Diagnostic Re-evaluation of Children with Congenital Hypothyroidism

 PII:S097475590900172-1
 

Objectives: To investigate the causes of congenital hypothyroidism in children more than 3 years of age and to document the frequency of transient vs permanent hypothyroidism.

Design: Hospital based observational study.

Setting: Pediatric endocrine clinic of a medical college.

Patients: Children over 3 years of age, on treatment for congenital hypothyroidism.

Intervention: Thyroid function test (TFT) and thyroid ultrasound was done. Children with agenesis or hemiagenesis in thyroid ultrasound were identified. In children with normal or equivocal thyroid ultrasound, thyroxine was stopped and followed. Children with abnormal TFT on follow up had thyroid scintigraphy with or without potassium perchlorate discharge, after which, thyroid hormone supplement was restarted. Children who remained euthyroid on follow up were labeled as having transient hypothyroidism.

Main Outcome Measure: Proportion of children with transient hypothyroidism.

Results: Among 36 children studied (20 boys and 16 girls), eighteen (50%) had transient hypothyroidism and fifteen (41.7%) had thyroid agenesis. There was one with hemiagenesis, one with ectopic thyroid and another with dyshormonogenesis (2.8% each). Initial TSH level at the time of diagnosis was higher in permanent hypothyroidism as compared with transient group (83.0 ± 31.6 vs 47.0 ± 33.1 mIU/mL; P= 0.002).

Conclusions: Thyroid hormone supplementation could be discontinued in 50% of children diagnosed with congenital hypothyroidism.

Key words: Children, Congenital hypothyroidism, Etiology, India, Transient hypothyroidism.

The incidence of congenital hypothyroidism in India varies from 1:2500 to 1:2800 live births(1). Nearly 75% of all infants with congenital hypothyroidism have thyroid dysgenesis, with hypoplasia or aplasia in 50 to 60%, ectopia in 25 to 35% and dyshormonogenesis due to biosynthetic defects in 10 to 30%. Congenital hypothyroidism could also result from transient abnormality in thyroid gland function, which subsequently recovers. The possible explanations include iodine deficiency, transplacental passage of maternal TSH-binding inhibitory antibodies, and maternal exposure to radioiodine, iodine or anti-thyroid drugs. In such situations, it may be possible to discontinue thyroxine therapy. Trials of with-holding thyroxine therapy are reported in the Western literature, but no such data is available from India. This study was done to look at different causes of congenital hypothyroidism and to determine the prevalence of transient hypothyroidism.

Measurements for serum TSH and total T4 were obtained at initial visit and at 4 wk; TSH at 8 wk and 14 wk, at the Regional Cancer Center, Thiruvananthapuram, using chemiluminescence immunoassay (reference range: TSH 0.25-6.3 mIU/L and T4 5.6-15 µg/dL). Thyroid volume was calculated by ultra-sonography using the ellipsoidal formula. Data from Gonzalez, et al.(3) were used to obtain cut-offs for the lower limit of thyroid size. Normal thyroid volume was taken as 2.2 ± 1.3 mL for children aged 3-6 years, 3.0 ± 1.7 mL for 6-12 years and 5.7 ± 3.1 mL for adolescents. Agenesis was diagnosed if no thyroid tissue was visualized in the neck. If only one lobe of thyroid was visualized normally, while the other lobe was not seen, hemiagenesis was diagnosed. When the thyroid volume appeared smaller than the lower limit of normal or if the radiologist could not say a definite opinion, it was taken as equivocal. Radionuclide tests were done at Regional Cancer Centre, Thiruvananthapuram, if TSH increased on thyroxine withdrawal. I-131 was the radionuclide agent used. Tc-99m study was done for one patient as the probe for I-131 uptake study was not available at that time. Perchlorate discharge test was done for one patient who had normal ultrasound and I-131 scan, but became hypothyroid on thyroxine withdrawal.

Thirty six children were included (Fig 1). None of the patients had any documented proof of permanent congenital hypothyroidism. All the patients were clinically euthyroid on thyroxine replacement at the time of enrollment. The mean (± SD) age of the study sample was 5.4 (± 2.7) years. There were 20 girls. The mean height centile was 27.8 (range 3rd to 90th centile). Hypothyroidism was diagnosed and treatment started at a mean age of 3.8 (± 6.1) months (range newborn to 27 months) (61.1% in the neonatal period, 72.2% by 3 months, 86.1% by 6 months and 91.7% by 1 year of age).

Fig.1 Patient flow with summary of results.

Transient hypothyroidism was seen in 18 patients (50%). The other 50% had some form of permanent congenital hypothyroidism. Among them, 15 patients (41.7%) had thyroid agenesis. There was one patient with hemiagenesis, one with ectopic thyroid and another with dyshormonogenesis (2.8% each). Initial TSH level at the time of diagnosis was significantly higher in the permanent hypothyroidism group as compared with those with transient hypothyroidism (83.0±31.6 vs 47.0±33.1 mIU/mL; P=0.002) (Fig.2). There was significant difference in the thyroxine dose between the two groups, when the total T4 dose was considered. But when weight/kg body weight was considered, although there was a trend towards higher dose requirement in the permanent hypothyroidism group, the difference did not reach statistical significance. There was no difference between the transient and permanent hypothyroidism groups in the height centiles achieved.

Fig.2 TSH at diagnosis (Box plot).

11. Panoutsopoulos G, Mengreli C, Ilias I, Batsakis C, Christakopoulou I. Scintigraphic evaluation of primary congenital hypothyroidism: results of the Greek screening program. Eur J Nucl Med 2001; 28: 529-533.