1. . Common Thyroid Disorders in Children Dr Sarar Mohamed FRCPCH (UK), MRCP (UK), CCST (Ire), CPT (Ire), DCH (Ire), MD Consultant Paediatric Endocrinologist & Metabolic Physician Associate Professor of Pediatrics King Saud University

2. . Agenda Thyroid Function Test Congenital Hypothyroidism coommon in peds. Newborn screening for congenital hypothyroidism Acquired hypothyroidism e.g. hashimoto thyroditis. Hyperthyroidism Causes of goiter

4. Thyroid Function: blood tests TSH0.4 –5.0 mU/L Free T4 (thyroxine)9.1 – 23.8 pM Free T3 (triiodothyronine)2.23-5.3 pM The main tests to be done is TSH and free T4

5. Dysfunction Thyroid Gland 1. Too little thyroxin – hypothyroidism a. short stature (acquired), developmental delay (congenital) 2. Too much thyroxin – hyperthyroidism a. Agitation, irritability, & weight loss Goiter is common in children with hypo/hyperthyroidsim due to both congenital and acquired diseases.

6. Hypothyroidism Decreased thyroid hormone levels Low T4 Possibly Low T3 too. Raised TSH (unless pituitary problem!)

7. Causes of hypothyroidism 1.Congenital 2.Autoimmune (Hashimoto) 1 st two are the main causes. 1.Iodine deficiency 2.Subacute thyroiditis usually viral infection. 3.Drugs (amiodarone) 4.Irradiation 5.Thyroid surgery 6.Central hypothyroidism (radiotherapy, surgery, tumor) secondary to any pituitary disease. 7.Any disease of the pituitary can lead to hypothyroidism..

8. Clinical features of Acquired hypothyroidism 1.Weight gain 2.Goitre 3.Short stature: any child with short stature should be worked up for hypothyrodism because it responds dramatically to thyroxin) 4.Fatigue 5.Constipation 6.Dry skin 7.Cold Intolerance 8.Hoarseness 9.Sinus Bradycardia.

9. Hypothyroidism with short stature

10. Diagnosis High TSH, low T4 Thyroid antibodies.

11. Hashimoto’s Disease Most common cause of acquired hypothyroidism Autoimmune lymphocytic thyroiditis Antithyroid antibodies: Thyroglobulin Ab Microsomal Ab TSH-R Ab (block) Females > Males Runs in Families!

12. Subacute (de Quervain’s) Thyroiditis Preceding viral infection Infiltration of the gland with granulomas Painful goitre Hyperthyroid phase  Hypothyroid phase

13. Treatment of Hypothyroidism Replacement of thyroid hormone medication: Thyroxine Daily thyroxine with follow up with thyroid function test. If congenital, treatment is needed for life. In acquired, you may stop the treatment when thyroid function test is back to normal but 50% will require treatment for life.

14. . Congenital Hypothyroid  Incidence 1:3000 – 4000 (more than PKU).  Female:Male is 2:1.  Almost all affected newborns have no S/S at birth because maternal thyroxine crosses the placenta; therefore, signs and symptoms will only appear if the mother has hypothyroid too.  Because of that, we do not rely on clinical assessment and need to do biochemical testing.

15. . Facts MotherFetus Mid-Gestation Immature Hypothalamic Pituitary Thyroid Axis Pregnancy Mother supplies T4 to fetus via placenta T4 Mature Hypothalamic Pituitary Thyroid Axis Normal Newborn Euthyroid Mother

16. Congenital Hypothyroidism: Causes 1.Agenesis or dysgenesis of thyroid gland 2.Dyshormonogenesis (structurally normal, but function is affected) 3.Ectopic gland 4.Maternal hypothyroidism.

17. . Clinical Features of Congenital Hypothyroidism non-specific signs and symptoms Finding % Lethargy96% Constipation92% Feeding problems83% Respiratory problems76% Dry skin76% Thick tongue67% Hoarse cry67% Umbilical hernia67% Prolonged jaundice12% Goiter8%

18. Newborn Screening Course facial feature and big tongue are classical for hypothyrodism Any newborn with jaundice must rule out hypothyrodism by checking TFT In neonates the most common cause is congenital but in later ages hoshimoto is more common. Babies present early with non-specific signs and symptoms.

