Does timing of testing and food intake alter results

1. In hypothyroidism, does timing of intake
and testing matter?
Karthik Balachandran
SRMC

2. Agenda
• Is there an effect of food intake?
• Does timing of testing matter?
• Is there an interaction - food # timing?
• What is the effect size?
• Is the effect size clinically relevant?
• What is the role of lab and assay variability?
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3. Physiology
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4. Rhythm
3/20Russel et al J Clin Endocrinol Metab 93: 2300–2306, 2008

5. Rhythm
4/20Russel et al J Clin Endocrinol Metab 93: 2300–2306, 2008

6. Pharmacokinetics of thyroxine
Absorption Jejunum and ileum
Bioavailablility 70 to 80%
Tmax 2- 3 hours
Protein binding 99.5
t 1/2 T4 : 6.2 (euthyroid) 7.5(hypothyroid) days
T3 :1.0 (euthyroid) 1.4 (hypothyroid) days
5/20Colucci P Eur Endocrinol. 2013;9(1):40–47

7. Does timing of testing matter?
• 52 healthy adults
• Testing on two days ( 8 AM and 10 AM)
• Fasting on day 1 , fasting and postprandial on day 2
• Effect of timing
8 AM 2.93 ± 1.62
10AM 2.74 ± 1.69
• No difference between 8 AM and 10 AM samples
6/20Mahadevan S et al Does Time of Sampling or Food Intake Alter Thyroid Function Test?
Indian J Endocrinol Metab. 2017;21(3):369–372

8. Does food intake matter ?
• 57 subjects
• Stanley Medical college Chennai
• Fasting and postprandial TFT done
• Cobas and Elecsys machines - standard analytical and functional
sensitivity
7/20Nair R. Does fasting or postprandial state affect thyroid function testing?
Indian J Endocrinol Metab. 2014;18(5):705–707

9. Does food intake matter?
8/20Rakesh Nair Indian J Endocrinol Metab. 2014;18(5):705–707

10. Why does fasting vs postprandial matter for
testing?
• TRH stimulates TSH secretion
• Somatostatin inhibits TSH secretion
• Food induced elevation of circulating somatostatin might
reduce post prandial TSH
• The observed change is NOT due to assay differences between
studies
• No difference in T4/T3
9/20Kamat V Eur J Endocrinol. 1995 Jul;133(1):75-9.

11. Is there a food # timing interaction?
Interaction When considering the relationship among three or
more variables, interaction describes a situation in
which the effect of one causal variable on an outcome
depends on the state of a second causal variable (that
is, when effects of the two causes are not additive)
• No studies of large enough sample size to specifically look for
this interaction
• Seems less likely 1
1
To be taken with a pinch of iodized salt
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12. How much does TSH change (effect size)?
• No patient level meta analysis to give pooled effect size
estimates
• Scobbo et al : 100 patients
• Fasting vs Postprandial : 26.39 % reduction in TSH
• R Nair et al - Fasting vs PP : 28.9 % reduction in TSH
11/20Scobbo W V Med J. 2004 Jul-Aug;100(4):138-42

13. Is the effect size/change clinically significant?
A difference is a difference only if it makes a difference
Charles Box
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14. Is the effect size/change clinically significant?
A difference is a difference only if it makes a difference
Charles Box
• Scobbo et al - 6 % reclassification
• Mahadevan et al - 75 % reclassification !!!
• Difference due to baseline TSH - reclassification more likely to
occur at / near the edges of normality
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15. Labs and thyroid
Things to remember
Do you know your assay method?
Do you know which machine is used?
Does the lab regularly contact you if there’s a discrepancy?
Is QC done regularly?
Are there automatic trouble shooting protocols?
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16. What is the role of lab and assay variability?
14/20Mahadevan S et al Indian J Endocrinol Metab. 2017;21(3):369–372

17. Does prolonged fasting change TSH?
• 64 patients
• Ramadan fasting
• Mean age 44 years
• Mean TSH pre-Ramadan was 2.37 ± 1.35 mIU/L, and
post-Ramadan, it was 4.69 ± 3.87 mIU/L
• Change in TSH not affected by timing of LT4 intake and interval
from meal
15/20Sheik A Endocr Pract. 2018 Oct 2;24(10):882-888

18. What about intermittent fasting?
• Data scarce
• Confounded by weight loss
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19. What about alternative schedules of thyroxine
intake?
• Alternate day, twice in a week and once weekly regimens
• Recommended by ATA for patients with poor compliance
• Morning vs Night - most studies show little to no difference
• Those that show difference - smaller studies without
randomization and cross over
17/20Skelin Endocrine. 2018 Nov;62(2):432-439

20. Summary
• Timing of testing doesn’t matter - as long as sample is given
before 11 AM
• Food intake matters - post prandial TSH lowering is consistent
• PP TSH lowering - around 25 %
• Reclassification depends on baseline TSH and likely to be more
important in reproductive age group women
• Lab and assay variability don’t contribute to fasting vs PP TFT
changes
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21. What can you do?
• Ask patients to give sample in fasting before 10 AM
• We need more data to check for interactions - ask lab to
mention fasting state and timing of sample collection - for later
data analysis
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22. Thank You !
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