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Falling Threshold for Treatment of Borderline Elevated Thyrotropin Levels—Balancing Benefits and Risks

I am perplexed - somehow can't believe this has not been posted here, yet cannot see any previous posts about it! At the risk of repeating...

Original Investigation | January 2014

Falling Threshold for Treatment of Borderline Elevated Thyrotropin Levels—Balancing Benefits and RisksEvidence From a Large Community-Based Study FREE

Peter N. Taylor, MSc, MRCP1,2; Ahmed Iqbal, MRCP3; Caroline Minassian, MSc4; Adrian Sayers, MSc2; Mohd S. Draman, MRCP1; Rosemary Greenwood, MSc5; William Hamilton, MD6; Onyebuchi Okosieme, MD, FRCP1; Vijay Panicker, PhD7; Sara L. Thomas, PhD4; Colin Dayan, PhD, FRCP1,3

[+] Author Affiliations

JAMA Intern Med. 2014;174(1):32-39. doi:10.1001/jamainternmed.2013.11312


Rates of thyroid hormone prescribing in the United States and the United Kingdom have increased substantially. If some of the increase is due to lowering the thyrotropin threshold for treatment, this may result in less benefit and greater harm.


To define trends in thyrotropin levels at the initiation of levothyroxine sodium therapy and the risk of developing a suppressed thyrotropin level following treatment.

Design, Setting, Participants, and Exposure

Retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. Among 52 298 individuals who received a prescription for levothyroxine between January 1, 2001, and October 30, 2009, we extracted data about the thyrotropin level before levothyroxine therapy initiation, clinical symptoms, and thyrotropin levels up to 5 years after levothyroxine was initiated. We excluded persons who had a history of hyperthyroidism, pituitary disease, or thyroid surgery; those who were taking thyroid-altering medication or if the levothyroxine prescription was related to pregnancy; and those who did not have a thyrotropin level measured within 3 months before the initiation of levothyroxine.

Main Outcomes and Measures

The median thyrotropin level at the time of the index levothyroxine prescription, the odds of initiation of levothyroxine therapy at thyrotropin levels of 10.0 mIU/L or less, and the age-stratified odds of developing a low or suppressed thyrotropin level after levothyroxine therapy.


Between 2001 and 2009, the median thyrotropin level at the initiation of levothyroxine therapy fell from 8.7 to 7.9 mIU/L. The odds ratio for prescribing levothyroxine at thyrotropin levels of 10.0 mIU/L or less in 2009 compared with 2001 (adjusted for changes in population demographics) was 1.30 (95% CI, 1.19-1.42; P < .001). Older individuals and individuals with cardiac risk factors had higher odds of initiation of levothyroxine therapy with a thyrotropin level 10.0 mIU/L or less. At 5 years after levothyroxine initiation, 5.8% of individuals had a thyrotropin level of <0.1 mIU/L. Individuals with depression or tiredness at baseline had increased odds of developing a suppressed thyrotropin level, whereas individuals with cardiac risk factors (eg, atrial fibrillation, diabetes mellitus, hypertension, and raised lipid levels) did not.

Conclusions and Relevance

We observed a trend toward levothyroxine treatment of more marginal degrees of hypothyroidism and a substantial risk of developing a suppressed thyrotropin level following therapy. Large-scale prospective studies are required to assess the risk-benefit ratio of current practice.

Primary hypothyroidism is one of the most common chronic disorders in Western populations1,2 and is largely managed in primary care.3,4 Levothyroxine sodium prescriptions in the United States have increased substantially in recent years (from 49.8 million in 2006 to 70.5 million in 2010).5 A similar increase has been observed in England and Wales, with levothyroxine prescriptions rising from 17.1 million (in 2006) to 23.4 million (in 2010),6 up from only 7 million prescriptions in 1998 data.7,8

Several factors have probably contributed to this rise. In England and Wales, a proportion may be attributed to a fall in the mean duration of prescriptions from 60 to 45 days. Thyroid function testing has also increased substantially,9,10 and in any year 18% to 25% of individuals have their thyroid function tested,4,9,11 likely resulting in increased case finding. However, an additional factor may be a lowering of the thyrotropin threshold at which levothyroxine is initiated. This practice would be important to identify because it might be associated with more marginal benefits and with increased relative risk of patient harm. The results of studies published before 2001 suggested that between 15% and 20% of individuals taking levothyroxine are overtreated and develop a low thyrotropin level,12,13 most likely because of inadequate monitoring. Overtreatment is associated with an increased risk of fractures14 and atrial fibrillation.15

American Thyroid Association guidelines recommend consideration of levothyroxine therapy at thyrotropin levels of 10.0 mIU/L or less when there are clear symptoms of hypothyroidism, positive thyroid autoantibodies, or evidence of atherosclerotic cardiovascular disease or heart failure (evidence level B). Data from Scotland in 2001 indicated that most patients had levothyroxine initiated at thyrotropin levels of 10.0 mIU/L or less, with 45% to 48% of patients having therapy commenced with a thyrotropin level less than 6.0 mIU/L.10

In this study, we used a large United Kingdom (UK) population-based database to examine trends in thyrotropin levels before and after levothyroxine therapy initiation since 2001 and assessed the potential for adverse outcomes from current practice.

Full article here:


[ Edited to add: See also responses here:


archinte.jamanetwork.com/ar... ]

3 Replies

Rod, what are they talking about? I'm sorry, I just can't take this in, it doesn't seem to make any sense. Could you possibly summerise it for me? Because if it's saying what I think it's saying... words fail me.

PS can't read the comments because you have to sign in..


I think it's just as terrible as you think it is! The most shocking bit to me if if when they talk about the 5.8% of patients who have a suppressed (I assume it's the same as TSH). And how this means any patient who starts replacement has a good chance of getting to this state! Which is presumably achieved as a result of lack of monitoring!

But also they are implying a (TSH?) of 10 or under is a controversial case.


Yes, that's what I thought. Things are going backwards, not forwards! That implies that the TSH is THE most important number and nothing else counts, and it is 'dangerous' for it to be suppressed and... that it implies over treating and... Words fail me. How can they be so ignorant when all the information proving the contrary is out there, on the net, just waiting to be read. And who wrote this piece of trash, anyway! And what hope is there for human-kind when there are people of influence out there spouting stuff like that?!?


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