulative incidence of autoimmune thyroiditis at 5 years: thyroperoxidase 0.40+/-0.13, thyroglobulin 0.38+/-0.15, and anti-nuclear antibodies 0.29+/-0.12, respectively. These data underline that autoimmunity in patients with DM1 is not only restricted to beta-cell antigens at the onset of disease. In particular, patients with positive thyroid and anti-nuclear antibodies are at high risk to develop autoimmune thyroiditis during the first 5 years of DM1.     

Etiology of childhood hypothyroidism

This study prospective without any selection bias included 80 of the 152 hypothyroid infants and children seen over the past six years. The clinical diagnosis was confirmed by TSH and thyroid hormone (T3, T4) studies. Scanning for thyroid with TC99m pertechnetate was carried out in all except seven older children with grade II and III goiters where 131I uptake studies were done. Serum thyroglobulin (RIA) was estimated and antithyroglobulin and antimicrosomal antibodies were tested. Based on thyroid 131I scan or 131I uptake, 52.5% had no demonstrable thyroid tissue except one with hypoplasia (Group I, n = 42), 25% had ectopic thyroid (Group II, n = 20), and 22.5% had normal or enlarged thyroid gland (Group III, n = 18). One hypothyroid patient of Group III had thyroiditis with high antibody titre and one was proved to have iodine deficiency). The mean age at time of diagnosis was lowest in Group I (age in months--30.3 +/- 36.2; 60.6 +/- 53.9; 106.2 +/- 69.3 in Groups I, II and III respectively. The intergroup differences in age were significant. The mean serum Tg levels increased progressively from Groups I to III. In the present series thyroid dysgenesis led to hypothyroidism in 77.5%, with athyreosis in 52.5% and ectopia in 25%. Dyshormonogenesis was noted in 20% and thyroiditis in 1.5%.     

Outcome of muscle and bone development in congenital heart disease

Muscles and bones of patients with congenital heart disease (CHD) are subject to various potentially deleterious influences during growth. The aim of the present study was to analyse the outcome of bone and muscle parameters in adolescents and young adults with a spectrum of CHD. Bone and muscle parameters of the forearm were examined at two standard sites, 4% and 65%, in 29 adolescents and young adults with CHD, aged 14-24 years, by quantitative computed tomography. For the entire study population, bone and muscle parameters did not deviate significantly from the reference values except for age- and gender-corrected body height (ASDS-height: -0.6+/-1.2, p=0.01). Both age- and gender- and height- and gender-corrected (HSDS) abnormal bone mass (BMC) was found at the distal radius in patients with Fontan repair (ASDS-BMC4%: -1.5+/-0.9, p=0.008; HSDS-BMC4%: -1.2+/-1.0, p=0.05) and in those in NYHA class III (ASDS-BMC4%: -1.3+/-0.4, p=0.001; HSDS-BMC4%: -1.4+/-0.5, p=0.004). There was minimal overlap between Fontan patients (n=6) and NYHA class III (5 Fontan patients were in NYHA class I or II). In conclusion, most patients with CHD show a normal muscle and bone development in proportion to their reduced body height. Further follow-up is required to determine whether patients in a worse clinical status (NYHA III) and those with single ventricle physiology are at increased risk of osteoporosis and fractures.     

Metaiodobenzylguanidine (mIBG) in treatment of 47 patients with neuroblastoma: results of the German Neuroblastoma Trial

