THYROID DISEASE

HYPOTHYROIDISM & HYPERTHYROIDISM

1. Thyroid disease By: Dr Ismah 1

2. Contents Physiology and development Epidemiology Hyperthyroidism Hypothyroidism 2

3. 3 1. Physiology and development

4. Thyroid glands descend to ant lower neck by the end of 1 st trimester 4

5. 5 Hypothalamic-pituitary-thyroid axis becomes functional in 2 nd trimester

6. 6 Peripheral metabolism of thyroid hormones matures in 3 rd trimester

7. T3, T4, TSH do not cross placenta in significant amount 7

8. Functions of thyroid hormones Target tissue Mechanism Nervous system Promote normal brain development Heart Increase number, affinity of beta adrenergic receptors Enhance responses to circulating catecholamine Muscle Increase protein breakdown Bone Promote normal growth and skeletal development Gut Associated with carbohydrate absorption Adipose tissue Stimulate lipolysis Lipoprotein Stimulate formation of LDL receptors Other Stimulate oxygen consumption by metabolically active tissues Increase metabolic rates Promote development of reproductive system Maturation of fetal lungs 8

9. Normal level of thyroid hormones Age TSH ( mIU /L) Free T4 ( pmol /L) Birth-D3 OL <21 26-65 D4 -D30 0.51-10.8 12-30 D31-1yr 0.39-7 9-16.1 ≥ 1 yr 0.4-6 13.2-22.2 9

10. 2. Epidemiology Hypothyroidism: Incidence of congenital hypothyroidism worldwide is 1:2500 - 4000 live births In Malaysia, it is reported as 1:3666 It is the commonest preventable cause of mental retardation in children 10

11. Hyperthyroidism: Study in US (2008) concluded that the incidence among individuals aged 0-11 years was 0.44 cases per 1000 population The incidence among individuals aged 12-17 years was 0.59 cases per 1000 population. Thus , the incidence increases throughout childhood, with a peak incidence in children aged 10-15 years 11

12. 3. Hypothyroidism Decreased free T4, increased TSH Primary, secondary or tertiary 12

13. A. Congenital hypothyroidism Causes Maldescent thyroid, athyrosis Dyshormonogenesis Iodine deficiency TSH deficiency 13

14. Clinical features FTT Feeding problem Prolonged jaundice Constipation Pale, cold, mottled skin Quiet baby Coarse face Large tongue Hoarse cry Goiter Umbilical hernia Delayed development 14 MOSTLY , ASYMPTOMATIC AT BIRTH

15. 15

16. 16 CORD TSH

17. Treatment Timing Should begin immediately after diagnosis is established If features of hypothyroidism are present, treatment is started urgently. Duration Treatment is life long E xcept in children suspected of having transient hypothyroidism where re-evaluation is done at 3 years of age. 17

18. Preparation L- thyroxine tablets The L- thyroxine tablet should be crushed, mixed with breast milk, formula, or water and fed to the infant. Tablets should not be mixed with soy formulas or any preparation containing iron (formulas or vitamins), both of which reduce the absorption of T4. 18

19. 19 Pediatric Protocol 3 rd ed

20. Goal of therapy To restore the euthyroid state Serum FT4 level usually normalise within 1-2 weeks, and then TSH usually become normal after 1 month of treatment. Some infants continue to have high serum TSH concentration (10 - 20 mU /L) despite normal serum FT4 values due to resetting of the pituitary-thyroid feedback threshold. Compliance to medication has to be reassessed and emphasised. 20

21. 21 Pediatric Protocol 3 rd ed

22. Follow up Monitor growth parameters and developmental assessment. Imaging studies If the FT4 is low and the TSH value is elevated, permanent hypothyroidism is confirmed and life-long L- thyroxine therapy is needed. 22

23. Measurement schedule (FT4, TSH) The recommended by American Academy of Pediatrics At 2 and 4 weeks after initiation of T4 treatment. Every 1 to 2 months during the first 6 months of life. Every 3 to 4 months between 6 months and 3 years of age. Every 6 to 12 months thereafter until growth is completed. After 4 weeks if medication is adjusted. At more frequent interval when compliance is questioned or abnormal values are obtained. 23

24. Re-evaluation of patients likely having transient hypothyroidism Can be due to factors primarily affecting the thyroid-like iodine deficiency or excess, maternal TSHR antibodies , maternal use of anti thyroid drugs This is best done at age 3 years when thyroid dependent brain growth is completed at this age. Stop L- thyroxine for 4 weeks then repeat thyroid function test: FT4, TSH. 24

