1 G Carvalho, SEMPR, Division of Endocrinology and Metabolism, Department of Medicine, Federal University of Paraná, Curitiba, Brazil carvalho.gisah@gmail.com.
2 G Paz-Filho, Oncology, Janssen-Cilag, Sydney, Australia.
3 C Mesa Junior, Endocrinology, Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil.
4 H Graf, Internal Medicine, Federal Universoity of Paraná, Curitiba, 80030-110, Brazil.
Abstract
Hypothyroidism is one of the most common hormone deficiencies in adults. Most of the cases, particularly those of overt hypothyroidism, are easily diagnosed and managed, with excellent outcomes if treated adequately. However, minor alterations of thyroid function determine nonspecific manifestations. Primary hypothyroidism due to chronic autoimmune thyroiditis is largely the most common cause of thyroid hormone deficiency. Central hypothyroidism is a rare and heterogeneous disorder characterized by decreased thyroid hormone secretion by an otherwise normal thyroid gland, due to lack of TSH. The standard treatment of primary and central hypothyroidism is hormone replacement therapy with levothyroxine sodium (LT4). Treatment guidelines of hypothyroidism recommend monotherapy with LT4 due to its efficacy, long-term experience, favorable side effect profile, ease of administration, good intestinal absorption, long serum half-life and low cost. Despite being easily treatable with a daily dose of LT4, many patients remain hypothyroid due to malabsorption syndromes, autoimmune gastritis, pancreatic and liver disorders, drug interactions, polymorphisms in type 2 deiodinase, high fiber diet, and more frequently, non-compliance to LT4 therapy. Compliance to levothyroxine treatment in hypothyroidism is compromised by daily and fasting schedule. Many adult patients remain hypothyroid due to all the above mentioned. and many attempts to improve levothyroxine therapy compliance and absorption have been made.
Thank you, this looks really interesting and a catch- all for those still symptomatic despite treatment, but am not absolutely clear what the term 'compliance' means in this context (maybe because I've never encountered it in this context before). Is it just 'taking it as instructed'?
Yes that is what it means - there appears to be a speight of Doctors explaining recalcitrant symptoms by accusing patients of not taking their Levothyroxine correctly, or at all...almost as if they are all singing to a secret hymn sheet.
Thanks for this. At least compliance is not first on the list unlike it appears to be in some doctors minds (as revealed in the recent BMJ paper post).
If they understood how awful levothyroxine makes some of us feel, they may actually realise that there can reasons why patients might be non-compliant! Would they shovel pills in their mouth daily if doing so made them feel really ill? No, I don't think so because it goes against the grain doesn't it!
The choice between dying of hypothyroidism or living a hell on Levothyroxine - not great at all....hopefully this paper will help in showing there are other valid reasons for Levothyroxine not properly restoring a euthyroid state.
pffft! "more frequently, non-compliance to LT4 therapy." Blame the patient when that is probably the least usual reason for not feeling well on levo only. At least they acknowledge there are other reasons.
Given that it appears the vast majority of patients are not told of the issues surrounding taking thyroid hormone replacements, they should not be expected to know things like the importance of taking regularly, away from food, etc.
To just have a prescription passed to you and then be left to it is grossly inadequate.
Non-compliance should never be used as a blame-laden term when the poor patient has never even been told what they are supposed to be compliant with!
My brain and mouth were compliant in that I took it in the right way. The issue was my pesky body the tissues of which could not comply with the doctors view of my bloods, and therefore my health. Some of us are simply outliers.
There is no reference given to this statement, and I think there ought to be :
Central hypothyroidism is a rare and heterogeneous disorder characterized by decreased thyroid hormone secretion by an otherwise normal thyroid gland, due to lack of TSH.
Where's the proof of the rarity? I think it is a lot more common than doctors believe.
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The synthetic thyroid hormone levothyroxine (LT4) is a cost effective treatment t hypothyroidism, with few side effects (5).
I wondered where the evidence came from for the above statement. Reference 5 is a paper published in 1927 (!) about the chemistry and synthesis of thyroxine.
5 Harington CR, Barger G. Chemistry of thyroxine–constitution and synthesis of thyroxine. Biochemestry. Journal. 1927 21 169–183.
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The recommended daily dose of LT4 is 1.6-1.7 Eg/kg body weight for most patients,
Given that the majority of members on here are adult women, and the doses people are prescribed vary from 25mcg up to 300mcg per day (roughly) then using body weight for dosing is utterly pointless. It doesn't even work as a way of determining starting dose.
