Thyroid disease assessment and management: summary of NICE guidance
BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m41 (Published 29 January 2020) Cite this as: BMJ 2020;368:m41All rapid responses
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Dear Editor,
We write to ask if the BMJ should reflect on its choice of advertisements associated with the publication. This week’s edition of the BMJ (8th February 2020) came wrapped in an advert for liothyronine. The use of liothyronine (T3) for the management of hypothyroidism remains controversial, with little evidence-base for its use. Its prescription is not supported by latest NICE guidance on the management of hypothyroidism published in this week’s BMJ (BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m41).
Given that the power of pharmaceutical advertising is likely to promote product prescription, we question whether it is a wise decision for the BMJ to advertise a product that has a questionable evidence base. The accompanying manufacturers’ prescribing information suggests up to 60 mcg liothyronine a day, a dose not recommended by any UK or European guideline that would cost the NHS £11,576 per annum for a single patient taking 6 x 10 mcg tablets per day. By comparison, guidance recommended use of levothyroxine (T4) would cost £62 per annum for a patient requiring 100 mcg once daily receiving a prescription every 28 days (levothyroxine price obtained from the British National Formulary).
The BMJ should be praised in that it has always set the bar very high when it comes to whether pharmaceutical companies should be involved in influencing clinicians to use their products. The cover of this week’s issue highlights an article questioning the involvement of industry in influencing indoor tanning research. The decision to advertise liothyroinine appears questionable and at odds with messages previously expressed by the BMJ. We would invite a review of the decision to advertise liothyronine in the very same issue in which guidance is published expressing caution against T3 use.
Yours sincerely,
Dr Augustin Brooks
Consultant Physician Diabetes
Royal Bournemouth Hospital
Dr Tristan Richardson
Consultant Physician Endocrinology
Royal Bournemouth Hospital
Competing interests: Dr Brooks declares that he has received honoraria from Astra Zeneca and Sanofi for speaking at educational events and sponsorship from Lilly and Janssen to attend conferences.
Dear Editor
The recently published NICE guidance on the management of thyroid disease recommends radioactive iodine (RAI) as the first-line treatment for Graves’ disease as it “results in better long-term outcomes than long-term anti-thyroid drugs (ATDs) in terms of thyroid status”. This statement is misleading as in all 5 studies of ATDs referenced, the failure to achieve euthyroidism was because the thyrotoxicosis relapsed after ATDs were discontinued (1, 2, 3, 4, 5). All available evidence suggest that very high rates of euthyroidism are achieved whilst the patients remain on ATDs (6, 7, 8, 9) and that life-long ATD therapy is affective at maintaining a euthyroid state in both Graves’ disease (6) and multinodular goitre (10).
Patients given RAI usually require life-long levothyroxine therapy and most can achieve biochemical euthyroidism. However, this does not equate with having normal thyroid physiology. Subjects on levothyroxine have lower serum T3 levels than TSH-matched controls and abnormal lipid profiles as well as higher body mass indices and reduced well-being and quality of life (11, 12).
RAI is an ablative treatment which destroys the physiological function of the thyroid. It is unknown whether Graves’ disease patients euthyroid on long-term ATDs have a normally functioning thyroid but there is no evidence to suggest otherwise. We believe long-term ATDs are a very effective treatment for Graves’ disease and that more research is needed in this area.
1. Abraham-Nordling M, Torring O, Hamberger B, Lundell G, Tallstedt L, Calissendorff J, et al. Graves' disease: a long-term quality-of-life follow up of patients randomized to treatment with antithyroid drugs, radioiodine, or surgery. Thyroid. 2005;15(11):1279-86.
2. Bartalena L, Marcocci C, Bogazzi F, Manetti L, Tanda ML, Dell'Unto E, et al. Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy. N Engl J Med. 1998;338(2):73-8.
3. Benker G, Reinwein D, Kahaly G, Tegler L, Alexander WD, Fassbinder J, et al. Is there a methimazole dose effect on remission rate in Graves' disease? Results from a long-term prospective study. The European Multicentre Trial Group of the Treatment of Hyperthyroidism with Antithyroid Drugs. Clin Endocrinol (Oxf). 1998;49(4):451-7.