25. B. Acquired hypothyroidism The commonest cause autoimmune thyroiditis i.e. Hashimoto thyroiditis 25

26. Clinical features Short stature Cold intolerance Dry skin Cold peripheries Bradycardia Thin, dry hair Goiter Slow relaxing reflexes Constipation Delayed puberty Obesity Slipped upper femoral epiphysis Learning difficulties 26

27. 27

28. Hashimoto thyroiditis In older children, adolescence + ve family h/o thyroid disease in 25-35% of patient Autoimmune process targeted the thyroid gland thus resulting in fibrosis and atrophy of thyroid glands 28

29. Firm, non tender, diffuse goiter Onset after 6 years old Associated with DM type 1, adrenal insufficiency and hypoparathyroidism , down syndrome, turner syndrome 29

30. Diagnosis Clinically Confirmed by serum antithyroid peroxidase and antithyroid globulin antibodies 30

31. Treatment L thyroxine Monitor TSH, FT4 6-12 monthly 31

32. 32 4 . Hyperthyroidism Increased T4, T3 & decreased TSH

33. Clinical features Systemic Anxiety Restlessness Sweating Diarrhea Weight loss Rapid growth in ht Tremor Tachycardia Warm peripheries Learning difficulty Behavior problems Psychosis 33

34. Eye signs (not common in children) Exophthalmos Ophthalmoplegia Lid retraction Lid lag 34

35. 35

36. 36 Lid retraction Exophthalmos

37. 37 Opthalmoplegia Lid lag means delay in moving the eyelid as the eye moves downwards

38. A. Graves’ disease Autonomous functioning of thyroid caused by thyroid stimulating immunoglobulins (TSIs) Increased thyroid hormones production and peripheral conversion Firm, diffuse goiter Common in girls, in adolescence 38

39. 39

40. Drugs Block thyroid hormones synthesis Carbimazole PTU Side effect: rash, fever, arthralgia, agranulocytosis , liver damage, lupus like syndrome Beta blockers e.g. propranolol To control cardiac manifestation Contraindicated in asthmatic pt 40

41. Surgery 41 Thyroidectomy Indications: Failed medical treatment Large goiters, especially with pressure effects S evere progressive ophthalmopathy

42. B. Thyroid storm Medical emergency. The mortality is 20 - 30 %. E xacerbation of the hyperthyroid state with evidence of decompensation in one or more organ systems P recipitated by stress including concurrent infections, surgery C linical diagnosis with features of severe thyrotoxicosis, hyperpyrexia and neuro -psychiatric manifestations such as delirium 42

43. Management 43 Rehydration   Treat hyperpyrexia ( use fans, tepid sponging and oral paracetamol) Do NOT use aspirin or NSAIDs   Beta sympathetic blocking agents Oral propanolol 40 mg qid , or I/V 1-2 mg 4-6hourly  

44. Iodide Oral saturated solution of potassium iodide (SSKI) 5 drops 6-hourly or I/V Sodium Iodide 500 mg 8 hourly or oral Lugol's iodine 5-10 drops, 6-hourly   Antithyroid Drugs Carbimazole 15-20 mg 6-hourly or propylthiouracil 150-200 mg 6-hourly   Corticosteroids I/V dexamethasone 2 mg 6-hourly or I/V hydrocortisone 200 mg 6-hourly   44

45. C. Other causes (rare) McCune-Albright syndrome Thyroid neoplasm TSH hypersecretion Subacute thyroiditis Excessive iodine or thyroid hormone ingestion 45

46. D. Neonatal hyperthyroidism Associated with infant of mother with Graves’ disease Transient placenta transfers of thyroid stimulating immunoglobulins (TSIs) Potentially fatal 46

47. Clinical features Irritability Tachycardia Polycythemia Craniosynthesis Poor feeding FTT 47

48. Treatment Minimally affected: observation Severe: Oral propranolol PTU Spontaneous resolution because of TSIs usually in 2-3 months of age 48

49. Take home message Important to understood the physiology of thyroid hormone Congenital hypothyroidism – screening, treat to prevent MR Patient education and compliance to treatment/follow up 49

50. 50 American Association of Clinical Endocrinologists (AACE)

51. References: Nelson Essential of Pediatrics 6 th ed Illustrated Textbook of Pediatrics 3 rd ed Pediatric Protocol 3 rd ed Practice Guidelines for Thyroid Disorders The Malaysian Consensus 2000 Thank You 51