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Understanding Thyroid Disease in Children: Development, Hormones, and Implications

Learn about thyroid development, hormonal changes at birth, TSH function, T4 regulation, and the role of thyroid hormones in growth, brain development, and energy production in children. Explore congenital hypothyroidism epidemiology, screening principles, and etiology.

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Understanding Thyroid Disease in Children: Development, Hormones, and Implications

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  1. INTRODUCTION • Thyroid Disease is the Most Common EndocrinopathyObserved in Children • Incidences, Presentations, and Clinical Consequences Differ Markedly than in adults • Failure to Diagnose and Treat Promptly may Lead to Irreversible Neurologic Damage

  2. THYROID GLAND • Derived from pharyngeal endoderm at 4/40 • Migrate from base of the tongue to cover the 2&3 tracheal rings. • Blood supply from ext. carotid & subclavian and blood flow is twice as renal blood flow/g tissue. • Starts producing thyroxin at 14/40.

  3. Thyroid Development • Orignatesfrom 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

  4. Fetal Thyroid Maturation: • TSH detectable by 12 wks • Feedback mechanisms established by 20 wks • T3 levels remain low • Reverse T3 levels high

  5. Placental and Fetal ThyroidMetabolism • Maternal and fetal glands are independent • Little T4 transplacental transfer • TSH does not cross the placenta although it is permeable to TRH, IgG, and thionamides • Fetal brain converts T4 to T3 efficiently • Effect of maternal hypothyroidism is most important in first trimester

  6. Thyroid Changes at Birth • Cord Blood Thyroid Levels are Influenced by gestational age withProgressive increase with approach to term. • TSH surge at birth followed by T4 and T3 rise to approximates maternal level but increases rapidly during the first week of life. • Lower rise in preterm Infants • High TSH in the first 5 days of life can give false positive neonatal screening

  7. THYROID HORMONES • Iodine & tyrosine form both T3 & T4 under TSH stimulation. • 10% of T4 production is autonomous and is present in patients with central hypothyroidism. • Less than 1% of T4 & T3 is free in plasma. • T4 is deiodinated in the tissues to either T3 (active) or reverse T3 (inactive). • When released into circulation T4 binds to: • Globulin TBG 75% • Prealbumin TBPA 20% • Albumin TBA 5%

  8. TSH • Is a Glico-protein with Molecular Wt of 28000 • Secreted by the anterior pituitary under influence of TRH • It stimulates iodine trapping,oxidation,organification, coupling and proteolysis of T4 & T3 • It also has trophic effect on thyroid gland

  9. T4 & T3 are feed-back regulators of TSH • TSH is stimulated by a-adrenergic agonists • TSH secretion is inhibited by: • Dopamine • Bromocreptine • Somatostatin • Corticosteroids

  10. THYROXINE (T4) • Conversion of T4 to T3 is decreased by: • Acute & chronic illnesses • b-adrenergic receptor blockers • Starvation & severe PEM • Corticosteroids • Propylthiouracil • High iodine intake (Wolff-Chaikoff effect

  11. Total T4 level is decreased in: • Premature infants • Hypopituitarism • Nephrotic syndrome • Liver cirrhosis • PEM • Protein losing entropathy

  12. Total T4 is decreased with the following drugs : • Steroids • Phenytoin • Salicylates • Sulfonamides • Testosterone • Maternal TBII

  13. Total T4 is increased with: • Acute thyroiditis • Acute hepatitis • Estrogen therapy • Clofibrate • iodides • Pregnancy • Maternal TSI

  14. Thyroid hormones are essential for: • Linear growth & pubertal development • Normal brain development & function • Energy production • Calcium mobilization from bone • Increasing sensitivity of b-adrenergic receptors to catecholeamines

  15. Hypothyroidism •Congenital • Acquired • – Primary • Surgery • Radiation • Autoimmune • Iodine Deficiency • – Secondary • Surgery • Radiation • Infiltrative • Tumor • – Primary • Thryoid Agenesis, Hypoplasia & mal-descent • Dyshormonogenesis • Iodine Deficiency • – Secondary • Hypopituitarism • Intake of goitrogens during pregnancy • Idiopathic

  16. CONGENITAL HYPOTHYROIDISM

  17. Epidemiology: • Incidence 1:4000 – Slightly higher in female infants – Higher in Asian babies – Lower in Black babies • Overt symptoms may not be present at birth • Profound effects on brain development, thus it is The most common cause of preventable mental retardation in children • Reliable testing available (T4 and/or TSH) • No sequelae if treatment initiated by 4 wks– 10-15 mcg/kg/d

  18. Principles of NewbornScreening • Relatively High Prevalence • Deleterious Consequence of Delayed Diagnosis • Difficult ClinicalRecognition • Reliable Method of Screening (sensitive & specific) • Safe, Effective Treatment available

