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Giorgio Radetti, Claudio Paganini, Roberto Crepaz, Walter Pittscheider and Lino Gentili

Radetti G, Paganini C, Crepaz R, Pittscheider W, Gentili L. Cardiovascular effects of long-term l-thyroxine therapy for Hashimoto's thyroiditis in children and adolescents. Eur J Endocrinol 1995;132:688–92. ISSN 0804–4643

Morphology and function of the left ventricle were evaluated by echo and Doppler examination in 16 females affected by Hashimoto's thyroiditis. aged 13.3 (4.5) years (range 7.9–24.6). They were on l-thyroxine (l-T4) treatment for a period of 2.8 (2.8) years (range 0.8–7.6) with a mean daily dose of 77 (18) μg/m2. Left ventricular mass, systolic and diastolic function, cardiac output and systemic vascular resistance did not differ from a control group matched for age, sex and body size. A further analysis of the patients according to thyrotrophin serum levels (less or more than 0.1 mU/l) gave similar results. Moreover, no relationship was found between echocardiographic findings and age, l-T4 daily doses, duration of treatment and serum level of thyroid hormones. We can therefore conclude that chronic l-T4 treatment for Hashimoto's thyroiditis at the given doses did not affect cardiac function and morphology in children and adolescents; however, a longer follow-up is needed before confirming the safety of this therapy in the long term.

Giorgio Radetti, Department of Paediatrics, Regional Hospital of Bolzano, via L Boehler no. 5, 39100 Bolzano, Italy

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Giorgio Radetti, Antonio Fanolla, Fiorenzo Lupi, Alessandro Sartorio and Graziano Grugni

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Giovanna Mantovani, Ernesto De Menis, Giorgio Borretta, Giorgio Radetti, Sara Bondioni, Anna Spada, Luca Persani and Paolo Beck-Peccoz

Objective: Mutations in the gene coding for the orphan nuclear receptor DAX1 cause X-linked adrenal hypoplasia congenita (AHC). Affected boys usually present with primary adrenal failure in early infancy or childhood. Impaired sexual development due to hypogonadotropic hypogonadism becomes manifest at the time of puberty. Moreover, evidence from Dax1 knockout mice and a limited number of patients with AHC, suggests that mutations in DAX1 may directly cause abnormalities in spermatogenesis. The aim of this study was to characterize clinically and genetically five patients with AHC.

Design: DNA sequencing analysis, endocrine testing, testicular ultrasound and semen analysis with 1-year follow-up after gonadotropin treatment.

Methods: We report on five men with classic AHC manifestations. Genomic DNA was extracted from patients’ peripheral blood leukocytes and the coding region, splice sites, and promoter (−240 bp) region of DAX1 were directly sequenced.

Results: Three known and two novel mutations were detected in the DAX1 coding sequence in these patients. Semen analysis was performed in four of the five patients and showed azoospermia. Twelvemonth treatment with gonadotropins did not restore fertility in these patients. All patients showed a normal testicular Doppler ultrasound, in contrast with that observed in Dax1-deficient mice, which display abnormalities in the rete testis.

Conclusions: These cases further expand the number of DAX1 mutations reported in the literature, as well as our clinical knowledge of this rare disease.

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Giorgio Radetti, Gianluca D’Addato, Davide Gatti, Mauro Bozzola and Silvano Adami

Objective: The aim was to investigate the effects of two different GH dosage regimens on growth, bone geometry and bone strength.

Subjects and methods: Final height; parentally adjusted final height; the metacarpal index (MI) SDS, the inner and outer diameters; and the total cross-sectional area (CSA), cortical CSA, medullary CSA and bone strength (Bending Breaking Resistance Index (BBRI)) were evaluated at the metacarpal site in two cohorts of GH-deficient children, treated with two different doses of GH. Group 1 (38 patients) was treated with 0.16 mg/kg body weight per week of GH and group 2 (37 patients) with 0.3 mg/kg per week.

Results: At the end of treatment, with group 1 vs group 2, height SDS was −0.84 ± 1.07 vs −0.46 ± 0.76, and parentally adjusted height SDS was 0.14 ± 1.08 vs 0.27 ± 0.82. Parentally adjusted relative height gain was 1.14 ± 0.89 vs 2.14 ± 0.72 SDS (P < 0.0001). MI SDS was 0.58 ± 1.31 vs −0.42 ± 1.54 (P < 0.005). MI SDS gain was 0.07 ± 1.41 vs −0.35 ± 1.85. There was no difference between groups in the outer and inner diameter, in the total and cortical CSAs, whereas medullary CSA was higher in group 2 (P < 0.05). BBRI was 10.02 ± 5.37 vs 11.52 ± 5.49 cm3, and BBRI gain was 3.33 ± 5.06 vs 6.88 ± 6.65 (P = 0.01). P values were assessed using student’s t-test.

Conclusion: Higher GH doses result in a greater height gain and improved bone strength.

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Filippo De Luca, Andrea Corrias, Mariacarolina Salerno, Malgorzata Wasniewska, Roberto Gastaldi, Alessandra Cassio, Alessandro Mussa, Tommaso Aversa, Giorgio Radetti and Teresa Arrigo

Objective

To compare the presentation and clinical course of Graves' disease (GD) in two pediatric populations consisting of 28 patients with Down's syndrome (DS) and 109 controls without DS respectively.