4. Kansara S, Kotwal N, Kumar K, Singh Y, Upreti V, Nachankar A. Effect of Antithyroid Therapies on Bone and Body Composition: A Prospective, Randomized, Clinical Study Comparing Antithyroid Drugs with Radioiodine Therapy. Indian J Endocrinol Metab. 2017;21(4):531-4.
5. Chen DY, Jing J, Schneider PF, Chen TH. Comparison of the long-term efficacy of low dose 131I versus antithyroid drugs in the treatment of hyperthyroidism. Nucl Med Commun. 2009;30(2):160-8.
6. Azizi F, Ataie L, Hedayati M, Mehrabi Y, Sheikholeslami F. Effect of long-term continuous methimazole treatment of hyperthyroidism: comparison with radioiodine. European Journal of Endocrinology. 2005;152(5):695-701.
7. Abraham P, Avenell A, McGeoch SC, Clark LF, Bevan JS. Antithyroid drug regimen for treating Graves' hyperthyroidism. Cochrane Database Syst Rev. 2010(1):CD003420.
8. Benker G, Vitti P, Kahaly G, Raue F, Tegler L, Hirche H, et al. Response to methimazole in Graves' disease. The European Multicenter Study Group. Clin Endocrinol (Oxf). 1995;43(3):257-63.
9. Torring O, Tallstedt L, Wallin G, Lundell G, Ljunggren JG, Taube A, et al. Graves' hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine--a prospective, randomized study. Thyroid Study Group. J Clin Endocrinol Metab. 1996;81(8):2986-93.
10. Azzizi F, Miralireza T, Elham M, Atieh A. Treatment of Toxic Multinodular Goiter: Comparison of Radioiodine and Long-Term Methimazole Treatment. Thyroid. 2019;29(5):625-30.
11. Peterson SJ, McAninch EA, Bianco AC. Is a Normal TSH Synonymous With "Euthyroidism" in Levothyroxine Monotherapy? J Clin Endocrinol Metab. 2016;101(12):4964-73.
12. Saravanan P, Chau WF, Roberts N, Vedhara K, Greenwood R, Dayan CM. Psychological well-being in patients on 'adequate' doses of l-thyroxine: results of a large, controlled community-based questionnaire study. Clin Endocrinol (Oxf). 2002;57(5):577-85.
Competing interests: No competing interests
Dear Editor
Having been heavily involved in supporting Public Petition PE1463 Thyroid and Adrenal Testing and Treatment in the Scottish Parliament for many years I was very disappointed in your article “ Thyroid disease assessment and management: summary of NICE guidance” published on 29th January.
In particular your statement “Natural thyroid extract or Liothyronine (alone or in combination with levothyroxine) is not recommended for treating people with primary hypothyroidism”
As you are aware Thyroid Disease is extremely common, but also a life limiting, debilitating chronic disease. Indeed, Levothyroxine is one of the most commonly prescribed drugs in the UK. However, at least 10% of thyroid patients, who are mainly women do not do well on Levothyroxine, a fact acknowledged by the medical establishment, and many have been fighting for years with Health Professionals to be suitably treated.
The long awaited NICE guidelines were hoped to be a solution to assist these thousands of patients who desperately need lifesaving alternatives such as Liothyronine, however, there were no clinical studies undertaken.
The guidelines actually state “Do not routinely offer Liothyronine for primary hypothyroidism, either alone or in combination with levothyroxine, because there is not enough evidence that it offers benefits over levothyroxine monotherapy, and its long-term adverse effects are uncertain”, this is clearly very different from what you are stating.
With “routinely” being the important word it is very important to acknowledge that patient treatment should be in line with the NICE guidelines on patient experience in adult NHS services – including details such as;
• knowing the patient as an individual
• tailoring healthcare services for each patient
• enabling patients to actively participate in their care, including communication, information and shared decision-making
Sadly, these guidelines are being ignored time and time again when it comes to the treatment of Thyroid conditions and I urge you to reissue the statement, clarifying that Liothyronine can indeed be prescribed in line with British Thyroid Association Liothyronine guidance. i.e. If a patient is deriving benefit from Liothyronine, having previously not benefited from levothyroxine alone, they should continue to be prescribed it on the NHS - and if a patient is not helped by levothyroxine, a trial of Liothyronine can be considered. The alternative is devastating for patients with their health and well-being compromised and their lives put at risk.