  19. Etiology of 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

  20. 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

  21. 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 dysgenesisMay have permanent neurocognitive deficit if present in utero • Resolves in 2-3 months as antibody clears

  22. Cretinism is : • A condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroidhormones (congenital hypothyroidism)

  23. Symptoms and Signs: • Gestational age > 42 weeks • Birth weight > 4 kg • Open posterior fontanel • Nasal stuffiness & discharge • Macroglossia • Constipation & abdominal distension • Feeding problems & vomiting

  24. Non pitting edema of lower limbs & feet • Coarse features • Umbilical hernia • Hoarseness of voice • Anemia • Decreased physical activity • Prolonged (>2/52) neonatal jaundice

  25. Dry, pale & mottled skin • Low hair line & dry, scanty hair • Hypothermia & peripheral cyanosis • Hypercarotenemia • Growth failure • Retarded bone age • Stumpy fingers & broad hands

  26. Skeletal abnormalities: • Infantile proportions • Hip & knee flexion • Exaggerated lumbar lordosis • Delayed teeth eruption • Under developed mandible • Delayed closure of anterior fontanel

  27. Neurological manifestations • Hypotonia& later spasticity • Lethargy • Ataxia • Deafness +Mutism • Mental retardation • Slow relaxation of deep tendon jerks

  28. OCCASIONAL FEATURES • Overt obesity • Myopathy & rheumatic pains • Speech disorder • Impaired night vision • Sleep apnea (central & obstructive) • Anasarca • Achlorhydria & low intrinsic factor • Decreased bone turnover • Decreased VIII, IX & platelets adhesion • Decreased GFR & hyponatremia • Hypertension • Increased levels of CK, LDH & AST • Abnormal EEG & high CSF protein • Psychiatric manifestations

  29. ASSOCIATIONS • Autoimmune diseases (Diabetes Mellitus) • Cardiomyopathy & CHD • Galactorrhoea • Muscular dystrophy + pseudohypertrophy (Kocher-Debre-Semelaigne)

  30. Hashimoto thyroiditis • Most common cause of aquired hypothyroidism • Female: male ratio 3:1 • Most children presents with asymptomatic goiter or non specific Symptoms • Most frequent in Down and turner syndromes

  31. DIAGNOSIS • Early detection by neonatal screening • High index of suspicion in all infants with increased risk • Overt clinical presentation • Confirm diagnosis by appropriate lab and radiological tests

  32. LABROTARY FINDINGS • Low (T4, RI uptake & T3 resin uptake) • High TSH in primary hypothyroidism • High serum cholesterol & carotene levels • Anaemia (normo, micro or macrocytic) • High urinary creatinine/hydroxyproline ratio • CXR: cardiomegaly • ECG: low voltage & bradycardia

  33. IMAGING TESTS • X-ray films can show: • Delayed bone age or epiphyseal dysgenesis • Anterior peaking of vertebrae • Coxavara & coxaplana • Thyroid radio-isotope scan • Thyroid ultrasound • CT or MRI

  34. 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 wktrial off of thyroxine

  35. TREATMENT • Life-long replacement therapy • 5 types of preparations are available: • L-thyroxin (T4) • Triiodothyronine (T3) • Synthetic mixture T4/T3 in 4:1 ratio • Desiccated thyroid (38mg T4 & 9mg T3/grain) • Thyroglobulin (36mg T4 & 12mg T3/grain)

  36. L-Thyroxin is the drug of choice. Start with small dose to avoid cardiac strain. • Dose is 10 mg/kg/day in infancy. In older children start with 25 mg/day and increase by 25 mg every 2 weeks till required dose. • Monitor clinical progress & hormones level

  37. PROGNOSIS • Is good for linear growth & physical features even if treatment is delayed • for mental and intellectual development early treatment is crucial. • Sometimes early treatment may fail to prevent mental subnormality due to severe intra-uterine deficiency of thyroid hormones

  38. Goiter: Differential Diagnosis • • Congenital • – Dyshormonogenesis • – Maternal Antibodies • • Blocking • • Stimulating • – Maternal Antithyroid drug • PTU, methimazole • – TSH receptor Activating • Mutation • – McCune Albright Syndrome • – Thyroid Tumor • • Acquired • – Inflammation • – Colloid • – Iodine Deficiency • – Goiterogen • – Infiltrative disease • – Toxic goiter • – Thyroglossal duct • cyst • – Adenoma • – Carcinoma

  39. 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

  40. 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

  41. 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

  42. • Treatment: • – PTU or Methimazole • – SSKI (If severe symptoms) • – Propranolol (If significant sympathetic symptoms (HR>160)

  43. 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

  44. • Other classic signs: • – Weight Loss, Polyphagia, Tachycardia, Increased Pulse • Pressure, Heat Intolerance, Diarrhea, Tremor

  45. Grave’s 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

  46. 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

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