Index. C Cancer patients, 205 CeH. See Central hypothyroidism (CeH) Cell surface transporters MCT8, 94 TH uptake, 94
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1 Index A Acquired CeH forms Allan Herndon Dudley syndrome, 89 cranial irradiation, 88 diminished FT4 serum levels, 88 NTI, 89 THAD, 90 TRH test, 89 Allan Herndon Dudley syndrome, 27, 89, 94 Angiogenesis, 16 Antithyroid drugs (ATDs), 75 therapy in children and adolescents, 211 remission, 211 side effects, 211 treatment options for GD, 211 ATDs. See Antithyroid drugs (ATDs) Athyreosis, 26, 52 Autoimmune thyroid disease tests, 42 Autoimmune thyroiditis, acute, subacute/chronic diseases, 179 HT (see Hashimoto s thyroiditis (HT)) B Benign thyroid nodules, 167 Biomarkers, neonatal screening autoimmune thyroid disease tests, 42 hormone concentration tests, 42 serum-binding protein tests, 42 thyroid-related protein tests, 43 C Cancer patients, 205 CeH. See Central hypothyroidism (CeH) Cell surface transporters MCT8, 94 TH uptake, 94 Central hypothyroidism (CeH) children acquired forms, causes, 84 inheritable forms, definition, 83 diagnosis, 83 mild forms, 83 prevalence, 83 replacement therapy, CH. See Congenital hypothyroidism (CH) Chemiluminescence immunoassay (CLIA), 45 Chronic autoimmune lymphocytic thyroiditis. See Hashimoto s thyroiditis (HT) CHTD. See Congenital hypothyroidism with thyroid dysgenesis (CHTD) Collective cell migration process, 6 Colloid goiter, 146, 151 Combined pituitary hormone deficiencies (CPHDs), 83 The Committee on Clinical Practice Issues of the American Society of Clinical Nutrition, 74 Congenital goiters dyshormonogenesis, G-protein α subunit, 148 thyroglossal duct cysts, 149 thyroid hemiagenesis, 149 TSH, 148 Congenital hemangioma/ hemangioendothelioma, 77 Congenital hypothyroidism (CH), 5. See also Etiology, CH causes of, 216 characteristics, 31 CH patients with thyroid dysgenesis, continuous health burden, definition, 51 Springer International Publishing Switzerland 2015 G. Bona et al. (eds.), Thyroid Diseases in Childhood: Recent Advances from Basic Science to Clinical Practice, DOI /
2 232 Congenital hypothyroidism (CH), 5. See also Etiology, CH ( cont. ) discordant monozygotic twins, 224 epidemiology primary CH, genetic causes, 223 genome-wide expression profile, 223 hormone substitution, 217 ipscs, 223 management counselling, 113 infants, 111 L-T4 dose, 113 L-T4 requirement, serum TSH, 115 severity, 112 T4/fT4, treatment, 112 ultrasound and iodine, 111 misperceptions, NBS (see Neonatal screening, CH) neurodevelopmental outcomes behavior and schooling problems, 120 hearing problems, 120 high-dose l-t4 therapy, 119 memory processes, 121 neonatal screening program, 118 psychomotor development, 122 QoL, school progression, 122 sensorimotor, TH deficiency, 117 primary (see Primary CH) regenerative medicine, 224 secondary (central), with thyroid dysgenesis, 224 thyroid hormones synthesis, 216 transient forms, 57 Congenital hypothyroidism with thyroid dysgenesis (CHTD), Congenital liver hemangiomas, 77 Congenital TSH deficiency, 57 CPHDs. See Combined pituitary hormone deficiencies (CPHDs) D Differentiated thyroid carcinoma (DTC) ATA management guidelines, 170 diagnostic whole-body scintigraphy, 171 levothyroxine therapy, lifelong follow-up, 171 lymph node involvement, 167 neck ultrasonography, 171 preoperative gross lymph node metastasis, 168 prophylactic central neck dissection, 167 thyroid follicle-derived tumor, 158 total thyroidectomy, DiGeorge syndrome, 5 DTC. See Differentiated thyroid carcinoma (DTC) Dutch NBS program, 44 Dyshormonogenesis, 27 IOD, 147 ITD, 147 ITDDs, 148 Pendred syndrome, thyroglobulin, 148 E Elastography, 165 Embryonic stem cells (ESCs) AFE, 218 culture pluripotent cells, 217 3D organoids, 219 EBs, 218 embryogenesis progression, 217 embryonic development, 219 endoderm-derived tissues, inner cell mass (ICM), 217 mesoderm-derived lineages, 218 molecular and morphological events, 217 neuronal cell types, 219 pluripotent stem cells, 219 totipotency, 217 Enzyme immunoassay (EIA), 45 ESCs. See Embryonic stem cells (ESCs) Etiology, CH central, 27 classification, 25, 26 description, 25 neonatal factors, 25 NKX2.1 mutations, 27 peripheral, 25, 27 permanent primary, 25, 26 secondary, 25 thyroid dysgenesis, 26 transient, 25 The European Society for Paediatric Endocrinology, 77 F Fetal development, TH in fetal growth, fetal maturation, FHPT, 17 growth Index
3 Index IGF-1 and IGF-2, 19 IL-6 gene expression and protein content, intrauterine growth, 19 IUGR, 20 thyroid dysfunctions, 20 implantation window angiogenesis, 16 NK cells, 16 TH and TSH, maternal thyroid function antithyroid drugs, Grave s disease, 21 hypothyroxinemia, 23 observational studies, 22 overt hyper-and hypothyroidism, 22 subclinical hyperthyroidism, 22 metabolism and biological activity in brain, 19 TH levels, 18 TH receptors (THr), 18 placenta, Fetal hyperthyroidism antithyroid drug treatment, 209, 210 diagnosis, 208 ft4 levels monitoring, 210 neonatal thyrotoxicosis, 207 overtreatment, 209 pathogenesis, 207 prognosis, 208 Fetal hypothalamic-pituitary-thyroid axis (FHPT), 17 Fetal maturation, TH adipose tissue, 21 cortisol, 20 heart, 21 liver, 21 lung, 21 FGF. See Fibroblast growth factor (FGF)-signals FHPT. See Fetal hypothalamic-pituitarythyroid axis (FHPT) Fibroblast growth factor (FGF)-signals, 5 Fine-needle aspiration biopsy (FNAB) definition, 166 diagnostic categories, 166 euthyroid and hypothyroid patients, 165 malignancies, 166 molecular and histochemical markers, 166 nodules with higher malignancy likelihood, 165 PTC, local and pulmonary metastatization, 166 solitary thyroid nodules, 165 thyroid ultrasound, Fluoroimmunoassay (FIA), 45 FNAB. See Fine-needle aspiration biopsy (FNAB) Follicular thyroid carcinoma (FTC), 158 Functional thyroid. See also Embryonic stem cells (ESCs) congenital hypothyroidism (CH), 216 cretinism, 216 defined media approach, 219 defined transcription factors, doxycycline-responsive promoter, 220 endoderm-derived organ, 215 endothelial cells, C cells and TFCs, 215 ESC-derived thyroid follicles, hypothyroid mice transplantation, feedback loop manner, 220 gland organogenesis, 216 immunofluorescence analysis, 220, 221 Matrigel, 220 morphological and terminal/functional differentiation, 216 NIS polarization and TG accumulation, 221 specification stage, thyroid follicle differentiation protocol, 220, 221 thyroid hormone synthesis, 220, 221 G GD. See Graves disease (GD) Genetic mutations heterozygous mutations, DUOX2, 76 TPO, 76 TSHR, 76 Goiter, in children and adolescents acute suppurative thyroiditis, 153 colloid goiter, 151 goitrogens, Graves disease, 152 HT, iodine deficiency goiter, 151 subacute thyroiditis, 153 differential diagnosis, Goitrogens, Graves disease (GD), 21, 152 antibodies mimic TSH action, 202 autoimmune diseases, 202 autoimmune neurological conditions, bone, 202 central and peripheral nervous system, 203 clinical phenotype, diagnosis, 204
