Is a Normal TSH Synonymous with “Euthyroidism” in Levothyroxine Monotherapy?

Maybe there is a distinct lack of references to diogenes' papers, but yet another paper which questions universal levothyroxine monotherapy.

[If already posted, let me know and I will delete this duplication.]

Is a Normal TSH Synonymous with “Euthyroidism” in Levothyroxine Monotherapy?

Sarah J. Peterson Ph.D., Elizabeth A. McAninch M.D., and Antonio C. Bianco M.D.

Address all correspondence and requests for reprints to: Corresponding author and person to whom reprint requests should be addressed: Antonio C. Bianco, M.D., Ph.D.,

Division of Endocrinology and Metabolism, Rush University Medical Center, 1735 W Harrison St; Cohn Building Rm 212; Chicago, IL 60612, USA

, Email:, Phone: 312–942-7131; Fax: 312–942-5271.


Received: July 11, 2016

Accepted: September 29, 2016

First Published Online: October 04, 2016



Levothyroxine (LT4) monotherapy is the standard of care for hypothyroidism.


To determine whether LT4 at doses that normalize the serum TSH is associated with normal markers of thyroid status.


Cross-sectional data from the US National Health and Nutrition Examination Survey (2001–2012) was used to evaluate 52 clinical parameters. LT4-users were compared to healthy controls and controls matched for age, sex, race, and serum TSH. Regression was used to evaluate for correlation with serum thyroxine (T4) and triiodothyronine (T3) levels.


9,981 participants with normal serum TSH were identified; 469 were LT4-treated.


Participants using LT4 had higher serum total and free T4 and lower serum total and free T3 than healthy or matched controls. This translated to ∽15–20% lower serum T3:T4 ratios in LT4 treatment, as has been shown in other cohorts. In comparison to matched controls, LT4-treated participants: had higher BMI despite report of consuming less calories/day/kg; were more likely to be taking beta-blockers, statins, and anti-depressants; and reported lower total metabolic equivalents. A serum TSH level below the mean in LT4-treated participants was associated with a higher serum free T4 but similar free and total T3; yet those with lower serum TSH levels exhibited higher serum HDL and lower serum LDL, triglycerides, and CRP. Age was associated with serum free T3:free T4 ratio in all participants; caloric intake was associated in LT4-treated individuals.


In a large population study, participants using LT4 exhibited lower serum T3:T4 ratios and differed in 12/52 objective and subjective measures.

Full paper as a PDF here:

11 Replies

  • Hopefully, Dr. Bianco is going to pursue the question further. This is encouraging: "Notwithstanding, the concept that establishing a normal serum TSH renders individuals on LT4 monotherapy clinically euthyroid should be revisited and QOL measures should be more highly prioritized in hypothyroidism research and professional guidelines." As Diogenes said a distinct lack of QOL studies and FT3 Values. Thanks Rod, good find. PR

  • TSH is irrelevant when taking any form of thyroxine.

  • It has one important role. That is to discover if patients are indeed taking their tablets. A surprising number forget, then remember just before a visit to the GP and take T4 or combo just before going. They will have a high TSH owing to their previous failure to take the tablets steadily and therefore non-compliance is easily discovered.

  • "Other investigators were unable to find any correlation between serum thyroid stimulating hormone (TSH) or serum free T4 and thyroid symptoms". In abstract:

  • Don't wish to grumble re Bianco's quite deliberate attempts to ignore our group, but the "green eyed god" I spoke of in another post is well in evidence. BUT it's useful in QOL determinations.

  • That conclusion blows me away, as conclusions in papers like this always do. Even in this abstract, those on T4 are far worse off than their matched people, and therefore than you'd expect if you evaluated based on TSH. They've got weight problems, heart problems, cholesterol problems, depression problems, and lower metabolisms.

    But in the conclusion this is understated to "They differed in a number of measures".

  • I cannot believe there is STILL "controversy" about whether a "normal" TSH renders the patient euthyroid. It doesn't. Why are we still hearing this $#!%$? (Pardon my impatience!)

  • Regardless of acknowledging or not other previous work, what this study does do is to bring to attention in the US thyroidological network the understanding of the inadequacies of T4 mono therapy in quite a lot of patients. This is important info from one of the chief US researchers in this field, and it is bound to have a significant influence on the prospects for liberalisation of treatment regimes to include T3. As is often shown, US medics react faster to new knowledge than the rather hidebound UK ones, but even the latter will have to acknowledge that new evidence from an important source is questioning their stance on the matter as it is at present. Good news in that regard!

  • Thanks for posting this extremely interesting article. I strongly suggest everyone not achieving satisfactory control of their hypothyroidism read the full article carefully. My personal clue for why after 20 years of satisfactory treatment on T4 I'm suddenly starting to get symptoms again is related to the finding that T4 to T3 conversation via the D2 deiodinase enzyme takes place in skeletal muscle. It therefore follows that as I'm approaching 60 andthe postmenopausal changes in my body include loss of muscle mass then result is likely to be less efficient conversion of T4 to T3 despite circulating T4 levels within the normal range. I will revisit my GP and take this article to support my request to add T3 supplementation to my medication.

    Thanks again for posting

  • That is an interesting way of looking at things. Skeletal muscle conversion is so very often ignored.

  • Delighted to see this 😊 A large scale study carried out by a leader in the field.

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