In addition to correcting the misinformation within your article, perhaps you would consider an article on the failings of thyroid and adrenal testing and treatment which is having a devastating effect on the health & wellbeing of countless women across the UK, and the fact that Liothyronine costs have increased by 6000% in the UK, causing Health Boards to stop prescribing on cost alone and forcing patients, who can afford it, to buy abroad.
I look forward to your response.
Your sincerely,
Elaine Smith
Member of the Scottish Parliament
Competing interests: No competing interests
Dear Editor
I am a hypothyroid patient who was terribly ill on levothyroxine monotherapy - 'normal or in-range' TSH, fT4, fT3 be damned. With the inclusion of T3, the change in my symptoms was incredible with complete resolution of brain fog, depression, inability to regulate body temperature. I now flourish on desiccated thyroid these 19 years later, after my epiphany.
Due to unresolved symptoms while on standard of care therapy, I lost about 10 years of life and my family lost me for those 10 years, my young children lost me, so my resentment of the myopia of endocrinology is founded on this damage to my family and to me, but this has also prompted me to learn and research and this has actually been wonderful...and upsetting. I note that many of these other responses have similar stories, yet endocrinology stubbornly clings to its dogma, still measuring and defining hypothyroidism and treatment via serum measures of these hormones that miss so very much.
I previously posted responses to BMJ 'Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline' (Published 14 May 2019) https://www.bmj.com/content/365/bmj.l2006 to share my experiences.
To add to the current comments about many issues with these guidelines, I want to cite those findings I mentioned in these previous responses regarding how rodents did NOT find euthroid status with levothyroxine monotherapy in all tissues; how rodent thyroids are very high in an endogenously made and largely unknown hormone, menaquinone-4 (MK-4); and how endocrinology has not even looked at humans to see if these rodent findings translate to humans. Further, the story behind levothyroxine usurping desiccated thyroid is a debacle that has now become dogma - these guidelines are incorrect to disparage desiccated thyroid.
This is particularly damning to much of dogma:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287526/
Is a Normal TSH Synonymous With “Euthyroidism” in Levothyroxine Monotherapy? (2017)
See slide 4 for how thyroid is extremely high in MK4 compared to other tissues, but please look at the whole thing:
https://www.omicsonline.org/abstract/recent-advances-in-vitamin-k-metabo...
Recent Advances in Vitamin K Metabolism (2014)
A side note about vitamin K metabolism:
It has long befuddled folks why MK-4 is the most common form of vitamin K in our tissues and yet when ingested, it is not found in serum - and we store vitamin K very poorly outside the liver; it is a fat soluble vitamin that is not able to build up or become toxic, but we recycle it to maintain coagulation homeostasis and it may well be the case that subclincal insufficiency is extremely common (1) - and understanding how ingestion of one form of vitamin K, vitamin K1, can become MK-4 is addressed here in this slide show. This is revolutionary stuff! Endocrinology should take notice.
https://www.intechopen.com/books/cell-signalling-thermodynamics-and-mole...
Vitamin K2: A Vitamin that Works like a Hormone, Impinging on Gene Expression (2018)
Ingested menaquinones also seem to follow this path to become vitamin K2 as MK-4. We can measure K1 in serum, but not MK-4, after ingestion unless the MK-4 is extraordinarily high, such as the therapeutic usage of it as 15mg doses, 3x/day, as used in Japan to treat osteoporosis.
That enzyme necessary to make MK-4 - UBIAD1 - also controls calcium and cholesterol. (look into UBIAD1)
Hypo folks tend to have high LDL-C, higher risk of a cardiovascular event, and supplementation of vitamin K2 in CKD patients lowered their cholesterol which rose again when supplementation stopped, so is this an issue for hypothyroid patients? Do hypothyroid patients have some derangement of these systems and pathways? It appears so.
The history of levothyroxine is nothing to be proud of. (2) Ironically, it is very unstable so batches are created to be higher in dosage so that they can diminish on the shelf, yet the supposed reason for creating this product was that desiccated thyroid was inconsistent in dosage. What irony. Instead of desiccated thyroid being unstable/inconsistent, it was the product levothyroxine that was unstable and inconsistent. Fears of T3 were promoted and all of endocrinology (apparently) bought it. Desiccated thyroid is very stable!
