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A normal starting dose of levothyroxine is 50 mcg per day. According to ATA, absorption is 60-80%. Let's assume 70% and let's assume 5 L of blood in the average human being.

50 mcg * 0.7 / 5.0 = 7 mcg/L
7 mcg/L = 7000 ng/L

According to this tool, 7000 ng/L of thyroxine is 9000 pmol/L. Free T4 is usually 0.03% of total T4 so I'd at first expect the dose to contribute 9000 * 0.03 = 270 pmol/L of free T4.

But a normal human range of free T4 is 10-24 pmol/L. Clearly I've made a mistake somewhere since the dose seems to be an order of magnitude too large.

What's the correct calculation? What is the expected average T4 increase when taking 50 mcg of levothyroxine?

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    You're assuming 100% of the absorbed levothyroxine ends up in the bloodstream. I don't think that's a valid assumption.
    – Carey Gregory ♦
    Aug 3, 2017 at 18:09
  • It is important to note that people tend to have different responses to thyroid hormone supplementation, requiring different quantities depending on multiple factors, so I'm not sure there's a reliable correlation between dosage and serum T4 measurements.
    – DoctorWhom
    Aug 4, 2017 at 6:57

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First of all, thyroid hormones are actively taken up into cells and accumulate there. Therefore, the apparent volume of distribution for T4 is 10 liters rather than 5 liters (1). Secondly, I would assume a slightly lower proportion of free T4 (0.02%) (1). That results in 90 pmol/L.

This is still above the reference range for FT4. However, T4 is rapidly converted to T3, rT3, 3,5-T2, thyronamines and iodothyroacetates (2). In combination, these mechanisms end up in plausible concentrations.

This scenario also explains, why even slight variations of parameters can end up in dramatic changes of hormone concentrations, e.g. in allostatic load (3).

  1. J. W. Dietrich, A. Tesche, C. R. Pickardt & U. Mitzdorf. Thyrotropic Feedback Control: Evidence For An Additional Ultrashort Feedback Loop From Fractal Analysis. Cybernetics and Systems Vol. 35 , Iss. 4, 2004. doi 10.1080/01969720490443354

  2. Hoermann R, Midgley JE, Larisch R, Dietrich JW. Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment. Front Endocrinol (Lausanne). 2015 Nov 20;6:177. doi 10.3389/fendo.2015.00177. PMID 26635726

  3. Chatzitomaris A, Hoermann R, Midgley JE, Hering S, Urban A, Dietrich B, Abood A, Klein HH, Dietrich JW. Thyroid Allostasis-Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. Front Endocrinol (Lausanne). 2017 Jul 20;8:163. doi 10.3389/fendo.2017.00163. PMID 28775711

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