Objective: Evaluation of the frequency of Graves' ophthalmopathy (GO) and its management in children and adolescents up to 18 years old with Graves' hyperthyroidism. Study design: This was a questionnaire study (QS) among members of the European Thyroid Association and the European Society for Paediatric Endocrinology. Approximately 300 QS were sent to members with electronic addresses and 110 QS were returned from 25 countries: 52 respondents said they had no experience with Graves' disease in this age group, but 67 respondents (23 paediatric and 44 adult endocrinologists) completed the QS. Results: Out of 1963 patients with juvenile Graves' hyperthyroidism seen by respondents in the last 10 years, 641 (33%) had GO; about one-third of GO cases were # 10 years old, and two-thirds were 11-18 years old. The prevalences of GO among juvenile Graves' hyperthyroidism were 36.6, 27.3 and 25.9% in countries in which the smoking prevalence among teenagers was $ 25, 20-25 and , 20% respectively (P , 0.0001 by x 2 test). When confronted with the standard case of a 13-year-old girl with Graves' hyperthyroidism and moderately severe active GO, the diagnostic approach included on average 4.9 biochemical tests (TSH, free thyroxine (FT 4 ) and TSH.R-Ab, 100-88% of respondents) and 2.4 specific investigations (thyroid ultrasound by 69%, orthopsy/visual fields/visual acuity by 64% and orbital magnetic resonance imaging or computed tomography by 63%). Antithyroid drugs were the treatment of choice for 94% of respondents; 70% recommended a wait-and-see policy and 28% corticosteroids for the co-existing GO. In variants of the standard case, a younger age did not affect therapeutic approach very much. Recurrent hyperthyroidism would still be treated with antithyroid drugs by 66%, and with 131 I by 25%. Worsening of GO or active GO when euthyroid would convince about two-thirds of respondents to initiate treatment of GO, preferably with steroids. Conclusion: GO occurs in 33% of patients with juvenile Graves' hyperthyroidism; its prevalence is higher in countries with a higher prevalence of smoking among teenagers. The diagnostic approach to the standard case of a 13-year-old with Graves' hyperthyroidism and moderately severe active GO involves on average five biochemical tests; thyroid as well as orbital imaging is done in 84% of cases. Antithyroid drugs remain the treatment of choice for 94% of respondents, and even so in case of recurrences (66%). For GO, 70% recommend a wait-and-see policy; intervention, preferably with steroids, is advocated by two-thirds of respondents in cases of worsening or still-active eye disease despite euthyroidism.European Journal of Endocrinology 153 515-520

The absence of significant evidence of linkage at any one locus in such a large dataset argues that genetic susceptibility to AITD reflects a number of loci, each with a modest effect. Linkage analysis may be limited in defining such loci, and large-scale association studies may prove to be more useful in identifying genetic susceptibility factors for AITD.

Thyroid hormones and leptin are both involved in the regulation of energy metabolism. Serum leptin concentrations were measured in women with thyrotoxicosis (n = 21, mean age 45 years) or hypothyroidism (n = 14, mean age 44 years) before and 3 months after restoration of the euthyroid state. Serum leptin concentration tended to increase in both hypothyroid (14.7+/-3.5 vs 17.8+/-3.9 ng/ml, p = 0.06) and thyrotoxic (11.9+/-1.7 vs 14.4+/-2.0, p = 0.08) women after treatment (values given as mean +/- SE in the untreated and the euthyroid state respectively). Body mass index (BMI) was lower in thyrotoxic women than in hypothyroid women in the untreated state (22.1+/-0.7 vs. 26.2+/-1.9, p < 0.05). BMI was not different between both groups after treatment (24.5+/-0.7 vs. 26.3+/-2.1, p = 0.37), due to an increase of BMI in the thyrotoxic women; BMI did not change in the hypothyroid group. After controlling for BMI in a multivariate regression analysis, serum leptin concentrations were lower in hypothyroid women than in thyrotoxic women (p < 0.05), whereas posttreatment values of leptin did not differ (p = 0.44). When leptin concentrations were expressed as standard deviation scores (Z-scores) from the mean value of female controls matched for BMI and age as reported earlier, Z-scores were lower in the hypothyroid than in the thyrotoxic women (-0.63+/-0.21 vs. 0.53+/-0.18, p = 0.001). After treatment, Z-scores did not deviate from the expected values (0.05+/-0.28 vs. 0.08+/-0.16, p = 0.98). Z-scores differed before and after treatment in both hypothyroid (p = 0.01) and thyrotoxic (p = 0.02) patients. In conclusion, these data obtained in thyrotoxic and hypothyroid women indicate that thyroid states modulates serum leptin concentrations independent of BMI, with a small decrease in hypothyroidism and a small increase in thyrotoxicosis.

Objective: Total peripheral vascular resistance (TPR) decreases in thyrotoxicosis and increases in hypothyroidism. Several mechanisms may be involved, including adaptation to changes in heat production and direct non-genomic effects of tri-iodothyronine (T 3 ) on vascular smooth muscle cells. The aim of this study was to see if changes in TPR are related to changes in plasma concentrations of the endothelial hormones adrenomedullin and endothelin-1 as well as other hormones affecting vasculature. Design: A prospective study. Subjects: Eleven hypothyroid patients (pretreatment: thyroid-stimulating hormone (TSH) 68 (38±201) mU/l, T 3 0.7 (0.35±1.5) nmol/l, fT 4 3.0 (2.0±5.9) pmol/l, median (range)) and 14 with hyperthyroidism (pretreatment: TSH 0.02 (,0.01±0.06) mU/l, T 3 6.4 (2.3±13.0) nmol/l, fT 4 56.1 (22.9±70.0) pmol/l) were studied before treatment and 3 months after reaching the euthyroid state. Blood collection was carried out simultaneously with the recording of finger arterial pressure (FINAP). Cardiac output and TPR were derived from stroke volume computations by modelling flow from the FINAP signal. Results: Thyroid-function tests of hypothyroid and thyrotoxic patients did not differ after restoration of the euthyroid state. TPR, expressed in arbitrary units (AU), decreased after correction of hypothyroidism (from 1X32^0X65 to 0X96^0X36 AU, P 0X04 and increased after correction of hyperthyroidism (from 0X75^0X18 to 1X10^0X35 AU, P 0X007X Adrenomedullin concentrations did not change during the transition from the hypothyroid state 3.2(0.9±11.0) pmol/l to the euthyroid state 4.9(0.9±8.6) pmol/l, but decreased after treatment of hyperthyroidism, from 5.2(0.9±11.0) pmol/l to 2.2(0.9±5.4) pmol/l. Plasma endothelin-1 was undetectable in all samples. Changes in TPR upon treatment correlated with log DfT 4 r 20X65Y P 0X001Y log DT 3 Y r 20X57Y P 0X006Y D noradrenaline r 0X54Y P 0X02 and D ANP (atrial natriuretic peptide) r 20X59Y P 0X004X Multiple linear regression analysis indicated that only T 3 was an independent determinant of TPR. Changes in T 3 accounted for 46% of the variability in the changes in TPR. Conclusions: TPR is reduced in thyrotoxicosis and increased in hypothyroidism. Restoration of the euthyroid state normalizes TPR. Changes in TPR are not related to plasma adrenomedullin concentrations, but 46% could be explained by changes in T 3 . Altered ANP secretion and adenergic tone may contribute to the T 3 -induced changes in TPR.