ADVERSE EVENT REPORTING IN PATIENTS TREATED WITH THYROID HORMONE EXTRACT

[helvella]

This is potentially a deeply concerning paper - especially given the way in which adverse events under desiccated thyroid are contrasted against those under levothyroxine. I think an awful lot of levothyroxine adverse events are not reported because so many have become just part of the scenery.

I'd be happy to see desiccated thyroid given a full and clean bill of health by the FDA, the MHRA and anyone else concerned. Though we would have to question the motivations of every player who takes part between now and some uncertain future in which that could occur.

It is particularly interesting that the best-known non-desiccated thyroid combination treatment in the USA is, or rather was, the USA product Thyrolar. Surely, if the issue were simply that animal-based products are inconsistent but synthetic are highly consistent, we'd have seen dominance of the market by Thyrolar? Instead of which it has been unobtainable for something like ten years or longer.

Note that some of the problem is stated to be the difficulty that primary care providers have - which is likely due to their confusion (read inexperience and lack of knowledge) - rather than the product itself? We could very easily argue that a vast number of levothyroxine dose adjustments we see people reporting indicated the same prescriber issues regarding levothyroxine. If they are so readily confused, what are they doing being let loose on patients AT ALL?

Endocr Pract. 2017 Feb 22. doi: 10.4158/EP161584.OR. [Epub ahead of print]

ADVERSE EVENT REPORTING IN PATIENTS TREATED WITH THYROID HORMONE EXTRACT.

Shrestha RT1, Malabanan A2, Haugen BR3, Levy EG4, Hennessey JV2.

Author information

• 1From: 1Division of Endocrinology, Diabetes and Metabolism, University of Minnesota, Minneapolis, Minnesota.

• 2Harvard Medical School, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Gryzmish 6, Boston MA 02215.

• 3Division of Endocrinology, Metabolism & Diabetes, University of Colorado Denver, Aurora, Colorado 80045.

• 4Division of Endocrinology, University of Miami, Miller School of Medicine, Miami FL.

Abstract

OBJECTIVE:

Thyroid hormone extract is used for the treatment of thyroid disorders but limited data exist on adverse events commonly noted by the physicians associated with this use. The purpose of this survey was to report adverse events observed by expert physicians managing patients treated for thyroid disease with thyroid hormones.

METHODS:

Members of the American Thyroid Association, The Endocrine Society and the American Association of Clinical Endocrinologists developed a survey instrument modeled on the FDA's reported adverse events for levothyroxine that would effectively assess the clinical experience of frequent prescribers of thyroid hormone. Survey links were emailed to physicians, and the websites of each society provided links to the data collection form.

RESULTS:

A total of 174 reports of adverse events occurring in patients on thyroid hormone extract were received. Ninety-one of these reports were accompanied by alterations in thyrotropin values and were further analyzed. Of these, 62 (68%) subjects had developed new symptoms associated with altered TSH. A majority of TSH changes and symptoms described were consistent with thyrotoxicosis (65%), 2 cases had developed arrhythmias. Reporters noted difficulty in dose adjustment by primary care providers due to confusion in interpreting thyroid function test results while on thyroid extract which often necessitated subspecialty referrals.

CONCLUSIONS:

These adverse event reports should stimulate consideration by FDA to regulate and monitoring of thyroid hormone extract use and consider standardizing these extracts to meet current standards of manufacture, hormone content, availability and shelf-life like the rigor to which preparations like Levothyroxine are monitored.

PMID: 28225316

DOI: 10.4158/EP161584.OR

ncbi.nlm.nih.gov/pubmed/282...

The full paper is available for free from this link:

journals.aace.com/doi/10.41...

[shaws]

Well Dr Lowe did his Rebuttal with the facts, figures but they did not even make a courtesy reply. Big Pharma, as we know, do not want patients to be aware they may fare better on an NDT than levothyroxine alone, especially when new Research is showing that many may need the addition of T3 to levothyroxine.

Quite a few of our members are happy and well on NDT.

thyroidscience.com/Criticis...

They never mention the adverse affects of levothyroxine that many suffer from but are given 'other' medications for those than a decent dose of levothyroxine.

[Wishingwell in reply to shaws]

Quite agree. Since ditching Levo for NDT I have wondered whether it was the adverse effects of Levo keeping me unwell or NDT making me well . Either way I know NDT is for me. Thank you for sharing this .

[shaws in reply to Wishingwell]

How come they never report the Adverse Effects of Levothyroxine which many on this forum have had or are having at present.

