Thyroid UK

Factors Contributing to High Levothyroxine Doses in Primary Hypothyroidism

A new study from the UK just released in Thyroid Journal.

Background: While few hypothyroid patients require more than the expected weight-related dose of levothyroxine, the underlying causes of larger-than-expected dosing requirements have not been studied in a single cohort. Our aim was to determine and quantify the multiple factors contributing to high-dose levothyroxine requirements in a cohort of patients with hypothyroidism.

Methods: The Grampian Automated Follow-Up Register (GAFUR) monitors around 17,500 hypothyroid patients. In 2008, 190 (1%) patients took >225 μg of levothyroxine daily. A questionnaire was sent to 174 patients (16 were untraceable) to assess causes and to offer blood tests for endomysial, parietal cell (PCA), and thyroid peroxidase (TPO) autoantibodies. Primary care practices were contacted for medication details. All patients with positive endomysial autoantibodies were referred to a gastroenterologist. Thyroid function tests and levothyroxine doses were re-evaluated in 2011.

Results: A total of 125 questionnaires (72%) were returned. Mean levothyroxine dose was 248 μg daily. Twenty-six patients (20.8%) took medication known to interfere with levothyroxine absorption, and 21 patients (16.8%) admitted to compliance issues. Seven patients had positive anti-endomysial antibodies on initial screening, with four being new diagnoses of celiac disease, and PCA were positive in 27 (21.6%) patients. At follow-up in 2011, the mean levothyroxine dose had decreased in patients on interfering medications and in the four new cases of celiac disease.

Conclusions: Causes of patients needing high-dose levothyroxine replacement include poor compliance, medication interference, PCA (as a marker of atrophic/autoimmune gastritis), and celiac disease. Doses can be decreased following advice regarding medication or after management of underlying conditions.

This study also demonstrates the prevalence of previously unrecognized celiac disease (3.2%), gastric parietal cell antibodies (21.6%), and vitamin B12 deficiency (5.5%) in patients on high-dose levothyroxine, and that PCA-positive patients with low serum B12 levels can require a higher dose/kg of levothyroxine.

The complete study is available free. PR

6 Replies

Thanks PR.

Whilst not earth-shattering, it is good when a paper rather confirms what has been repeatedly mentioned here.

I was a bit disappointed at the limited emphasis on the effects of food. Mentioned but not very strongly.

A shame that only those with what the study felt was a high dose were able to benefit from the support and investigation.

I hope that this statement about non-compliance:

It is important to address this in a nonaccusatory manner and give patient-centered advice to optimize compliance.

... is really meant at face value. Would not wish it to be done in the sort-of patronising way I fear could happen. We have seen all too many patients who have no idea of the importance of keeping at it steadily every day. We are used to medicines which if we miss the odd dose have little real effect.



Rod, yes, limited viewpoint regarding nutrition which is to be expected unfortunately. At least they pointed to some things being missed, as you mentioned, which are regularly talked about here. Along with this article they had two on cancer and the ATA 2014 Treatment Guidelines in their email. Although there is some very good science being done I am continually amazed at how detached from reality the profession seems to be. PR

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Interesting. Thanks.


shaws, I wonder how many doctors in the UK will actually read this. PR


Very few, I suspect, PR, 'cos thyroid isn't complicated is it? Thanks for posting, I'll read the full article tomorrow :)


Probably none I think. The reason being that they are stuck in their guidelines 'mode' and I don't think they read research papers at all despite all the good research being turned out. I believe that most only have a smattering knowledge of illnesses unless they happen to have (or family) a condition themselves.

From the experiences of some members here, they have come across cold, arrogant and unsympathetic people which makes me wonder why they became doctors. They lack the humanitarian gene when faced with poorly patients whom they diagnose as 'hypochondriacs'. Yet we come across some who go the extra mile who are then hauled before the authorities because they think and medicate outside the box and assist their patients to wellness.

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