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      Thyroid function in children and adolescents with Hashimoto's thyroiditis after l-thyroxine discontinuation

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          Abstract

          Objective

          Thyroid function may recover in patients with Hashimoto’s thyroiditis (HT).

          Design

          To investigate thyroid function and the need to resume l-thyroxine treatment after its discontinuation.

          Setting

          Nine Italian pediatric endocrinology centers.

          Patients

          148 children and adolescents (25 m and 123 f) with HT on treatment with l-thyroxine for at least one year.

          Intervention and main outcome measure

          Treatment was discontinued in all patients, and serum TSH and fT4 concentrations were measured at the time of treatment discontinuation and then after 2, 6, 12 and 24 months. Therapy with l-thyroxine was re-instituted when TSH rose >10 U/L and/or fT4 was below the normal range. The patients were followed up when TSH concentrations were between 5 and 10 U/L and fT4 was in the normal range.

          Results

          At baseline, TSH was in the normal range in 139 patients, and was between 5 and 10 U/L in 9 patients. Treatment was re-instituted after 2 months in 37 (25.5%) patients, after 6 months in 13 patients (6.99%), after 12 months in 12 patients (8.6%), and after 24 months in an additional 3 patients (3.1%). At 24 months, 34 patients (34.3%) still required no treatment. TSH concentration >10 U/L at the time of diagnosis was the only predictive factor for the deterioration of thyroid function after l-thyroxine discontinuation.

          Conclusions

          This study confirms that not all children with HT need life-long therapy with l-thyroxine, and the discontinuation of treatment in patients with a TSH level <10 U/L at the time of diagnosis should be considered.

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          Most cited references30

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          Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.

          Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors. The "gold standard" glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo, but neither is easily implemented in large studies. Thus, it is of interest to develop a simple, accurate method for assessing insulin sensitivity that is useful for clinical investigations. We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sampled iv glucose tolerance tests on 28 nonobese, 13 obese, and 15 type 2 diabetic subjects. We obtained correlations between indexes of insulin sensitivity from glucose clamp studies (SI(Clamp)) and minimal model analysis (SI(MM)) that were comparable to previous reports (r = 0.57). We performed a sensitivity analysis on our data and discovered that physiological steady state values [i.e. fasting insulin (I(0)) and glucose (G(0))] contain critical information about insulin sensitivity. We defined a quantitative insulin sensitivity check index (QUICKI = 1/[log(I(0)) + log(G(0))]) that has substantially better correlation with SI(Clamp) (r = 0.78) than the correlation we observed between SI(MM) and SI(Clamp). Moreover, we observed a comparable overall correlation between QUICKI and SI(Clamp) in a totally independent group of 21 obese and 14 nonobese subjects from another institution. We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research.
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            2014 European Thyroid Association Guidelines for the Management of Subclinical Hypothyroidism in Pregnancy and in Children

            This guideline has been produced as the official statement of the European Thyroid Association guideline committee. Subclinical hypothyroidism (SCH) in pregnancy is defined as a thyroid-stimulating hormone (TSH) level above the pregnancy-related reference range with a normal serum thyroxine concentration. Isolated hypothyroxinaemia (defined as a thyroxine level below the 2.5th centile of the pregnancy-related reference range with a normal TSH level) is also recognized in pregnancy. In the majority of SCH the cause is autoimmune thyroiditis but may also be due to iodine deficiency. The cause of isolated hypothyroxinaemia is usually not apparent, but iodine deficiency may be a factor. SCH and isolated hypothyroxinaemia are both associated with adverse obstetric outcomes. Levothyroxine therapy may ameliorate some of these with SCH but not in isolated hypothyroxinaemia. SCH and isolated hypothyroxinaemia are both associated with neuro-intellectual impairment of the child, but there is no evidence that maternal levothyroxine therapy improves this outcome. Targeted antenatal screening for thyroid function will miss a substantial percentage of women with thyroid dysfunction. In children SCH (serum TSH concentration >5.5-10 mU/l) normalizes in >70% and persists in the majority of the remaining patients over the subsequent 5 years, but rarely worsens. There is a lack of studies examining the impact of SCH on the neuropsychological development of children under the age of 3 years. In older children, the evidence for an association between SCH and impaired neuropsychological development is inconsistent. Good quality studies examining the effect of treatment of SCH in children are lacking.
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              Studies of insulin resistance in patients with clinical and subclinical hypothyroidism.