I must point out that when a crossover trial comparing desiccated thyroid and levothyroxine monotherapy was conducted, about HALF preferred the desiccated! (3) And the desiccated folks actually lost weight whereas the T4 folks did not. Hard to argue with this preference- we should listen and see things differently. ASAP
What does this tell us? Maybe that much more than the usual biomarkers within the usual ranges are needed to achieve optimal wellness and true euthroid status. Maybe we misunderstand what we measure and miss important aspects of thyroid functioning such as this endogenously made MK-4. Maybe MUCH more than the usual cited 10 - 15% of 'non-responders' to levothyroxine monotherapy exist and suboptimal treatment is the norm. Maybe incidence of hypothyroidism is much, much higher than about 5%, but with current definitions this cannot be seen. Maybe endocrinology needs an overhaul.
I certainly think so.
(1)
https://www.semanticscholar.org/paper/Vitamin-K%2C-an-example-of-triage-...
Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? (2009)
(2)
http://medcraveonline.com/MOJBB/MOJBB-05-00082.pdf
Theoretical aspects of levothyroxine: bioavailability and drug stability (2018)
(there are aspects of this - including the conclusion that T4 alone is best - with which I can quibble, but "oral preparations for Levothyroxine sodium cannot sustain potency throughout its shelf life, and the amount of active ingredient varies from batch to batch." says it all)
(3)
https://www.ncbi.nlm.nih.gov/pubmed/23539727
Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study. (2013)
Competing interests: No competing interests
Dear Editor
I whole-heartedly concur with all those who have responded and with their arguments. They hit the nail on the head. I plead with the authors to read them again.
I feel there has been a failure with the medical 'system' world-wide in the treatment of hypothyroid disease. There is more than just 'primary hypothyroidism' and you don't differentiate one from the other.
Unfortunately we in NZ have to rely on the NICE guidelines too and we hear the same misguided 'one-liners' when we ask for appropriate treatment from Dr's here. Better education to treat hypothyroidism is needed.
For the record NDT used in NZ (is not funded) and is USP approved - 'US Pharmacopeia is a reference of uniform preparations for the most commonly used drugs - with tests to ensure their quality, potency and purity'.
Any safety issues can be ameliorated if a medical professional knows how to test, dose & titrate - it's not the medication itself that is the issue.
There are hundreds of thousands (probably millions) of us worldwide taking NDT and T3 and we don't have issues when treated by knowledgeable Dr's - (issues which you wrongly base off poor quality research that excludes the very populations that need to be included).
These unclear guidelines put pressure on all Dr's to conform to the rules or be targeted with peer pressure. This does not help those clients who are suffering from secondary hypothyroidism, genetic polymorphisms, autoimmune thyroid disease, etc.
We have offered up enough evidence, argument and research to blow these guidelines out of the water - what does it take for this to be exposed? 20/20, 60 minutes or some other investigative news show? (or a class action lawsuit?)
I note; 'people have the right to be included in decisions about their care'. We cannot get the care we need if the decision is governed by a 'guideline' and (or mostly) 'cost' plus repeated misinformation. Our health comes first not the almighty dollar. The governments created drug buying systems that could be rorted - so they need to fix it (we shouldn't have to suffer for it).
These guidelines immediately rule out any discussion or inclusion and the Dr's use the guidelines as 'law' - which is very misleading, most people search an article very quickly (skim read) and look for key words - one sentence is all it takes and your medication is withdrawn (they are very busy people after all).
The guidelines say with regard to the decisions - that they 'use words to show strength (or certainty) of their recommendations'. How about using further resources available to them, or listening to (and hearing) the very people this affects?
As for point 1.3.5 - There is no evidence to show Levothyroxine shows any more benefit either.
There is evidence on the benefits of NDT in Hoang et al 2013. There is much more new research out there.
The suppressed TSH theory is another red-herring - 1+1 = 2 not 33. Thyrotoxicosis due to Graves is a different metabolic pathway with very different symptoms than a suppressed TSH when medicated with appropriate quantities of T3 or NDT to reduce symptoms in hypothyroid disease.
As another responder said too - the ratio's used to debunk NDT are another convenient red-herring taken from one old, small paper and perpetuated for eternity. Please find the other side of the record and play it.
