Source of data: Children in the age group 5 years-18 years who reported to OPD and IPD of the Department of Pediatrics in VIMS and RC from Jan 2017 to June 2018. Assuming a prevalence of 2-14%, a sample size of 60 Beta thalassemia major patients were included in this study.

Inclusion criteria:

1.Children 4 to 18 years age group with proven Beta thalassemia major.

2.Child received blood transfusions for more than 2 years.

3.Children with serum ferritin level >700(ng/ml).

Exclusion criteria:

1.Children with thalassemia minor or intermedia.

2.Children less than 4 years of age.

3.Children with primary thyroid dysfunction and other endocrinal dysfunction.

4.Children on thyroxine, any antithyroid drugs, or any other hormonal therapy

5.Children with any other chronic illness.

Method of collection of Data:

Counseling was done to the parents of patients and voluntary written informed consent was obtained from parents of patients for enrolling in the study. A detailed history was obtained from each patient regarding the age of diagnosis, frequency of transfusions, compliance to transfusion, and chelation was noted. 3ml of fasting blood sample from venous blood under strict aseptic precautions is taken to assess serum levels of thyroxine(T4), tri-iodo-thyroxine (T3), thyroid-stimulating hormone (TSH) and Ferritin using Chemiluminescence Immunoassay method in DXC860i machine. Data were entered into a Microsoft Excel datasheet and were analyzed using SPSS 22 version software. Categorical data was represented in the form of Frequencies and proportions. Chi-square test or Fischer’s exact test (for 2x2 tables only) was used as a test of significance for qualitative data. Continuous data were represented as mean and standard deviation. Independent t-test or Mann Whitney U test was used as a test of significance to identify the mean difference between two quantitative variables and qualitative variables respectively.

Mean Hb was 7.15 ± 1.94 g/dl, mean Ferritin (ng/ml) was 1296.64 ± 1009.6, mean T3(pg/ml) was 2.44 ± 1.03, mean T4(ng/dl) was 3.14 ± 2.73 and mean TSH (mIu/L) was 4.58 ± 2.28 (Table 3).

In the present study, 3( 5%) had a haemic murmur,1( 1.7%) had hepatomegaly,50( 83.3%) had hepatosplenomegaly and 9(15%) had splenomegaly. In the study,3 subjects(5%) had a history of use of chelators and57 (95%)subjects were not on chelators. In this study, 1.7% had A- blood group, 26.7% had A+ve blood group, 18.3% had AB+ ve, 1.7% had B-ve, 35% had B+ve and 16.7% had O+ve blood group. In this study,8.5% had mild anemia, 40.7% had moderate anemia and 50.8% had severe anemia.

Table-4: Correlation of Serum Ferritin with T3, T4, and TSH.

In this study, there was a significant negative correlation between Ferritin and T3 levels. i.e. with an increase in Ferritin level, there was a decrease in T3 levels and vice versa. There was a positive correlation between Ferritin and T4, TSH levels. i.e. with an increase in Ferritin level, there was an increase in T4, TSH levels, and vice versa. However, the correlation was significant with TSH.

Fig-1: Scatter plot showing negative Correlation of Serum Ferritin with T3.

Table-5: Hypothyroidism in the subjects.

In the study, 6.8% had overt hypothyroidism, 13.6% had subclinical hypothyroidism and 79.7% had euthyroid status (Table 5).

Fig-5: Height and Weight Centile classification among study subjects.

In the study, 45% had height <3rd centile, 15% had 3rd to 10th centile, 31.7% had 10th to 25th centile and 8.3% had 25th to 50th centile height.

In the study, 15% had weight <3rd centile, 20% had 3rd to 10th centile, 3.3% had 10th to 25th centile, 55% had 25th to 50th centile Height and 6.7% had 50th to 75th centile weight (Figure 5).

According to the Thalassemia International Federation, only about 200,000 patients with thalassemia major are alive and registered as receiving regular treatment around the world [7].

The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemia patients but is complicated by citrate toxicity and subsequent iron overload resulting in a high incidence of endocrine abnormalities in children, adolescents, and young adults.

Endocrinopathies are now amongst the common complications of thalassemia but determining the exact prevalence is difficult because of differences in age of first exposure to chelation therapy and the continuing improvement in survival in well-chelated patients.

An exaggerated TSH response to stimulation by thyrotrophin-releasing-hormone (TRH) was found by De Sanctis et al in 8 of 24 thalassaemias studied and a third of those went on to develop sub-clinical or overt hypothyroidism three to eleven years later [18].

This suggests the development of thyroid disease may have a fairly protracted course. De Sanctis et al in another study showed that good compliance with chelation therapy appeared to improve thyroid function [19].

In a study done by Jaipuria. R et al hypothyroidism was found in 23.3%(14out of 60)of β thalassemia patients. Out of these, compensated hypothyroid (normal T3 and T4 with raised TSH) was seen in 9 patients (15%) and decompensated hypothyroid (decrease T3 or T4 and Raised TSH) was seen in 5 patients (8.33%).

There was a significant positive correlation of TSH levels with serum ferritin levels, age, and transfusion index [20]. Parijat et al found that 5% (8 out of 163) of thalassemia patients had overt clinical hypothyroidism that required treatment whereas a much greater percentage have sub-clinical compensated hypothyroidism with normal T4 and T3 but high TSH levels [21].

A study done by Eshragi Pet al showed that hypothyroidism was diagnosed in 14 %( 19out of 130) of patients [22]. Chirico et al. followed up 72 thalassaemic patients demonstrated ferritin levels correlate positively with both TSH and thyroid volume on ultrasonography and can predict progression of thyroid disease [23].

The current study included children from 4 to 18 years age group(58.3% males and 41.7% females) who have received transfusions for more than two years and found out that 30% were in the age group <5 years, 50% were in the age group 6 to 10 years and 20% were in the age group 11 to 15 years. The mean age of subjects was 7.73±2.916 years.

Among 60 children who were included in this study, four children (6.8%) had overt hypothyroidism, eight children (13.6%) had subclinical hypothyroidism. This is comparable with other national and international studies done on thyroid dysfunction in beta-thalassemia which were described in Table 6.

hypogonadism, osteoporosis, dilated myocardiopathy, cirrhosis of the liver could not be investigated due to financial constraints.

Thalassemia patients have a high prevalence of endocrinological abnormalities. Several studies at different centers have demonstrated the increased prevalence of endocrinopathies in patients with thalassemia. Improvements in protocols of transfusion regime and chelating therapy should hopefully improve the care and quality of life of these patients. Early recognition and treatment of endocrine failure in poly-transfused beta-thalassemia major patients is a significant part of the holistic management of the disease. This is particularly true for thyroid dysfunction because hypothyroidism could be implicated in growth problems so commonly envisaged in these patients.

Hence regular screening of beta-thalassemia major patients for Serum T₃, Serum T₄, Serum TSH for early detection and timely treatment could improve the quality of life of these patients. Also, detection of hypothyroidism is important as inexpensive oral replacement therapy is readily available. Further studies including more patients covering most parts of India and other ethnic races groups are needed to have substantial evidence to do a regular screening of serum T3, T4, and TSH level estimation in thalassemia major patients.

All the authors, Dr. Rohit Khandelwal, Dr. Muralidhar Gundluru, Dr. Leeni Mehta K participated equally in this study.