Hypothyroidism is the most prevalent hormone deficiency caused by the production of insufficient amount of thyroid hormone. This may be due to failure of the thyroid gland to produce adequate amounts of hormone or failure of the pituitary gland to produce thyroid-stimulating hormone (TSH), or thyrotropin. In addition, hypothyroidism can result from the resistance to thyrotropin. Thyrotropin resistance hypothyroidism is a condition of thyroid refractoriness to TSH stimulation characterized by high levels of serum TSH, normal/reduced levels of serum thyroid hormone and a normal/hypoplastic thyroid gland. In general, hypothyroidism is more common among Whites and females than Africans and males, respectively.
Ahlbom et al. (1997) investigated an affected family from Egypt. They mapped the TSHR gene on radiation panels and identified 2 flanking DNA markers which were analyzed for linkage analysis. Assuming homogeneity, the 2-point lod score at theta = 0.1 was -4.8 for one marker and -5.8 for the second, thus excluding linkage to TSHR. Even when the data were analyzed with allowance for heterogeneity, there was no evidence of linkage to the TSHR gene. Ahlbom et al. (1997) concluded that if mutation of the TSHR gene causes familial congenital hypothyroidism in humans, it affects only a small proportion of cases.
Daoud et al. (1989) performed a retrospective study to assess the incidence rate of congenital hypothyroidism in Kuwait. In the period between 1981 and 1987, 25 affected children were diagnosed in a single regional hospital in the country, resulting in an incidence of 1:3476 live births. Diagnosis was based primarily on clinical manifestations, and confirmed by thyroid function tests. Most patients (48%) were diagnosed after the age of 6-months. Only in the last couple of years in the study were two children identified via neonatal screening. Mental development was observed to be best in children who received thyroid hormone replacement within the first 6-months, stressing the importance of early diagnosis.
Elbualy et al. (1998) reported their experience on screening congenital hypothyroidism in newborns born at the Royal and Khoula Hospitals, Oman, between 1991 and 1995. The samples were four milliliters of cord blood from which the thyroid stimulating hormone (TSH) was measured with an immunoradiometric method (IRMA) with I125 as a radiolabel till 1991, but after that the method was changed to microparticle enzyme immunoassay (MEIA). The recall of babies for confirmatory thyroid function tests (TSH and free thyroxine) depended on the level of the cord blood TSH, which was significant if it was above 20 IU/L but the cut off point was further increased to 30 IU/L after 1993. Two cases with CBTSH of >100 mIU/ml were not tracable for confirmatory tests. Out of the recalls, 87% were false positives which Elbualy and colleagues (1998) explained as due to the measurement of cord blood TSH, which is known to surge at birth. During the study period, 36,000 babies were screened and 13 Omani patients were diagnosed with congenital hypothyroidism making an incidence of 1:2,000 to 1:2,300 (less than the Caucasian population but similar to that published in Saudi Arabia). All patients were treated within the first month of life with a mean age of 13 days. The male: female ratio was 8: 7 (sex of one baby was unknown). One baby was born to a hypothyroid mother who was on externally administered thyroxine while pregnant. The children who had classical features of the disease subsequently had delayed milestones and were frequently monitored. The exact causes of congenital hypothyroidism in these babies were not known as no pertechnicate scans were done.
In 2003, the Hamad Medical Corporation, in partnership with the University Children's Hospital of Heidelberg built a comprehensive newborn screening program. Between December 2003 and July 2006, Lindner et al. (2007) investigated 25,214 neonates born in Qatar for inborn errors of metabolism and endocrine disorders. Eight of these neonates were diagnosed with congenital hypothyroidism. Age at which NBS result was received ranged from 6-days to 14-days, while age at start of treatment varied from 2-days to 12-days. The incidence was comparable to that reported from other parts of the world.
Ahlbom et al. (1997) investigated an affected family from Syria. They mapped the TSHR gene on radiation panels and identified 2 flanking DNA markers which were analyzed for linkage analysis [See: Egypt > Ahlbom et al., 1997].
Al-Hosani et al. (2003) performed a study to evaluate the progress of the UAE national newborn screening program and to determine the incidence of congenital hypothyroidism (CH) in the UAE. Blood was collected by heel prick onto a filter paper and tested for TSH levels. Investigations for confirmation and cause of CH included thyroid function studies of T3, T4, free T4 and TSH, technetium-99m thyroid scan where possible and thyroglobulin and thyroid antibodies when indicated. Over a period of six years, 138718 newborns were screened with a CH incidence of 1:1570. Data showed that coverage was acceptable in all districts except Dubai. There was a satisfactory increase in the coverage from 1998 to 2000 in all districts which reached 65%; however, this percentage was still bellow the international standard. A comparison of the timeliness of screening program indicators showed that the UAE indicators improved between 1998 and 2000 and now approximate international standard. The program protocol had a high recall rate for CH (0.09%). Apparent sensitivity (100%) and specificity (>99%) for CH were acceptable. The positive predictive value (PPV) of 79.6% for CH indicated an acceptable number of false-positives. Of 55 confirmed cases, 45 had abnormal screenings (TSH > 20 mU/L) and 10 had borderline TSH (10-20 mU/L). Thyroid ectopy was most common (44.4%). Moreover, the high percentage of patients having normally located glands and high uptake (41.7%) suggested dyshormonogenesis.