Prevalence and factors associated with hypothyroidism in children with sickle cell anemia aged 6 months -17 years attending the sickle cell clinic, Mulago hospital, Uganda

Abstract

Background: Sickle cell anemia (SCA) is characterized by defective hemoglobin synthesis, hemolytic anemia, frequent thrombosis and chronic end organ damage including the endocrine organs like the thyroid gland. Some studies have demonstrated a relationship between hypothyroidism and SCA with a prevalence of 6% in children and adolescents. The recurrent episodes of hemolysis leading to iron overload, vaso-occlusive crises (VOCs), micro-vasculature obstruction due to red blood cell (RBC) entrapment and frequent blood transfusions in SCA are the mechanisms implicated in the development of hypothyroidism. It is also important to note that the symptoms of hypothyroidism in SCA are not obvious. Most of the symptoms like cold intolerance, constipation are mimicked by SCA and others by behavioural adaptation by the patients. In Uganda, we do not screen children with SCA for hypothyroidism despite the impact it may have on the growth and development of these children. Objective: The study aimed to determine the prevalence and factors associated with hypothyroidism among children with SCA aged 6 months to 17 years attending the Sickle Cell Clinic (SCC), Mulago hospital. Methods: A cross-sectional study of children aged 6 months -17 years with a confirmed diagnosis of SCA, no prior diagnosis of hypothyroidism and in their steady state attending the SCC in Mulago hospital was conducted. Data was collected over a period of 2 months using a structured questionnaire that was administered after seeking informed consent from guardians or parents and assent from the children as appropriate. A blood sample was used for analysis for thyroid stimulating hormone (TSH) and free thyroxine (FT4). The data collected was entered into a password protected computer using Epi data 3.1 and analyzed using STATA version 14. Bivariable xiv and multivariable analysis using logistic regression models was utilized to determine the factors associated with hypothyroidism. A p-value< 0.05 was considered as significant. Results: Of the 332 children enrolled, 50.3% (167/332) were female; their median age (IQR) was 6 (3-10) years. Sixty out of 332 (18.1%) had hypothyroidism (95% CI: 14.3 - 22.6), all of whom had sub-clinical hypothyroidism. The factors associated with hypothyroidism were: constipation [Adjusted OR: 3.05 (95% CI:1.04 - 8.97) p=0.043] and male sex [Adjusted OR:1.96 (95% CI:1.09 - 3.53) p= 0.025]. Conclusion and recommendations: Approximately 1 in 5 children (18.1%) had hypothyroidism in this study. Males and children who presented with constipation were more likely to have hypothyroidism. This suggests that clinicians should screen all children with SCA who present with constipation for hypothyroidism and those found with hypothyroidism treated appropriately to improve their growth and quality of life