Ovarian cysts in young girls with hypothyroidism: follow-up and effect of treatment

Ovarian cysts have been reported in girls with longstanding uncompensated primary hypothyroidism. Restoration of euthyroid state has been associated with resolution of these cysts; long-term follow-up of these patients is however lacking. We evaluated the outcome in ten girls with ovarian cysts and hypothyroidism managed at our hospital with special emphasis on subsequent pubertal development and ovarian imaging. Patients were diagnosed at the age of 8.6 +/- 2.3 years (mean +/- SD) with severe uncompensated primary hypothyroidism (TSH levels >100 mIU/l in all; 509.3 +/- 651 mIU/l) and growth retardation (height SDS -4.1 +/- 1.8). Nine girls had vaginal bleeding at diagnosis; five also had thelarche. LH and FSH levels were prepubertal in all patients. Ovarian cysts were bilateral in eight girls (80%); internal septation was noted in six. Thyroxine replacement (4.1 +/- 0.7 microg/kg/day) led to normalization of TSH levels with reversal of pubertal changes and regression of ovarian cysts in all patients 2.2 +/- 1.0 months after treatment. At last follow-up 3.5 +/- 2.6 years after initiation of treatment at the age of 12.0 +/- 2.3 years, all patients had normal ovarian size in ultrasound evaluation with six girls progressing to normal puberty. Our study emphasizes the need to exclude hypothyroidism in young girls with ovarian cysts. Identification of hypothyroidism in these girls obviates the need for extensive investigations.     

The clinical course of Hashimoto's thryoiditis in children and adolescents: 6 years longitudinal follow-up

Forty-six children and adolescents with Hashimoto's thyroiditis were followed up for 5.9 +/- 0.3 years. The mean age at diagnosis was 12.4 +/- 1.7 years (range 9-15.4 yr). The patients were divided into three groups according to thyroid function: group 1 (n = 28) included patients who had normal concentrations of free thyroxine (FT4) and thyrotropin (TSH); group 2 (n = 8) included patients who had normal FT4 and elevated TSH, consistent with compensated hypothyroidism; group 3 (n = 10) included patients who had low FT4 and elevated TSH consistent with overt hypothyroidism. After 5.9 years of follow-up, four out of eight patients with compensated hypothyroidism had normal thyroid function and the other four patients developed overt hypothyroidism. Thyroxine therapy was administered in patients with overt hypothyroidism including the four patients with compensated hypothyroidism who later presented with overt hypothyroidism. All patients in both euthyroid and hypothyroid groups had normal growth and puberty. Final adult height was 0.43 +/- 0.80 SDS which was 1.58 +/- 3.03 cm above mid-parental height. The mean age at menarche (n = 43) was 12.4 +/- 1.1 years, which was not different from normal children. The goiter remained the same size in most of the patients with euthyroidism without thyroxine therapy, but decreased in patients with overt hypothyroidism after thyroxine therapy.     

Thyroid dysfunction after haematopoietic stem cell transplantation during childhood.]

To evaluate the percentage and risk factors of thyroid dysfunction in 79 children who underwent bone marrow transplantation in a single centre. PATIENTS AND METHODS: The mean age of the cohort was 6.8 and mean follow-up 5.5 years. The 79 patients were divided in two groups according to the pretransplant conditioning regimen: fractionated total body irradiation (TBI)(N=54), chemotherapy with Busulphan (N=25). Thyroid function was evaluated by thyroid-stimulating hormone (TSH) and free thyroxine (fT4) tests. Overt hypothyroidism was defined by low fT4 blood levels and TSH > 4 mU/l, and compensated hypothyroidism by normal fT4 index and TSH >4 mU/L. RESULTS: The six-year probability of hypothyroidism was 36 +/-6% for the whole group of 79 patients, 49 +/-8% after TBI and 9 +/-6% in the Busulphan group (P <0.001). Neither gender, nor primary disease, nor presence of graft versus host disease were found to be statistically significant for occurrence of hypothyroidism in the TBI group. However, a younger age seemed to influence statistically the 6-year probability of hypothyroidism in the TBI group: 59 +/-9% if age <7.7 years versus 34 +/-13% if age >7.7 years (P =0.02). CONCLUSION: A careful follow-up of thyroid function is recommended even without TBI conditioning regimen. Young age as a potential risk factor of hypothyroidism has never been described and needs to be studied in a larger cohort.     