Also the TSH theories and taking 6 months to settle - have you looked at this paper: https://doi.org/10.1210/jcem-70-2-403) . How many doctors know TSH levels can fluctuate like this in a single day in a single person?
Using words like clients are 'dissatisfied' with T4 medication or are not 'compliant' is another convenient and somewhat arrogant response to fob off our un-explainable blood results and symptoms. We are sick and tired of being sick on T4 and it being our fault, the only thing we want is to get well and stay well - these guidelines will keep us sick as now Dr's feel they have to withdraw us from our 2nd line of treatment which we were put on after the 1st line of treatment did not work for us (and made some of us much sicker in fact).
Let's make these guidelines much clearer on the second line of treatment - more work needs to be done, so don't give yourself a pat on the back yet.
I'd hate for this to go down in history as another 'unfortunate experiment'. (feel free to look up 'The Carwright Inquiry 1988).
Competing interests: No competing interests
Dear Editor.
With all due respect, during the NICE 2019 guideline consultation process numerous studies from reputable medical and endocrine journals were submitted to NICE that widely challenge the evidence base of these guidelines. Studies that were submitted challenge: (i) historic randomised control trials, (ii) historic studies linking a low/suppressed TSH to adverse effects, (iii) the widely held belief amongst doctors and endocrinologists that patient complaints on the standard hypothyroid treatment are due to other illness, psychological issues e.g. Somatoform Disorder, or in patients heads, (iv) TSH guided management of treatment dose; and (v) the assumption that TSH measurement directly mirrors T4 and T3 levels in patients. Studies submitted to NICE that widely challenge the evidence base of these guidelines have been published by some of the most highly qualified endocrinologists and thyroid scientists in the world like Anthony Toft, Scottish endocrinologist of 30 years, highly respected and ex-President of the Royal College of Physicians, Edinburgh. They are published in reputable medical journals and highly respected databases like Scopus. Studies submitted to NICE during the consultation process also included the Hoang et al, 2013 Randomised Control Trial on Desiccated Thyroid Extract (DTE) showing that DTE is safe and effective, even when patients TSH is low/suppressed. Long term studies showing that Liothyronine is safe and effective were submitted too.
In addition to the studies submitted to NICE during the consultation process that widely challenge the evidence base of these guidelines, thyroid patient groups across the UK with the support of international patients groups expressed their concerns to NICE about the draft NICE 2019 guidelines on multiple occasions.
Despite receiving numerous scientific studies that challenge the evidence base of NICE 2019 guidelines and feedback from patient groups, few patient concerns and these scientific studies are not reflected in these guidelines. What happened?
According to Anthony Toft and other highly qualified endocrinologists and thyroid scientists, scientific discoveries on thyroid physiology in the last few decades are of such size and scale that international thyroid guidelines require reassessment. Nice 2019 guidelines are not a reassessment based on new scientific discoveries on thyroid physiology e.g. the discovery of the TSH-T3 shunt and how this influences the relationship between TSH and thyroid hormones. NICE 2019 guidelines remain essentially unchanged with minor tweaks that show little change from previous NICE guidelines. I agree with another reply here which states that they are written as if the evidence base on which they are based is solid hard data, when in fact it is not. NICE have a responsibility to UK doctors who will use these guidelines to publish the list of scientific studies and patient survey data that was submitted and then de-prioritised/excluded by the team who developed these guidelines so that doctors are made aware of their limitations and applicability to every patient who walks in to their consulting rooms - this is what the American Thyroid Association do when they publish their guidelines. Greater transparency of process is required, historic gold standard thyroid studies require critical review and greater listening to patients and their concerns remains urgently needed.
Competing interests: No competing interests
Dear Editor
It is very interesting to me that there have been no responses to this article from the medics who control the management of thyroid conditions and prescriptions for their patients. There is such differing treatment across the country which it was hoped the guidelines would address.
It seems there is very little interest in this subject by the profession. Patients will continue to receive what amounts to scandalous treatment in many cases where problems are dismissed or attributed to other causes, most often depression for which medication is readily given.
With thousands of people in patient forums highlighting the current situation in the UK regarding Thyroid disease treatment, what a poor reflection this is on our medical education that it cannot keep up to date with current world treatment ,let alone other European countries, where alternatives to TSH and Levothyroxine are recognized and provided at affordable prices.
