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Rob Lindsay, MD Adjunct Professor of Pediatrics University of Utah School of Medicine 10 year old girl with documented autoimmune (Hashimoto) thyroiditis and hypothyroidism. Her initial TSH was > 1000mU/L.  Type 1 Diabetes Mellitus  Down Syndrome  Turner’s Syndrome  Celiac Disease  Klinefelter’s Syndrome  Serum Free T4 and TSH are sufficient  Serum T3 levels often misleading    If measuring total T4 also do T3 resin uptake or thyroid binding protein Antithyroglobulin and antithyroid peroxidase antibodies Thyroid imaging rarely indicated NHANES III (1988 – 1994) Adolescents 12-19 years of age  6.3% positive antithyroglobulin  4.8% positive antithyroid peroxidase antibodies  2:1 Female:Male 105 children with positive antibodies and normal TSH followed for 5 years:  65% remained euthyroid  10% developed mild TSH elevation  26% developed TSH twofold above normal 55 children with positive antibodies and mildly elevated TSH levels:  29% reverted to normal TSH  29% were unchanged  42% developed TSH twofold above normal     1:3000 to 1:4000 in newborn infants More common in Hispanic and Native American infants at 1:2000 Less common in African American infants at 1:32,000 Consistently 2:1 Female:Male  85% are sporadic – 15% hereditary  90% permanent – 10% transient  Only 5% suspected by clinical diagnosis ◦ At time of newborn screen ◦ At 2-3 weeks of age  Birth weight and length normal  OFC slightly increased  Gestational age > 42 weeks in 33%  Primary T4 measurement with backup TSH  Primary TSH measurement  Recall rate (T4 <10%, TSH > 20 mU/L ◦ Primary T4 - 0.3% ◦ Primary TSH – 0.05%  Free T4 – Upper half of normal range: ◦ 1.4 – 2.3 ng/dl  TSH < 10 mU/L ◦ May take one month of treatment  Before Newborn Screening: ◦ If diagnosed between birth and 3 months  IQ = 89 ◦ If diagnosed between 3 and 6 months  IQ = 71 ◦ If diagnosed after 6 months  IQ = 54 1 year-old child with undiagnosed/untreated congenital hypothyroidism who was born before national screening programs for this condition. She was treated with replacement thyroid hormone, and 6 months later had a more normal facial appearance but significant developmental delays due to delay in diagnosis and treatment.  New England Congenital Hypothyroidism Collaborative ◦ Verbal IQ ◦ Performance IQ ◦ Full Scale IQ At 6 years of age. 109 107 109  New England Congenital Hypothyrodism Collaborative ◦ Inadequate treatment in first 3 years IQ = 87 A small proportion may have:  Language deficits  Problems with visual-spatial integration  Ataxia  Gross and fine motor incoordination  Muscle tone abnormalities  Short attention span  Strabismus  10% will have sensorineural deafness       Baloch Z, Carayon P, Conte-Devolx B, et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid 2003; 13:3. Cassio A, Ricci G, Baronio F, et al. Long-term clinical significance of thyroid autoimmunity in children with celiac disease. J Pediatr 2010; 156:292. Chiesa A, Gruñeiro de Papendieck L, Keselman A, et al. Final height in longterm primary hypothyroid children. J Pediatr Endocrinol Metab 1998; 11:51. Chiovato L, Larizza D, Bendinelli G, et al. Autoimmune hypothyroidism and hyperthyroidism in patients with Turner’s syndrome. Eur J Endocrinol 1996; 134-568. de Vries S, Bulvik S, Phillip M. Chronic autoimmune thyroiditis in children and adolescents: at presentation and during long-term follow-up. Arch Dis Child 2009; 94:33 Elmlinger MW, Kühnel W, Lambrecht HG, Ranke MB. Reference intervals from birth to adulthood for serum thyroxine (T4 ), triiodothyronine (T3), free T3, free T4, thyroxine binding globulin (TBG) and thyrotropin (TSH). Clin Chem Lab Med 2001: 39;973.        Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002; 87:489. Lazar L, Frumkin RB, Battat E, et al. Natural history of thyroid function tests over 5 years in a large pediatric cohort. J Clin Endocrinol Metab 2009; 94:1678. Lindsay AN, Voorhess ML, MacGillivray MH. Multicystic ovaries detected by sonography in children with hypothyroidism. AJDC 1980; 134:588. Lindsay AN, Voorhess ML, MacGillivray MH. Multicystic ovaries in primary hypothyroidism. Obstetrics & Gynecology 1983; 61:433. Lindsay AN, Voorhess ML. Slipped capital femoral epiphysis in hypothyroidism. AJDC 1984; 138:1149. Moore DC. Natural course of ‘subclinical; hypothyroidism in childhood and adolescence. Arch Pediatr Adolesc Med 1996; 150:293. Nelson JC, Clark SJ, Borut DL, et al. Age-related changes in serum free thyroxine during childhood and adolescence. J Pediatr 1993; 123:899.       Ozer G, Yüksel B, Kozanoġlu M, et al. Growth and development of 290 hypothyroidic patients at diagnosis. Acta Paediatr Jpn 1995; 37:145. Radetti ML, Gottardi E, Bona G, et al. The natural history of euthyroid Hashimoto’s thyroiditis in children. J Pediatr 2006; 149:827. Rallison ML, Dobyns BM, Meikle AW, et al. Natural history of thyroid abnormalities: prevalence, incidence and regression of thyroid diseases in adolescents and young adults. Am J Med 1991; 91:363. Rivkees SA, Bode HH, Crawford JD. Long-term growth in juvenile acquired hypothyroidism: the failure to achieve normal adult stature. N Engl J Med 1988; 318:599. Sattar N, Lazare F, Kacer M, et al. Celiac disease in children, adolescents, and young adults with autoimmune thyroid disease. J Pediatr 2011; 158:272. Sklar CA, Qazi R, David R. Juvenile autoimmune thyroiditis. Hormonal status at presentation and after long-term follow-up. Am J Dis Child 1986; 140:877.