Influence of severity of congenital hypothyroidism and adequacy of treatment on school achievement in young adolescents: a population-based cohort study

AIM: To evaluate whether precociously treated subjects with congenital hypothyroidism (CH) are at risk of poor school performance in early adolescence, and to investigate which factors affect their school achievement. METHODS: All children treated early for congenital hypothyroidism and born in France during the first 7 y (1979-1985) of the national screening program for congenital hypothyroidism were selected for the study. School performance during childhood, assessed according to age at entry into the first grade of secondary school, was evaluated as normal (usually 11 y of age) vs late entry (> or = 12 y). The national register of children with congenital hypothyroidism enabled a comparison to be made with data from the national population for the same school years. RESULTS: School achievement was similar among the 682 patients with CH and in the national population. After an adjustment for the sex and socioprofessional category of the parents, the severity of CH as assessed by the type (athyreosis. the most severe vs other types), the initial low serum T4 levels (< or = 53 nmol/L vs >53 nmol/L), and the profound bone maturation delay (absence vs presence of the two knee epiphyseal ossification centres at diagnosis), initially low L-thyroxine dosage (below vs > or = 7 microg/kg/day), the absence of near normalization of thyroid hormone levels after 15 d of treatment and poor adequacy of treatment throughout childhood were associated with an increased risk of school delay. School achievement was unaffected by the age at start of treatment (mean age = 22.8 +/- 6.8 d). In a multivariate logistic regression analysis, recurrent episodes of insufficiently suppressed TSH levels (> or = 15 mUi/L at least four times during follow-up from the age of 6 mo onwards) were the most important variable associated with school delay. CONCLUSION: Careful follow-up of the adequacy of treatment is required throughout childhood, to reduce the risk of school delay.     

Linear growth in children with congenital hypothyroidism detected by neonatal screening and treated early: a longitudinal study

We performed a longitudinal study of a cohort of 74 children with congenital hypothyroidism (CH) detected by neonatal screening (Buenos Aires Province, Argentina) up to the age of 3 years old, in order to study linear growth and the relationship with the severity of CH at diagnosis. The mean age at diagnosis and the start of the treatment was 16.9 +/- 5.2 days. The patients were divided into group 1--severe CH (pretreatment T4 level <4 microg/dl) (n = 47)--and group 2--less severe CH (pretreatment T4 level > or = 4 microg/dl) (n = 27). Patients with CH treated early showed a sexually dimorphic pattern of growth: girls tended to be longer than boys at all ages. Boys showed some delay of growth during the first year. No difference was found in linear growth between the two groups (more/less severe CH). Height was normal in both sexes at the age of 3 years old.     

Influence of timing and dose of thyroid hormone replacement on development in infants with congenital hypothyroidism

OBJECTIVES: To test whether early treatment with a high initial dose of levothyroxine can prevent suboptimal mental development in all neonates with congenital hypothyroidism (CH). STUDY DESIGN: Sixty-one patients, 27 with severe CH and 34 with mild CH, were treated either early (<13 days) or late (> or =13 days) with either a high initial dose of levothyroxine (> or =9.5 microg/kg/d) or a low initial dose (<9.5 microg/kg/d). With these criteria, 4 treatment groups were formed. The results of the Bayley test, performed at the age of 10 to 30 months and expressed as mental developmental index (MDI) and psychomotor developmental index (PDI), were related to socioeconomic status, treatment group, initial free thyroxine (FT(4)) concentration, and mean FT(4) concentration during the first 3 months of treatment (FT(4)-A) and the ensuing 9 months (FT(4)-B). RESULTS: Mean (+/- SD) MDI was 113 +/- 14, and mean PDI was 114 +/- 12. In the severe CH group, only the patients treated early with a high initial dose had normal MDI scores (124 +/- 16), whereas the scores of the other groups ranged from 97 to 103. In contrast, all patients in the mild CH group had normal scores (range, 122-125), except those in the group treated late with a low initial dose, whose score was 110 +/- 10. Forty-three percent of the variance in MDI and PDI scores was explained by treatment factors, such as the treatment group, initial FT(4) concentration, FT(4)-A, and FT(4)-B. CONCLUSIONS: Our data suggest that optimal treatment includes achievement of euthyroidism before the third week of life by initiation of therapy before 13 days with a levothyroxine dose above 9.5 microg/kg/d and maintenance of FT(4) concentrations in the upper normal range during the first year. Thus treated, patients with CH can achieve normal psychomotor development at 10 to 30 months, irrespective of the severity of the disease.     

