Management of hyperthyroidism in children.

INTRODUCTION: Treatment of hyperthyroidism in children differs according to its etiology; in particular, the optimal therapy of Graves' disease (GD) remains a matter of debate and there is currently no evidence-based therapeutic strategy that is universally adopted in all the countries. Areas covered: The most recent treatment strategies in the different pediatric conditions which may be associated with hyperthyroidism. We searched PubMed and Cochrane (1990 to 2016) in order to identify articles to include in this review using the following terms: Hyperthyroidism, Childhood, Antithyroid drug therapy, Thyroidectomy, Radioactive iodine. Expert commentary: Although pharmacological therapy represents the first-line approach for GD children, we recommend to individualize, as much as possible, the overall therapeutic approach, with no prejudices towards radical therapies, particularly in the cases with frequent relapses. Clinical and laboratory preferential criteria for an individualized therapeutic approach to GD children are given. Treatment procedures for hyperthyroid children without GD are also discussed.

Early Discrimination between Transient and Permanent Congenital Hypothyroidism in Children with Eutopic Gland.

AIM: To analyze the factors that might allow an early discrimination between permanent (P) and transient (T) congenital hypothyroidism (CH). METHODS: Clinical, biochemical and imaging data of 64 children with eutopic gland, who were positively screened and treated for CH during the period 1998-2011, were retrospectively analyzed. RESULTS: During a 3-year treatment period, the mean doses of L-thyroxine (L-T4) per kilogram of body weight at various times were significantly lower in the 46 children with T CH than in the remaining 18 with P CH. No patients with T CH had required any increment of the doses of L-T4 per kilogram of body weight to maintain normal thyroid-stimulating hormone levels over time, whereas 16/18 children with P CH during the same period had needed some dose increments (p < 0.0001). CONCLUSIONS: (a) L-T4 requirements >4.9 µg/kg/day at 12 months or >4.27 µg/kg/day at 24 months are highly suggestive of P CH, irrespective of gland ultrasonography; (b) L-T4 requirements <1.7 µg/kg/day at 12 months or <1.45 µg/kg/day at 24 months are highly suggestive of T CH, at least in the cases with eutopic gland, and (c) the analysis of L-T4 requirements during the first years of treatment might allow an early discrimination between T and P CH in the cases with eutopic gland.

Peculiarities of autoimmune thyroid diseases in children with Turner or Down syndrome: an overview.

UNLABELLED: Aim of this commentary is to summarize the salient literature news on the relationships between autoimmune thyroid diseases (ATDs) and either Down syndrome (DS) or Turner syndrome (TS).According to literature reports both Hashimoto's thyroiditis (HT) and Graves' disease (GD) are more frequent in children with DS or TS than in those without these chromosomopathies.An up-regulation of proinflammatory cytokines might be responsible for the enhanced susceptibility of TS children to ATDs, whereas a dysregulation of immune system may favor the development of ATDs in DS.In TS children biochemical presentation of HT is less severe than in peer controls. In both DS and TS GD picture at the time of diagnosis is not significantly different than in the pediatric general population.The evolution over time of GD in DS and TS does not differ from that observed in the pediatric general population, whereas the evolution of HT in both TS and DS is more severe than in girls without these chromosomopathies. CONCLUSIONS: The association with TS or DS is able to affect both epidemiology and course of ATDs by conditioning: a) an increased susceptibility to these disorders; b) a less severe biochemical presentation and a more severe evolutive pattern of HT in TS girls; c) a more severe biochemical presentation and evolution of HT in DS patients.

Inhibin B in adolescents and young adults with Turner syndrome.

OBJECTIVE: Primary gonadal failure may occur in most individuals with Turner syndrome (TS). Since ovaries in TS girls undergo premature apoptosis and cryopreservation of ovarian tissue is now feasible, it would be useful to identify a reliable marker of ovarian reserve in these patients. We planned to evaluate ovarian function in a group of TS patients by measuring both traditional markers and inhibin B and to compare these results with those of a control group. STUDY DESIGN: We enrolled 23 patients with TS and 17 age-matched healthy girls. The median age of our TS patients was 17.6 years. Three out of the 23 patients (13%) showed spontaneous pubertal development and regular menstrual cycles; the remaining 20 (86.9%) presented with primary amenorrhea. RESULTS: The median level of inhibin B in the TS patients with primary amenorrhea was 42 pg/mL and did not differ significantly among the different subgroups in relation to karyotype. The median inhibin B level in the control group was significantly higher than in the TS girls with primary amenorrhea (83 vs. 42 pg/mL, p<0.00001). In the three patients with TS and spontaneous menstrual cycles, the inhibin B levels were significantly higher when compared to the values of the TS girls with primary amenorrhea. CONCLUSION: TS patients with primary amenorrhea have significantly lower levels of inhibin B than TS girls with spontaneous puberty and healthy controls. Inhibin B does not correlate with follicle-stimulating hormone/luteinizing hormone. If our results are confirmed in further studies, inhibin B could become a first-line screening test for assessing ovarian reserve and a longitudinal marker of the possible decline of ovarian function in TS.

The importance of disease prevalence in assessing the diagnostic value of a test: endoscopic markers in celiac disease.

