Murntaz Lakhani  ( Departments of Paediatrics and Pathology, The Aga Khan University Hospital, Karachi. )
Mohammad Khurshid  ( Departments of Paediatrics and Pathology, The Aga Khan University Hospital, Karachi. )
Shehla H. Naqvi  ( Departments of Paediatrics and Pathology, The Aga Khan University Hospital, Karachi. )
Mohammad Akber  ( Departments of Paediatrics and Pathology, The Aga Khan University Hospital, Karachi. )

Congenital hypothyroidism is a preventable cause of mental retardation. Since clinical signs of congenital hypothyroidism do not generally become obvious before three months of age, screening programmes have been introduced in North America and Europe, which consist of T4 or TSH screening on newborn infants on the third day of life. The screening for congenital hypothyroidism was initiated in Pakistan by the Aga Khan University Hospital (AKUH) in March 1987. By April 1988, 5000 neonates were screened and five cases of congenital hypothyroidism were diagnosed. The study revealed the incidence of hypothyroidism to be one case per 1000 newborns which is about 4 times more than that in the West (JPMA 39: 282, 1989).

Association of mental retardation with con­genital hypothyroidism was first described in the 15th century but the horror of cretinism was ex­pressed by Osler in 1897¹. In the same decade the treatment of congenital hypothyroidism with thy­roid extract was reported. Sixty years after the intro­duction of thyroid replacement therapy, it was reali­sed that although the treatment abolished the physi­cal manifestations of congenital hypothyroidism, “unless it was started within the first few weeks of life serious intellectual and neurological deficits fre­quently persisted²”. The pre and post-natal periods are critical for brain development. Thyroid hormone is essential for the development and growth of brain^3-5. Autop­sies in the human infant with congenital hypothy­roidism shows hypoplasia of the cerebellar and cerebral cortices, edema and incomplete myelina­tion⁶. Neither T% T4 or TSH cross placental barrier to any significant degree. The fetal pituitary thyroid axis binctions independently of the maternal axis, and maternal thyroid hormones do not protect aga­inst congenital hypothyroidism. In 1972, Klein and associates⁷ showed that if the treatment of hypothyroid infants was started before the age of 3 months, mean 1.0. of patients was 89 whereas it was 70 when treatment was started between 3 and 6 months of age and only 54 if treat­ment was delayed beyond six months. Early clinical diagnosis is difficult. Few infants show diagnostic features of hypothyroidism at birth. The early mani­festations are subtle, non-specific and the stigmata of “aggravated creatinism” develop only slowly. For these reasons, even in the best of circumstances less than half the children with congenital hypo-thy­roidism are identified before three months of age, making the potential benefit of neonatal screening evident. A preliminary report of mass screening pro­gramme from Quebec (Canada) showed a hypo­thyroidism incidence of 1/7000 new-borns⁸. It also showed that radio-immunoassay for detection of T4 in dried filter paper blood spot was effective in detecting thyroid hormone abnormalities with an acceptable percentage of false positive measure­ments and no false negative results. The second International Conference on Neonatal Thyroid Sc­reening⁹ indicated a prevalence of primary hypo­thyroidism to be aproximately one in 3800 to 4000 infants worldwide⁹. Screening in North West health region of England showed a significantly higher incidence of congenital hypothyroidism in Asian families - 1/918 compared with 113391 in non-Asians¹⁰. To measure both thyroxine (T4) and thyroid stimulating hormone (TSH) on all specimen is ideal but expensive. The pros and cons of using either hormone as primary screen are listed in Table I¹¹. Japan, most of the European countries and some states in North America are using TSH screening as primary method¹². The reported increased incidence of con­genital hypothyroidism in babies born to Asian mothers had initiated our interest in carrying out screening in Pakistan where the incidence of con­genital hypothyroidism is not known:

From March 1987 to September 1988, 5000 neonates were screened. All neonates delivered at Aga Khan University Hospital and 4 maternity homes situated in metropolitan Karachi were in­cluded in the study. Capillary blood samples were collected on 3 circles on the filter paper provided by AKUH labo­ratory. A questionnaire regarding maternal health was filled before the collection of blood, especially regarding family history of thyroid disorder. The site chosen to obtain blood was the planter surface of the toot (Figure).