Height prognosis in children with late-diagnosed congenital hypothyroidism.

It is a general belief that early and adequate thyroid hormone replacement achieves normalization of growth as well as disappearance of clinical sings and symptoms of hypothyroidism. Due to the lack of comprehensive growth studies, height prognosis has remained controversial in late-diagnosed hypothyroidic children. The limited number of previous studies have suggested permanent height deficit in these children. In this study we present longitudinal growth and final height of 20 children (14 females and 6 males) in whom the duration of hypothyroidism before onset of therapy varied from three to 12.6 years. The etiological distribution of cases revealed ectopic thyroid tissue in nine cases, agenesis in seven, and dyshormonogenesis in four cases. At the time of the diagnosis all hypothyroidic children had severe growth retardation (mean height SDS +/- SD -3.95+/-1.07) due to prolonged hypothyroidism. Although the catch-up spurt corrected an important part of the initial height deficit in all patients, only nine patients reached or exceeded their target height, and the final height of five patients remained below 2 SD of mean. Despite treatment, prolonged hypothyroidism may result in compromised adult height in some patients. The contributing factors to this height deficit may include the duration of hypothyroidism, the height deficit at the time of the diagnosis, etiological differences and the diminished potential for catch-up growth in late-diagnosed hypothyroidism.     

Catch-up growth in severe juvenile hypothyroidism: treatment with a GnRH analog

Anecdotal reports suggest that the addition of a gonadotropin releasing hormone (GnRH) analog (GnRHa) in addition to L-thyroxine (LT4) replacement may increase adult stature in children with severe longstanding hypothyroidism by prolonging the pubertal growth period. This retrospective chart review compares the height outcome and body mass index in 33 children (21 treated with LT4 alone and 12 treated with LT4 + GnRHa) with severe longstanding hypothyroidism and bone age delay. Seventeen controls and six GnRHa-treated patients were followed to adult height (BA >14 yr [F]/16 yr [M] and/or growth velocity < 2 cm/yr). At diagnosis, GnRHa-treated patients were 1) older and shorter for chronological age, and 2) more advanced in puberty and bone age. Despite these differences, at adult height, both groups had similar improvements in height Z scores, similar height deficits, and comparable adult heights. Changes in BMI Z score were similar for both groups. Our study suggests that the addition of GnRHa to LT4 may improve interval growth without imposing a risk of obesity in children with longstanding severe hypothyroidism.     

Usefulness of the long-acting insulin analogue glargine in basal-bolus therapy for Japanese children and adolescents with type 1 diabetes mellitus

The aim of this study was to evaluate the efficacy of long-acting insulin analogue glargine (G) changing from NPH in basal-bolus therapy for Japanese children and adolescents with type 1 diabetes mellitus (DM1). Thirty patients (11 M, 19 F) with DM1 aged 13.3 +/- 4.5 years were included in the study. Mean fasting blood glucose level was significantly decreased (baseline: 142.5 +/- 39.3 vs 127.1 +/- 24.0, 129.0 +/- 29.1, 121.1 +/- 26.0 mg/dl at 3, 6, 12 months, respectively, p <0.01), and mean HbA(1c) was significantly decreased (baseline: 8.06 +/- 0.85 vs 7.69 +/- 0.89, 7.57 +/- 0.93, 7.36 +/- 0.95%, at 3, 6, 12 months, respectively, p <0.01) after changing to G from NPH. Severe hypoglycemia rarely occurred during the study period. In conclusion, basal-bolus therapy using G resulted in improved overall glycemic control with a low risk of severe hypoglycemia in Japanese pediatric patients with DM1.     

