Background. Thyroid peroxidase gene (TPO) mutations are one of the most common causes of thyroid dyshormonogenesis in patients with congenital hypothyroidism (CH). In this study, the prevalence of TPO gene mutations in patients with thyroid dyshormonogenesis in Isfahan was investigated. Methods. In this cross-sectional study, genomic DNA of 41 patients with permanent CH due to thyroid dyshormonogenesis was extracted using the salting out method. The 17 exonic regions of the TPO gene were amplified. SSCP technique was performed for scanning of the exonic regions of the TPO gene, except exon 8. DNA sequencing was performed for those with different migration patterns in SSCP by chain termination method. Exon 8 was sequenced directly in all patients. In 4 patients, all fragments were also sequenced. Results. One missense mutation c.2669G > A (NM_000547.5) at exon 15 (14th coding exon) in one patient in homozygous form and seven different single nucleotide polymorphisms (SNPs) in exons 1, 7, 8, 11, and 15 of TPO gene. Conclusion. The TPO gene mutations among CH patients with dyshormonogenesis in Isfahan were less frequent in comparison with other similar studies. It may be due to the presence of other unknown gene mutations which could not be detected by SSCP and sequencing methods.

Objective

Thyroid hormone is necessary for normal development of the auditory system. The aim of this study was to investigate the rate of hearing impairment in congenitally hypothyroid (CH) patients, and its relation with factors such as CH severity and age at starting treatment, during CH screening program in Isfahan.

Methods

Hearing acuity was assessed in two groups of children with (94 patients aged 4 months – 3 years) and without CH (450), between 2000-2006. Otoacostic emission (OAE) was performed by a two step method. After two tests without OAE signals bilaterally, they were referred for auditory brainstem response (ABR) test. Subjects with both OAE and ABR abnormal test results were considered to have hearing problem. Obtained data was compared in case and control group and also CH patients with and without hearing impairment.

Findings

Three (3.2%) of patients and 1 of control group (0.2%) were diagnosed with sensorineural hearing loss. The rate of hearing loss was not different significantly in two studied groups (P>0.05). There was no difference between age of starting treatment and first T4 and TSH level in CH patients with and without hearing loss (P>0.05). CH neonates with hearing impairment had thyroid dyshormonogenesis according to the follow up results.

Conclusion

The rate of hearing loss was low among our studied CH patients. It may be due to proper management of CH patients. In view of the fact that all CH neonates were dyshormonogentic and considering the relation between certain gene mutations and hearing impairment in CH patients, further studies with larger sample size, with regard to different etiologies of CH should be investigated to indicate the possible gene mutations related to hearing loss in CH.

BACKGROUND:

The aim of this study was to compare the usefulness of ultrasonography and scintigraphy in diagnosing the etiology of primary congenital hypothyroidism (CH).

METHODS:

The newborns that were examined by both thyroid scintigraphy and ultrasonography during CH screening program in Isfahan were included in this study. The ultrasonographic findings were compared with the scintigraphic findings and the sensitivity and specificity of the ultrasonography was determined.

RESULTS:

During this study, 102 CH newborns were studied. According to the ultrasonographic results, 61.8%, 26.5%, 2.9% and 8.8% of them had normal thyroid gland, agenesia, ectopia and hypoplasia, respectively, and according to scintigraphic results, 55.9%, 35.3% and 8.8% of them had normal thyroid gland, agenesia and ectopia, respectively. Ultrasound detected sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratio were 77%, 92%, 89%, 84%, 9.6 and 0.25, respectively. The sensitivity and specificity of ultrasonography compared with thyroid scintigraphy in diagnosis of thyroid gland ectopia was 33% and 100%, respectively.

CONCLUSIONS:

Though thyroid ultrasonography failed to diagnose 67% of ectopic cases and nonfunctioning thyroid gland, it had the ability to determine the anatomy of thyroid gland. So, considering some limitations of scintigraphy, we concluded that ultrasonography is a relatively appropriate imaging tool for diagnosing CH etiologies, especially in the initial phase of CH screening.

Objectives:

Early and proper treatment is crucial to prevent neuropsychologic deficits in congenital hypothyroidism (CH). Considering the high prevalence of CH in Isfahan, the aim of this study was to evaluate the outcome of treatment in CH patients.

Methods:

In this study CH neonates diagnosed during screening program in Isfahan from May 2002 to September 2009 were studied. Frequent visits were performed to CH patients to monitor and follow their treatments. Quality of treatment was assessed by evaluating mean age of treatment initiation and mean TSH and T4 levels before and after treatment and during the first and second years according to their normal reference ranges.

Results:

Of 225,224 screened neonates, 536 were diagnosed as CH patients. The prevalence of CH was 1/420 live births. Mean age at starting treatment was 22.9 ± 13.2 days. In 93.7% of patients, treatment was begun before the 45th day of life. In the first measurement after initiating the treatment, T4 and TSH were not in their acceptable range in 3.9% and 9.8% of CH patients, respectively. Mean T4 and TSH reached to normal range during the treatment period. T4 reached the normal range earlier than TSH.

Conclusions:

The mean age of treatment initiation was in acceptable range but the findings suggest that both early and high-dose treatments are crucial for optimal treatment, especially in patients with severe CH. Further studies are needed to determine the outcome of treatment specially regarding to different etiologies of CH.