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The Many Faces of Hypothyroidism. Rob Lindsay, MD Adjunct Professor of Pediatrics University of Utah School of Medicine. Thyroid Gland Enlargement. 10 year old girl with documented autoimmune (Hashimoto) thyroiditis and hypothyroidism. Her initial TSH was > 1000mU/L. Associations. - PowerPoint PPT Presentation
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The Many Faces of
HypothyroidismRob Lindsay, MD
Adjunct Professor of PediatricsUniversity of Utah School of Medicine
Thyroid Gland Enlargement
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
Associations
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
Diagnostic Studies
NHANES III (1988 – 1994)
Adolescents 12-19 years of age 6.3% positive antithyroglobulin 4.8% positive antithyroid peroxidase
antibodies 2:1 Female:Male
Epidemiology
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
Epidemiology – Natural History
55 children with positive antibodies and mildly elevated TSH levels:
29% reverted to normal TSH
29% were unchanged
42% developed TSH twofold above normal
Epidemiology – Natural History
Congenital Hypothyroidism - Incidence
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
Congenital Hypothyroidism - Etiology
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%
Clinical Manifestations
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%
Newborn Screening
Free T4 – Upper half of normal range:◦ 1.4 – 2.3 ng/dl
TSH < 10 mU/L◦ May take one month of treatment
Treatment Goals
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
Prognosis
Undiagnosed/Untreated
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 109◦ Performance IQ 107◦ Full Scale IQ 109
At 6 years of age.
Prognosis
New England Congenital Hypo-thyrodism Collaborative
◦Inadequate treatment in first 3 years
IQ = 87
Prognosis
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
Prognosis
1st Grade
2nd Grade
3rd Grade
4th Grade
5th Grade
6th Grade
6th Grade
7th Grade
8th Grade
10th Grade
11th Grade
12th Grade
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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
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Bibliography
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.
Bibliography (cont.)
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.
Bibliography (cont.)