In patients with heart disease, low doses of LT4 should be started, with slow increases in the absence of angina or other cardiac symptoms such as tachyarrhythmias.
This statement will keep lots of people under-dosed. It is quite common for fast heart rate and arrhythmia to occur when dose is too low, and for the problem to disappear when dose is adequate.
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Many patients fail to show clinical and biochemical response to the expected dose of LT4, which is most frequently attributed to poor compliance (8).
Reference 8 is to this paper :
8 Ain KB, Refetoff S, Fein HG, Weintraub BD. Pseudomalabsorption of levothyroxine. JAMA 1991 266 2118-2120.
I can't find the full paper but the abstract can be found here :
And the shocker is how many patients this paper was based on - just 4 !!!!
PATIENTS:
--Four patients, seen within two decades, with clinical and biochemical hypothyroidism while receiving levothyroxine, were evaluated for selective malabsorption of this hormone.
I looked at some of the related papers/similar articles given on the right side of the pubmed link above (on the subject of pseudomalabsorption of Levothyroxine) and all the ones I looked at were case reports or case histories looking at, at most, three patients. Some of them were only reporting on one patient.
So this "common" problem is based on the flimsiest of evidence.
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It has been shown that as many as 40% of patients on LT4 replacement have TSH serum levels out of the reference range (27), which may lead to clinical signs and symptoms of hypothyroidism and its related comorbidities, and determine a negative impact on healthrelated quality of life (HRQoL) (28). Therefore, adequate LT4 therapy should be given in primary hypothyroidism with the objective to maintain serum TSH within the reference range.
Reference 27 is to this paper :
27 Vigário Pdos S, Vaisman F, Coeli CM, Ward L, Graf H, Carvalho G, Júnior RM, Vaisman M. Inadequate levothyroxine replacement for primary hypothyroidism is associated with poor healthrelated quality of lifea Brazilian multicentre study. Endocrine 2013 44 434-440.
I got tired after getting this far so I haven't commented further on the paper. However, a quick read through suggests it is slightly better than some papers I've read (but since most of the competition is poor that isn't saying much).
Like most papers relating to the thyroid there were bits and pieces that grated a lot and rubbed me up the wrong way.
In my book, use of terms like "rare" and "common" in such documents should always be qualified by the appropriate number. I wholeheartedly agree it seems likely that people with some degree of pituitary impairment affecting things like TSH production would be far more common than the severe cases that are more often recognised.
Years ago, my GP phoned me at home, asking if I was taking my levothyroxine. I said, of course I am. Are you sure? Omg! Yes, I'm sure!
Same GP totally ignored my request for a blood test, change of dose, endorse referral, 3 years ago, when I felt very unwell. She is no longer my GP. I changed practice after I got the help I needed by visiting a good doctor in London.
The blame the patient, through the non compliance remark is, at times, a harsh judgement, and often, a total cop out!
But, as you say, some recognition is given that treatment given is not always in the best interest of individual patients.
Not posted on here for ages, but all I can say is that since i started taking Levo Sodium I have never looked back and its been quite a few years now. I am fit, got back to my normal weight in no time, I am 71 and still do hi impact aerobics, combat and weights. Also I find it very important to keep up with old friends and socialise and get out and about if possible. The reason I stopped posting on here is that I feel very guilty because there are so many people who post on here who seem so ill and maybe could have been misdiagnosed in the first place or have a lot of other things going on with their health and in their lives, which are making them ill.
Before I went on Levo (now stable at 125mcg) I did not know what was wrong with me. Felt cold all the time, ached in every bone and joint of my body, suffered night cramps and sweats, pretty unbearable, I knew there was something horrible going on with my body. It took 3 visits to the doctors to get diagnosed, but eventually after a few google sessions of my own symptoms etc., and with notes in hand of my own corresponding symptoms, I went to a very good lady doctor within the practice who listened and did all the tests and ureka the rest is history. I only wish it was the same for everyone out there, but obviously it is not.
I cannot stress enough how very important it is, (especially now as the doctors are so stretched) and you only have 10 minutes to explain yourself, that you make notes of your symptoms prior to your visit, and any doctor worth their metal will be glad you did. Also lots of people get all hot and bothered when they go to the doctors and may not come over as clear as they think they do, or forget the most importants details. Try it, Good Luck, it worked for me.
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Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism.....a study
