Thyroid Disease in Children docx

Thyroid Disease in Children Thyroid Disease in Children Paul Paul Hruz Hruz MD PhD MD PhD Department of Department of Pediactrics Pediactrics September 2005 September 2005 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 Lecture Outline • Disorders of Thyroid Development • Thyroid Disease in the Newborn • Hypothyroidism in Children • Hyperthyroidism in Children • Thryoid Nodules Thyroid Physiology of the Fetus and Newborn • Normal Thyroid Development • Thyroid Status in Premature Infants • Transplacental Passage of Thyroid Ab • Newborn Screening • Congenital Hypothyroidism 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 Genetic Factors Impacting Thyroid Development Fetal Thyroid Maturation • TSH detectable by 12 wks • Feedback mechanisms established by 20 wks • T3 levels remain low • Reverse T3 levels high Placental and Fetal Thyroid Metabolism • Independent fetal axis – Limited T 4 exchange – Placental type 3 deiodoinase • Effect of maternal hypothyroidism – Most important in first trimester • Permeable to TRH, IgG and thionamides Thyroid Changes at Birth • TSH surge at birth followed by T 4 and T 3 rise • Important for interpreting newborn screen results • Lower rise in preterm infants Cord Blood Thryoid Levels • Influenced by gestational age • Progressive increase with approach to term [...]... Activating Mutation – McCune Albright Syndrome – Thyroid Tumor • Acquired – – – – – – – Inflammation Colloid Iodine Deficiency Goiterogen Infiltrative disease Toxic goiter Thyroglossal duct cyst – Adenoma – Carcinoma Endemic Goiter • Usually euthryoid • Diffuse gland enlargement • Rare in US (iodized salt provides adequate iodine source) • Rule out autoimmune thyroiditis • Treament Doses in Children. .. • Elevated T4, Free T4, T3 levels • Positive Thyroid Stimulating Antibodies: (May be helpful if exophthalmos absent) – Thyroid Peroxidase – Thyroglobulin – Thyroid Stimulating Immunoglobulin 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 (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... symptoms (HR>160) 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 Graves Disease: Diagnosis •... cases • Most common in premature infants • Causes: – Iodine deficiency or excess – Maternal antithyroid medication – Maternal TSH receptor blocking antibodies 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... Effective Treatment Available Thyroid Effects in the Fetus and Neonate 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 –.. .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 Principles of Newborn Screening • Relatively High Prevalence • Deleterious Consequence of Delayed Diagnosis • Difficult Clinical Recognition • Reliable Method of Screening (sensitive & specific)... present in utero • Resolves in 2-3 months as antibody clears 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... thyroxine Hypothyroidism • Congenital – Primary • Thryoid Agenesis • Dyshormonogenesis • Iodine Deficiency – Secondary • Hypopituitarism – Isolated – Multiple hormone deficiency • Acquired – Primary • • • • Surgery Radiation Autoimmune Iodine Deficiency – Secondary • • • • Surgery Radiation Infiltrative Tumor Common Symptoms and Signs of Hypothyroidism in Children Growth Failure in Childhood Hypothyroidism... Hypothyroidism Hypothyroidism: Treatment 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 Goiter: Differential Diagnosis • Congenital – Dyshormonogenesis – Maternal Antibodies • Blocking • Stimulating – Maternal Antithyroid drug • PTU, . Neurologic Damage Lecture Outline • Disorders of Thyroid Development • Thyroid Disease in the Newborn • Hypothyroidism in Children • Hyperthyroidism in Children • Thryoid Nodules Thyroid Physiology of. 2005 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. Thyroid Disease in Children Thyroid Disease in Children Paul Paul Hruz Hruz MD PhD MD PhD Department of Department of Pediactrics Pediactrics September 2005 September 2005 Introduction •