Mariella Valenzise

Evaluation of the autoimmune regulator (AIRE) gene mutations in a cohort of Italian patients with autoimmune‐polyendocrinopathy‐candidiasis‐ectodermal‐dystrophy (APECED) and in their relatives

Objective   Autoimmune‐polyendocrinopathy‐candidiasis‐ectodermal‐dystrophy (APECED) is a rare syndrome characterized by chronic candidiasis, chronic hypoparathyroidism and Addisons disease. APECED has been associated with mutations in autoimmune regulator (AIRE) gene. Our aim is to perform a genetic analysis of the AIRE gene in Italian APECED patients and in their relatives.

Linear growth and intellectual outcome in children with long-term idiopathic subclinical hypothyroidism

OBJECTIVE The treatment of children with subclinical hypothyroidism (SH) is controversial for TSH values between 4.5 and 10 mU/l. The aim of this cross-sectional, controlled study was to evaluate growth and intellectual outcome in children with persistent SH who have never been treated with levothyroxine. DESIGN AND METHODS Clinical and auxological parameters, thyroid function, and intellectual outcome were evaluated in 36 children with persistent SH at the age of 9.7±0.6 (range 4-18.0) years. Children had been followed longitudinally for 3.3±0.3 (range 2.0-9.3) years, from first diagnosis of SH until enrollment in the study. Thirty-six age- and sex-matched children were enrolled in the study as controls. RESULTS At study entry, height (-0.8±0.2 SDS), bone age/chronological age (BA/CA ratio 0.92±0.6), and body mass index (BMI -0.1±0.2 SDS) in SH children were normal. Despite long-term duration of SH, none of these parameters showed a worsening with respect to height (-0.7±0.2 SDS), BA/CA (0.97±0.03), and BMI (-0.1±0.2) at the time of first SH detection. None of the children showed overt signs or symptoms of hypothyroidism during the follow-up. Verbal (99.1±2.2), performance (100.4±1.9), and full-scale (99.7±1.9) intelligence quotient (IQ) scores in SH children were normal and comparable to those of controls. No relationship was detected between IQ scores and the degree or duration of SH. CONCLUSIONS Persistent SH in children is not associated with alterations in growth, bone maturation, BMI, and cognitive function or other complaints that could be ascribed to SH even after several years without therapeutic intervention.

Direct comparison between continuous and coseasonal regimen for sublingual immunotherapy in children with grass allergy: a randomized controlled study.

To cite this article: Pajno GB, Caminiti L, Crisafulli G, Vita D, Valenzise M, De Luca R, Passalacqua G. Direct comparison between continuous and coseasonal regimen for sublingual immunotherapy in children with grass allergy: A randomized controlled study. Pediatr Allergy Immunol 2011: 22: 803–807.

Comparative Evaluation of Therapy with L -Thyroxine versus No Treatment in Children with Idiopathic and Mild Subclinical Hypothyroidism

Background: The question of whether children with subclinical hypothyroidism (SH) should be treated or not is controversial due to the lack of studies on outcomes of SH children treated with L-thyroxine (L-T4) versus those receiving no therapy. Objectives: (a) To evaluate thyroid tests under L-T4 and after therapy withdrawal in 69 SH children (group A) and (b) to compare our results with those recorded in 92 untreated children (group B). Design: Group A children were treated for 24 months and TSH and FT4 levels 3 months after therapy withdrawal were compared with those measured in group B at the end of follow-up in order to investigate treatment effects. Results: The prevalence of children who had normalized TSH at the end of follow-up was higher in group A, but the prevalence of those who had normalized or maintained unchanged TSH was similar in the two groups, as was the prevalence of children who exhibited a TSH increase >10 mU/l. In group A, TSH values at 27 months were associated with baseline values. Conclusions: (a) Two-year treatment in SH children is unable to modify posttherapy outcome of hyperthyrotropinemia; (b) therapy is unable to prevent the risk of further TSH increase after treatment withdrawal, and (c) posttherapy TSH outcome is conditioned by baseline TSH.

