Beta thalassemia is a significant public health challenge, particularly in regions where consanguineous marriages are prevalent, such as the Mediterranean, Middle East, and South Asia [1, 2]. This autosomal recessive disorder arises from mutations in the beta-globin gene, leading to defective hemoglobin synthesis and chronic anemia [3]. Globally, an estimated 80-90 million people are carriers of beta thalassemia, with approximately 300,000-400,000 new cases of severe hemoglobinopathies born annually [4, 5].

The burden of beta thalassemia is amplified in low- and middle-income countries, where limited resources constrain effective management and prevention strategies.

The clinical manifestations of beta thalassemia vary widely, ranging from asymptomatic carrier states to severe, transfusion-dependent anemia. For patients with beta thalassemia major, regular blood transfusions are a cornerstone of management, improving survival and quality of life. However, repeated transfusions result in progressive iron overload, posing severe risks to organ health [6, 7]. Iron overload, primarily due to transfusions and increased gastrointestinal absorption, leads to deposition in vital organs such as the heart, liver, and endocrine glands, causing significant morbidity and mortality [8].

Iron overload-induced oxidative stress is a critical mechanism underlying organ dysfunction in transfusion-dependent beta thalassemia patients. The production of free radicals due to excess iron results in lipid peroxidation, mitochondrial damage, and apoptosis, particularly affecting organs such as the thyroid gland, pituitary, pancreas, and heart [9]. Endocrine complications, including hypothyroidism, hypogonadism, and diabetes mellitus, arise from iron deposition in endocrine tissues. Cardiomyopathy and heart failure, secondary to myocardial siderosis, remain leading causes of death in this population[10].

Although the availability of imaging modalities such as T2*-weighted magnetic resonance imaging (T2* MRI) has improved the ability to detect early iron deposition in tissues [11]. However, such advanced imaging techniques are often inaccessible in resource-constrained settings, underscoring the need for reliable and cost-effective biomarkers. Serum ferritin, although commonly used, has limitations in accurately reflecting tissue iron deposition [12].

This study aims to explore the prevalence of thyroid and cardiac complications in pediatric beta thalassemia patients and evaluate their correlation with serum ferritin levels. Such investigations are vital for early detection and targeted management of complications in this vulnerable population.

A cross-sectional study was conducted at Mahatma Gandhi Memorial Hospital, Warangal, from September 2022 to April 2024. Fifty pediatric patients diagnosed with beta thalassemia major/intermedia were enrolled based on inclusion criteria. Detailed clinical histories, physical examinations, and investigations, including complete blood counts, serum ferritin, thyroid profiles, Electrocardiogram (ECG), and 2D echocardiography, were performed. Statistical analyses were conducted using SPSS software, with a p-value <0.05 considered significant.

This hospital-based cross-sectional study included 50 pediatric beta-thalassemia patients aged 2–12 years. Below are the key findings:

1. Demographic Data
• Age Distribution: Most patients (46%) were aged 6–9 years, followed by 2–5 years (36%), and 10–12 years (18%).
• Gender: Male patients (56%) outnumbered females (44%).
• Residence: 52% were from urban areas, while 48% were from rural regions.
• Socioeconomic Status: A majority (56%) were from low-income families.

Figures 1: Bar chart for age distribution

Figure 2 : Pie chart for gender distribution

1. Clinical Profile
• Growth disturbances: 58% had both stunting and wasting, 22% had stunting only, and 16% had wasting only.
• Recurrent Infections: Respiratory infections (38%) were the most common, followed by urinary tract infections (22%) and sepsis (14%).

Figure3:  Distribution of subjects basing on their clinical profile.

Table 1: Clinical profile table summarizing growth and infections

.

1. Blood Transfusions and Serum Ferritin
• Most patients (86%) required monthly transfusions.
• Serum Ferritin Levels: 58% had levels between 2000–4000 ng/mL, with a mean of 1414 ± 1125 ng/mL.

Table 2: Serum ferritin levels.

1. Thyroid Profile
• Hypothyroidism was present in 26% of patients, with an average TSH level of 5.93 ± 2.54 IU/mL.
• No significant correlation between serum ferritin and hypothyroidism (p = 0.624).

Table 3: Thyroid hormone levels (T3, T4, TSH).