Design and methods

The evolution over time of GD was determined in both groups according to the clinical changes and the variations in TSH, free thyroxine, and TSH receptor autoantibodies serum levels during the entire follow-up.

Results

Female prevalence (50 vs 81.6%; χ 2=12.0, P<0.0005) and average age at GD presentation (9.9±4.4 vs 11.5±3.5 years, P<0.05) were significantly lower in DS group than in controls. Clinical responsiveness to methimazole therapy was significantly better in DS patients, as demonstrated by both the lower relapse rates after the first cycle withdrawal (7.1 vs 31.2%; χ 2=7.4, P<0.005) and the higher persistent remission rates after definitive therapy withdrawal (46.4 vs 26.7%; χ 2=4.1, P<0.05). Moreover, in DS group, no patients needed surgery or radioiodine ablation, whereas non-pharmacological treatment was necessary in 11% of controls (χ 2=3.8, P<0.05). Antecedents of Hashimoto's thyroiditis (HT) were documented in 21.4% of DS patients and in 3.7% of controls (χ 2=10.4, P<0.005). Association with other autoimmune diseases was detected in 32.1% of DS cases and in 12.8% of controls (χ 2=5.94, P<0.025).

Conclusions

GD in DS children and adolescents is characterized by several peculiarities: i) earlier presentation; ii) no gender predominance; iii) less severe clinical course; iv) higher frequency of documented HT antecedents; v) more frequent association with other autoimmune diseases.

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Chiara Guzzetti, Anastasia Ibba, Sabrina Pilia, Nadia Beltrami, Natascia Di Iorgi, Alessandra Rollo, Nadia Fratangeli, Giorgio Radetti, Stefano Zucchini, Mohamad Maghnie, Marco Cappa and Sandro Loche

Objective

The diagnosis of GH deficiency (GHD) in children and adolescents is established when GH concentrations fail to reach an arbitrary cut-off level after at least two provocative tests. The objective of the study was to define the optimal GH cut-offs to provocative tests in children and adolescents.

Design

Retrospective study in 372 subjects who underwent evaluation of GH secretion. GH and IGF-I were measured by chemiluminescence assay in all samples. Receiver operating characteristic (ROC) analysis was used to evaluate the optimal GH cut-offs and the diagnostic accuracy of provocative tests.

Methods

Seventy four patients with organic GHD (GH peak <10μg/L after two provocative tests) and 298 control subjects (GH response >10μg/L to at least one test) were included in the study. The provocative tests used were arginine, insulin tolerance test (ITT) and clonidine. Diagnostic criteria based on cut-offs identified by ROC analysis (best pair of values for sensitivity and specificity) were evaluated for each test individually and for each test combined with IGF-I SDS.

Results

The optimal GH cut-off for arginine resulted 6.5μg/L, 5.1μg/L for ITT and 6.8μg/L for clonidine. IGF-I SDS has low accuracy in diagnosing GHD (AUC=0.85). The combination of the results of provocative tests with IGF-I concentrations increased the specificity.

Conclusions

The results of the ROC analysis showed that the cut-off limits which discriminate between normal and GHD are lower than those commonly employed. IGF-I is characterized by low diagnostic accuracy.

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Mario Rotondi, Gloria Groppelli, Laura Croce, Francesco Latrofa, Giuseppe Ancona, Francesca Coperchini, Daniela Pasquali, Carlo Cappelli, Alessandro Fugazza, Valeria Guazzoni, Giorgio Radetti and Luca Chiovato

Objective:

The association between chronic autoimmune thyroiditis (CAT) and differentiated thyroid cancer (DTC) remains controversial. The incidence of DTC increases when screening procedures are implemented, as typically occurs in CAT patients being routinely submitted to thyroid ultrasound (US). The aim of this study was to longitudinally evaluate the long-term development of DTC in patients with CAT.

Design and methods:

A retrospective longitudinal cohort study was designed. For the study, 510 patients with chronic autoimmune thyroiditis (CAT) with a 10-year follow-up were enrolled. Patients were divided in two groups according to the presence (CAT+ NOD+; n = 115) or absence (CAT+ NOD−; n = 395) of co-existent nodules at diagnosis. The main outcome measures were appearance of new thyroid-nodules and development of DTC during follow-up.

Results:

During a 10-year median follow-up period, new thyroid-nodules were detected in 34/115 (29.5%) patients in the CAT+ NOD+ group and in 41/395 (10.3%) in the CAT+ NOD− group (P < 0.001). Logistic regression analysis showed that thyroid-volume at diagnosis and belonging to the CAT+ NOD+ group significantly predicted the appearance of a new thyroid nodule during follow-up, independently of baseline age and sex. Among the 75 patients experiencing the appearance of a new nodule, 27 (39%) met the criteria for fine-needle-aspiration-cytology (FNAC). A benign cytological diagnosis was rendered in all cases.

Conclusions:

In our series of CAT patients, the appearance of new thyroid-nodules was frequent, but none of them were found to be malignant. The presence of CAT appears to be associated with a negligible risk of developing clinically overt DTC.