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M. S. Laurent de Angulo and H. H. van Gelderen

ABSTRACT

An attempt has been made to determine the value of the lysine-8-vasopressin test when used together with the insulin-induced hypoglycaemia and the metyrapone test for the differentiation between hypothalamic and pituitary secondary adrenocortical insufficiency. This study was carried out in 65 children and adolescents with various disorders associated with growth retardation or overweight. The criteria for normal responses to the tests were based on findings in a 'control' group consisting of children with short stature without endocrinological disease. These criteria have been discussed in detail.

In the control group, the concordance between the results of each of the tests was good. As far as the groups with proven or possible hypothalamic and/or pituitary disorders were concerned, discrepancies between the LVP test results and those of the ITT were found in a considerably higher proportion of cases. The combination of an abnormal ITT and a normal LVP test was encountered significantly more often than the reverse situation. This is in agreement with the hypothesis that LVP acts directly on the adenohypophysis while ITT acts at the hypothalamic or higher levels. The LVP test seems to be a valuable additionto the tests of hypothalamic-hypophyseal function.

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Gerhard Ulrich Exner, Andrea Prader, Urs Elsasser, and Max Anliker

Abstract.

125I Computed Tomography (CT) allows for the selective determination of trabecular and compact bone mineral parameters in the radius. Using this technique the effects of high dose oestrogen treatment in 11 tall girls, and of high dose testosterone treatment in 5 tall boys were monitored. In both groups trabecular bone density (TBD) increased steadily during treatment at a rate of about 1% per month. Also in both groups the compact bone mineral increased steadily. These results are compared with those from a cross sectional study on 49 normal children and 36 normal adults, in whom TBD was found to be independent of age and sex, so that the increases in TBD in both treatment groups can be attributed directly to the influence of the sex hormones. Since the compact bone mineral is higher in adults than in children it cannot yet be decided whether the increases seen in the treated patients are related to the sex hormone treatment, or reflect only the normal development of the bone during adolescence.

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Paul Starr and John Nicoloff

ABSTRACT

Measurement of PBI values in healthy pre-adolescent Negro school children (N = 437) revealed a mean value of 6.4 ±.06 mg/100 ml while in a similar population of Caucasian children (N = 614) a normal mean value of 5.6 ±.07 mg/100 ml was observed. The difference had a P value <.001. Comparison of 131I T3 red cell uptake values in these two groups demonstrated a significant depression (P <.01) in the Negro children. TBG saturation capacities of Caucasian children were 24.7 ± 0.6 (S.E.M.) for ages 6 to 11 years and 21.3 ± 1.1 for ages 12 to 19 years which were not different from the adult values of 22.9 ± 0.8. In Negro children these values were 28.9 ± 0.7 for ages 6 to 11 and 25.4 ± 1.9 for ages 12 to 19 which were significantly different from their Caucasian counterparts. Adult Negro PBI values of 5.6 ± 0.25 and TBG of 24.5 ± 1.5 were not different from adult Caucasian values. Thyroxine-binding pre-albumin (TBPA) saturation capacities were significantly depressed in pre-adolescents (Caucasian 71 ± 7; Negro 69 ± 4) and adolescents (Caucasian 105 ± 13; Negro 109 ± 19) below the normal adult values but no racial difference was displayed. It is now apparent that racial origin must be a consideration in the evaluation of pre-adolescent and adolescent PBI and 131I T3 red cell uptake results and that TBPA and TBG capacities may normally alter during puberty in a manner independent of each other rather than reciprocally as has been recently proposed.

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W. Croughs, H. K. A. Visser, M. G. Woldring, and A. Bakker

The kinetics of thyroxin metabolism in adult man has been studied extensively (1, 2). In children only the data of Haddad (3) on 17 euthyroid children between 3 and 9 years of age are available.

Thyroxin turnover studies were carried out in 19 children between 3 and 15 years of age: euthyroid control 5; pituitary insufficiency 4; hypothyroidism during treatment 2; off treatment for 2 months 1; adolescent goiter 3; obesity 3 and one 3 years old eumetabolic child who had an iodine goiter at birth. Fractional rate of turnover K, thyroxin degradation rate D and other data were calculated according to Sterling cs. (2). In part of the children the thyroid gland was blocked with propylthiouracil; in the others also the thyroxin secretion rate S was calculated according to Ingbar cs. (1).