From 1984 to 1989, 47 children with relapsed, refractory, and/or metastasized neuroblastoma were treated with 131I-metaiodobenzylguanidine (mIBG) in several different treatment combinations. At initial diagnosis, 36 children had Evans stage IV and 11 stage III disease. In 16 of the 47 children, tumor recurred after complete remission prior to mIBG treatment, 26 of 47 progressed from residual or nonresponding tumor, and in 5 of 47 tumor progression during chemotherapy was observed. Altogether the children were treated with a total of 112 courses (range 1-6) with a mean dosage of 8.9 +/- 6.7 mCi/kg body weight/treatment course. Total dose was 283.2 +/- 203.7 mCi for stage III and 388.9 +/- 218.6 mCi for stage IV. Nine of 47 children reached a complete or a very good partial remission (CR and VGPR) from mIBG treatment alone, 13 of 47 achieved partial remission (PR). In an early analysis, 10 patients treated with mIBG in the neuroblastoma trial NB 85 of the German Society of Pediatric Oncology showed no significant difference in survival time compared with 30 conventionally treated children. However, the recent therapy series has been done with higher doses of mIBG, and during improved therapeutic scanning many more bone lesions could be detected than during earlier diagnostic scanning. We conclude that mIBG treatment has not yet fulfilled the expectations for it but still seems for certain indications to be a promising tool to treat neuroblastoma in the future. Moreover, the frontier of neuroblastoma detection is still advancing.     

Electrogastrography in children and adolescents with type 1 diabetes: weak correlation with metabolic control parameters

AIM: To evaluate gastric myoelectrical activity with respect to duration and metabolic control of type 1 diabetes mellitus (T1DM). METHODS: 172 children and adolescents with T1DM (mean 14.4+/-3.7 y), divided into subgroups depending on diabetes duration (< 5 and > 5 y), and 35 healthy controls (mean 13.93+/-3.59 y) were examined. All subjects underwent electrogastrography (EGG) performed after overnight fasting. In subjects with T1DM, haemoglobin A1c (HbA1c) and blood glucose levels during EGG records were measured. RESULTS: 15.69% of T1DM patients and 91.42% of the controls fulfilled normal EGG criteria (p < 0.001). T1DM subjects had a lower percentage of fasting normogastria (34.56+/-27.35% vs 69.84+/-18.16%, p = 0.0001) and higher bradygastria (51.97+/-30.24% vs 19.11+/-15.01%, p = 0.0001) compared to controls. In diabetic patients, an increase in postprandial normogastria (60.37+/-23.96% vs 76.68+/-12.38, p < 0.05) and a decrease in bradygastria percentage (25.67+/-21.01% vs 9.58+/-7.13%, p < 0.05) was observed. In children with disease < 5 y, diabetes duration correlated with power ratio (r = - 0.27, p = 0.01), postprandial normogastria (r = - 0.24, p = 0.03) and tachygastria (r = 0.25, p = 0.02). Weak correlations between EGG parameters and glucose (preprandial dominant frequency r = - 0.19, p < 0.05; postprandial normogastria r = 0.23, p < 0.01) and HbA1c levels (preprandial bradygastria r = 0.19, postprandial dominant power r = 0.23; p < 0.05) were observed. CONCLUSION: Gastric myoelectrical rhythm derangement is present in a large proportion of young diabetic patients. Bradygastria is the most prominent EGG abnormality. Weak correlation was found between EGG parameters and diabetes metabolic control.     

GADA positivity at onset of type 1 diabetes is a risk factor for the development of autoimmune thyroiditis

Kordonouri O, Charpentier N, Hartmann R. GADA positivity at onset of type 1 diabetes is a risk factor for the development of autoimmune thyroiditis. Aim: To evaluate whether the presence of diabetes‐specific autoantibodies may predict the development of autoimmune thyroiditis (AIT) in children with type 1 diabetes (T1D). Methods: Glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase IA2 antibodies (IA2A), and insulin autoantibodies (IAA) were determined at T1D onset in 341 children and adolescents. Thyroid antibodies (anti‐TG, anti‐TPO), thyroid stimulating hormone (TSH), T₃ and T₄ were measured in 335 patients at T1D onset and thereafter annually with a follow‐up time of 1–15 yr. In case of thyroid antibody positivity and/or TSH elevation, thyroid gland sonography was performed. Treatment with l ‐thyroxine was started if persistent elevation of TSH and/or thyroid volume was present. Results: The majority of patients (92.1%) had at least one T1D antibody (71.6% GADA, 73.0% IA2A, and 44.9% IAA). GADA positive patients were older than those without GADA (p < 0.001). Thyroid autoimmunity was found in 15 of 335 patients (4.5%) at T1D onset with female preponderance (p = 0.013). At the end of follow‐up, 70 patients (20.9%) had developed thyroid autoantibodies [cumulative incidence (CI) 0.36 ± 0.06 at 10 yr of T1D]. In 30 patients (9.0%), AIT was diagnosed up to 9.4 yr after T1D onset (CI 0.24 ± 0.06 at 10 yr). AIT incidence was not influenced by IAA or IA2A positivity. In multivariate analysis, GADA positive patients were estimated to have a 3.5‐fold increased risk of AIT (CI 0.31 ± 0.11 at 10 yr) compared to those without GADA (p = 0.024). Conclusion: Based on the present results, a special focus should be given to GADA positive patients concerning screening for AIT as they are at increased risk to develop autoimmune thyroiditis.     