Doctors shut their eyes and look on the patient as deranged but who are only so unwell they are quite desperate for an answer which isn't forthcoming from the medical profession. Forcing people to remain very unwell with a myriad of clinical symptoms yet being told 'your TSH is normal' never mind that the patient is not 'normal' with symptoms.

[Spareribs in reply to shaws]

Perhaps on Levo they aren't called "adverse effects" only "side effects".....

which doesn't sound as bad and should be expected with any medicine/drug.

[shaws in reply to Spareribs]

- Considering there are 300+ clinical symptoms and GPs don't know one.

[thyroidnodules in reply to shaws]

I did ok on levo. however, I noticed my left leg swelled up slightly on it. I also put on more weight. I decided to try ndt and my leg is a lot better and although I have not lost a lot of weight - maybe only a few pounds, I have not gained. I am sure if I got on a proper diet I could lose and am now trying this

[shaws in reply to thyroidnodules]

Maybe a tiny increase in dose would help with swelling. Unexplained swelling is a clinical symtom. If you read first comment on the following link it is a very good explanation.

web.archive.org/web/2010103...

[SmallBlueThing]

I came across this about Levothyroxine today: medicines.org.uk/emc/medici...

Excerpts (with typos corrected) I found interesting:

For patients aged over 50 years, with or without cardiac disease, clinical response is probably a more acceptable criterion of dosage, rather than serum levels.

An ECG before starting treatment with levothyroxine is advised, as changes induced by hypothyroidism may be confused with evidence of ischaemia.

Beta Blockers: levothyroxine (thyroxine) accelerates metabolism of propranolol, atenolol and sotalol.

Beta blockers may decrease the peripheral conversion of levothyroxine to triiodothyronine.

Oestrogen, oestrogen containing products (including hormone replacement therapy) and oral contraceptives may increase the requirement of thyroid therapy dosage.

[bluebug in reply to SmallBlueThing]

So are those yellow card reports finally working?

For anyone who doesn't know what they are if you have adverse drug effects which basically means side effects from any drug you can report them YOURSELF using the yellow card system. You can refuse to allow the researchers access to your GP and/or your medical notes. In theory your healthcare professional is suppose to report them but in practice few do in the UK.

The reason to report them is the more side effects that are noted in the general population taking the drug then big pharma is actually forced to release more research information especially if it's negative.

yellowcard.gov.uk

[helvella in reply to bluebug]

100% endorse the use of Yellow Cards.

The Teva issue of a few years ago was picked up because of them - even if the small number sent in by doctors were given extra prominence by the people who look at them.

[bluebug in reply to helvella]

One kind of contraceptive pill was withdrawn Europe wide because French doctors submitted their equivalent of yellow cards. In the UK doctors have a habit of fobbing of patients over drug side effects, so it leaves it up to patients to report the issues.

At least on this forum we can tell people they aren't going "mad", "crazy" or making things up if they mention something that is clearly a side effect to a prescribed medicine, and to yellow card it.

[helvella in reply to bluebug]

Numbers matter.

If one or two patients report something over a year, it could easily be dismissed. If one or two thousand report the same thing, it cannot so easily be dismissed.

Any future inquiry into why an issue was not acted on would have access to this information and might take a very dim view if vast numbers of Yellow Card reports had been ignored. That thought will hang in the minds of those involved.

[SmallBlueThing in reply to bluebug]

I yellow carded a beta blocker and am considering the three calcium channel blockers I've tried.

Then there was the iodine dressing. No point the nurse asking me if I had a thyroid problem if, at the time and after eight years' tests, I'd not been told I had.

[shaws in reply to SmallBlueThing]

This should be circulated to all Endocrinologists/doctors.

'clinical response is probably a more acceptable criterion of dosage'

[silverfox7]

Yes I agree more of us should be submitting yellow when the drug isn't doing what it's supposed to. Alright in some. Asked it may well be down to the person overseeing our medication but may be if the figures increased things may be looked into.

[Gcart]

Just wonder how many people treated on T 4 alone are alright?

I know 2 of 2 known to me who arent .

I have suggested they should get their blood ranges/ask more questions etc but I can tell they think doctor knows best .

Old school !!

If I had bad itching , extra sweating , more palpatations on a certain brand of levo , is that a yellow card ? Because I would report it

[bluebug in reply to Gcart]

Yes definitely.

Make sure you have the medication infront of you if possible to put manufacturer and batch information in.

I reported having bone pain on high dose vitamin D supplements because it wasn't listed as a side effect and someone else complained of also having it. Some others must have also reported it as a year later it was mentioned as a possible side effect. It said something like there have been reports of increased bone pain while taking this.

