1. THYROID DISEASE WHAT THE PEDIATRICIAN NEED TO KNOW ABOUT SOME Dalia M Y M Al-Abdulrazzaq B.M.B.Ch.,MScCH,FAAP,FRCPC Division of Pediatric Endocrinology Department of Pediatrics Faculty of Medicine University of Kuwait

2. Agenda 3 short case presentations Audience response Some science Some evidence Conclusions Recommendations

3. Case 1 A 4 month old previously healthy boy was seen for episodes of jitteriness. He was born in Kuwait Maternity hospital on July 2015 to a 30 year old healthy mother. Birth weight was 4800 gm (+2.63 SDS). On Examination

4. https://www.google.ca/search?q=umbilical+hernia&biw =1280&bih=654&source=lnms&tbm=isch&sa=X&ved= 0ahUKEwjFtMHqmrjKAhVInBoKHV6CD0cQ_AUIBigB #tbm=isch&q=umbilical+hernia+in+infant

5. Audience Reponse What test would you order as priority for your diagnostic work-up ? 1- Liver function test 2- Blood glucose 3- Thyroid function test 4- ECG

6. Audience Reponse What test would you order as a priority for your diagnostic work-up ? 1- Liver function test 2- Blood glucose 3- Thyroid function test 4- ECG

7. Beckwith–Wiedemann syndrome https://www.google.ca/search?q=umbilical+hernia&biw =1280&bih=654&source=lnms&tbm=isch&sa=X&ved= 0ahUKEwjFtMHqmrjKAhVInBoKHV6CD0cQ_AUIBigB #tbm=isch&q=umbilical+hernia+in+infant

8. CH: Some science CH is one of the most common preventable causes of mental retardation. Although percentages of specific etiologies vary from country to country, ranges are as follows: - Ectopic thyroid - 25-50% - Thyroid agenesis - 20-50% - Dyshormonogenesis - 4-15% - Hypothalamic-pituitary dysfunction - 10-15%

9. S&S of CH Decreased activity Large anterior fontanelle Poor feeding and weight gain Small stature or poor growth Jaundice Decreased stooling or constipation Hypotonia Hoarse cry Coarse facial features Macroglossia Large fontanelles Umbilical hernia Mottled, cool, and dry skin Developmental delay Pallor Myxedema Goiter

10. https://www.google.ca/search?q=thyroid+gland+newborn&biw=1280&bih=654&source=lnms&tbm=isch& sa=X&ved=0ahUKEwibpL7DgbjKAhUCVRQKHaMiBpMQ_AUIBigB#tbm=isch&q=congenital+hypothyroi dism

12. CH: Some evidence Timing of the normalization of thyroid function may influence the outcome. (Zoeller RT 2004) Normal development can be achieved in most patients, although some may have subtle neurocognitive deficits. (Grosse SD 2011) NBS is the most effective way of preventing mental retardation and ensuring normal IQ in this patient population. (Rastogi MV 2010, Grüters A 2012)

13. Case 1 Conclusion Screening programs have led to the successful early detection and treatment of infants with CH. Early detection and treatment of CH through neonatal screening prevents neurodevelopmental disability and optimizes developmental outcomes.

14. Recommendations Suspect an infant with CH  ASK about NBS result. Review local NBS protocol. In case of abnormal thyroid NBS  CONSULT an endocrinologist.

15. Congenital Hypothyroidism Resources 1- European Society for Paediatric Endocrinology Consensus Guidelines on Screening, Diagnosis, and Management of Congenital Hypothyroidism Juliane LégerJuliane Léger, Antonella Olivieri, Malcolm Donaldson, Toni Torresani, Heiko Krude, Guy van Vliet, Michel Polak, and Gary Butler, on behalf of ESPE-PES-SLEP-JSPE-APEG- APPES-ISPAE, and the Congenital Hypothyroidism Consensus Conference GroupAntonella OlivieriMalcolm DonaldsonToni TorresaniHeiko KrudeGuy van VlietMichel PolakGary Butler J Clin Endocrinol Metab. 2014 Feb; 99(2): 363–384. 2- Update of Newborn Screening and Therapy for Congenital Hypothyroidism The Public Health Committee and Lawson Wilkins Pediatric Endocrine Society and Committee on Genetics, American Thyroid Association, Rosalind S. Brown, and American Academy of Pediatrics, Susan R. Rose, and the Section on Endocrinology. Pediatrics 2006;117;2290-2303

16. Case 2 A 4 month old previously health boy was seen for episodes of jitteriness. He was born in Kuwait Maternity hospital on July 2015 to a 30 year old healthy mother. Birth weight was 4800 gm (+2.63 SDS). On exmaination