Competing interests: No competing interests
Dear Editor
I am afraid that there is an error in the above article which may cause many clinicians to immediately discount prescribing liothyronine to their patients.
Bullet point three which states, "Natural thyroid extract or liothyronine (alone or in combination with levothyroxine) is not recommended for treating people with primary hypothyroidism" is incorrect.
The NICE guideline actually stares, "Do not routinely offer liothyronine for primary hypothyroidism, either alone or in combination with levothyroxine, because there is not enough evidence that it offers benefits over levothyroxine monotherapy, and its long-term adverse effects are uncertain."
Further on in the guideline (page 34) NICE explain why they made their recommendations which includes:
"However, the committee noted that some of the trials did show some small benefits in specific quality of life domains and anecdotal evidence from some committee members suggested beneficial effects of combination treatment with levothyroxine and liothyronine in small subgroups of patients. The committee were aware that some people reported still feeling unwell with levothyroxine monotherapy and agreed that in this group adding liothyronine could potentially have greater benefit than in the general population with hypothyroidism, although there are no trials in this population."
Thyroid UK is disappointed in the wording "routinely" as this has been used in previous guidance causing many patients to have their liothyronine prescriptions withdrawn. Thyroid UK was a co-author of a major report, "The Liothyronine Dossier, Case Details with Clear Evidence that NHS England Guidance on Prescription of Liothyronine is not being followed by CCGs" which was significant in helping NHS England to revise their prescribing guidance making it much clearer that a cohort of patients who need liothyronine should receive it.
Another disappointing aspect of the NICE guideline is that although NICE do reference the clarified NHS England guidance, this seems to be buried near the end of the guideline document on page 50 and not placed with the other references on page 26. NICE have not yet responded to my query regarding this.
Whilst I understand that the quality of the evidence regarding liothyronine was poor, NICE have accepted the experience of the clinicians on the panel rather than the anecdotal evidence of thousands of patients, especially those that have been taking liothyronine for many years and who have now had this withdrawn, often without seeing a thyroid specialist endocrinologist.
Thyroid UK would very much like to see the wording changed in the NICE guideline to enable clarification for clinicians and CCGs.
Competing interests: No competing interests
Dear Editor
The NICE guidelines fail to take into account research studies indicating the existence of genetic mutations which impair a person's ability to convert Thyroxine into Triiodothyronine, such as: "Common Variation in the DIO2 Gene Predicts Baseline Psychological Well-Being and Response to Combination Thyroxine Plus Triiodothyronine Therapy in Hypothyroid Patients", by V Panicker, P Saravanan, B Vaidya, J Evans, A Hattersley, T Frayling & C Dayan. http://press.endocrine.org/doi/pdf/10.1210/jc.2008-1301.
Reporting and summarising the NICE paper guidelines whilst failing to provide critical analysis in light of available research is a missed opportunity to further the knowledge in this field and to educate the health professionals who are working to help patients address the hypothyroidism with which they are afflicted.
With reference to the lack of evidence claimed for the efficacy of Liothyronine, I would like to offer this analogy:
Thyroid medications are like antibiotics...give too little antibiotic and/or the wrong type of antibiotic, the antibiotic doesn't work (lack of efficacy). Give the right amount of the right kind of antibiotic, the antibiotic works.
I ask the authors to be critical that the NICE guidelines fail to differentiate between those people with hypothyroidism who have lost thyroid function completely (either because their thyroid has completely failed, or it has been surgically removed, or destroyed by RAI), with those who retain some functionality in their thyroid. The people without a functioning thyroid have lost their thyroid's ability to produce Triiodothyronine and its ability to convert Levothyroxine to Triiodothyronine.
Competing interests: Diagrnosed hypothyroidism that responded poorly to levothyroxine leaving me with continuing hypothyroid symptoms despite blood tests being within specified range
Re: Thyroid disease assessment and management: summary of NICE guidance
Dear Editor
This article really just reiterates the recommendations of the recent NICE guidelines which are available to all online. Most NICE recommendations are based on randomised clinical trial evidence. This is not the case for L-thyroxine treatment. Treatment of hypothyroidism with L-thyroxine is effective for most patients and is cost effective. However, its use is only supported by expert opinion as well as historical and cost considerations.