Prevalence of hypercontractility in male and female infants with vesico-ureteral reflux.

PURPOSE: To establish whether infants with vesico-ureteral reflux (VUR) have bladder dysfunction, with difference in gender, age at presentation and severity. PATIENTS AND METHODS: 37 infants (24 male and 13 female) aged 2 to 24 months with II degrees to V degrees degree VUR underwent cystometry. Of those, 10 underwent natural filling cystometry. We considered: instability and maximal voiding detrusor pressure (VDP) to be "high" when it exceeded 90 cm H2O. We defined hypercontractility as high VDP and/or instability. RESULTS: The prevalence of hypercontractility was 75% (18/24) in male and 46% (6/13) in female infants (p<0.004). High VDP was found in 50% (12/24) of male and 7% (1/13) of female patients (p < 0.001); no significant difference was found between male (25%) and female ones (38%) with instability alone.The mean VDP was significantly higher in male than in female infants (p < 0.001), in patients < 1 year of age than in older ones (p<0.001) and in severe than in moderate reflux (p<0.006). The mean voiding detrusor pressure of male infants was higher in severe (108+/-46cm H2O) and bilateral (101.3+/-44cm H2O) than in moderate (76+/-24 cm H2O) and unilateral (73.7+/-24 cm H2O) and in infants < 1 year of age (101.7+/-42 cm H2O) than in older ones (70.2+/-21 cm H2O). Natural filling cystometry confirmed the results of standard urodynamic studies. CONCLUSIONS: Bladder dysfunction is confirmed also in infants with reflux, particularly in male younger patients, and it differs in gender. The pathogenesis of congenital reflux is not always a feature of malformation of the vesico-ureteral junction; therefore, patients with bladder dysfunction must be identified early.     

Use of infliximab in the treatment of Crohn's disease in children and adolescents

BACKGROUND: Crohn's disease is often poorly responsive to conventional therapy with corticosteroids and immunomodulators. A novel chimeric antibody to tumor necrosis factor-alpha, infliximab, has shown utility in the treatment of refractory Crohn's disease in adults. PURPOSE: To evaluate the efficacy of open-label administration of infliximab in children and adolescents with active intestinal Crohn's disease. METHODS: Chart review of the experience with 19 subjects (mean age 14.4 years, range 9 to 19 years) receiving 1 to 3 infusions of infliximab (5 mg/kg/dose) over a 12-week period for corticosteroid-resistant disease (n = 7) or corticosteroid dependence (n = 12). Disease activity was monitored by physician global assessment and the Pediatric Crohn's Disease Activity Index. RESULTS: Significant initial improvement (first 4 weeks after infusion) was noted in all subjects, with Pediatric Crohn's Disease Activity Index values decreasing significantly (mean +/- SD, 42.1 +/- 13.7 to 10.0 +/- 5.6, P <.0001). Over the subsequent 8-week period, 8 of 19 treated subjects had worsening of symptoms, although none deteriorated to severe activity. The mean Pediatric Crohn's Disease Activity Index at 12 weeks was 26.8 +/- 16. 4. The mean daily prednisone dosages at baseline, 4 weeks, and 12 weeks were 28 +/- 14 mg, 20 +/- 12 mg, and 8 +/- 12 mg, respectively (P <.01). Adverse effects were noted in 3 patients during infusion (dyspnea, rash) and were self-limited. CONCLUSIONS: Infliximab is associated with short-term clinical improvement in children and adolescents with severe Crohn's disease. The rapid return of disease activity in some patients suggests that additional dosing strategies may be required. Long-term safety necessitates close monitoring.     