The area was wiped with 70% alcohol for one minute and allowed to dry. Skin was punctured in one continuous deliberate motion in a direction almost perpendicular to the puncture site to a depth of about 2.5 mm with a lancet. The first drop of blood was wiped off with a dry sterile swab and then the blood was collected directly from the heel on to the three circles of the filter paper. After the blood spots had dried, filter paper was sent to the laboratory. The T4 and TSH levels were measured from the blood on the filter paper by radioimmunoassay using Coat-A-count Neonatal T4 and TSH double antibody system by RIA (Diagnostic Products Cor­poration, Los Angeles, USA). If the specimen was found to have low T4 and high TSH then the cons centrations of T4 and TSH were confirmed on the venous sample. The established laboratory normal values ranged from: for capillary spccimens:T4, 6.9-26.4 and TSH, <20,uIU/ml., for venous sam-pies: T4, 4.5- 12.5 ug/dl and TSH 0.3-4.5 uIU/ml.

Of the 5000 neonates screened, 6% (300) had low T4 and normal TSH, 13% (65) had high TSH but normalT4,whiie six (0.12%) had lowT4 and high TSH. Six neonates with low T4 and high TSH were recalled for Venous sampling.

Five out of six were confirmed to have congenital hypothyroidism even on this basis of low T4 and high TSH level in serum specimen. One neonate had normal T4 but slightly elevated TSH on venous sampling which could be seen in compensated hypothyroidism. Out of 300 (6%) neonates with low T4 and normal TSH 9 were recalled for Venous sampling 8 out of 9 had normal T4 and TSH in serum. One infant with very low T4 and normal TSH in serum sample was further tested with T3 resin uptake which was significantly elevated. This is an indirect evidence of TBG deficiency. Of 65 neonates with high TSH and nonnalT4, nine were recalled. Eight out of 9 had normal values of T4 and TSH in serum sample, while one neonate had normal T4 and slightly elevated TSH which is usually seen in cases of compensated hypothyroid­ism. Details of five diagnosed cases is given in Table II.

In case I there was a past history treated maternal hypothyroidism. In case V, mother had a large goitre inspite of thyroidectomy done twice. This neonate at the time of recall already had sym­ptoms of congenital hypothyroidism which were pro­longed neonatal jaundice requiring hospitalisation, severe constipation and umbilical hernia. In four cases diagnosis were further confirmed radiologi­cally. X-ray of both knees revealed either absent or rudimentary tibia! and/or femoral epiphy-sis which is an evidence of delayed bone age in a term infant, an important feature of congenital hypothyroi­dism.

The objective of a screening programme for congenital hypothyroidism is early detection and treatment to minimise neurological deficiencies¹. This report has revealed four-fold higher incidence of the disease in the screened population as com­pared to figures from North America and Europe. This incidence has been calculated excluding two cases of compensated hypothyroidism. The cause for this high incidence in our popu­lation is not clear. Radioisotope scanning of thyroid gland in these infants was not possible due to lack of facilities. This would have helped in identifying the etiology. Nutritional iodine deficiency leading to thyroid disorder is a common problem in the northern mountainous regions of Pakistan. However, this is not a common clinical problem in the seaside locale of Karachi. Although the disease is known to be more common in females, in this study there were 3 males and 2 females. Since there is a maternal history of thyroid disorder in two out of five cases, maternal an­tibodies may be responsible for this increased in­cidence but they were not tested. However, in one case where there was no history of maternal thyroid disorder, maternal serum was tested for antibodies which was negative. Our study also confirmed the previously desc­ribed higher rate of false positive with T4 as com­pared to TSH testing. Since 90% of the cases of congenital hypothyroidism are primary in nature, TSH screening will become the future screening measure in our laboratory.

The help of physicians and nurses of the Aga Khan University Hospital, The Aga Khan Mater­nity Homes and Sobraj Maternity Home is grateful­ly acknowledged. We are also indebted to Abdul Aziz for Secre­tarial help. We also thank medical student Jamal Muba­rak for working out normal laboratory values of T4 and TSH in laboratory at AKUH.

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