4 234 Graves disease (GD) ( cont. ) etiological factors, 182 eye involvement, 203 genetic susceptibility to disease, involuntary movement disorders, 203 Moyamoya disease, 204 muscle function, 202 pretibial edema, 203 symmetrical goiter and biochemical profiles, 203 tachycardia, 202 Th2-type autoimmune disease, 201 thyroid hormones secretion, 202 TRAbs, 183 H Hashimoto s thyroiditis (HT), 101, autoimmune extrathyroidal diseases, 180 clinical features, 185, 186 constitutional, environmental and clinical factors, 181 diagnosis, 180, 183 diffuse lymphocytic infiltration, 204 DS/TS, 181 endocrine autoimmune disease, 204 epidemiological peculiarity, 180 GD, goiter and acquired hypothyroidism, 180 hyperthyroid phase, 205 inflammatory thyroid disorder, and nodular disease, pathogenesis, autoimmune conditions, 181 pathophysiology, prevalence, 180 and SH, 188 thyroid echogenicity from G1 to G4 patterns, 184 thyroid function tests, 184 time and long-term prognosis, TPOAbs, 183, 204 treatment, TSHR-Abs, 205 US criteria for, 183 Hormone concentration tests, 42 HT. See Hashimoto s thyroiditis (HT) Human PAX8 mutations molecular mechanisms cell-type-specific mutation analysis, 68 inactivation, PAX8 allele, 68 missense mutations, 68 qualitative defect hypothesis, thyroid echogenicity, 70 thyroid histology, mosaic PAX8 mutation carrier, 69 Index ultrasonography, 70 screening, 67 thyroid dysgenesis, 67 Hyperthyroidism. See also Fetal hyperthyroidism; Neonatal hyperthyroidism cancer patients, 205 in childhood and adolescence ATD therapy, 211 ß blockers, 211 RAI, 212 surgical treatment, GD (see Graves disease (GD)) HT (see Hashimoto s thyroiditis (HT)) imaging, 207 long-term outcomes, 212 RTH (see Resistance to thyroid hormones (RTHs)) TH serum levels, 201 TNs (see Thyroid nodules (TN)) TSHoma, 206 Hyperthyrotropinemia, 74, I IDD. See Iodine deficiency disorders (IDD) Inheritable CeH forms biallelic TSHβ mutations, 85 hypothalamic and pituitary genes, 85 IGSF1 transcripts, 87 nocturnal TSH surge, 87 phenotypes, 86 pituitary feedback mechanism, 87 INRICH. See Italian National Registry of Infants with Congenital Hypothyroidism (INRICH) Insulin-like growth factors (IGFs), 19 Intrauterine growth retardation (IUGR), 20 Iodide organification defects (IOD), 147 Iodide transport defects (ITD), 147 Iodine deficiency adverse effects, 139 in childhood intellectual disability, SH, 137 somatic growth, goiter, 130 IDD, 132 maternal iodine-deficient diets, 73 pregnancy and infancy birth weight and infant growth, 136 endemic cretinism, neonatal and infant mortality, 136 neurological defects, neurological development, 133
5 Index pregnancy and lactation, preterm infants, 74 prophylaxis and treatment salt fortification, 138 serum Tg, sources and metabolism, thyroid function, thyroid-stimulating hormone, 131 UIC, WHO recommendations, Iodine deficiency disorders (IDD), 132 Iodine excess thyroid hormone synthesis, 74 Wolff Chaikoff effect, 74 Iodotyrosine deiodinase defects (ITDD), 148 Italian National Registry of Infants with Congenital Hypothyroidism (INRICH), 52, 55 ITD. See Iodide transport defects (ITD) ITDD. See Iodotyrosine deiodinase defects (ITDD) L Levothyroxine therapy ATA task force, thyroid carcinoma, treatment, 169 TSH suppression, 170 M Maternal antithyroid drugs, 75 Maternal autoimmune thyroid disease autoimmune thyroiditis, 75 resampling, 76 TRBAb production, 75 McCune Albright syndrome, 205 Median thyroid primordium (thyroid anlage), 2 Medullary thyroid cancer (MTC) syndromes calcitonin levels monitoring, 171 distant metastases, 172 MEN type 2 syndromes, 160 RET activating mutations, 160 sporadic and hereditary forms, 168 surgery of, 168 MTC. See Medullary thyroid cancer (MTC) syndromes N Natural killer (NK) cells, 16 NBS. See Newborn screening (NBS) 235 Neonatal hyperthyroidism diagnosis, glucocorticoids and digoxin, 210 medical treatment, 210 neonatal thyrotoxicosis, 207, 210 prognosis, 209 propranolol and Lugol s solution, 210 Neonatal screening, CH. See also Newborn screening (NBS) analytical methods and technology, screening, biomarkers, DBS, quality assurance policy, 47 Newborn screening (NBS) continuous