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. 2021 Jan 19;36(6):1726–1733. doi: 10.1007/s11606-020-06403-y

Table 1.

Characteristics of the Selected Studies

Country Author, year (ref.) Study type Number of patients (female/male) Age (mean) years LT4 dose PPI dose TSH mU/l before PPI TSH mU/l after PPI Follow-up Quality
Italy Centanni, 200625 Interventional, non-randomized controlled study 10 (F) NS

1.58 μg/kg/day tablets (Eutirox®)

Was taken at least 1 h before breakfast

omeprazole

40 mg/day

0.1 1.70 6 months Low risk of bias*
UK Irving, 201526 Observational, retrospective 1491 58.1

Tablets.

For at least 6 months

omeprazole, pantoprazole, lansoprazole esomeprazole rabeprazole 1.51 ± 2.64 1.69 ± 2.83 6 months Good quality**
USA Sachmechi, 200727 Observational, retrospective

37

(30 F, 7 M)

59 ± 7.5

25 to 200 μg/day (mean 82.8 ± 40.3)

(tablets)

For at least 6 months

lansoprazole 30 mg/day 2.34 ± 1.3 3.0 ± 2.2 2–6 months Good quality**
Brazil Abi-Abib, 2014,31 Interventional, uncontrolled before–after study

All: 19

Group omeprazole 20 mg:

10 (8 F 2 M).

Group omeprazole 40 mg:

9 (8 F, 1 M).

Group 1 (omeprazole 20 mg):

54.6 ± 10.9

Group 2 (omeprazole 40 mg):

50.6 ± 10.2

Tablets (Puran T4®) for at least 1 year. Was taken at least 30 min before PPI, and PPI 15 min before breakfast

Group 1: omeprazole 20 mg (Neoprazol®)

Group 2: omeprazole 40 mg (Neoprazol®)

All: 2.48 ± 1.12.

Group omeprazole 20 mg: 2.45 ± 0.98.

Group omeprazole 40 mg: 2.51 ± 1.33.

All: 2.76 ± 1.75.

Group omeprazole 20 mg: 2.80 ± 1.80.

Group omeprazole 40 mg: 2.71 ± 1.79.

3 months Low risk of bias*
Italy Trifiró. 2015,28 Quasi-experimental pre–post analysis 3787 54.6 ± 14.47 NS NS NS TSH levels increased with the concomitant use of PPI (adjusted IRR: 1.02; 95% CI: 1.01–1.03) 15 days Low risk of bias*
Italy Saraceno, 201237 Interventional non-randomized crossover study

All: 15 (12 F, 3 M).

Group 1 (REP): 6

Group 2 (SUP): 9

NS Tablets and then oral solution (Tirosint®)

omeprazole (n = 7)

pantoprazole (n = 5)

lansoprazole (n = 3)

NS

Group 1 (REP) LT4 tablet and PPI: 2.77 ± 2.05.

LT4 solution and PPI: 1.63 ± 0.66.

Group 2 (SUP) LT4 tablet and PPI: 1.15 ± 1.85.

LT4 solution and PPI: 0.12 ± 0.12

2 months after switch Moderate risk of bias*
Italy Vita, 201438 Interventional non-randomized study

All: 24 (18 F, 6 M)

Group 1 (REP): 14 (11 F, 3 M)

Group 2 (SUP): 10 (7 F, 3 M)

All: 56.2 ± 14.5

Group 1: 63.3 ± 11.2

Group 2: 46.7 ± 13.2

Tablets and then oral solution

(Tirosint®)

1.5 μg/kg/day ± 0.4.

Was taken 30 min before PPI and 60 min before breakfast

omeprazole (n = 9)

pantoprazole (n = 7)

lansoprazole (n = 6)

esomeprazole (n = 2)

NS

Group 1 (REP) LT4 tablet and PPI: 5.4 ± 4.3.

LT4 solution and PPI: 1.7 ± 1.0.

Group 2 (SUP) LT4 tablet and PPI: 2.1 ± 2.7

LT4 solution and PPI: 0.1 ± 0.3

Group 1:

20.0 ± 7.5 weeks

Group 2:

28.8 ± 15.2 weeks

Low risk of bias*

*The Risk Of Bias In Non-randomized Studies – of Interventions (ROBINS-I)30 tool was used to evaluate seven bias domains as low, moderate, or serious risk of bias

**Assessed by the Newcastle–Ottawa Scale29 for observational studies with a score of 8/9 (maximum of 9 points). Score > 6 points is considered to be of high quality. NS not specified, TSH thyroid-stimulating hormone, LT4 levothyroxine, PPI proton pump inhibitor, NOS Newcastle–Ottawa Scale, F female, M male, REP replacement therapy, SUP suppressive therapy, IRR incidence rate ratio