Results: Values for D and S were in good agreement. Mean value for K in 5 normal

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Michel Binoux and Micheline Gourmelen

Abstract. Using a protein-binding assay which measures mainly IGF I, serum levels of insulin-like growth factor (IGF) were determined in 263 children and adolescents of constitutionally variant stature but with normal GH secretion following provocative stimuli. A positive correlation was found between height age and the logarithm of IGF levels (r = 0.67, P < 0.001). Furthermore, a correlation was found in the tall and short subjects as a group between the ratio of IGF/normal IGF for age and between the ratio of growth rate/normal growth rate for age (r = 0.53, P < 0.001). Subjects were compared at the same stage of development. At a given bone age or stage of puberty, tall subjects had significantly higher IGF levels than short subjects (P < 0.005). After the completion of growth, IGF levels in both short and tall subjects stabilized within the normal range. Nevertheless, their mean levels remained significantly different (P < 0.001). Our results suggest that in normal children and adolescents, differences in IGF I secretion may be at least partially responsible for the individual differences in growth.

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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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Luca Chiovato, Daniela Larizza, Giovanna Bendinelli, Massimo Tonacchera, Michele Marinò, Claudia Mammoli, Renata Lorini, Francesca Severi, and Aldo Pinchera

Chiovato L, Larizza D, Bendinelli G, Tonacchera M, Marinò M, Mammoli C, Lorini R, Severi F, Pinchera A. Autoimmune hypothyroidism and hyperthyroidism in patients with Turner's syndrome. Eur J Endocrinol 1996;134:568–75. ISSN 0804–4643

A high prevalence of autoimmune thyroid disease (AITD) has been described in Turner's syndrome (TS) but the extent of this association is controversial for the prevalence of thyroid autoantibody and the clinical impact of thyroid dysfunction. In this study we searched for thyroid disease and thyroid autoantibodies in patients with TS. Seventy-five unselected TS patients (age range 3–30 years) were studied. Sera were tested for thyroid hormones, thyrotropin (TSH), thyroglobulin (TG-ab) and thyroperoxidase (TPO-ab) antibodies. The TSH-receptor antibodies with thyroid-stimulating (TS-ab) or TSH-blocking activity (TSHB-ab) were measured in the IgG fraction using a bioassay. Ten out of 75 (13.3%) TS patients had AITD: eight had autoimmune thyroiditis (AT) (six with subclinical and two with overt hypothyroidism and one with euthyroidism) and one had Graves' disease. The prevalence of AITD increased significantly (p < 0.05) from the first (15%) to the third (30%) decade of life. The prevalence of TPO-ab and/or TG-ab (20%) was higher (p < 0.05) in TS than in age-matched female controls and increased from the first (15%) to the third (30%) decade of life. Clinical AITD was diagnosed in 46% of TS patients with TPO-ab and/or TG-ab. Thyroid-stimulating antibody was detected in the hyperthyroid patient, and TSHB-ab was found in one of eight patients with hypothyroid AT. It was concluded that: TS patients are at higher than average risk of developing AITD not only in adolescence and adult age but also in childhood; hypothyroidism, mainly subclinical, is the most frequent thyroid dysfunction; elevated TPO-ab and/or TG-ab alone do not imply thyroid dysfunction; TS-ab or TSHB-ab are always associated with thyroid dysfunction although most cases of autoimmune hypothyroidism are not due to the latter antibody.

Luca Chiovato, Istituto di Endocrinologia, Università di Pisa, Viale del Tirreno, 64, 56018 Tirrenia, Pisa, Italy

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Eva Al Taji, Heike Biebermann, Zdeňka Límanová, Olga Hníková, Jaroslav Zikmund, Christof Dame, Annette Grüters, Jan Lebl, and Heiko Krude

Objective: Mutations in NKX2.1, NKX2.5, FOXE1 and PAX8 genes, encoding for transcription factors involved in the development of the thyroid gland, have been identified in a minority of patients with syndromic and non-syndromic congenital hypothyroidism (CH).

Design: In a phenotype-selected cohort of 170 Czech paediatric and adolescent patients with non-goitre CH, including thyroid dysgenesis, or non-goitre early-onset hypothyroidism, PAX8, NKX2.1, NKX2.5, FOXE1 and HHEX genes were analysed for mutations.

Methods: NKX2.1, NKX2.5, FOXE1 and HHEX genes were directly sequenced in patients with syndromic CH. PAX8 mutational screening was performed in all 170 patients by single-stranded conformation polymorphism, followed by direct sequencing of samples with abnormal findings. The R52P PAX8 mutation was functionally characterized by DNA binding studies.