Nasal quantity of respiratory syncytical virus correlates with disease severity in hospitalized infants

OBJECTIVE: To evaluate the relationship between nasal quantity of respiratory syncytial virus (RSV) and disease severity in hospitalized infants without underlying cardiopulmonary disease or immunodeficiency. METHODS: Nasal aspirates were obtained from hospitalized infants <24 months of age with recently identified RSV infection and evaluated for RSV quantity by a standard plaque assay on HEp-2 cell monolayers. Subjects were classified as having "severe" disease if they required mechanical ventilation at the time of sample collection and as having "nonsevere" disease if they did not. Linear modeling was used to determine the relationship between nasal RSV quantity and various independent variables, including disease severity. RESULTS: Nasal aspirates from 39 patients were evaluated. Age, gender and mean duration of time from symptom onset to sample acquisition (5 days) were similar between the severe (n = 15) and nonsevere (n = 24) groups. Significantly more infants were born at <35 weeks gestation in the severe disease group (7 of 15 vs. 3 of 24, P = 0.017), and infants born at <35 weeks gestation were significantly more likely to be of non-Caucasian ethnicity than were infants born at > or =35 weeks gestation (8 of 10 vs. 12 of 29, P = 0.035). The linear model found that higher nasal RSV quantities were associated with severe disease [mean +/- SEM, 5.06 +/- 0.34 log plaque-forming units (pfu)/ml vs. 3.91 +/- 0.35 log pfu/ml, P = 0.022], gestational age > or =35 weeks (5.44 +/- 0.27 log pfu/ml vs. 3.52 +/- 0.45 log pfu/ml, P = 0.002) and non-Caucasian ethnicity (5.16 +/- 0.30 log pfu/ml vs. 3.80 +/- 0.37 log pfu/ml, P = 0.006). CONCLUSIONS: Nasal RSV quantity correlates with disease severity in hospitalized infants with recently identified RSV infection.     

Longitudinal study on thyroid function in patients with thalassemia major

Primary hypothyroidism is one of the most frequent complications observed in patients suffering from thalassemia. We investigated thyroid function in a group of patients attending the Pediatric Department of Cardarelli Hospital in order to determine in how many patients thyroid function worsened during a 12 year-period of follow up. PATIENTS AND MEASUREMENTS: Fifty patients with beta-thalassemia major (27 females and 23 males), mean age 25.7+/-1.4 years, were re-evaluated according to the criteria of Faglia et al. Thyroid dysfunction was defined as follows: overt hypothyroidism (low FT4 and increased TSH levels >10 microU/ml); compensated hypothyroidism (normal FT4, TSH 5-10 microU/ml, and abnormal TRH test); subclinical hypothyroidism (normal FT4, basal TSH 0-5 microU/ml, abnormal TRH test). Correlation with hematological, biochemical and growth parameters was evaluated. RESULTS: Ten out of 50 patients evaluated in a previous study had moved to other centers, and four patients had died from cardiac problems. Thus, 36 patients completed a 12 year-period of follow-up. In 25% of the patients the degree of thyroid dysfunction worsened with different degrees of severity. The prevalence of overt hypothyroidism had risen to 13.9% from 8.4%. No cases of secondary hypothyroidism were observed, and anti-thyroglobulin and anti-thyroperoxidase (TPO) antibody titers were negative in all patients. Five (28%) out of 17 patients with normal thyroid function previously (one female, four male) showed an exaggerated TSH response to a TRH test, with normal serum levels of FT4, and they were classified as having subclinical hypothyroidism; while another patient died of cardiac complications. Four out of twelve patients with previous subclinical hypothyroidism showed worsening with a different degree of severity: two females changed to compensated hypothyroidism, and two males to overt hypothyroidism. Furthermore, two out of six patients with compensated hypothyroidism and one out of four patients with overt hypothyroidism died of cardiac failure. In all patients there was no correlation between serum ferritin levels, blood transfusion, pretransfusion Hb levels and worsening of thyroid function. Echographic data showed features of dishomogeneity of the parenchyma with different degrees of severity in accordance with the criteria of Sostre and Reyes. The highest score was observed in all patients with overt and compensated hypothyroidism. CONCLUSIONS: A slow worsening of thyroid function was observed in 25% of the studied patients and only two of them developed overt hypothyroidism. The echographic pattern seems to be strongly predictive of thyroid dysfunction.     