19. . suspect Clinical Confirm Rx & FU Biochemical (screening) Lab ( TSH & FT4 ) T scan B age Optional Thyroxine Congenital Hypothyroidism X Growth & D TSH & FT4

20. Newborn Screening Definitions Every new born baby has hypothyroidism until proven otherwise, which is tested by umbilical cord sampling (showing high TSH and low T4). The treatment is usually thyroxine for life. Screening: search for a disease in a large unselected population PKU Congenital hypothyroidism Method: If umbilical cord blood TSH is high then you should do thyroid function test and other imaging studies if necessary

21. . Principal of newborn screening Aim is to identify affected infants before development of clinical signs Objective : Eradication of MR (mental retardation) secondary to CH (congenital hypothyroidism). The earlier dx the better IQ

22. . Screening Technique cord blood TSH at birth blood spot in a filter paper obtained by heel prick for TSH /T4 at 3- 5 days (because thyroxine reaches a rise in these days) to check peripheral blood. The test is called “Guthrie” test.

23. Newborn Screening

24. . Clinical Outcome (the outcome is worse if the mother has hypothyroidism). Pre-screening data: –Mean IQ = 76 Post-screening data: –Children screened & treated by age 25 days Mean IQ = 104 Age of Diagnosis % with IQ > 85 3 months78% 6 months19% > 7 months0%

25. Newborn Screening > screening< screening

26. . Congenital Hypothyroidism X

27. In the congenital cause of hypothyroidism, some babies do not have the symptoms because they get the thyroxine from the mother in the first and half of the second trimester and so there is no diseases manifestation. If the child presents with symptoms, this means that the mother is hypothyroid and that is difficult to treat. Newborn Screening

28. Follow-up (TSH) should be done every 2 months for the first year because it takes 2 months to reflect the change in TSH, then every 6 months with growth assessment every 3-6 months. If TSH is elevated increase the dose of thyroxine. Newborn Screening

29. Hyperthyroidism Increased thyroid hormone levels High T4 +/- High T3 Low (suppressed) TSH

30. Causes of hyperthyroidism Graves Disease most common where they present very similarly to adults. Overtreatment with thyroxin; therefore, close monitoring of dosage in hypothyroidism. Thyroid adenoma (rare) Transient neonatal thyrotoxicosis: when the mother has graves disease her antibodies might cross the placenta and stimulate the thyroid function but at the age of 4-6 months it disappears alone without treatment..

31. Graves’ Disease Most common cause of hyperthyroidism TSH-R antibody (stimulating) Main presentation: Goitre, proptosis

32. Hyperthyroidism S&S Heat intolerance Hyperactivity, irritability Weight loss (normal to increased appetite) diarrhea Tremor, Palpitations Diaphoresis (sweating) Lid retraction & Lid Lag (thyroid stare) Proptosis Menstrual irregularity Goitre Tachcardia

33. Neonatal hyperthyroidism born to mother with Graves’ disease A Color Atlas of Endocrinology p51

34. Grave’s ophthalmopathy

35. Hyperthyroid Eye Disease

36. Investigations TSH, free T3&T4 Thyroid antibodies (TSH receptors antibodies) Radionucleotide thyroid scan (incease uptake).

38. Hyperthyroidism Treatment –Beta-blockers –Carbimazole is the most commonly used drug in children –PTU (propylthiouracil) is avoided because it causes liver failure (commonest cause) and requires LFT follow up. Usually used in adolescents. If medical treatment fails we start radioactive iodine if it fails surgery is last line. –Radioactive iodine (in adults); enough to keep the person on thyroxine for life. –Surgery (rare) Radioactive therapy and surgery are usually avoided in children and only used in case medical therapy has failed. 40-70% relapse after 2 years of treatment

39. Quiz What is the obvious abnormality of this 14 years old girl? What are the most likely causes? How do you investigate? You 1. TSH T3 T4 if results are abnormal you do 2.nuclear scan you can also measure immunoglobulin 3. Routine ultrasound or U/S radioisotope to check gland function How do you treat?depends on the cause if hypothyroid give thyroxin if hyperthyroid give antithyroid.

40. Causes of goiter Physiological (puberty) is the commonest in adolescents its an euthyroid state, you don’t treat it and it resolves by itself. Secondary to Iodine deficiency (fourth commonest cause) Hashimoto thyroiditis (hypothyroidism is the second commonest cause) Graves disease (3 rd commonest cause) Tumor (very rare) Congenital (maternal antithyroid drugs, maternal hyperthyroidism, dyshormonogenesis).

41. Quiz u 16 year 7 month u Growth failure x 1 1/2 years  Labs  Labs: TSH: 1008 µIU/ ml(0.3-5.0) T4: <1.0 µg/dl(4-12) Antithyro Ab. 232 U/ml(0-1) A-perox Ab.592 IU/ml(<0.3) Prolactin: 29 ng/ml (2-18) patient asked about prognosis what you tell? In hashimoto 50 % will respond to thyroxin treatment and normalize by 5-10 years and 50% will relapse. 41

42. Newborn Screening