Targeted radioimmunotherapy for leptomeningeal cancer using (131)I-3F8

BACKGROUND: Intrathecal antibody-based targeted therapies may have clinical potential for patients with leptomeningeal (LM) cancer. PROCEDURE: Five patients with GD2-positive LM tumors were injected with 1-2 mCi intra-Ommaya (131)I-3F8, a murine IgG3 antibody specific for GD2. Serial cerebrospinal fluid (CSF) and serum samples and SPECT imagings (4, 24, and 48 hr) were performed to predict radiation doses to the tumor and normal brain and blood prior to the administration of larger therapeutic doses. RESULTS: Side effects included self-limited fever, headache, and vomiting. Focal (131)I-3F8 uptake consistent with tumors was seen along the craniospinal axis in four patients. Calculated radiation dose to the CSF was 14.9-56 cGy/mCi and to blood and other organs outside the CNS less than 2 cGy/mCi. CONCLUSIONS: Intraventricular (131)I-3F8 successfully detected LM disease and resulted in a large favorable CSF/blood ratio. Intraventricular (131)I-3F8 may have clinical utility in the diagnosis and radioimmunotherapy of GD2-positive LM cancers. Med. Pediatr. Oncol. 35:716-718. 2000.     

Differing pathogenesis of perinatal bilirubinemia in glucose-6-phosphate dehydrogenase-deficient versus-normal neonates

The objective was to compare the contribution to perinatal bilirubinemia of hemolysis and UDP-glucuronosyltransferase (UGT) gene promoter polymorphism, seen in Gilbert's syndrome, between glucose-6-phosphate dehydrogenase (G-6-PD)-deficient and -normal neonates. Serum total bilirubin (STB) values from 52 G-6-PD-deficient and 166 G-6-PD-normal term, male neonates, sampled within 3 h of delivery (first sample) and on d 3 (second sample), were analyzed in relation to blood carboxyhemoglobin corrected for inspired CO (COHbc), an accurate index of hemolysis, and UGT promoter genotype. COHbc values (% total Hb) were greater in G-6-PD-deficient neonates than controls: first sample 1.00 +/- 0.25% versus 0.84 +/- 0.24%, p < 0.0001; second sample 0.83 +/- 0.20% versus 0.76 +/- 0.19%, p = 0.002. First sample COHbc and STB values did not correlate in either the G-6-PD-deficient or control groups, whereas second sample COHbc values correlated significantly with corresponding STB values in the control population only (r = 0.28, p = 0.0007). At second sampling, there was a higher allele frequency of the variant UGT promoter among those with STB values > or =75th percentile than those <75th among the G-6-PD-deficient neonates (0.60 versus 0.33, respectively, p = 0.025), but not controls (0.31 versus 0.40, respectively, p = 0.24). Among those infants with at least one variant UGT promoter allele, STB values were higher in the G-6-PD-deficient neonates than controls at second sampling only (181 +/- 56 microM versus 149 +/- 46 microM, respectively, p = 0.03). Both within and between the G-6-PD-deficient and control groups, our data demonstrate changing and differing contributions of hemolysis and UGT promoter polymorphism to bilirubinemia during the first 3 d of life.