At what time of day is Thyroid-Stimulating Hormone (TSH) typically at its highest level?

TSH Peaks During the Night (Between 11 PM and 4 AM)

TSH reaches its highest levels during the late evening and early morning hours, typically peaking between 11 PM and 4 AM, with the nadir (lowest point) occurring between 7 AM and 2 PM. 1, 2

Detailed Circadian Pattern of TSH Secretion

Peak Hours (Nocturnal Surge)

• TSH levels are highest from 8 PM to 2 AM, with the most pronounced surge occurring during sleep 1
• The nocturnal TSH surge represents a consistent circadian rhythm that occurs in healthy individuals 3, 4
• Peak TSH values during the night can be 2-3 times higher than daytime values in normal subjects 3

Nadir Hours (Lowest Levels)

• TSH reaches its lowest point from 7 AM to 2 PM, with the nadir typically occurring in late morning 1
• Morning TSH values (measured at 8:30 AM) are significantly lower than nighttime values in healthy individuals 3

Clinical Significance of TSH Timing

Why the Nocturnal TSH Surge Doesn't Increase Thyroid Hormones

• TSH molecules secreted at night have reduced bioactivity compared to daytime TSH, which explains why thyroid hormone levels don't rise after the nocturnal surge 4
• The nighttime TSH has a higher percentage of less mature, differently glycosylated forms with lower biological potency 4
• The ratio of TSH bioactivity to immunoreactivity (TSH B/I) is higher during the day (1.4 ± 0.6) than at night (1.1 ± 0.6) in normal subjects 4

Impact on Thyroid Hormone Levels

• Thyroxine (T4) peaks from 8 AM to 12 PM and reaches its lowest levels from 11 PM to 3 AM 1
• Triiodothyronine (T3) is highest from 7 AM to 1 PM and lowest from 11 PM to 3 AM 1
• These thyroid hormone patterns are inverse to the TSH pattern, reflecting the feedback regulation of the hypothalamic-pituitary-thyroid axis 1

Practical Implications for Testing and Treatment

Optimal Timing for TSH Testing

• Morning TSH measurements (7 AM - 2 PM) provide the most consistent baseline values for clinical decision-making, as they represent the nadir of the circadian rhythm 1
• The diurnal variations in TSH are minor and do not exceed the normal range, making routine testing valid at any time of day 1
• However, serial measurements should be obtained at the same time of day to minimize variability from circadian fluctuations 1

Levothyroxine Timing Considerations

• Bedtime administration of levothyroxine results in better absorption compared to morning dosing, with 24-hour average TSH of 1.2 ± 0.3 mU/L for bedtime vs 5.1 ± 0.9 mU/L for morning ingestion 2
• Nighttime dosing produces higher free T4 levels (19.3 ± 0.7 pmol/L vs 16.7 ± 1.0 pmol/L) and higher T3 levels compared to morning administration 2
• The circadian TSH rhythm remains intact regardless of levothyroxine timing, with the nocturnal surge preserved 2

Alterations in Disease States

Primary Hypothyroidism

• The nocturnal TSH surge is absent or blunted in 6 out of 9 patients with overt primary hypothyroidism 5
• The deficient nocturnal TSH rise in hypothyroidism (22 ± 51%) is significantly reduced compared to controls (82 ± 41%) 5
• TSH pulse amplitude increases dramatically in hypothyroidism (36.9 ± 31.4 mU/L in overt and 2.8 ± 1.9 mU/L in subclinical vs 0.4 ± 0.2 mU/L in controls), but pulse frequency remains unchanged at approximately 10 pulses per 24 hours 5

Major Depression

• The nocturnal TSH surge is abolished in 14 of 15 patients with untreated major endogenous depression 3
• Morning and nighttime TSH values do not differ in depressed patients, unlike the normal 2-3 fold difference seen in controls 3
• Mean nighttime TSH values are significantly reduced in depressives (1.5 ± 0.3 mU/L) compared to controls (3.1 ± 0.3 mU/L) 3

Common Pitfalls to Avoid

• Don't assume abnormal TSH timing patterns indicate thyroid disease alone—loss of the nocturnal surge may indicate central hypothyroidism, depression, or other hypothalamic-pituitary dysfunction 3
• Don't rely solely on morning TSH and TRH stimulation tests to evaluate hypothalamic-pituitary-thyroid axis function, as the loss of nocturnal TSH surge is a more sensitive indicator of axis alterations 3
• Don't interpret elevated nighttime TSH as requiring treatment adjustment without considering the normal circadian variation 1, 4