1. Cardiac Findings
• ECG: 36% had abnormal findings, while 64% were normal.
• Echocardiography: 72% showed increased left ventricular mass, 50% had tricuspid regurgitation, and 24% had pulmonary hypertension.
• No significant correlation between serum ferritin and cardiac findings.

Tables 4: summary of ECG and Echocardiography findings

Figure 4: Bar chart of key echocardiographic abnormalities.

1. Diagnostic Accuracy
• Echocardiography demonstrated higher sensitivity (91.23%) compared to ECG (82.58%) for detecting cardiac complications.

Table 5: Comparative table for ECG and echocardiography sensitivity, specificity, and diagnostic accuracy

The findings of this study align with existing literature highlighting the high prevalence of endocrine and cardiac complications in beta thalassemia patients. Hypothyroidism, particularly subclinical, is a frequent manifestation due to iron deposition in the thyroid gland [13]. Iron overload causes fibrosis and oxidative damage, impairing thyroid function. Similar results were reported by Mogharab et al. and Panchal et al., who identified subclinical hypothyroidism as a predominant feature among transfusion-dependent beta thalassemia patients [14, 15].

Cardiac abnormalities remain a leading cause of morbidity and mortality in beta thalassemia. The observed prevalence of left ventricular hypertrophy and pulmonary hypertension in this study is consistent with findings from Khider et al. and Belhoul et al. [16, 17]. Chronic anemia, myocardial siderosis, and hypoxia collectively contribute to cardiac remodeling and dysfunction. Despite the elevated serum ferritin levels in most patients, the lack of significant correlation with cardiac complications suggests that serum ferritin alone is insufficient to predict tissue-specific iron deposition [18].

Advanced imaging modalities, such as T2* MRI, offer a more accurate assessment of myocardial and hepatic iron overload. However, the limited availability and high cost of such techniques make them inaccessible in many regions [19]. Echocardiography, although less specific, serves as a valuable and cost-effective tool for periodic cardiac monitoring [20].

The lack of correlation between serum ferritin levels and organ dysfunction in this study underscores the complexity of iron overload pathophysiology. Factors such as individual variability in iron absorption, chelation efficacy, and genetic predisposition may influence the extent of tissue damage. Future research should focus on identifying reliable biomarkers and improving access to advanced diagnostic tools [21].

Implications for Clinical Practice

Regular monitoring of serum ferritin levels, thyroid function, and cardiac parameters is essential for the comprehensive management of beta thalassemia patients. Early initiation of iron chelation therapy, tailored to individual needs, can mitigate the progression of complications. Multidisciplinary care involving pediatricians, endocrinologists, and cardiologists is crucial for optimizing outcomes [22].

Educational initiatives targeting families and healthcare providers can enhance awareness of the importance of treatment adherence and early complication detection. Genetic counseling and carrier screening programs can play a pivotal role in reducing the incidence of beta thalassemia, particularly in high-risk populations [23].

This study highlights the significant burden of thyroid and cardiac complications in pediatric beta thalassemia patients. While hypothyroidism and cardiac abnormalities are prevalent, their correlation with serum ferritin levels is not statistically significant, emphasizing the need for alternative diagnostic approaches [24]. Regular monitoring and a multidisciplinary approach to care are essential for improving the quality of life and survival of beta thalassemia patients. Further research is warranted to identify robust biomarkers and evaluate the long-term efficacy of current management strategies.

SOURCE OF FUNDING: Nil

 CONFLICT OF INTEREST: None

AUTHOR’S CONTRIBUTIONS

Mopuru Khyathi Keerthana worked on conceptualization, methodology, investigation, formal analysis, validation and software, writing- original draft preparation of the article.

Subhan Basha Bukkapatnam has worked on conceptualization, methodology, software, formal analysis, data curation, validation, writing-reviewing and editing, Visualization, supervision and project administration

Vasudev Kompally has worked on conceptualization, methodology, investigation, formal analysis, validation, resources, reviewing and editing, supervision, and project administration

All authors have read and agreed to the published version of the manuscript.

ACKNOWLEDGEMENTS:

We express our appreciation and gratitude to all the parents and care givers of the babies for supporting our study by giving consent without which this can never happen. We are thankful to Department of Pediatrics, Department of Radiology, Department of Biochemistry, Hospital Administration, who have assisted and supported in this research.

