Systemic Thyroid Hormone Status During Levothyr... - Thyroid UK

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Systemic Thyroid Hormone Status During Levothyroxine Therapy In Hypothyroidism: A Systematic Review and Meta-Analysis


Evidence of the need for T3, in at least some hypothyroid patients, seems to be pouring in these days.

Getting that translated into receiving combination T4/T3 treatment seem as far away as ever - and disappearing all too fast.

Systemic Thyroid Hormone Status During Levothyroxine Therapy In Hypothyroidism: A Systematic Review and Meta-Analysis

Elizabeth A McAninch, M.D Kumar B Rajan, Ph.D Corinne H Miller, M.L.I.S Antonio C Bianco, M.D., Ph.D

The Journal of Clinical Endocrinology & Metabolism, jc.2018-01361,


15 August 2018



The standard of care for overt hypothyroidism is levothyroxine at doses that normalize serum TSH levels. Whether this approach universally restores thyroid hormone signaling is unknown.


To review studies of overt hypothyroidism in which participants were treated with levothyroxine to normalize serum TSH levels and measured other objective markers of thyroid hormone signaling.


Databases were searched for studies that reported objective markers of thyroid hormone signaling (serum low-density lipoprotein (LDL), total cholesterol (TC), sex hormone-binding globulin (SHBG), creatine kinase and/or ferritin levels; cognition, energy expenditure, and/or renal function) in levothyroxine monotherapy for overt, primary hypothyroidism among nonpregnant adults with normal serum TSH levels. For studies with LDL, TC and SHBG outcomes, data were pooled using random effects meta-analysis.


A total of 99 studies met inclusion criteria, including 65 that reported serum cholesterol data. Meta-analysis showed that levothyroxine-treated hypothyroid participants with normal serum TSH levels had 3.31 ± 1.64 mg/dL higher serum LDL levels (p=0.044) and 9.60 ± 3.55 mg/dL higher serum TC levels (p=0.007) compared to controls. In studies that did not concomitantly assess healthy controls, serum LDL levels were 138.3 ± 4.6 mg/dL (p<0.001) and serum TC levels were 209.6 ± 3.4 mg/dL (p<0.001). Meta-analysis of 2 studies showed no significant difference between SHBG levels of levothyroxine-treated participants and controls.


In studies that utilized levothyroxine monotherapy at doses that normalized the serum TSH for overt, primary hypothyroidism, not all systemic biological markers of thyroid hormone signaling were normalized, including serum LDL and TC levels.

A Medscape overview of this paper is available - subject to free registration:

6 Replies

How can uk endocrinology keep ignoring current research surely the facts will eventually discredit the T4 monotherapy is gold standard and the only treatment needed brigade keeping so many people extremely unwell. It as if we are stuck in some sort of time warp divorced from reality.

Thank you for this, helvella. I have read many studies on the internet which talk of not using tsh tests to treat/diagnose and the treatment of hypothyroidism with combination T3/T4 therapy (I even gave a copy of Dr. Peatfield’s book to my doctor) but the standard diagnosis and treatment never varies.

Considering that that CCGs are stopping T3 because of cost, could they not prescribe NDT instead? I do not know the relative costs of these drugs but the current cost to the nhs of T3 wouldn’t be hard to beat.

(I read in Dr. Kendrick’s book ‘Doctoring Data’ about the practice in the US of not letting heart attack patients move for weeks on end - resulting in a huge rise in deaths. This flawed treatment went on for about a decade before someone had the temerity to question it and the medical profession decided that they should after all be getting patients moving. This does not bode well for T3.)

Zephyrbear in reply to penny

This was published on the GP Online website in July 2017:

'CCGs are imposing bans on GPs prescribing drugs available OTC just days after NHS England began a consultation on the issue, despite warnings that GPs refusing to prescribe medicines their patients need could be in breach of their contracts. [...] GPC clinical and prescribing policy lead Dr Andrew Green has condemned the move, warning that CCGs do not have the power to ban GPs prescribing medicines that patients need.'

penny in reply to Zephyrbear

The move may be condemned by Dr Andrew Green but the posts on here are telling a different story; my T3 was stopped without notice by my GP.

Zephyrbear in reply to penny

Then you should go back and threaten him with a negligence suit if he doesn't agree to reinstate your prescription.

From the same article:

‘West Lancashire GPs need to ensure that they comply with their GMS contractual requirements, and if faced with upsetting their CCG or placing themselves in breach of the regulations they should upset their CCG every time.'

This would apply equally to all GP, irrespective of where they're based.

"Among theories for the continued symptoms in some patients is that serum TSH may not be as precise a measure as is needed to represent the ideal marker of normal thyroid function" - well, who'da thunk it.

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