Microsoft PowerPoint - Thyroid Disease in Children

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Microsoft PowerPoint - Thyroid Disease in Children

  1. 1. Thyroid Disease in Children Paul Hruz MD PhD Department of Pediactrics September 2005
  2. 2. Introduction • Thyroid Disease is the Most Common Endocrinopathy Observed in Children • While the Disease Processes Present are Similar to Those in Adults, the Incidences, Presentations, and Clinical Consequences Can Differ Markedly • Failure to Diagnose and Treat Promply May Lead to Irreversible Neurologic Damage
  3. 3. Lecture Outline • Disorders of Thyroid Development • Thyroid Disease in the Newborn • Hypothyroidism in Children • Hyperthyroidism in Children • Thryoid Nodules
  4. 4. Thyroid Physiology of the Fetus and Newborn • Normal Thyroid Development • Thyroid Status in Premature Infants • Transplacental Passage of Thyroid Ab • Newborn Screening • Congenital Hypothyroidism
  5. 5. Thyroid Development • Orignates from thyroid diverticulum and ultimobranchial bodies • Ontogeny influenced by several transcription factors (TTF, PAX8, HOX3) • Largely complete by 10-12 weeks • Gradual Maturation in Hypothalamic -Pituitary-Thyroid Axis
  6. 6. Genetic Factors Impacting Thyroid Development
  7. 7. Fetal Thyroid Maturation • TSH detectable by 12 wks • Feedback mechanisms established by 20 wks • T3 levels remain low • Reverse T3 levels high
  8. 8. Placental and Fetal Thyroid Metabolism • Independent fetal axis – Limited T4 exchange – Placental type 3 deiodoinase • Effect of maternal hypothyroidism – Most important in first trimester • Permeable to TRH, IgG and thionamides
  9. 9. Thyroid Changes at Birth • TSH surge at birth followed by T4 and T3 rise • Important for interpreting newborn screen results • Lower rise in preterm infants
  10. 10. Cord Blood Thryoid Levels • Influenced by gestational age • Progressive increase with approach to term
  11. 11. Thyroid Status in Premature Infants • Relative immaturity of axis • Nadir at 2-3 wks • Influences – Illness, – Iodine exposure, – T4 clearance, – Iodine stores • TSH usually not elevated
  12. 12. Principles of Newborn Screening • Relatively High Prevalence • Deleterious Consequence of Delayed Diagnosis • Difficult Clinical Recognition • Reliable Method of Screening (sensitive & specific) • Safe, Effective Treatment Available
  13. 13. Thyroid Effects in the Fetus and Neonate
  14. 14. Congenital Hypothryoidism • Incidence 1:4000 – Slightly higher in female infants – Higher in Asian babies – Lower in Black babies • Primarily Sporadic Occurance • Overt symptoms may not be present at birth • Profound effects on brain development • Reliable testing available (T4 and/or TSH) • No sequelae if treatment initiated by 4 wks – 10-15 mcg/kg/d
  15. 15. Etiology of Primary Congenital Hypothryoidism • Extensive testing for precise etiology is generally not necessary (will not change immediate care plans) • May allow assessment of risk in future pregnancies • May allow early determination of transient vs permanent disease
  16. 16. Transient Congenital Hypothyroidism • Defined as abnormal newborn screen with abnormal confirmatory labs – 75-80% of abnormal screens due to false + • Incidence estimated to be ~10% of cases • Most common in premature infants • Causes: – Iodine deficiency or excess – Maternal antithyroid medication – Maternal TSH receptor blocking antibodies
  17. 17. Maternal TSH receptor blocking antibodies • Incidence estimated at 1:180,000 • Often history of treated Graves in mom – Mothers may have unrecognized hypothryoidism • Infant will not have goiter – Difficult to distinguish from thyroid dysgenesis • May have permanent neurocognitive deficit if present in utero • Resolves in 2-3 months as antibody clears
  18. 18. Treatment Guidelines • Confirm all abnormal newborn screens with laboratory TSH and free T4 – Borderline results may require repeat testing in 2-4 wks • If repeat labs abnormal, begin thryoxine (25-37.5 mcg/day) – Goal is to start treatment within first month of life • Recheck q 2-3 months and adjust dose if necessary • If no need to increase dose by 2 ½ -3 yrs, give 4 wk trial off of thyroxine
  19. 19. Hypothyroidism • Congenital • Acquired – Primary – Primary • Thryoid Agenesis • Surgery • Dyshormonogenesis • Radiation • Iodine Deficiency • Autoimmune – Secondary • Iodine Deficiency • Hypopituitarism – Secondary – Isolated • Surgery – Multiple hormone deficiency • Radiation • Infiltrative • Tumor
  20. 20. Common Symptoms and Signs of Hypothyroidism in Children
  21. 21. Growth Failure in Childhood Hypothyroidism
  22. 22. Hypothyroidism: Treatment
  23. 23. Hashimotos Thyroiditis • Most common cause of acquired hypothyroidism • Female:Male (3:1) • Most children present with asymptomatic goiter • Clinical Symptoms may be nonspecific • More frequent in Down and Turner Syndrome