[SilverAvocado in reply to Gcart]

I wonder the same. Also have 2 hypo friends who don't do well on it. Funny thing is that when I first met both they told me they were on Levo and it was great for them. It's only when we became better friends I found out the truth.

Which makes me suspicious whenever anyone says they are fine on it. I think people get bullied into putting up with the symptoms they have, told it's their own fault if they aren't well, or of course told that they have several other illnesses.

[Katepots]

I was so unwell on Levo and feeling human again on NDT. I would never go back. If proper trials were done then Levo would not come out well at all. Especially if they included all the patients that had heart/cholesterol problems on Levo.

[helvella in reply to Katepots]

My cholesterol problem on levothyroxine is that it is too low.

[Katepots in reply to helvella]

We are all so different! Mine rocketed but now at a healthy level 😀

[Treepie]

The method refers to being modelled on the method the FDA uses for adverse effects for Levothyroxine. That seems fair enough. There have been posts on here that show NDT does not work for everybody. The real problem is that we do not have the opportunity to try different treatments on the NHS. Medical Minds are closed to experiment and cost assists closure.

I do agree ,however,that the motivation and funding of the researchers needs careful examination.

[helvella in reply to Treepie]

It seems fair enough except that they seem to be damning desiccated thyroid because practitioners are incapable of correct dosing. Not because of the product itself.

It is concerning that there were apparent cases of misdosing which they attribute to potency of the product but they need to be investigated properly and not be assumed to be manufacturer issues. We see many people who take their desiccated thyroid in all sorts of seemingly random ways - with or without food and drink, when they remember, upping and downing by the hour, and so on. These practices need to be eliminated as possible causes. Indeed, the actual products need to be properly and failry assessed.

(Armour used to have an animal laboratory in which batches of product were tested in order to ensure consistency. In many ways, biological effect is the best test but I ssupect they mostly rely on laboratory assays now.)

[Treepie in reply to helvella]

Agreed, but it is clear from many posts on here that there is not good guidance on when and how to take Levo. My request to have Mercury not TEVA was met yesterday ,I am assured, but the tabs came in a pharmacists bottle with no brand name on the label .The instruction was to take in the morning.

[helvella in reply to Treepie]

Guidance on taking levothyroxine has marginally improved. My latest says:

The tablets should be swallowed, with a drink of water, in the morning at least 30 minutes and preferably one hour before breakfast.

The pharmacy also added a warning about caffeine - which has never previously appeared.

At least the EMC documents describe the tablets sufficiently - if your eyes are able to see them well enough - to identify them for sure.

[Katepots]

The trouble is that Drs surgeries are just a business these days and there is no money to be had in prescribing NDT. It's not about treating us and getting us well it's all about drug companies and profit!

[linda96 in reply to Katepots]

I think we are all just waking up to that fact. The NHS depends on customers just as much as the pharmaceutical companies do. The more customers the more cash to be injected into the NHS system from government.

[linda96]

I have made a report using the yellow card scheme. I had prompt reply and follow up. They asked if I would allow the company making the product would be allowed to come and pick up their product for testing and I said no, fearing a backlash. Not heard anything since. Is the yellow card system run by the manufacturers or paid for by the manufacturers? Iv had no follow up since.

[humanbean in reply to linda96]

As far as I know, the Yellow Card system is run by the MHRA (Medicines and Healthcare products Regulatory Agency).

And who funds the MHRA?

The pharmaceutical companies. (Apart from the part of it which is to do with approving medical devices rather than drugs. That part is paid for by the government.)

en.wikipedia.org/wiki/Medic...

[linda96 in reply to humanbean]

Oh damn, the pharmaceutical companies have everything their own way. How come we lost control? It's the insidiousness of it all, destroying what should most preserved of all, the good will of the people who paid in faithfully their taxes to build up a world beating medical health system. I hope the people who have shares in pharmaceuticals have a proper look at what's really happening.

[helvella in reply to linda96]

Even if the pharmaceutical companies are funding it, that doesn't actually mean that all reports are thrown into the bin, unread.

Nonetheless, I agree that there are deep questions to be asked - and answered.

[linda96 in reply to helvella]

Thank you Helvella, sad state of affairs isn't it? I must find as soon as possible my rose tinted spectacles... Er where did I put them, I miss them so much...

[Wishingwell]

Glad I read all of this thread as I hadn't heard of the yellow card. Also wasn't aware of issues with TEVA which was the last batch Levo I was prescribed ( but never took ) so I will look into this.

[helvella in reply to Wishingwell]

The Teva issue was in 2013 (from memory) hence the emphasis on New Formulation since Teva returned to the market late year.