Association of pharmacogenomic, clinical and behavioural factors with oral levothyroxine (LT-4) dose of hypothyroid patients in Sri Lanka: a matched case control study

• Main Authors: S. S. Dalugodage (Author), Gayan Bowatte (Author), Charles Antonypillai (Author), S. Rajapakse (Author), T. M. I. U. K. Tennakoon (Author)
• Format: Book
• Published: BMC, 2024-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/s12920-024-01849-z; 1755-8794
• Keywords: Hypothyroidism; Levothyroxine; Dose requirement; Single nucleotide polymorphisms (SNPs); Patient compliance; Comorbidities; Internal medicine; RC31-1245; Genetics; QH426-470
• Source: BMC Medical Genomics, Vol 17, Iss 1, Pp 1-7 (2024)

Abstract Background Hypothyroidism is a common endocrine disorder that exerts a substantial influence on people all over the world. Levothyroxine (LT-4) is the drug of choice for the treatment of hypothyroidism and the starting oral dose is typically ranging from 1.5 to 1.7 µg/kg/day. The target is to achieve an optimum serum TSH level of 0.4-4.0 mIU/L; hence, the dose is titrated accordingly. Once the LT-4 dose is adjusted to obtain the target TSH level, it usually remains stable for a long period of time in most cases. However, some of the patients require frequent dose adjustments and some of them require unusually high doses. Therefore, the aim of this study is to determine the association of pharmacogenomic, clinical and behavioural factors with the oral levothyroxine (LT-4) dose requirement of hypothyroid patients in Sri Lanka. Method This study will be conducted as a matched case-control study and will involve primary hypothyroid patients who visit the diabetes and endocrinology clinic at the National Hospital, Kandy, Sri Lanka. We will recruit a total of 292 cases and select 292 controls from the clinic who are matched in terms of age, sex and Body Mass Index (BMI). An interviewer-administered questionnaire will be used to collect data from the participants (n = 584). Of the 584 patients, blood samples will be collected from a sub-sample (n = 150) for DNA extraction. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) will be performed for single nucleotide polymorphisms (SNP) analysis. Discussion Frequent dose adjustments of levothyroxine cause a serious economic burden to the healthcare system. By identifying the root causes of the variations in LT-4 dosage, a more comprehensive comprehension of hypothyroidism and its management can be attained in Sri Lanka. Furthermore, upon identification of a positive association/correlation between genetic polymorphisms and the LT-4 dose, SNP profiles can be used as a possible genetic marker for dose adjustment determination in future patients.