Treatment Trial of Subclinical Hypothyroidism in Down Syndrome
Treatment Trial of Subclinical Hypothyroidism in Down Syndrome
The purpose of this research study is to learn about the effects of treating subclinical
 hypothyroidism (SCH) with thyroid hormone replacement in children and adolescents with Down
 syndrome (DS). We hypothesize that treatment of SCH with thyroid hormone replacement will
 improve cardiometabolic health and quality of life.
The American Academy of Pediatrics (AAP) recommends yearly screening of thyroid studies in
 DS. Clinical experience suggests that thyroid stimulating hormone (TSH) concentrations in the
 subclinical hypothyroid range (5-10 milli international units(mIU/L)) are not uncommon in DS,
 but the benefits and risks of treating SCH in the DS population are not known. In adults, SCH
 has been associated with increased cardiometabolic risk (CMR) and individuals with DS may be
 at increased cardiometabolic risk as well.

 Data in children with SCH are limited. Despite the recommendations to screen for thyroid
 dysfunction, evidence to guide management of elevated TSH in children with DS is equally
 sparse. In non-DS children, TSH>4.65 mIU/L was associated with lower HDL. One year of
 levothyroxine treatment in short children with subclinical hypothyroidism and short stature
 improved growth velocity. Left ventricular (LV) function and LV mass (by echocardiography)
 was not different in 16 children with DS and subclinical hypothyroidism (TSH>6.5 mIU/L; mean
 TSH = 7.8 mIU/L) vs. 25 children with DS and normal TSH. However, these findings may be
 limited by the small sample size. An intervention study of 7 subjects age 2-42 years with DS
 and hypothyroidism, defined as low T4 and normal or elevated TSH (0.2-18.9 mIU/L) on 8 weeks
 of levothyroxine treatment did not improve developmental or functional outcomes.
 Anthropometrics and CMR factors were not examined. In contrast, increased TSH in the absence
 of overt congenital hypothyroidism is common in neonates with DS and prompted a randomized
 controlled trial (RCT) in 181 neonates with DS. TSH-directed levothyroxine treatment was
 associated with better growth, weight gain, and motor development after 24 months compared to
 placebo. These findings highlight that the "asymptomatic" component of subclinical
 hypothyroidism may have medically-relevant effects. This study will provide potentially
 clinically relevant preliminary evidence for the treatment of subclinical hypothyroidism in
 DS.
Inclusion Criteria:

 -  Males and females, ages 8 - 20 years

 -  Diagnosis of Down syndrome

 -  Subclinical hypothyroidism: TSH level between 5 - 10 mIU/L, normal T4

 -  Parental/guardian permission (informed consent) and if appropriate, child assent

 -  Females who are at least 11 years of age or who are menarchal must have a negative
 urine/serum pregnancy test

 -  Committed to adherence to levothyroxine treatment and study completion

 Exclusion Criteria:

 -  Pregnancy

 -  Type 1/Type 2 diabetes

 -  Chronic medical conditions or medication use that can affect growth, nutrition, blood
 glucose, insulin secretion, or thyroid function (such as lithium or certain seizure
 medications)

 -  Current use of levothyroxine or anti-thyroid hormone

 -  Cyanotic congenital heart disease, or pulmonary hypertension (as described by last
 echo report in subjects with CHD), or congenital heart disease considered medically
 unstable by the study cardiologists