BACKGROUND/AIMS: We evaluated the diagnostic variability and reproducibility of endoscopic signs in two populations with a different pretest likelihood of celiac disease (CD). METHODS: We recruited 289 CD patients (both adults and children) in a multicenter prospective study. Group 1 (high risk) included 111 patients referred for positive serology. Group 2 (low risk) included 178 unselected patients. Mosaic pattern, reduction/loss of Kerckring's folds, scalloping of the valvulae conniventes and a nodular pattern were the endoscopic findings looked for in the duodenum. RESULTS: In group 1, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of endoscopic findings were 100, 84.6, 94.2 and 100% in adults, and 86.8, 9.1, 82.1 and 12.5% in children. In group 2, the sensitivity, specificity, PPV and NPV of endoscopic findings were 33.3, 91.4, 7.7 and 98.5% in adults, and noncalculable, 78.3, 0.0 and 100% in children. Comparing group 1 and group 2, there was a statistically significant difference in sensitivity and PPV in adults, and in specificity, PPV and NPV in children. Concerning the reproducibility of endoscopic findings, a wide variability of κ values was found. CONCLUSION: Endoscopic signs have low reproducibility for CD, and their diagnostic value in selecting patients for multiple intestinal biopsies is unacceptable, especially in populations with low disease prevalence.

Diagnosis on a positive fashion of nonorganic failure to thrive.

AIMS: To study the predictive value of predefined symptoms and signs for allocating children into one of two groups: nonorganic and organic failure to thrive. PATIENTS AND METHODS: Two hundred eight outpatients (6 months-14 years old) suffering from failure to thrive (FTT) were included in the study. Predefined symptoms and signs were considered as potential predictors of organic/nonorganic failure to thrive. All patients underwent an established diagnostic work up in order to exclude organic causes of FTT. RESULTS: The percentage of patients without any organic symptom (negative predictive value), who were diagnosed as NOFTT was 92%; the percentage of patients having nonorganic symptoms only (positive predictive value), who were diagnosed as NOFTT was 96%, while their absence does not exclude a NOFTT diagnosis as well (negative predictive value = 41%). CONCLUSION: The detection of at least one nonorganic symptom or sign, with the exclusion of any organic symptom, can support a diagnosis of nonorganic FTT and therefore only few laboratory investigations seem to be warranted.

Effects of disease activity on anti-Saccharomyces cerevisiae antibodies: implications for diagnosis and follow-up of children with Crohn's disease.

BACKGROUND: To determine diagnostic accuracy of anti-Saccharomyces cerevisiae antibodies (ASCA) in identifying children with inflammatory bowel disease (IBD) and to differentiate Crohn's disease (CD) from other IBD forms; and to determine the effect of medical or surgical treatment and of disease location and activity on ASCA titers. METHODS: Serum samples were obtained from 196 IBD children and 142 controls. ASCA IgA and IgG titers were measured by ELISA. Measurements were repeated during the follow up of CD children. RESULTS: ASCA titers were significantly higher in CD than in other IBD and in control patients. Combination of IgA and IgG ASCA positivity was highly specific for CD. Medical treatment and disease location did not influence assay results. Significantly lower ASCA titers were obtained in CD children with intestinal resection compared to CD-affected children who did not undergo surgical resection. ASCA titers correlated significantly with disease activity, and children with severe active disease showed higher ASCA values compared to those in remission. A significant reduction of ASCA was observed during the follow-up of CD children when clinical remission was achieved. CONCLUSIONS: The diagnostic accuracy of ASCA is influenced by disease activity and this suggests an additional use for the follow-up of CD children of this assay.

Is intestinal biopsy always needed for diagnosis of celiac disease?

OBJECTIVE: Intestinal biopsy is required for a diagnosis of celiac disease (CD). The aim of this study was to assess diagnostic accuracy of transglutaminase antibodies (TGA) in comparison and in association with that of antiemdomysial antibodies (AEA), calculating the post-test odds of having the disease, to verify whether some patients might avoid undergoing intestinal biopsy for a diagnosis of CD. METHODS: A total of 181 consecutive patients (131 < 18 yr), referred to our celiac clinic by primary care physicians for suspect CD. Overall diagnostic accuracy, negative predictive value, and likelihood ratio (LR) were calculated both for each serological test and for serial testing (TGA and after AEA, assuming the post-test probability of TGA as pretest probability of AEA). Both serological determination and histological evaluation were blindly performed. Histology of duodenal mucosa was considered the gold standard. RESULTS: The overall accuracy of TGA and of AEA were 92.8% (89.1-96.6) and 93.4% (89.7-97.0), respectively. The negative predictive value of TGA and AEA were 97.2% (91.9-102.6) and 87.2% (77.7-96.8), respectively. Positive likelihood ratios for TGA and AEA were 3.89 (3.40-4.38) and 7.48 (6.73-8.23), respectively. Serial testing, in groups of patients with prevalence of CD estimated higher than 75%, such as those with classic symptoms of CD, would provide a post-test probability of more than 99%. CONCLUSIONS: Our results suggest that serial testing with TGA and AEA might allow, in some cases, the avoidance of intestinal biopsy to confirm the diagnosis of CD.

Diagnosis of celiac disease in pregnancy and puerperium: think about it.

We report 10 cases of celiac disease (CD) diagnosed after a pregnancy. During late pregnancy and/or puerperium a latent CD may be unmasked, so patients with mild gastrointestinal symptoms or anemia in pregnancy should be investigated to detect the disease before it might seriously affect maternofetal health.