  24. 24. Goiter: Differential Diagnosis • Congenital • Acquired – Dyshormonogenesis – Inflammation – Maternal Antibodies – Colloid • Blocking – Iodine Deficiency • Stimulating – Goiterogen – Maternal Antithyroid drug – Infiltrative disease • PTU, methimazole – Toxic goiter – TSH receptor Activating – Thyroglossal duct Mutation cyst – McCune Albright Syndrome – Adenoma – Thyroid Tumor – Carcinoma
  25. 25. Endemic Goiter • Usually euthryoid • Diffuse gland enlargement • Rare in US (iodized salt provides adequate iodine source) • Rule out autoimmune thyroiditis • Treament Doses in Children (6-12 months) – Infants 100 mcg/d – Children 200 mcg/day – Adolescents 200-300 mcg/d
  26. 26. Hyperthyroidism • Graves Disease (>95% of Cases) – Relatively rare in children – Incidence increases with puberty – Female:Male (3-5:1) • Neonatal Graves – Transplacental Antibodies • Hashitoxicosis • TSH receptor mutations (gain of function) – McCune Albright syndrome • Subacute Thyroiditis • Exogenous thyroxine Exposure
  27. 27. Neonatal Hyperthyroidism • Almost always transient • Usually associated with maternal Graves – Transplacental passage of TSI – Blocking and stimulating Abs may coexist • Incidence ~1:50,000 infants – 1-2% of moms with Graves disease • Often presents in first week of life – Emerges with clearance of maternal thionamide • Treatment – PTU or Methimazole – SSKI (If severe symptoms) – Propranolol (If significant sympathetic symptoms (HR>160)
  28. 28. Clinical Signs of Hyperthyroidism in Children • Change in School Performance • Insomnia • Restlessness and Irritability • Nocturia • Bone age advancement • Infants – Premature birth, Craniosynostosis, Poor feeding, Failure to Thrive • Other classic signs – Weight Loss, Polyphagia, Tachycardia, Increased Pulse Pressure, Heat Intolerance, Diarrhea, Tremor
  29. 29. Graves Disease: Diagnosis • Suppressed TSH • Elevated T4, Free T4, T3 levels • Positive Thyroid Stimulating Antibodies: (May be helpful if exophthalmos absent) – Thyroid Peroxidase – Thyroglobulin – Thyroid Stimulating Immunoglobulin
  30. 30. Treatment of Graves’ Disease • Radioactive Iodine – Preferred treatment in older children and adolescents – Theoretical risk of radiation not established – Possible increased risk of thryoid cancer (<5yrs) • Thionamides (methimazole, PTU) – Agranulocytosis, hepatitis, rash – Poor long term remission rates – Difficult to titrate dose, frequent monitoring – Poor compliance in adolescents • Surgical Thyroidectomy – Rarely indicated
  31. 31. Colloid (Nontoxic) Goiter • Diffuse enlargement of thryoid gland evident usually during pubertal years • Normal thyroid function tests • Often family history • May represent mild autoimmune thryoiditis – TPO Ab titer may be helpful to distinguish • May be associated with nodular goiter as adults • Therapy usually not necessary – May respond to thryoid suppression (controversial)
  32. 32. Thryoid Nodules • Low Prevalence in Children (0.2% <16 yrs) • Higher Incidence of Malignancy (18-22%) • Evaluation – Ultrasound can assist in detection but not helpful to distinguish benign from malignant nodules – Uptake scan generally not helpful (Hot nodules can be malignant) – Fine needle aspiration (90% accuracy) – Excisional biopsy • Majority are due to colloid cysts or follicular adenomas
  33. 33. Thyroid Cancer • Carcinoma is rare (1.5% in kids <15 yrs) – Papillary Carcinoma ~85-90% – Medullary Carcinoma ~5% – Follicular and Anaplastic Carcinoma • Risk Factors – Ionizing Radiation (esp if < 5 yrs) – Iodine Deficiency – Autoimmune thyroiditis – Prolonged TSH elevation – Family history (MEN)
  34. 34. Thyroid Cancer in MEN • Agressiveness: MEN2B>MEN2A>familial MTC • Prophylactic thryoidectomy – MEN2B <6 months – MEN2A <5 years
  35. 35. Case #1 • Term 3.25 kg male newborn infant with newborn screen (obtained on DOL #3) reported on DOL#10 with T4 of 20 mcg/dL and TSH 12.5. Infant doing well. No family history of thryoid disease. Mom healthy. 3 healthy sibs – What would you do next?
  36. 36. Case #1 (Continued) • Repeat TSH: 8.5 mcIU/ml, free T4: 1.2 ng/dL – What would you do now? • Follow-up labs in 2 weeks: – TSH 8, T4 8.5 mcg/dL • Started 25 mcg Synthroid q day, repeat labs 4 weeks later with TSH 2.5, T4 10.5 • At 2 ½ years of age, pt is still on 25 mcg Synthroid with normal TFTs.
  37. 37. Case #1 (continued) • Synthroid discontinued, TSH repeated 4 weeks later – Normal (4 mcIU/ml) • Diagnosis? – Transient congenital hypothyroidism
  38. 38. Case #2 • 3 wk old former 25 wk EGA female infant followed in NICU. On ventillator, PDA, TPN dependent, Wt 700 gm. TSH 2.3, free T4 0.6 ng/dL. – To treat or not to treat?
  39. 39. Case #3 • 13 year old girl with declining growth velocity for “several years”. No pubertal changes. Height currently at -3 S.D., Wt at 25%ile. Quiet personality. Presented with hip pain. No goiter • Initial labs showed TSH >300, T4 1.6 mcg/dL

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