Type 2 diabetes mellitus in African-American adolescents: impaired beta-cell function in the face of severe insulin resistance

We have previously demonstrated abnormalities in insulin secretion in adolescents with type 2 diabetes mellitus (DM2) in response to the mixed meal test and to glucagon. In order to further assess beta-cell function in DM2, we measured insulin and C-peptide responses to oral glucose in adolescents with DM2 in comparison to non-diabetic obese and lean adolescents. We studied 20 patients with DM2, 25 obese adolescents with matching body mass index (BMI) (33.8 +/- 1.4 vs 34.3 +/- 1.0 kg/m2), and 12 non-obese control adolescents (BMI 22.6 +/- 0.6 kg/m2). Mean age, sex and sexual maturation did not differ between the three groups. All adolescents with DM2 had negative islet cell antibodies (ICA); five patients were on diet and 15 on insulin treatment. Fasting lipid profiles were determined in all participants. Plasma glucose and serum C-peptide and insulin levels were measured at 0, 30, 60, 90, and 120 min after an oral glucose load. The C-peptide increment (deltaCP) was calculated as peak minus fasting C-peptide. Area under the curve (AUC) was estimated using the trapezoid method. Insulin resistance was estimated using the HOMA model (HOMA-IR). The first phase of insulin secretion (PH1) was computed using a previously published formula. Serum triglyceride levels were significantly higher in the patients with DM2 compared to the non-obese controls (1.4 +/- 0.1 vs 0.9 +/- 0.1 mmol/l; p = 0.02). Plasma glucose AUC was greater in the patients with DM2 compared to the obese and non-obese control groups (1,660 +/- 130 vs 717 +/- 17 vs 647 +/- 14 mmol/l x min; p < 0.0001). ACP was lower in adolescents with DM2 than in obese and non-obese adolescents (761 +/- 132 vs 1,721 +/- 165 vs 1,225 +/- 165 pmol/l; p < 0.001). Insulin AUC was lower in the patients with DM2 compared to obese controls (888 +/- 206 vs 1,606 +/- 166 pmol/l x h; p = 0.009), but comparable to that of the non-obese controls (888 +/- 206 vs 852 +/- 222 pmol/l x h; p = 0.9). Insulin AUC was also higher in the obese than in the non-obese group (p = 0.05). PH1 was significantly higher in the obese group compared to the patients with DM2 as well as to the non-obese controls (2,614 +/- 2,47.9 vs 929.6 +/- 403.5 vs 1,946 +/- 300.6 pmol/l, respectively; p = 0.001). PH1 was also higher in the non-obese controls than in the patients with DM2 (p = 0.05). HOMA-IR was three-fold higher in the patients with DM2 than in the BMI-matched obese group, and five-fold higher than in the lean controls (14.3 +/- 1.2 vs 5.4 +/- 0.8 vs 2.9 +/- 0.4; p = 0.0002). Adolescents with DM2 have dyslipidemia, a significant cardiovascular risk factor. Decreased beta-cell function is characteristic of adolescents with DM2 in the presence of severe insulin resistance.     

Thyroid dysfunction and high thyroid stimulating hormone levels in children with Down's syndrome

In order to delineate the spectrum of thyroid abnormalities in children with Down's syndrome (DS), first visit height data (SDS) and serum TSH, T4 and antiperoxidase antibodies concentrations were retrospectively evaluated in 137 children (71 girls) with DS (0.04-16 years). RESULTS: Congenital hypothyroidism was detected in 2.9% of patients. Thyroid disease occurred in 9%: four hyperthyroidism and eight hypothyroidism. Overt thyroid disease was always related to thyroid autoimmunity. The remaining 121 patients had normal T4 levels but increased mean TSH compared with controls (4.7 +/- 2.8 vs 2.3 +/- 1.3 mU/l). According to TSH levels, they were divided into two groups: G1 (n = 68) with normal TSH (<5 mU/l), and G2 (n = 53) with high TSH (> 5 mU/l). T4 levels were significantly lower in G2 (p < 0.01 vs G1 and controls). Height SDS was not different. CONCLUSIONS: Thyroid disorders are frequent in children with DS. Subtle thyroid abnormalities found in patients with DS with no evidence of clinical dysfunction need further investigation to demonstrate whether there is a need for therapeutic intervention.     