health burden, functional CH, 34 goal, 32 incidence, 33 initial diagnostic procedure and follow-up, molecular diagnosis and personalized medicine, specificity, 32 Newborn Screening Quality Assurance Program (NSQAP), 44 NK. See Natural killer (NK) cells Nodular disease and HT cancer prevalence, 186 thyroid cancer, occurrence, 185 with/without predictive value for cancer, 186, 187 The Nomenclature Committee of the American Thyroid Association, 46 Nonthyroidal illness (NTI), 89 Northwest Regional Newborn Screening Program, 58 NSQAP. See Newborn Screening Quality Assurance Program (NSQAP) NTI. See Nonthyroidal illness (NTI) Nuclear receptors, O Ontogenesis E10 mouse embryo, 3, 4 endoderm lineage, 3, 4 FGF-signals, 5 prime mover, 5 process of gastrulation, 3, 4 ptfc, 3 4 thyroid anlage, 3, 5
6 236 P Paired-box 8 (PAX8) mutations in humans decreased echogenicity, thyroid, 66 extrathyroidal manifestation, 67 frequency, 67 molecular mechanisms, thyroid hypoplasia, 66 ontogeny/physiology locations, missense PAX8 mutations, NKX2-1, 66 overexpression, PAX8, 66 paired domain, 63 proliferation defect, 64 Papillary thyroid carcinoma (PTC), 158 Pendred syndrome, Pituitary incidentalomas, 101 Precursors of thyroid follicular cells (ptfc), 3 4, 6 Premature infants hypothalamic-pituitary immaturity, 77 multiple variations, thyroid function, 77 Primary CH demographic changes, incidence case control studies, 54 modifications, rate, 53 premature birth and multiple pregnancy, screening, screening strategies and lowering TSH cutoff, seasonality, 54 PTC. See Papillary thyroid carcinoma (PTC) PTFC. See Precursors of thyroid follicular cells (ptfc) Q Quality assurance policy, NBS classification, 47 guidelines and reference procedures, 47 written procedures, 47 Quality of life (QoL), R Radioactive iodine (RAI) therapy in childhood and adolescence, hyperthyroidism, 212 levothyroxine administration, postsurgical treatment, DTC, 168 recombinant human TSH (rhtsh), 169 risks, 169 treatment, 169 Radioimmunoassay (RIA), 45 RAI. See Radioactive iodine (RAI) therapy Rearranged during transfection (RET), 160 Refetoff s syndrome, 27 Resistance to thyroid hormones (RTHs) homozygous mutations, 206 TH analogue, dextrothyroxine (d-t 4 ), 206 THRA and THRB genes, 206 Resistance to thyroid hormones syndrome (RTH β) cardiovascular symptoms, 98 description, 96 dominant negative effect, 96 goiter, hearing system, 101 homozygous patients, 96 immune system, 99 metabolism, neurological system, skeletal abnormalities, 98 subjects with GRTH, 97 TRβ mutations, 97 visual system, RET. See Rearranged during transfection (RET) RTHs. See Resistance to thyroid hormones (RTHs) Index S Scintigraphy, 165 Secondary (central) CH congenital TSH deficiency, 57 Northwest Regional Newborn Screening Program, 58 Sensorimotor, Serum-binding protein tests, 42 Serum Tg, SH. See Subclinical hypothyroidism (SH) Solitary thyroid nodule, 205 Stippled epiphyses, 98 Stokes shift, 45 Subacute thyroiditis, 153 Subclinical hypothyroidism (SH), 22, 137 clinical presentations, 195 definition, 193 diagnostic flow-chart, 195, 196 epidemiology, etiology of, 194 history of, 196
7 Index hypothyroidism, symptoms of, 195 isolated hyperthyrotropinemia, 193 mild hyperthyrotropinemia, 197 nonthyroidal illnesses, 194 overt hypothyroidism, 196 overweight/obesity, 194 transient neonatal hyperthyrotropinemia, 194 treatment, TSH pathway, TSH values, 196 T T4-backup TSH strategy, CH screening, THAD. See Thyroid hormone action defects (THAD) TH receptors (THr), 18 Thyroglobulin, 148 Thyroglossal duct cysts, 149 Thyroid carcinoma. See also Thyroid nodules (TN) anaplastic thyroid cancer, 170 DTC surgery, levothyroxine therapy, MTC surgery, 168 