Late hormonal function after testicular torsion

INTRODUCTION Testicular torsion may be an important cause of male infertility. We aimed to investigate the late hormonal function in patients with testicular ischemia/reperfusion injury of the testis after orchidectomy or detorsion. METHODS Twenty patients (mean age, 13.6 years) were prospectively evaluated at a mean of 5 years after testicular torsion. The serum follicle-stimulating hormone, luteinizing hormone (before and after gonadotropin-releasing hormone stimulation), testosterone, and inhibin B were measured. Fifteen age-matched adolescents without evidence of endocrine disease were used as controls for inhibin B values. Data are quoted as mean +/- SEM. RESULTS Twelve patients were treated with detorsion and orchidopexy, and 8 underwent orchidectomy. Serum follicle-stimulating hormone, luteinizing hormone, and testosterone were all within the reference range. Inhibin B levels were significantly reduced in the 2 groups compared with the controls (34.5 +/- 5.2 vs 63.9 +/- 12.8 pg/mL, P = .02), but were not significantly different between the orchidectomy group and the group that underwent detorsion (41.3 +/- 9.7 vs 30.4 +/- 5.9 pg/mL, P = .41). CONCLUSION Hormonal testicular function can be compromised after testicular torsion, although the type of surgery (orchidectomy or orchidopexy) does not seem to change the effect of this ischemia/reperfusion injury.

Subclinical hypothyroidism: The state of the art

Subclinical hypothyroidism (SH) is a common clinical problem, particularly in adulthood and the elderly. Its prevalence is conditioned by several etiological and risk factors. The highest age- and sex-specific rates are in women over 60. SH may be associated with manifestations of mild thyroid failure, which may reverse under levothyroxine (L-T4) therapy. The risk of progression to overt hypothyroidism is distinctly higher in cases with underlying thyroid disease. A population routine screening is not generally recommended, but screening is encouraged in high-risk groups. L-T4 therapy may be indicated in subjects with TSH levels which are repeatedly and consistently elevated (>10 μIU/ml) and may be considered in those with TSH ranging between 4.5–5.5 and 10 μIU/ml, particularly if anti-thyroid antibodies are positive and/or hypothyroid symptoms are present. Treatment should be based, at least initially, on L-T4 low doses.

Defective Autoimmune Regulator-Dependent Central Tolerance to Myelin Protein Zero Is Linked to Autoimmune Peripheral Neuropathy

Chronic inflammatory demyelinating polyneuropathy is a debilitating autoimmune disease characterized by peripheral nerve demyelination and dysfunction. How the autoimmune response is initiated, identity of provoking Ags, and pathogenic effector mechanisms are not well defined. The autoimmune regulator (Aire) plays a critical role in central tolerance by promoting thymic expression of self-Ags and deletion of self-reactive T cells. In this study, we used mice with hypomorphic Aire function and two patients with Aire mutations to define how Aire deficiency results in spontaneous autoimmune peripheral neuropathy. Autoimmunity against peripheral nerves in both mice and humans targets myelin protein zero, an Ag for which expression is Aire-regulated in the thymus. Consistent with a defect in thymic tolerance, CD4+ T cells are sufficient to transfer disease in mice and produce IFN-γ in infiltrated peripheral nerves. Our findings suggest that defective Aire-mediated central tolerance to myelin protein zero initiates an autoimmune Th1 effector response toward peripheral nerves.

Thyroid Function Patterns at Hashimoto’s Thyroiditis Presentation in Childhood and Adolescence Are Mainly Conditioned by Patients’ Age

