Awasthi Avivar, Chakraborty Partha Pratim, Agrawal Neeti, Sinha Anirban, Pandey Anuj Kumar, Maiti Animesh
Department of Endocrinology, Kasturba Medical College, Manipal, Karnataka, India.
Department of Endocrinology & Metabolism, Medical College, Kolkata, MCH 4th floor, 88 College Street, Kolkata, West Bengal, 700073, India.
Thyroid Res. 2023 Jun 1;16(1):15. doi: 10.1186/s13044-023-00156-6.
One of the common causes of suboptimal control of thyroid stimulating hormone (TSH) in levothyroxine-treated hypothyroidism is coadministration of proton pump inhibitors (PPIs). Morning administration of pantoprazole has been shown to suppress intragastric pH to a greater extent. We therefore aimed to determine the effect of pantoprazole at different time points of the day on thyroid function test (TFT) in levothyroxine-treated overt primary hypothyroidism.
In this single centre, hospital based, prospective, two arm cross-over study (AB, BA), participants were randomized into 2 groups based on morning (6:00 am - 7:00 am simultaneously with the scheduled levothyroxine tablet) (group M) and evening (30 min before dinner) intake of 40 mg pantoprazole tablet (group N). After the initial 6 weeks (period 1), a washout period of 1 week for pantoprazole was given, and then both the groups crossed over for another 6 weeks (period 2). Patients were instructed to continue the same brand of levothyroxine tablet at empty stomach 1-hour before breakfast. Serum TSH was measured at baseline, week 6, and week 13.
Data from 30 patients, who completed the study with 100% compliance, were analysed. Mean TSH values of the study participants were significantly higher both at week 6 and week 13 compared to the baseline. Mean baseline serum TSH concentrations for groups M and N were 2.70 (± 1.36), and 2.20 (± 1.06) µlU/mL, respectively. Mean serum TSH concentrations at the end periods 1 and 2 for group M were 3.78 (± 4.29), and 3.76 (± 2.77) while the levels in group N were 3.30 (± 1.90), and 4.53 (± 4.590) µlU/mL, respectively. There was a significant rise in serum TSH concentration across periods 1 and 2 in both the groups (F = 3.87, p = 0.03). Within group changes in TSH across periods 1 and 2 were not statistically significant. Similarly difference in TSH between the groups, either at 6 weeks or at 13 weeks, were also not statistically significant.
Concomitant use of pantoprazole, even for 6 weeks, leads to significant elevation in serum TSH in levothyroxine-treated patients who are biochemically euthyroid, irrespective of timing of pantoprazole intake. Early morning and night-time administration of pantoprazole have similar effect on TFT in these patients.
在左甲状腺素治疗的甲状腺功能减退症中，促甲状腺激素（TSH）控制不佳的常见原因之一是质子泵抑制剂（PPI）的联合使用。已证明早晨服用泮托拉唑可更大程度地抑制胃内pH值。因此，我们旨在确定一天中不同时间点的泮托拉唑对左甲状腺素治疗的显性原发性甲状腺功能减退症患者甲状腺功能测试（TFT）的影响。
在这项单中心、基于医院的前瞻性双臂交叉研究（AB、BA）中，参与者根据早晨（上午6:00 - 7:00，与预定的左甲状腺素片同时服用）（M组）和晚上（晚餐前30分钟）服用40毫克泮托拉唑片（N组）被随机分为两组。在最初的6周（第1阶段）后，给予1周的泮托拉唑洗脱期，然后两组交叉再进行6周（第2阶段）。患者被指示在早餐前1小时空腹继续服用同一品牌的左甲状腺素片。在基线、第6周和第13周测量血清TSH。
分析了30例以100%的依从性完成研究的患者的数据。与基线相比，研究参与者在第6周和第13周的平均TSH值均显著更高。M组和N组的平均基线血清TSH浓度分别为2.70（±1.36）和2.20（± 1.06）μlU/mL。M组在第1阶段和第2阶段结束时的平均血清TSH浓度分别为3.78（±4.29）和3.76（±2.77），而N组的水平分别为3.30（±1.90）和4.53（±4.590）μlU/mL。两组在第1阶段和第2阶段血清TSH浓度均有显著升高（F = 3.87，p = 0.03）。第1阶段和第2阶段内TSH在组内的变化无统计学意义。同样，两组在6周或13周时TSH的差异也无统计学意义。
泮托拉唑的联合使用，即使使用6周，也会导致左甲状腺素治疗的生化甲状腺功能正常患者的血清TSH显著升高，无论泮托拉唑的服用时间如何。早晨和夜间服用泮托拉唑对这些患者的TFT有相似的影响。