Growth in early treated congenital hypothyroidism

The growth of 361 children with congenital hypothyroidism diagnosed by screening was assessed by estimating mean values for height, weight, body mass index (BMI), and head circumference on each birthday up to the age of 4 years. In the group of children with severe congenital hypothyroidism (pretreatment plasma thyroxine < or = 30 nmol/l), the mean heights at 1 and 2 years were less than standards for healthy children, but this may be due to technical factors related to difficulties in measuring young infants and the method used to estimate height on each birthday. By the age of 3-4 years the values for mean height in the children with either severe or less severe congenital hypothyroidism were equal to or greater than those for healthy children. At all ages mean head circumference in boys and girls with severe congenital hypothyroidism was greater than standards for healthy children, but this only reached statistical significance in girls at 1 year. With the exception of the results for boys at 1 year, mean values for BMI were slightly greater in the children with severe congenital hypothyroidism. The mean BMI results for children with either severe or less severe congenital hypothyroidism were significantly greater than those for healthy French children at all ages, but they showed the same trends with increasing age. It is concluded that by the age of 3-4 years stature is essentially normal in children with early treated congenital hypothyroidism but that the increased head size reported before screening may still be evident in early infancy.     

甲状腺功能低下对新生期大鼠海马神经元凋亡及Bcl-2、Bax基因表达的影响

目的　探讨甲状腺功能低下 (简称甲低 )对新生期大鼠海马神经元凋亡及Bcl 2、Bax基因表达的影响。方法　孕 15天SD大鼠丙基硫氧嘧啶 (5 0mg/d)灌胃造成仔鼠甲低动物模型。采用化学发光法测定 1、5、10、15日龄仔鼠血清FT3 及FT4水平。取各日龄海马组织 ,应用光镜和透射电镜观察神经元形态学特点 ,琼脂糖凝胶电泳检测DNA降解片段 ,WesternBlotting检测Bcl 2和Bax基因蛋白表达的变化。结果　模型仔鼠各日龄血清FT4水平始终接近于药盒检测限 (2 8nmol/L) ,显著低于对照仔鼠 (1、5日龄P均 <0 0 1;10、15日龄P均 <0 0 0 1) ;血清FT3 较同日龄对照仔鼠降低 (1日龄P <0 0 5 ;其他日龄P均 <0 0 1)。模型仔鼠海马组织光镜下变性神经元增多 ,透射电镜下神经元凋亡明显增加 ,以 10、15日龄为著。DNA片段分析显示模型仔鼠各日龄均出现不同程度的DNA降解片段 ,对照仔鼠仅在 10日龄可见少量DNA降解片段。WesternBlotting结果显示对照仔鼠Bcl 2蛋白各日龄间表达水平不同 (P <0 0 5 ) ,1、5日龄表达较高 ,10日龄有所下降 ,15日龄回升 ;各日龄模型仔鼠与对照组相比表达水平明显下降 (1日龄 1 95± 0 2 7比 2 5 9± 0 19,P <0 0 5 ;5日龄 1 86± 0 2 4比 2 4 7± 0 17,P <0 0 5 ;10日龄 1 2 9± 0 2 2比 1     

Contributions of bone maturation measurements to the differential diagnosis of neonatal transient hypothyroidism versus dyshormonogenetic congenital hypothyroidism