RAI, RET kinase inhibitors, 170 Thyroid dysfunction, 55 Thyroid dysgenesis, 26, 67 Thyroid ectopy, 26 Thyroid embryogenesis adult thyroid follicles, 1 TFC, 1 thyroid morphogenesis, 2 in animal models merging of UBBs, 7 ontogenesis, 3 5 in the postnatal thyroid, 6 7 precursors of TFCs, 6 proteins, 6 translocation and lobe formation, 6 TSH/Tshr signaling, 7 CHTD, genes Fgfr2, 11 Hox3 genes, 11 Nkx2-5, 10 in humans median thyroid primordium (thyroid anlage), 2 morphogenesis, 2 organogenesis, UBBs (lateral thyroid component), 2 3 making thyroid in vitro, 12 medicine translational approach, 11 thyroid toolkit genes Foxe1, 9 gene interactions, 10 Hhex, 9 10 Nkx2-1, 8 Pax8, 9 Thyroid enlargement congenital goiters, neonatal goiters ID, 150 maternal antibodies/goitrogens, nodular goiters ID, 150 maternal antibodies/goitrogens, TV, Thyroid follicular cells (TFC), 1 Thyroid hemiagenesis, 149 Thyroid hormone action cell surface transporters, 94 deiodination system, differential diagnosis, RTH β, metabolism disorders childhood growth retardation, 107 deficiencies, multiple selenoproteins, 107 DIOs, 106 mild bilateral high-frequency hearing loss, 107 SBP2, 106 selenoproteins, 106 therapy, 107 nuclear receptors, resistance, mutations in THRB gene ( see Resistance to thyroid hormones syndrome (RTH β)) resistance, RTH α constipation, 104 neurological and cognitive impairment, therapy, therapy, 103 Thyroid hormone action defects (THAD), 90 Thyroid hormone resistance, 27 Thyroid hypoplasia, 26 Thyroid neoplasms MTC syndromes, 160 pediatric differentiated thyroid cancer, follicular origin MAPK,
8 238 Thyroid neoplasms ( cont. ) nonmedullary, 161 thyroid morphogenesis pathway, 161 syndromic disorders, Thyroid nodules (TN). See also Thyroid neoplasms adult guidelines to pediatric population, 161 autoimmunity and cancer relationship, 159 autonomous thyroid nodules, 205 benign thyroid nodules, 167 clinical evaluation, 163 with congenital hypothyroidism, 159 diagnosis and workup, 158 elastography, 165 epidemiology, 158 family and patient s history, 163 FNAB, heterogeneous group, clinical entities, 159 ionizing radiations, laboratory tests, 164 McCune Albright syndrome, 205 non-neoplastic, 158 prognosis, 172 scintigraphy, 165 solitary thyroid nodule, 205 thyroid follicle-derived tumors, 158 thyroid ultrasound, TSH signaling, TSH-cAMP intrathyroidal pathway, 159 Thyroid-related protein tests, 43 Thyroid scintigraphy, 207 Thyroid ultrasound cardinal imaging tool, 164 color Doppler sonography, 164 malignancy with, features, Thyroid volume (TV) measurement, 145 normative data, 145 ultrasound, 145 Thyrotropin receptor blocking antibodies (TRBAb), Time-resolved fluoroimmunoassay (TR-FIA), 45 Toxic adenoma, 205 Transient forms, CH, 57 Transient neonatal hypothyroidism causes, 73 congenital hemangioma/ hemangioendothelioma, 77 drugs, 74 genetic mutations, 76 hyperthyrotropinemia, intrauterine exposure, maternal antithyroid drugs, 75 maternal and neonatal iodine deficiency/ excess, prematurity critically ill newborn, 77 transplacental passage, maternal TSH receptor, treatment reevaluation, thyroid axis, 78 TSH concentration, Transthyretin (TTR), TRBAb. See Thyrotropin receptor blocking antibodies (TRBAb) TR-FIA. See Time-resolved fluoroimmunoassay (TR-FIA) TSHoma, 206 U UBBs. See Ultimobranchial bodies (UBBs) UIC. See Urinary iodine concentration (UIC) Ultimobranchial bodies (UBBs) expression of Nkx2-1, 7 lateral thyroid component, 2 3 transcription factor Islet1, 7 Uncoupling protein 1 (UCP1) level, 21 Urinary iodine concentration (UIC), 74, , 134, 138 W Wolff Chaikoff effect, 74 World Health Organization (WHO), 127, , 138, 145 Index
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