Subclinical hypothyroidism

Dr.YASSIN ALSALEH

CASE SCENARIO• 4 year old child case of chronic

constipation ,obesity found to have abnormal TFT:• TSH :8 high FT4:17 normal • what is the next step???

Synonyms • Compensated hypothyroidism.• latent hypothyroidism. • preclinical hypothyroidism. • euthyroid

hyperthyrotropinemia.

Introduction• Definition:• SCH is biochemically defined

as (TSH) is above the upper-limit of the statistically defined reference range • while the serum free

thyroxine (FT4) is within its reference range.

TSH↑

FT4 N

Laboratory definition• TSH is secreted in a pulsatile manner

and shows diurnal variation.• The levels may vary based on the

time of sampling as well as its relation to food.• TSH is false high In about 0.5 to 5%

of patient samples.

Laboratory definition

mildly increased (4.5–10 mIU/l) severely increased (>10 mIU/l)

TSH

Pediatric > one month of age

• The prevalence of SCH in the pediatric population is 2%

EPIDEMIOLOGY

Manifestations• Asymptomatic.

• A goiter is the most common manifestation.

• weight gain.• increased cholesterol levels.• impaired growth velocity.• anemia.• sleepiness, weakness.• impaired psychomotor and cognitive

development.

Manifestations

etiologycauses

anatomicallythyroidal

others(association)

pathophysiologicalidiopathic

autoimmune

Thyroidal Causes• Autoimmune thyroiditis

(HASHIMOTOS) . (most common) 50-80% of cases.• Developmental anomalies

(hypoplasia, hemiagensis). • TSH Resistance syndrome (RTSH).

other causes • newborns classified false positive at

congenital hypothyroidism screening .(up to 70%)• SGA . Up to 50% .• Down’s syndrome. up to 32%• William’ syndrome. Up to 31.5%.

others• diabetes mellitus (11%).• cystic fibrosis.• celiac disease. • chronic renal failure.

• obesity up to 25%.

Natural History and Progression

TSH

Normalized 30-40%

>70% if TSH

<10

Overt hypothyroi

dism 1-10% Up to

20% if Autoimm

une

SCH

ProgressionNon-autoimmune ‘idiopathic’ SCH

• either discovered on newborn screening or later during childhood.• normalizes in 36–88% of patients

Progression• Risk factor for progression to overt

hypothyroidism• Goiter.• TSH levels.• Presence of thryoglobulin antibody. • progressive increase in anti-thyroid

peroxidase (TPO) antibodies .• female sex.• family history of thyroid disorder

Therapy

• There is no consensus on therapy of SCH in children.

Therapy

NO YES

• Studies analyzing height, growth velocity, and puberty did not confirm a negative influence of SH.

• few studies showed beneficial effect on idiopathic short stature and SCH.

Effects of Therapy on Growth velocity

• Studies showed improve metabolic control in type 1 diabetics.• improvement in growth velocity.

• Improvement was better in patients with higher TSH at entry.

Effects of Therapy on diabetic patients

Therapy in Autoimmune Thyroid Disease

• Prophylactic L-T4 therapy of patients with euthyroid AITD reduces serological markers of autoimmune thyroiditis.• L-T4 therapy might be useful for

stopping progression of the disease.

Therapy (goiter)

• L-thyroxine therapy reduce thyroid volume in those patients with goiter.

Therapy (obese child)

• hyperthyrotropinemia in obesity is a consequence rather than a cause.

• therefore L-T4 therapy is unnecessary in obese children.

• Patients should be encouraged to implement appropriate diet and exercise programs

Therapy (migrane)

• children aged between 5 and 15 yrs diagnosed with SH suffered more frequently from the migraines which were also lasting longer.

Effects of SCH on Neuropsychological Development

• Neuropsychological Development was not impaired in patient with SH as compared to euthyroid children.

Effects of SCH on Cardiovascular system

• children and adolescents with SCH were found to have significant impairment of diastolic and longitudinal systolic cardiac function on echocardiography

Effects of SCH on lipid metabolisim

• A significantly higher concentration of serum total and low-density lipoprotein (LDL) cholesterol was found in children with SCH as compared to euthyroid children

Management • TSH between 4.5 and 10 mIU/l should be

followed-up.

• TSH > 10 mIU/l with normal FT4 levels may be treated.

• Especially in presence of :1- goiter .2- positive antibodies .3- signs and symptoms.

Management

• Start with small dose.• Monitor TFT every 6-8 weeks.• Consider imaging if TSH is

persistently high.

conclusion• SH in children seems to be a remitting

process with a low risk of evolution toward overt hypothyroidism.

• The initial presence of goiter and elevated TG-Abs and a progressive increase in TPO-Abs and TSH values predict a progression toward overt hypothyroidism.

• Replacement therapy is not justified in children with SH but with TSH 4.5–10 mIU/l, no goiter, and negative antithyroid antibodies

conclusion

References 1- Seshadri KG. Subclinical hypothyroidism in

children.Indian J Endocrine Metababolisim 2012;16:S156-8.

2-FRANCESCA CALACIURA . Subclinical Hypothyroidism in Early Childhood:A Frequent Outcome of Transient Neonatal Hyperthyrotropinemia .The Journal of Clinical Endocrinology & Metabolism 87(7):3209–3214

References3- M SHRIRAAM AND M SRIDHAR .Subclinical

Hypothyroidism in Children . INDIAN PEDIATRICS .VOLUME 51-NOVEMBER 15, 2015

4- Yardena Tenenbaum-Rakover. Approach to Subclinical Hypothyroidism in Children. http://dx.doi.org/10.5772/5513.2013

5- John Lazarus. 2014 European Thyroid Association Guidelines for the Management of Subclinical Hypothyroidism in Pregnancy and in Children. Eur Thyroid J 2014;3:76–94

References

6-Aneta Gawlik. Subclinical Hypothyroidism in Children and Adolescents:Is It Clinically Relevant? International Journal of Endocrinology. 2015.

7-Wasniewska M, Elevated TSH levels normalize or remain unchanged in the majority of children with subclinical hypothyroidism. Eur J Endocrinol 2009;160:417-21.

References8- Alice Monzani,Natural history of subclinical

hypothyroidism in children and adolescents and potential effects of replacement therapy: a review. European Journal of Endocrinology (2013) 168 R1–R11

9- Emel Torun1, Subclinical hypothyroidism in obese children .Dicle Medical Journal.2013