The guideline does not cater for the 15% or so of hypothyroid patients who continue to experience hypothyroid symptoms in spite of what appears to be adequate L-thyroxine replacement. The 17 available clinical trials comparing combined T3 and T4 treatment with L-thyroxine alone confirm that the combination is, at worst, non-inferior but is perfectly safe and preferred by the majority of patients. (1) The same applies to treatment with thyroid extract. (2)
Communications received by the journal from lay people in the wake of this article confirm that we are not, as clinicians, hitting the mark in our treatment of many patients with thyroid disease. A recent survey carried out under the auspices of the American Thyroid Association (3) confirmed that many hypothyroid patients were dissatisfied with their treatment and took matters into their own hands seeking treatment with either combined T3 and T4 or thyroid extract. A further study by the same organisation confirmed that physicians deviated from the guidelines in their prescribing habits to accommodate hypothyroid patients who were not satisfied by their treatment. (4) Guidelines may not reflect what patients think and how physicians prescribe. Guidelines respond slowly to clinical need, while expert opinion is rapidly coming round to the notion that hypothyroid patients with persistent symptoms require treatment that includes T3. (5-7) Simply “tweaking” the dose of L-thyroxine does not solve the problems of many hypothyroid patients. (8) Available evidence suggest that treatment with triiodothyronine is perfectly safe, (9) while higher levels of free T4 may increase risk of atrial fibrillation and cognitive decline.
The guidelines suggest that radioactive iodine should be regarded as a front-line treatment of thyrotoxicosis. This is partly on health economic grounds. However, many patients have reservations about radiotherapy for hyperthyroidism which is, after all, a relatively benign condition. My view is that radioactive iodine should be reserved for patients who cannot tolerate or comply with anti-thyroid drug treatment or who are at high risk from their hyperthyroidism. Patients with Graves’ disease treated with radioactive iodine are likely to become hypothyroid. Because of uncertainties around the management of hypothyroidism, many patients who have this treatment end up regretting it.
The treatment of thyroid disease still has many controversies and uncertainties. Until these are resolved, the onus on professionals is to regard patient choice and opinion and to have an open mind on treatments that may not be recommended or accepted by experts.
References
1. Eligar V, Taylor PN, Okosieme OE, Leese GP, and Dayan CM. Thyroxine replacement: a clinical endocrinologist's viewpoint. Ann Clin Biochem. 2016;53(Pt 4):421-33.
2. Hoang TD, Olsen CH, Mai VQ, Clyde PW, and Shakir MK. Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study. J Clin Endocrinol Metab. 2013;98(5):1982-90.
3. Peterson SJ, Cappola AR, Castro MR, Dayan CM, Farwell AP, Hennessey JV, et al. An Online Survey of Hypothyroid Patients Demonstrates Prominent Dissatisfaction. Thyroid. 2018;28(6):707-21.
4. Jonklaas J, Tefera E, and Shara N. Short-Term Time Trends in Prescribing Therapy for Hypothyroidism: Results of a Survey of American Thyroid Association Members. Front Endocrinol (Lausanne). 2019;10:31.
5. Akirov A, Fazelzad R, Ezzat S, Thabane L, and Sawka AM. A Systematic Review and Meta-Analysis of Patient Preferences for Combination Thyroid Hormone Treatment for Hypothyroidism. Front Endocrinol (Lausanne). 2019;10:477.
6. McAninch EA, and Bianco AC. The Swinging Pendulum in Treatment for Hypothyroidism: From (and Toward?) Combination Therapy. Front Endocrinol (Lausanne). 2019;10:446.
7. Wiersinga WM. T4 + T3 combination therapy: any progress? Endocrine. 2019;66(1):70-8.
8. Samuels MH, Kolobova I, Niederhausen M, Purnell JQ, and Schuff KG. Effects of Altering Levothyroxine Dose on Energy Expenditure and Body Composition in Subjects Treated With LT4. J Clin Endocrinol Metab. 2018;103(11):4163-75.
9. Leese GP, Soto-Pedre E, and Donnelly LA. Liothyronine use in a 17 year observational population-based study - the tears study. Clin Endocrinol (Oxf). 2016;85(6):918-25.
Competing interests: No competing interests