              Although clinical hypothyroidism (HO) is associated with insulin resistance, there is no information on insulin action in subclinical hypothyroidism (SHO). To investigate this, we assessed the sensitivity of glucose metabolism to insulin both in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes with flow cytometry) in 21 euthyroid subjects (EU), 12 patients with HO, and 13 patients with SHO. All three groups had comparable plasma glucose levels, with the HO and SHO having higher plasma insulin than the EU (P<0.05). Homeostasis model assessment index was increased in HO (1.97+/-0.22) and SHO (1.99+/-0.13) versus EU (1.27+/-0.16, P<0.05), while Matsuda index was decreased in HO (3.89+/-0.36) and SHO (4.26+/-0.48) versus EU (7.76+/-0.87, P<0.001), suggesting insulin resistance in both fasting and post-glucose state. At 100 microU/ml insulin: i) GLUT4 levels on the monocyte plasma membrane were decreased in both HO (215+/-19 mean fluorescence intensity, MFI) and SHO (218+/-24 MFI) versus EU (270+/-25 MFI, P=0.03 and 0.04 respectively), and ii) glucose transport rates in monocytes from HO (481+/-30 MFI) and SHO (462+/-19 MFI) were decreased versus EU (571+/-15 MFI, P=0.04 and 0.004 respectively). In patients with HO and SHO: i) insulin resistance was comparable; ii) insulin-stimulated rates of glucose transport in isolated monocytes were decreased due to impaired translocation of GLUT4 glucose transporters on the plasma membrane; iii) these findings could justify the increased risk for insulin resistance-associated disorders, such as cardiovascular disease, observed in patients with HO or SHO.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                May 2017
                27 March 2017
                : 6
                : 4
                : 206-212
                Affiliations
                [1 ]Pediatrics Regional Hospital, Bolzano, Italy
                [2 ]Pediatrics University Federico II, Naples, Italy
                [3 ]Pediatric Endocrinology Ospedale Pedatrico Microcitemico ‘A. Cao’ – AOB Cagliari, Cagliari, Italy
                [4 ]Pediatric Endocrinology Bambino Gesù Children Hospital, Roma, Italy
                [5 ]Divisione di Endocrinologia Pediatrica Ospedale Infantile Regina Margherita, Torino, Italy
                [6 ]Department of Pediatrics University of Bologna, Bologna, Italy
                [7 ]Department of Pediatrics University of Pisa, Pisa, Italy
                [8 ]Paediatric Department Gaslini Hospital, Genova, Italy
                [9 ]Unit of Internal Medicine and Endocrinology Fondazione Salvatore Maugeri I.R.C.C.S., ISPESL Laboratory for Endocrine Disruptors, University of Pavia, Pavia, Italy
                [10 ]Department of Biostatistics Regional Hospital, Bolzano, Italy
                [11 ]Department of Pediatrics Vita-Salute San Raffaele University, Milan, Italy
                Author notes
                Correspondence should be addressed to G Radetti; Email: giorgio.radetti@ 123456gmail.com
                Article
                EC170023
                10.1530/EC-17-0023
                5434746
                28348002
                c7c86769-be54-4dde-b76e-e0983142db66
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 24 March 2017
                : 27 March 2017
                Categories
                Research

                hashimoto’s thyroiditis,children,l-thyroxine treatment,subclinical hypothyroidism,autoimmune thyroiditis

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