Results: We identified a novel PAX8 mutation R52P, dominantly inherited in a three-generation pedigree and leading to non-congenital, early-onset, non-goitre, non-autoimmune hypothyroidism with gradual postnatal regression of the thyroid size and function. The R52P PAX8 mutation results in the substitution of a highly conserved residue of the DNA-binding domain with a loss-of-function effect. Conclusions: The very low frequency of genetic defects in a population-based cohort of children affected by non-goitre congenital and early-onset hypothyroidism, even in a phenotype-focussed screening study, suggests the pathogenetic role of either non-classic genetic mechanisms or the involvement of genes unknown so far. Identification of a novel PAX8 mutation in a particular variant of non-congenital early-onset hypothyroidism indicates a key function of PAX8 in the postnatal growth and functional maintenance of the thyroid gland.

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Caroline A Steele, Ian A MacFarlane, Joanne Blair, Daniel J Cuthbertson, Mohammed Didi, Conor Mallucci, Mohsen Javadpour, and Christina Daousi

Objective

To elucidate the long-term outcomes of pituitary adenomas diagnosed in childhood and adolescence, knowledge of which remains sparse.

Design and methods

A retrospective review of patients aged ≤21 years at diagnosis of pituitary adenoma, attending a neuroendocrine service in Liverpool, UK, between 1984–2009.

Results

There were 41 patients (33 female), mean age at diagnosis 17.3 years (range 11–21) and mean follow-up 9.6 years; 29 patients had prolactinomas (15 macroprolactinomas), 6 non-functioning pituitary adenomas (NFPAs), 5 Cushing's disease (CD) and 1 acromegaly. All prolactinoma patients received dopamine agonists (DAs) and three also underwent pituitary surgery. Furthermore, ten patients underwent surgery: five with CD, one with acromegaly and four with NFPA. Four received radiotherapy after surgery. Another ten patients received hormone replacement: nine hydrocortisone, five thyroxine, seven sex steroids and five GH; another seven had severe asymptomatic GH deficiency. Three female patients were treated for infertility (two successfully). Thirteen patients gained significant weight (body mass index (BMI) increase >2 kg/m2) since diagnosis and 16 in total are now obese (BMI>30 kg/m2). Five were treated with orlistat and one attended a weight management service. Two received antihypertensive medications, two had type 2 diabetes and four were treated for dyslipidaemia.

Conclusions

This is one of the largest reviews of patients aged 21 or younger at diagnosis of pituitary adenoma followed up by a single service. Two-thirds had prolactinomas, all were treated with DAs and three underwent surgery. Increased cardiovascular risk factors (obesity and dyslipidaemia) and infertility are important sequelae and active identification and treatment are necessary.

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Malgorzata Wasniewska, Mariacarolina Salerno, Alessandra Cassio, Andrea Corrias, Tommaso Aversa, Giuseppina Zirilli, Donatella Capalbo, Milva Bal, Alessandro Mussa, and Filippo De Luca

Objective

To prospectively evaluate the course of subclinical hypothyroidism (SH) in children and adolescents with no underlying diseases and no risk factors, which might interfere with the progression of SH.

Design

Clinical status, thyroid function, and autoimmunity were prospectively evaluated at entry and after 6, 12, and 24 months in 92 young patients (mean age 8.1±3.0 years) with idiopathic SH.

Results

During the study, mean TSH levels showed a trend toward a progressive decrease while FT4 levels remained unchanged. Overall, 38 patients normalized their TSH (group A): 16 patients between 6 and 12 months, and 22 patients between 12 and 24 months. Among the remaining 54 patients, the majority maintained TSH within the baseline values (group B), whereas 11 exhibited a further increase in TSH above 10 mU/l (group C). Baseline TSH and FT4 levels were similar in the patients who normalized TSH, compared with those with persistent hyperthyrotropinemia. Even in the patients of group C, both TSH and FT4 at entry were not different with respect to those of groups A and B. No patients showed any symptoms of hypothyroidism during follow-up and no changes in both height and body mass index were observed throughout the observation period.

Conclusions

(a) The natural course of TSH values in a pediatric population with idiopathic SH is characterized by a progressive decrease over time; (b) the majority of patients (88%) normalized or maintained unchanged their TSH; and (c) TSH changes were not associated with either FT4 values or clinical status or auxological parameters.