17. https://www.google.ca/search?q=umbilical+hernia&biw =1280&bih=654&source=lnms&tbm=isch&sa=X&ved= 0ahUKEwjFtMHqmrjKAhVInBoKHV6CD0cQ_AUIBigB #tbm=isch&q=umbilical+hernia+in+infant

18. You are seeing this patient in Mubarak Al-Kabeer Hospital. You asked for a thyroid function test as you were suspecting CH. Results were as follows: TSH 7.1 uU/mL (0.27 – 4.2) fT4 16.3 pmol/L (7.8 – 16)

19. Audience response What would be you next step ? 1- Repeat TFT now to confirm CH. 2- Follow-up TFT in 4-8 weeks. 3- Start LT4 immediately as to decrease chance of future developmental delay. 4- Order a thyroid scan

20. What would be you next step ? 1- Repeat TFT now to confirm CH. 2- Follow-up TFT in 4-8 weeks. 3- Start LT4 immediately as to decrease chance of future developmental delay. 4- Order a thyroid scan

21. STILL Beckwith–Wiedemann syndrome https://www.google.ca/search?q=umbilical+hernia&biw =1280&bih=654&source=lnms&tbm=isch&sa=X&ved= 0ahUKEwjFtMHqmrjKAhVInBoKHV6CD0cQ_AUIBigB #tbm=isch&q=umbilical+hernia+in+infant

22. Some science TSH levels change in the first year of life depending on age. TSH surges within the first 15 - 60 minutes of life reaching peak levels between 25 - 160 at about 30 minutes. Values then decline rapidly within one week. Reference values as per laboratory. TSH reference values as per Esoterix: 1 - 11m0.9 - 7.7 Prepubertal0.6 - 5.5 Pubertal children and adults0.5 - 4.8

23. Some evidence

24. Conclusion TFT reference values are different by age

25. Recommendations Contact your local Lab for TFT reference values according to age. If TSH levels are persistently above 10 uU/mL  Replacement therapy indicated

26. Case 3 A 12 year old girl was referred to the Pediatrics OPD with concerns of increased weight. She has been gaining weight gradually in the past 3 years. On review, her food intake seems to increasing with multiple snacking. She has no will to do any physical activities and prefers her video games. She has been not sleeping well and feels tired during the day. Her maternal aunt and grandmother are suffering from hypothyroidism unspecified. Her weight was 62.5 kg, height 146.7 cm, and BMI 29 kg/m2 (+2.66 SDS).

27. Case 3 cont’ As part of the workup done at the polyclinic, TFT showed the following: TSH 9.2 uU/mL (0.27 – 4.2) fT4 7.9 pmol/L (7.8 – 16) Thyroid US was done at a private hospital and showed Increased thyroid volume and vascularity

28. Audience response What would be your next step ? 1- Start L-T4 2- Refer for FNA 3- Repeat TFT and US 4- Refer for dietician and life style counselling

29. Audience response What would be your next step ? 1- Start L-T4 2- Refer for FNA 3- Repeat TFT and US 4- Refer for dietician and life style counselling

30. Some science Body composition and thyroid hormones are closely: - regulation of basal metabolism - thermogenesis - lipid and glucose metabolism - food intake and fat oxidation Hypothyroidism causes a weight increase together with a decrease in basal metabolic rate and thermogenesis. Abnormalities in thyroid function may be secondary to weight excess.

31. Some science Suggested theories: - increased deiodinase activity  increase total triiodothyronine (T3) and free T3 (fT3). - defense mechanism, capable of counteracting the accumulation of fat by increasing the energy expenditure, basal metabolic rate and the total energy expenditure. - expressions of TSH and thyroid hormones are reduced in adipocytes of obese subjects. - Inflammatory state.

32. Some evidence

33. Obesity associated with increased thyroid volume

35. Conclusions Obese children may show different degrees of alterations pertaining to thyroid function. Caution is recommended when diagnosing Hashimoto’s thyroiditis in these patients. The diagnosis should not be based just upon a pathological ultrasound, without establishing the presence of anti-thyroid antibodies. Regarding treatment, these children do not require any treatment.

36. Recommendations DO NOT blame the thyroid!!!!

37. Useful Resources Thyroid Function and Obesity Silvia Longhi Silvia Longhi 1 and Giorgio Radetti 1Giorgio Radetti J Clin Res Pediatr Endocrinol. 2013 Mar; 5(Suppl 1): 40–44. Published online 2013 Mar 1. doi: 10.4274/Jcrpe.85610.4274/Jcrpe.856 PMCID: PMC3608008

38. d.alabdulrazzaq@hsc.edu.kw