AIM: To a) evaluate the contribution of bone maturation in the diagnosis of neonatal transient hypothyroidism versus dyshormonogenetic congenital hypothyroidism in full-term newborns, and b) use bone maturation to test the hypothesis that neonatal transient hypothyroidism is perinatal in onset. MATERIALS AND METHODS: The study included 20 patients with dyshormonogenetic and 43 with transient hypothyroidism. Thyroid function and measurements of the distal femoral epiphysis area, obtained at the time of first confirmatory diagnosis, were compared between the two groups. The epiphysis area in two control groups with normal thyroid function was also measured and compared with that in patients with transient hypothyroidism, at age 1-3 d (control A), or at the age when normal thyroid function was confirmed (control B). RESULTS: Mean epiphysis area was 0.04 cm2 in patients with dyshormonogenetic versus 0.22 cm2 in patients with transient hypothyroidism (p < 0.0001). An area <0.05 cm2 was limited to patients with dyshormonogenetic hypothyroidism. Conversely, a normal area (>0.2 cm2) was only observed in patients with transient hypothyroidism. Mean epiphysis areas in control A (0.20 cm2) and in patients with transient hypothyroidism were similar (p = 0.37), consistent with perinatal onset of transient hypothyroidism. Mean epiphysis area in control B (0.31 cm2) was significantly greater than in patients with transient hypothyroidism (p < 0.01). CONCLUSIONS: A short duration of hypothyroidism can significantly delay bone maturation. Examination of bone maturation at initial confirmatory evaluation yields important information pertaining to congenital hypothyroidism, not only to predict intellectual development, but also to evaluate the risk of dyshormonogenetic hypothyroidism.     

Hepatic fibrosis with choledochal cyst in infants and children - an immunohistochemical assessment.

METHODS: The study population was divided into 4 groups: 12 infants with choledochal cyst, aged 4 m to 12 m, were classified as the infant choledochal cyst (ICC) group; 36 children, aged 1 y to 14 y, were classified as the children with choledochal cyst (CCC) group; while 18 patients, aged 2 m to 5 m, with biliary atresia (BA) were included as positive controls; and 14 infants, aged 1 d to 3 y, who died from non-liver diseases served as negative controls (CON). Liver specimens were examined using H&E sections to score fibrosis by means of Ohkuma's classification, and immunohistochemical sections were evaluated by counting the cells positive for cytokeratin (CK) and human leukocyte antigen-DR (HLA-DR) to discover the pathogenic factors of fibrosis. RESULTS: Most ICC patients had clinical biliary obstruction. The liver fibrosis score was highest in the BA group (2.9 +/- 0.7). The fibrosis score in the ICC group was higher (2.5 +/- 0.9) than that of the CCC (1.5 +/- 1.2; p < 0.05) and of the CON (0.1 +/- 0.4; p < 0.01) groups. The densities of CK-positive cells were 164 +/- 80/HP, 253 +/- 165/HP, 70 +/- 57/HP and 23 +/- 12/HP in the BA, ICC, CCC and CON groups, respectively, and differed significantly (p < 0.01) with the exception of the ICC vs. the BA group. The densities of HLA-DR positive cells were 130 +/- 72/HP, 98 +/- 54/HP, 96 +/- 50/HP and 36 +/- 13/HP in the portal area in the BA, ICC, CCC and CON groups, respectively. The density was lowest in the CON group (p < 0.01). CONCLUSION: In patients with choledochal cyst, liver fibrosis is more common and severe in infants than in children. Obstruction of the bile duct and proliferation of bile duct cells were the main pathogenic factors for fibrosis, while HLA-DR mediating immuno-injury may play a limited role.     

Iodixanol Pharmacokinetics in Children

The objective of this report was to study the elimination pharmacokinetics of iodixanol in children. Iodixanol (Visipaque, Nycomed Inc., Wayne, PA, USA) is a new iso-osmolar iodinated radiocontrast agent. We hypothesized that elimination of this agent would be dependent on age-related differences in renal clearance. Seven centers enrolled 43 patients. Cardiac catheterization was performed in 41 patients and cranial computed tomography in 2. Patients were entered into 5 age groups: newborn to <2 months, 2 to <6 months, 6 months to <1 year, 1 to <3 years, and 3 to 6 months of age that is comparable to normal adults. Prolonged elimination in children <6 months of age is related to renal immaturity.