The Many Faces of Hypothyroidism

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

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

9. Associations • Type 1 Diabetes Mellitus • Down Syndrome • Turner’s Syndrome • Celiac Disease • Klinefelter’s Syndrome

10. Diagnostic Studies • 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

12. Epidemiology NHANES III (1988 – 1994) Adolescents 12-19 years of age • 6.3% positive antithyroglobulin • 4.8% positive antithyroid peroxidase antibodies • 2:1 Female:Male

13. Epidemiology – Natural History 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

14. 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

34. 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

35. Congenital Hypothyroidism - Etiology • 85% are sporadic – 15% hereditary • 90% permanent – 10% transient

38. Clinical Manifestations • 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%

39. Newborn Screening • 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%

40. Treatment Goals • Free T4 – Upper half of normal range: • 1.4 – 2.3 ng/dl • TSH < 10 mU/L • May take one month of treatment

42. Prognosis • 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

43. 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.

44. Prognosis • New England Congenital Hypothyroidism Collaborative • Verbal IQ 109 • Performance IQ 107 • Full Scale IQ 109 At 6 years of age.

45. Prognosis • New England Congenital Hypo-thyrodism Collaborative • Inadequate treatment in first 3 years IQ = 87

46. 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

47. 1st Grade

48. 2nd Grade

49. 3rd Grade

50. 4th Grade