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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.

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The many faces of hypothyroidism

The Many Faces of Hypothyroidism

Rob Lindsay, MD

Adjunct Professor of Pediatrics

University of Utah School of Medicine


Thyroid gland enlargement
Thyroid Gland Enlargement

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


Associations
Associations

  • Type 1 Diabetes Mellitus

  • Down Syndrome

  • Turner’s Syndrome

  • Celiac Disease

  • Klinefelter’s Syndrome


Diagnostic studies
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


Epidemiology
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


Epidemiology natural history
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


Epidemiology natural history1
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


Congenital hypothyroidism incidence
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


Congenital hypothyroidism etiology
Congenital Hypothyroidism - Etiology

  • 85% are sporadic – 15% hereditary

  • 90% permanent – 10% transient


Clinical manifestations
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%


Newborn screening
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%


Treatment goals
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


Prognosis
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


Undiagnosed untreated
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.


Prognosis1
Prognosis

  • New England Congenital Hypothyroidism Collaborative

    • Verbal IQ 109

    • Performance IQ 107

    • Full Scale IQ 109

      At 6 years of age.


Prognosis2
Prognosis

  • New England Congenital Hypo-thyrodism Collaborative

    • Inadequate treatment in first 3 years

      IQ = 87


Prognosis3
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


1 st grade
1st Grade


2 nd grade
2nd Grade


3 rd grade
3rd Grade


4 th grade
4th Grade


5 th grade
5th Grade


6 th grade
6th Grade


6 th grade1
6th Grade


7 th grade
7th Grade


8 th grade
8th Grade


10 th grade
10th Grade


11 th grade
11th Grade


12 th grade
12th Grade


Bibliography
Bibliography

  • 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 long-term primary hypothyroid children. J PediatrEndocrinolMetab 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). ClinChem Lab Med 2001: 39;973.


Bibliography cont
Bibliography (cont.)

  • 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 ClinEndocrinolMetab 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 ClinEndocrinolMetab 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 PediatrAdolesc 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 cont1
Bibliography (cont.)

  • Ozer G, Yüksel B, Kozanoġlu M, et al. Growth and development of 290 hypothyroidic patients at diagnosis. ActaPaediatrJpn 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.


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