Furthermore, they found that TSH levels were above the 80th percentile in all foetuses and FT4 were below the 50th percentile in the majority. (1). In 95 % of cases, Down syndrome is due to non – dysjunction of chromosome 21, while the remaining cases are either due to translocation or mosaicism (2-4). DS is usually associated with increased risk of medical problems including gastrointestinal, cardiac, and pulmonary anomalies as well as developmental delay and endocrine abnormalities (5). Among the endocrine abnormalities, thyroid dysfunction is the commonest. It is estimated to occur in 4-8% of children with Down syndrome (6). The spectrum of thyroid dysfunction in patients with DS include congenital hypothyroidism, subclinical hypothyroidism, acquired hypothyroidism (autoimmune C non autoimmune), and hyperthyroidism (7). Congenital hypothyroidism (CH) Overt congenital hypothyroidism refers to elevated plasma TSH ( 10 mIU/l) associated with low plasma T4 occurring at birth and in most cases diagnosed with neonatal screening (8). The prevalence of CH in DS is usually estimated to be 28-35 times higher than its prevalence in the general population (9). In FH1 (BRD-K4477) the general population CH which is considered one of the most common preventable causes of mental retardation, is usually detected in 1 in 2000 to 3000 live births via neonatal screening. The reported incidence of CH in Down syndrome is much higher, varying between 1: 113 and 1: 141 live births (10-12). Furthermore, the female preponderance observed in the general population with CH has not been found in patients with CH and DS (1). The presence of CH increases the risk of the presence of other anomalies including congenital cardiac disease, respiratory distress syndrome, and gastrointestinal anomalies (13). The presence of CH in DS further increases the risk of congenital anomalies especially gastrointestinal and cardiovascular anomalies when compared to patients with DS without CH (5, 13-15). A co-existence of CH and gastrointestinal anomalies is usually observed in DS. Jaruratanasirikul et al reported that Down syndrome babies with gastrointestinal anomalies at birth were 8.6 times more likely to have CH (16). Most cases of reported CH are due to thyroid hypoplasia (8, 17, 17). Other ultrasound findings included thyroid ectopia, athyreosis, or partial agenesis, but all are uncommon causes of CH (8, 9, 9). However, in most cases there is no abnormality on ultrasound scanning (17, 20-22). Luton et al. studied the development of 13 human fetal DS thyroid glands between 23 and 33 weeks of gestation. They found that thyroid glands in DS were smaller in size and had fewer and smaller follicles compared to control thyroid glands. This FH1 (BRD-K4477) was confirmed by immunohistological analysis with anti-NKX2 – 1 antibody. Fewer stained colloids were found upon antithyroglobulin staining. Furthermore, they found that TSH levels were above the 80th percentile in all foetuses and FT4 were below the 50th percentile in the majority. This supports the observation that thyroid hypoplasia is the commonest abnormality in DS patients with CH (23). Few studies looked at the possible etiology of CH in FH1 (BRD-K4477) patients with DS. Some hypotheses have been suggested including the following (1, 5): Exaggerated response to TRH stimulation: delayed maturation of the hypothalamic – pituitary – thyroid axis leading to higher TSH levels with normal fT4 and fT3 levels and unfavorable antithyroid antibodies in the first 3 years of life (24). Peripheral resistance to Ctsl thyroid hormones: leading to inappropriate TSH secretion. This was postulated to be due to abnormal thyroid hormone receptor function (24). Inappropriate TSH release, due to a central disorder, or due to altered dopaminergic control resulting from reduction in dopamine production. Dopamine is an inhibitor of TSH (17, 24). TSH insensitivity (5). Reduced TSH bioactivity (5). Subclinical hypothyroidism (SH) SH refers to isolated elevation of TSH with normal thyroid hormone levels. Some authors refer to it as moderate hypothyroidism (5), or compensated hypothyroidism or isolated thyrotropinaemia (10). SH is probably the most common detected thyroid abnormality in these subjects (10). The incidence of SH varies in the literature depending mainly on the study size, and the TSH cut off for the definition of SH (1, 5, 5). Generally, TSH above 5 mIU/L is considered above the normal range in many places. Some studies refer to cases where TSH is usually less than 20 mIU/L as compensated hypothyroidism (5, 22). Others have defined two individual entities depending on whether TSH level is usually between 6 and 10 mIU/L or 11 and 20 mIU/L (5). The questions that need to be clarified regarding.