1. Cooley TB, Lee P. A series of severe anemia cases. Am J Med. 1925. doi:10.1016/0002-9343(25)90001-3
2. Whipple GH. The concept of thalassemia. J Hematol. 1936.
3. Weatherall DJ, Clegg JB. The thalassemias: a global health problem. Nat Rev Genet. 2001;2(4):253-263. doi:10.1038/35072079
4. Rund D, Rachmilewitz E. Pathophysiology of beta thalassemia. Ann N Y Acad Sci. 2005;1054:1-9. doi:10.1196/annals.1345.002
5. Borgna-Pignatti C, Galanello R. Survival and complications in thalassemia. Ann N Y Acad Sci. 2005. doi:10.1196/annals.1345.004
6. Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V. Guidelines for the management of transfusion-dependent thalassemia (TDT). 3rd ed. Thalassemia International Federation; 2014.
7. Taher AT, Musallam KM, Karimi M, Cappellini MD. Contemporary approaches to treat beta-thalassemia. J Blood Med. 2011;2:43-52. doi:10.2147/JBM.S13947
8. Porter JB, de Witte T, Cappellini MD. Iron overload in beta thalassemia: causes and consequences. Hematology. 2001;1(1):89-96. doi:10.1182/blood-2010-06-293514
9. Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood. 1997;89(3):739-761.
10. Derchi G, Forni GL, Campisi S. Endocrine complications in beta-thalassemia major. J Endocrinol Invest. 2010;33(2):135-140. doi:10.1007/BF03346574
11. Anderson LJ, Holden S, Davis B, et al. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J. 2001;22(23):2171-2179. doi:10.1053/euhj.2001.2822
12. De Sanctis V, Soliman AT, Elsedfy H, et al. Thyroid disorders in beta-thalassemia major: an update. Mediterr J Hematol Infect Dis. 2016;8(1):e2016057. doi:10.4084/mjhid.2016.057
13. Mogharab F, Ebrahimi S, Azarkivan A. Prevalence of hypothyroidism in beta-thalassemia patients. J Endocrinol Invest. 2019;42(5):509-515. doi:10.1007/s40618-019-01007-y
14. Panchal R, Sahni A, Gupta S. Thyroid dysfunction in children with beta-thalassemia major. Indian Pediatr. 2018;55(9):784-787. doi:10.1007/s13312-018-1372-5
15. Khider NA, Jasim HN. Cardiac and thyroid complications in beta-thalassemia major. J Pediatr Hematol Oncol. 2017;39(4):249-254. doi:10.1097/MPH.0000000000000798
16. Belhoul KM, Bakir ML, Kadhim AM, et al. Prevalence of complications among patients with beta-thalassemia major treated at Dubai Thalassemia Center. Ann Saudi Med. 2013;33(1):18-21. doi:10.5144/0256-4947.2013.18
17. Suriapperuma T, Premawardhena A, Mudiyanse RM, et al. Iron overload and its clinical consequences in patients with beta-thalassemia major. Southeast Asian J Trop Med Public Health. 2015;46(1):103-112.
18. Taher A, El-Beshlawy A, Cappellini MD. Update on the use of deferasirox in the management of iron overload. Ther Adv Hematol. 2013;4(2):87-101. doi:10.1177/2040620712471258
19. Cappellini MD, Farmakis D, Porter J, Taher A. Guidelines for the management of non-transfusion-dependent thalassemia (NTDT). Thalassemia International Federation; 2013.
20. Voskaridou E, Terpos E, Spyridaki M, et al. Myocardial iron overload assessment in thalassemia major: comparison between echocardiography and T2* MRI. Ann Hematol. 2008;87(2):131-136. doi:10.1007/s00277-007-0381-y
21. Hahalis G, Kremastinos DT, Terzis G, et al. Heart failure in beta-thalassemia: a 5-year study. Am J Med. 2001;111(5):349-354. doi:10.1016/S0002-9343(01)00876-0
22. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010;5:11. doi:10.1186/1750-1172-5-11
23. Weatherall DJ. The challenge of thalassemia for the developing countries. Ann N Y Acad Sci. 2005;1054:11-17. doi:10.1196/annals.1345.003
24. Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood. 2011;118(13):3479-3488. doi:10.1182/blood-2010-08-300335