Congenital hypothyroidism

congenital hypothyroidism

1. Congenital Hypothyroidism Dr.Shivani Bansal

2. Thyroid gland Thyroid is an endocrine gland situated at the root of the neck on either side of the trachea. It has 2 lobes,which are connected in the middle by isthmus.

3. Hormones of thyroid gland- It secretes 3 hormones- Tetraiodothyronine or T4( thyroxine ) Tri- iodothyronine or T3 Calcitonin Function - Increase BMR - stimulates growth in children - increase oxygen consumption - stimulate protein synthesis - affect the carbohydrate ,lipid and vitamin metabolism

4. Thyroid development and physiology Fetal Development -the fetal thyroid bilobed shape is recognised by 7 weeks of gestation. Characterstic thyroid follicle cells and colloid formation is seen by 10 weeks Thyroglobulin synthesis occurs from 4 weeks Iodine trapping occurs by 8-10 weeks Thyroxine (t4) and triiodothyronine (t3) synthesis and secretion occur from 12 weeks of gestation

5. Hypothalamic neurons synthesise thyrotropin releasing hormone (TRH) by 6 to 8 weeks. Pitutary portal vessel system begins development by 8 to 10 weeks. Thyroid stimulating hormone (TSH) secretion is evident by 12 weeks of gestation. Thyroid Physiology- the main function of thyroid gland is to synthesise t4 and t3. The only known physiologic role of iodine is in the synthesis of these hormones The recommended dietary allowance of iodine is 30 ug /kg/24 hour for infants,90-120 ug /24 hour for children,and 150 ug /24 hour for adolescent and adults

6. Synthesis of thyroid hormones

7. The metabolic patency of t3 is 3 to 4 times that of t4 In adults thyroid produces approx 100 ug of t4 and 20 ug of t3 daily Only 20% of circulating t3 is secreted by thyroid The remainder is produced by de-iodination of t4 in liver ,kidney and other peripheral tissues by type I 5 ‘ deiodinase .

8. Thyroid regulation

9. Hypothyroidism Results from deficient production of thyroid hormone or a defect in thyroid hormone receptor activity disese may manifest from birth or acquired

10. Congenital Hypothyroidism- Congenital hypothyroidism (CH) is defined as thyroid hormone deficiency present at birth most cases of congenital hypothyroidism are not herediatory and result from thyroid dysgenesis Some cases may be famalial,usually caused by one of the inborn errors of thyroid hormone synthesis and may be associated with goiter. Incidence 1: 4,000 newborns worldwide Hispanic, American Indian/Alaska Native people (1:2,000 newborns) Black 1:3,2000 in black Americans

11. Etiology Common form of thyroid dysgenesis Aplasia Hypoplasia Ectopic gland (66%) Cause of thyroid dysgenesis is unknown (85% sporadic, 15% hereditary) Mutations Inborn errors of T4 synthesis, secretion, or utilization (2/3 heritable cases) Transient Hypothyroidism Maternal Autoimmune thyroiditis Maternal medication for Graves’ disease Endemic cretinism from iodine deficiency

12. Etiologic classification Central or ( Hypopitutary hypothyroidism) PIT 1 mutations-deficiency of TSH,GH and prolactin PROP 1 mutations-deficiency of TSH, GH, prolactin ,LH ,FSH +_ ACTH TRH defeciency TRH unresponsiveness TSH defeciency Multiple pitutary defeciency ex cranio pharyngioma TSH unresponsiveness Primary hypothyroidism Defect of fetal thyroid development- aplasia,hypoplasia,ectopia Defect in hormone synthesis-Iodine transport defect, thyroid peroxidase defect,Thyroglobulin synthesis defect Defect in thyroid hormone transport Iodine defecincy -neurological type , myxedematous type Maternal antibodies- thyrotropine receptor antibody Maternal medications-radio iodine , iodide,amiodarone

13. Clinical Manifestations Infants protected for 1 st few wks of life Fraction of maternal thyroid hormone crosses placenta >40 wk GA Head size Slightly higher % due to brain myxedema Large fontanels & wide sutures Macroglossia Distended abdomen with umbilical hernia Rough dry skin Skin cold with mottling Sensorineural deafness (10%) Other congenital anomalies (10%)

14. Sluggish feeding Constipation Lethargic Sleep more, needs to be awakened to feed Hoarse cry Hypothermia Cardiomegaly Murmur Asymptomatic pericardial effusion Macrocytic anemia Hypotonic with slow reflexes Prolonged physiological jaundice

15. If undiagnosed at a later age… Slow linear growth Loss of IQ Ataxia Gross/fine motor incordination Hypotonia & spasticity Speech disorders Attention deficit Strabismus Sensorineural deafness (10%)

