1. Elevated TSH To Treat or not to Treat
The 2nd Al Jahra International
Pediatric Conference
5th -7th May 2017
Dr Zaidan Al Mazidi
Sabah Hospital

2. Objectives:
TSH reference range.
Definition of Subclinical hypothyroidism.
Options for management.
Plan before stating treatment.
When to order thyroid Function in SCH.
DD of transient and persistent mildly raised TSH.
Plan for management of SCH.

3. TSH Reference Range in Pediatrics
TSH at
2-5 days < 25 mlU/L
at 15 days < 15 mlU/L
at 1 mo old < 9
Up to 15 yr < 6.5 mlU/L

4. Definition of Subclinical Hypothyroidism (compensated hypothyroidism)
It is a normal FT4 level and a mildly elevated TSH (5–10 mU/L), i.e. The TSH is above the reference range.
There is a broad differences between adults and children TSH reference as it depends upon patient’s age.
TSH concentrations as high as 9.64 mIU/l in the first month after birth is normal.

5. In SCH Elevated TSH
What to do? (3 scenarios)
1. To start treatment, or
2. Close follow-up, or
3. Precede to to further investigations.

6. First Option
1. Why to Start Treatment Immediately?
Raised TSH in early infancy is not acquired.
High TSH may be a compensated congenital conditions.
And it may progress to overt hypothyroidism and its impact on cognitive development.
Studies show that congenital hypothyroidism can cause developmental delay and slow growth.

7. Studies of Persistently Elevated TSH Beyond the Age of One Year
Cases of (resistance to TSH) are attributed to mutations in the TSHR (TSH receptors). Characterized by thyroid dysgenesis, kidney abnormalities and pseudohypoparathyroidism.

8. Causes and associations of subclinical hypothyroidism in children

9. Second Option
2. Why to continue with close follow-up.
It is uncommon to progress to overt hypothyroidism.
On follow-up, elevated TSH normalizes, or
TSH persists but does not increase.
Many studies from different countries revealed recovery of thyroid function over time.
On stating treatment, the dose was not increased in many patients by time.

11. It is estimated that about 5 out of 100 people have subclinical hypothyroidism. Slightly elevated TSH levels are usually detected by accident during a routine examination. Experts do not fully agree on how to decide in which cases subclinical hypothyroidism should be treated.

12. Third Option Why to precede to to further investigations. To rule out:
* TSH receptor mutation.
* Autoimmune thyroiditis.
*Hypoplastic thyroid.
Other syndromes as Down and William.
Aplastic
Normal

13. What should be the Initial Response to Mildly raised TSH
Frequent TSH monitoring (4-6 mo):
Continue F/U if no significance rise of TSH.
Long interval F/U if TSH normalizes.
To start treatment if TSH is rising (> 15 mU/L)
specially with a low FT4 during the first 2 years of life (a period of brain development).

14. Disadvantage of staring treatment (TSH < 10):
1.Drug side effects.
2.More frequent TSH monitoring.
Un necessary coasts.

15. When to Order Thyroid Function in SCH
Growth deceleration.
Family history of hypothyroidism.
Un explained weight gain.
Symptoms of hypothyroidism.
Thyroid US revealed hypoplasia.

16. Transient and Persistent TSH Elevation
TSH levels in healthy individuals tend to fluctuate during the day (2 mlU/L) as well as over time.
IUGR children may have an abnormal TSH set point.
There are several reports linking obesity to increased TSH, and there is a strong correlation between BMI and TSH.
Maternal autoimmune thyroiditis.

17. Studies of permanent TSH elevation revealed 10-28% of TSH receptor gene mutation and thyroid gland developmental anomalies.

18. Plan for management of SCH
Order only FT4 and TSH.
Do not order thyroid antibodies as it is positive in 13% of of the total population.
Goiter is a risk factor.
Repeating TFT in 6 mo time to allow time for normalization and if progress to hypothyroidism order for thyroid AB.

19. Conclusion
If TSH is in the range of 5-10 mU/L for 2 years follow-up, it is unlikely to progress to hypothyroidism (except with goiter or positive thyroid AB).
In boarder line conditions, and if treatment was started, it worth trying drug tapering or try a one month off treatment at age of 3 years.

20. Reference
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Keselman A, Chiesa A, Malozowski S, Vieytes A, Heinrich JJ, Gruñeiro de Papendieck L. Abnormal responses to TRH in children born small for gestational age that failed to catch up. Hormone Research. 2009;72(3):167–171.
Chikunguwo S, Brethauer S, Nirujogi V, et al. Influence of obesity and surgical weight loss on thyroid hormone levels. Surgery for Obesity and Related Diseases. 2007;3(6):631–635.
Narumi S, Muroya K, Abe Y, et al. TSHR mutations as a cause of congenital hypothyroidism in Japan: a population-based genetic epidemiology study. Journal of Clinical Endocrinology and Metabolism. 2009;94(4):1317–1323.
Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III) Journal of Clinical Endocrinology and Metabolism.
Díez JJ, Iglesias P. Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure. Journal of Clinical Endocrinology and Metabolism. 2004;89(10):4890–4897.
Clinical evolution of autoimmune thyroiditis in children and adolescents.Fava A, Oliverio R, Giuliano S, Parlato G, Michniewicz A, Indrieri A, Gregnuoli A, Belfiore AThyroid Apr; 19(4):361-7.
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22. Thanks