Department of Endocrinology, Medical Centre of Postgraduate Education, Warsaw, Poland.
Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland.
Endokrynol Pol. 2020;71(5):441-465. doi: 10.5603/EP.a2020.0065.
Hypothyroidism is a common endocrine disorder affecting 3-15% of the adult population in subclinical form and 0.3-0.8% as overt disease. The mainstay of treatment is replacement monotherapy with levothyroxine (LT4). Currently several oral LT4 formulations including tablets, softgel capsules, and liquid formulations are available. Liquid LT4 is manufactured as LT4 solution in 85% glycerol and 96% ethanol and as LT4 solution in purified water and glycerol. The latest formulation, Tirosint SOL, gained FDA approval in 2017. To evaluate the clinical utility of liquid LT4 we reviewed the literature using three databases: PubMed/MEDLINE, Scopus, and Embase and found 405 articles among which 23 prospective and two retrospective studies were further evaluated. Finally, several case reports on rare clinical conditions were discussed. Our review demonstrated that liquid LT4 was more effective than tablet formulation in patients with malabsorption caused by interfering diseases, drugs, and bariatric surgery. The better pharmacokinetics of liquid LT4 was also confirmed in subjects without malabsorption: patients on replacement or suppressive therapy, who switched from tablet to liquid formulation in equivalent dose, gained better hormonal control, and required less frequent TSH measurements. The drug also appeared effective and easy to handle in patients fed by enteric tube. Liquid LT4 appeared equally effective whenever taken before or during breakfast. The analysis of the drug utility in particular populations including newborns, pregnant women, and the elderly confirmed the high value and safety of liquid LT4. However, in neonates the higher incidence of TSH suppression on liquid in comparison to tablet LT4 therapy was noted, and particular attention to avoid over-treatment must be paid. Concluding: the literature review revealed that liquid LT4 is especially advantageous in patients with malabsorption and the critically ill, but it seems also very promising in common therapy. The lack of alcohol content in the new formulation makes Tirosint SOL especially attractive.
甲状腺功能减退症是一种常见的内分泌疾病，亚临床形式影响 3-15%的成年人口，显性疾病影响 0.3-0.8%。治疗的主要方法是使用左甲状腺素（LT4）进行替代单药治疗。目前，有几种口服 LT4 制剂，包括片剂、软胶囊和液体制剂。液体制剂 LT4 以 85%甘油和 96%乙醇中的 LT4 溶液以及以纯化水和甘油中的 LT4 溶液的形式生产。最新的制剂 Tirosint SOL 于 2017 年获得 FDA 批准。为了评估液体 LT4 的临床实用性，我们使用三个数据库：PubMed/MEDLINE、Scopus 和 Embase 检索文献，共找到 405 篇文章，其中进一步评估了 23 项前瞻性研究和 2 项回顾性研究。最后，讨论了一些罕见临床情况下的病例报告。我们的综述表明，在因疾病、药物和减肥手术导致吸收不良的患者中，液体 LT4 比片剂制剂更有效。在没有吸收不良的患者中，液体 LT4 的更好药代动力学也得到了证实：接受替代或抑制治疗的患者，从片剂转为等剂量的液体制剂，获得了更好的激素控制，并且需要进行更频繁的 TSH 测量的频率降低。在通过肠内管喂养的患者中，药物也表现出有效且易于处理。液体 LT4 无论在早餐前还是早餐时服用，似乎都同样有效。对包括新生儿、孕妇和老年人在内的特殊人群的药物实用性分析证实了液体 LT4 的高价值和安全性。然而，在新生儿中，与片剂 LT4 治疗相比，液体 LT4 导致 TSH 抑制的发生率更高，因此必须特别注意避免过度治疗。总之：文献综述表明，液体 LT4 特别有利于吸收不良和重症患者，但在常规治疗中似乎也很有前途。新配方中不含酒精，这使得 Tirosint SOL 特别有吸引力。