Background: There are few studies investigating the factors which may affect different biochemical presentations of Hashimoto’s thyroiditis (HT) and these are frequently based on limited pediatric populations. Aims: (1) To assess the frequency of thyroid function patterns at HT diagnosis in 608 children and adolescents, and (2) to analyze the factors that affect thyroid status at diagnosis. Results: At presentation, test results showed euthyroidism in 52.1% of patients (subgroup A), overt or subclinical hypothyroidism in 41.4%, and overt or subclinical hyperthyroidism in 6.5%. The mean age of patients with thyroid dysfunctions (subgroup B) was significantly lower than that of subgroup A, and the rate of children below 10 years of age was significantly greater in subgroup B. Other variables related to thyroid function patterns were prepubertal status; association with either Down or Turner syndromes, which correlated with increased risk of thyroid dysfunctions, and association with other autoimmune diseases, which correlated with decreased risk of thyroid dysfunctions. None of the remaining factors analyzed were associated with increased risk of thyroid dysfunctions. Conclusions: Biochemical thyroid function patterns at HT presentation in childhood and adolescence are mainly conditioned by patients’ age.

AIRE gene mutations and autoantibodies to interferon omega in patients with chronic hypoparathyroidism without APECED

Objective  To assess autoimmune regulator (AIRE) gene mutations, class II HLA haplotypes, and organ‐ or non‐organ‐specific autoantibodies in patients with chronic hypoparathyroidism (CH) without associated Addison’s disease (AD) or chronic candidiasis (CC).

Adherence to sublingual immunotherapy in preschool children.

Editor, Specific immunotherapy is the only effective causal treatment that can modify the natural history of respiratory allergy (1). This effect is important in children, where a secondary prevention is desirable. Sublingual administration (SLIT) is accepted as a valid therapeutic option (2), and children represent an ideal population for SLIT, because of the good safety profile (2). Nonetheless, as per all chronic treatments, adherence is essential, but no data are available in preschool children. We assessed the adherence to SLIT in children aged <6 yrs and analyzed the factors possibly affecting adherence itself. Children (age, 3–6 yrs) referred for respiratory diseases (bronchial asthma and/or rhinitis) and eligible for SLIT were enrolled. None had food allergy (possible confounding factor), and respiratory symptoms had to be present at least in the previous 6 months. The diagnosis of allergic asthma/ rhinitis was made according to guidelines (3, 4). Patients receiving SLIT were stratified according to age: group A (3£ yrs <4.0), group B (4.0£ yrs <5.0), group C (5.0£ yrs <6.0). All the procedures involved standard clinical approaches; thus, the study was simply notified to the Ethical Committee of the University of Messina, and all parents provided written informed consent. Children were followed up during the 2-yr observation period with 3-month regular visits. SLIT extracts were from Stallergénes, Lofarma, ALK– Abellò, Allergopharma. Parents were allowed to choose drops or tablets, and SLIT was given according to manufacturers’ recommendations. The administration technique was checked by pediatricians, using a placebo. Specific diary cards to assess the adherence (pre-compiled list), side effects, and reasons for discontinuation/temporary interruption of SLIT (free answers) were given to parents and collected at each visit. The time and reasons for interruption/discontinuation were carefully recorded. The remaining vials/tablets were checked at control visits. If >80% of the scheduled doses were taken, the patient was considered adherent. One hundred and fifty children (3–5.9 yrs, 86 boys) received SLIT for respiratory allergy (76% drops and 24% tablets). All suffered from allergic asthma and/or rhinitis from at least 6 months, and all received standard medications (antihistamines, intranasal corticosteroids, inhaled corticosteroids, bronchodilators). Mite SLIT accounted for 89.4% of prescriptions. Overall, 46% of 150 children discontinued SLIT. The percentage of discontinuations during the first year was significantly higher in group A than in groups B (52% vs. 18%, v = 12.7, p = 0.035) and C (52% vs. 13%, v 2 = 17.33, p = 0.032), whereas during the second year, there was no difference between groups (v 2 > 0.5). The reasons for discontinuation, as determined by parents’ interviews, are summarized in Table 1. The most common cause for withdrawal in group A was the subjective discomfort in keeping under the tongue drops/tablets, or children’s refusal, without apparent side effects. The refusal was generally attributed to unpleasant taste. For groups B and C, withdrawals were attributed to ineffectiveness, or to family problems, not better defined. All withdrawals occurred during the first 3 months of treatment in group A, and within the first 6 months in the other groups. In those patients who did not discontinue SLIT, short interruptions (all <5 days), as a