A prospective study exploring determinants of response to combination Levothyroxine–Liothyronine (LT4+LT3) Therapy versus Levothyroxine Monotherapy in Symptomatic Hypothyroid patients with normal TSH Levels.
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 1
研究概览
简要总结
This study proposes a prospective, open label, randomized controlled trial to evaluate determinants of response to combination levothyroxine liothyronine (LT4 and LT3) therapy compared with levothyroxine (LT4) monotherapy in symptomatic hypothyroid patients with normal TSH levels. Although LT4 monotherapy achieves biochemical euthyroidism in most patients, approximately 5 to 10 percent continue to experience persistent symptoms such as fatigue, cognitive dysfunction, mood disturbances, and weight gain. This suggests possible tissue level hypothyroidism due to impaired peripheral conversion of T4 to T3, altered intracellular transport, or genetic variations affecting thyroid hormone metabolism and action. Combination therapy may better replicate physiological thyroid hormone signalling in selected individuals, but predictors of response remain unclear.
Adults aged 18 to 65 years with normal serum TSH, a ThyPRO 39 score greater than 32, and stable LT4 therapy will be enrolled. Participants will be randomized to continue LT4 monotherapy or switch to LT4 and LT3 in a fixed physiological ratio of 15 to 1. Quality of life will be assessed using the validated ThyPRO 39 questionnaire. Biochemical parameters including serum TSH, free T4, free T3, lipid profile, sex hormone binding globulin (SHBG), and the free T3 to free T4 ratio will be measured. Thyroid hormone sensitivity will be assessed using the Thyroid Feedback Quantile based Index (TFQI).
The primary outcome is the change in ThyPRO 39 composite score at 12 weeks. Secondary outcomes include changes in biochemical markers and correlations between quality of life improvement and surrogate markers of tissue thyroid hormone action. The study aims to identify biochemical predictors that may help select patients most likely to benefit from combination therapy and support a personalized approach to hypothyroidism management.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Normal serum TSH ThyPRO 39 score more than 32 On stable LT4 dose for more than or equal to 3 months Adequate replacement more than or equal to 6 months.
排除标准
- •Diabetes mellitus with a HbA1c more than 7 percent Serious systemic illness or malignancy Overt autoimmune disease Fibromyalgia Chronic fatigue Drugs influencing thyroid function, pregnancy, or hormonal contraceptive use.
研究者
Dr Sonali Appaiah
Department of Endocrinology 2nd Floor Unit of Hope Building St Johns Medical College and Hospital