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The Many Faces of Hypothyroidism Rob Lindsay, MD Adjunct Professor of Pediatrics University of Utah School of Medicine

The Many Faces of Hypothyroidism

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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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Page 1: The Many Faces of Hypothyroidism

The Many Faces of

HypothyroidismRob Lindsay, MD

Adjunct Professor of PediatricsUniversity of Utah School of Medicine

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Thyroid Gland Enlargement

10 year old girl with documented autoimmune (Hashimoto) thyroiditis and hypothyroidism. Her initial TSH was > 1000mU/L.

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Type 1 Diabetes Mellitus

Down Syndrome

Turner’s Syndrome

Celiac Disease

Klinefelter’s Syndrome

Associations

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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

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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

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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

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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

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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

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85% are sporadic – 15% hereditary

90% permanent – 10% transient

Congenital Hypothyroidism - Etiology

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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

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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

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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

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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

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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.

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New England Congenital Hypothyroidism Collaborative

◦ Verbal IQ 109◦ Performance IQ 107◦ Full Scale IQ 109

At 6 years of age.

Prognosis

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New England Congenital Hypo-thyrodism Collaborative

◦Inadequate treatment in first 3 years

IQ = 87

Prognosis

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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

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1st Grade

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2nd Grade

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3rd Grade

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4th Grade

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5th Grade

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6th Grade

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6th Grade

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7th Grade

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8th Grade

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10th Grade

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11th Grade

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12th Grade

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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 long-term 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.

Bibliography

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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.)

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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.)

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