16. Diagnosis: Primary hypothyroidism- low serum T4 & T3 and elevated TSH values Free T4 and free T3 are more specific TSH is extremely sensitive index of primary hypothyroidism Radiographic studies- significant delay in skl . Maturation, epiphyseal dysgenesis Imaging studies (U/S, radioisotope scan)- anatomical & functional status Thyroid antibody study- autoimmune thyroiditis Sec./Tertiary hypothyroidism- TSH levels low or undectable with subnormal levels of T3 & T4 as well as free T4 & T3 and associated deficiency of other pitutiary hormones

17. Radiological finding Retardation of osseous development Absence of distal epiphysis Epiphyseal dysgenesis Deformity ( beaking ) of 12 th thoracic or 1 st or 2 nd lumbar vertebra Skull show large fontanels and wide sutures

18. Epiphyseal dysgenesis Shortening of long bone Large fontanel and wide suture

19. Screening Started in Mid-1970’s Measure T4 & TSH > 48 hrs of life T4 – false-positive rate 0.30% TSH – false-positive 0.05% Preterm infants have higher false-positive If +  confirm  thyroid US or thyroid uptake scan If maternal autoimmune thyroid disease  measure TSH-binding inhibitor Ig If iodine exposure/deficiency  measure urinary iodine

20. Screening Ideal is universal newborn screening at 3-4 days of age. Universal screening: Most cases are sporadic in Iodine sufficient areas and intellectual impairment can be prevented if treatment is initiated early. In the absence of universal screening, newborns with following indications must be screened: 1.Having clinical features of congenital hypothyroidism or family history. 2.History of thyroid disease or anti-thyroid medication intake in mother. 3.Presence of other conditions like Down’s syndrome, trisomy 18, neural tube defects, congenital heart disease, metabolic disorders, familial autoimmune disorders are associated with higher prevalence of congenital hypothyroidism.

21. Screening Approaches Newborn screening is done using cord blood or by heel prick sample on dried blood spot filter paper at 2 nd and 5th days of life. Three approaches are being used for screening: 1. Primary TSH, back upT4 2. Primary T4, back up TSH 3. Concomitant T4and TSH

22. Screening Approaches 1. Primary TSH, back upT4: TSH is measured first. T4 is measured only if TSH is > 20 mu/L. 2. Primary T4, back up TSH: •T4is checked first •If it is low (< 6.5 μg / dL ), then TSH is also checked. • This is likely to miss milder/ subclinical cases of CH in which T4is initially normal with elevated TSH. 3. Concomitant T4and TSH: •It is the most sensitive approach but incurs higher cost. Abnormal values on screening should always be confirmed by a venous sample, using age appropriate cut-offs.

23. Approach to a newborn with positive screening test for Congenital Hypothyroidism Positive screening test on filter paper sample Serum T4/Free T4, TSH Abnormal Thyroid scan Ectopic Ectopic thyroid gland Normal Normal Absent uptake START TREATMENT-DON’T WAIT FOR SCAN

24. Age based reference values of thyroid hormones

25. Treatment Infants with low T4 and elevated TSH should be started on L- Thyroxine as soon as the diagnosis is made. Initial dose of L- Thyroxine is 10-15 μg /Kg/day. Infants with severe hypothyroidism (very low T4, very high TSH and absence of distal femoral and proximal tibial epiphyses on radiograph of knee) should be started with the highest dose of 15μg/Kg/day.

26. Preferred preparation is Sodium Levothyroxine . It has uniform potency, reliable absorption and good bioavailability. Daily dose should be crushed and placed directly on the tongue in the morning. Iron and Calcium preparations interfere with its absorption. If a dose is missed, then double dose should be given on the next day.

27. Monitoring: T4 andTSH should be monitored according to following schedule. 0 to 6 months Every month 6 months to 2 years Every 2- 3 months Beyond 2 years Every 6 months 6 to 8 weeks after any dose change. It takes less than a week for T4to raise and 4-5 weeks for TSH to normalize. Overtreatment- craniosynotosis & temprament problem

28. Prognosis: Final outcome in CH is closely related to the : - nature & severity of underlying thyroid abnormality. - age at diagnosis & onset of treatment - adequacy & regularity of treament Worldwide neonatal screening programs for CH have a significant impact on reducing intellectual deficits in hypothyroid infants diagnosed & treated early Early diagnosis & adequate treatment from 1 st week of life leads to normal linear growth & intelligence

29. In severe affected infant with lowest T4 level have reduce IQ level & neuropsychological sequelae . Without treatment child have mental deficient & growth retarted . Delay in diagnosis & failure to correct initial hypothyroxinemia rapidly, inadequate treatment & poor compliance in first 2-3 yrs of life result in variable degree of brain damage. When onset of hypothyroidism occur after 2yr of age, outlook for normal development is much better even if diagnosis & treatment have been delayed.

30. Thank you……..