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New Study Reveals Why 1 in 6 Hypothyroid Patients Still Feels Bad on Levothyroxine

Doctors often treat an underactive thyroid (hypothyroidism) with levothyroxine (T4). New research is revealing that many people also need T3 to feel good.
Problems with thyroid nurse examining a patient

What do you think the # 1 most prescribed drug in America is? No, it’s not a statin. According to the last statistics we have seen it is a drug for thyroid replacement called levothyroxine. Over 120 million prescriptions were dispensed annually. Did you know that one of the most controversial and contentious issues in endocrinology has to do with the best treatment for hypothyroidism. Most doctors insist that standard treatment with levothyroxine (L-T4, Levothroid, Levoxyl, Synthroid, Tirosint, Unithroid) is the answer to a sluggish or inactive thyroid gland. They reject natural thyroid or supplementation with T3 (Cytomel or compounded slow-release products) as unnecessary or unreliable.

Why Levothyroxine Alone Might Not Be Adequate

Many people with hypothyroidism (estimates range from 12 to 15% of patients or higher) complain of symptoms when they are treated with standard levothyroxine. Even when blood tests (TSH & TH) suggest that thyroid function is normalized, these individuals feel like crap. They complain of fatigue, impaired cognition or “foggy brain,” weight gain, and general malaise.

Until now, many endocrinologists and a lot of primary care physicians were inclined to chalk up such complaints as psychosomatic, ie, all in the head. They did not wish to contemplate a problem with the standard treatment regimen. That is starting to change. A splendid article published in one of the most cautious and respected medical journals in the world, the Annals of Internal Medicine, Jan. 5, 2016, offers a nuanced insights into patient management.

The article is titled “The History and Future of Treatment of Hypothyroidism.” You can access the full article for free at this link. The authors point out that 10% to 15% of patients treated with standard levothyroxine “monotherapy” are “dissatisfied as a result of residual symptoms of hypothyroidism, including neurocognitive impairment…” In other words, patients often complained of symptoms such as brain fog, confusion, fatigue or depression even after their lab tests appeared to be normalized.

Here is just one example from a visitor to our website:

“I have been on Synthroid for 40 years. I definitely have problems that have grown over the years. I go for my TSH blood test and it comes back within the normal range. So the doctor prescribes my usual .125 mg Synthroid and sends me on my way.

“When I show him my swollen feet and legs and the stasis dermatitis now forming on my lower legs, he says, “You have venous insufficiency. Wear compression stockings and elevate your legs as much as possible.”

“When I had two separate incidents of depression and anxiety, I was prescribed the antidepressant Paxil. I took myself off that after one year when my legs swelled up even more than usual.

“I suffer from constipation, lack of energy and lower back pain and have not been able to lose weight for years. My muscles ache all the time and my feet hurt constantly when I walk very far.

“I ‘ll be 66 years old in a few weeks and I feel like I am 80. I read all the articles and am very aware of the foods I should and should not eat. All my doctor cares about is the TSH test, and as long as the result comes back within the normal range he is happy and assumes all is well with my thyroid.” K.H.

How Do We Get from T4 to T3?

To understand the complexity of thyroid supplementation, we need to take a quick detour into some basic biology. Don’t panic! We will do our best to make this understandable.

The thyroid gland makes a few hormones but we are only going to focus on two, T4 (thyroxine) and T3 (triiodothyronine). The numbers T4 and T3 represent the number of iodine atoms ( 4 and 3 respectively) attached to the basic hormone structure.

Thyroxine (T4) is a prohormone and is relatively inactive. It has to be converted to T3 by the body. An enzyme removes one of the iodine atoms to accomplish this. As much as 80% of T4 is converted to T3. T3 is three to five times more potent than T4. So the efficient conversion of T4 to T3 is critical, and levels of circulating “free” T3 are essential to well being.

The New Discovery

Okay, before your eyes glaze over, let’s get to the new and exciting research. A team of investigators led by endocrinologists at Rush University Medical Center (in Chicago, IL) has published studies in the Journal of Clinical Investigation (online, Jan 2, 2015) and the Journal of Clinical Endocrinology & Metabolism (online, Jan. 8, 2015).

Their animal research involved removing rat thyroid glands. When the scientists tried to normalize hormone levels with just levothyroxine (L-T4) they were unsuccessful. The animals demonstrated signs of hypothyroidism, especially within the brain, which might account for why some humans complain of cognitive dysfunction on T4 alone. The investigators were able to normalize circulating T3 levels and improve symptoms by supplementing T4 with extra T3.

Their human study uncovered genetic variability in patients suffering from hypothyroidism. They estimate that the mutation exists in 12% to 36% of the population. It makes it harder to convert T4 to T3. The scientists detected negative brain changes in patients that have difficulty making the T4 to T3 conversion. Such patients generally prefer a treatment regimen that involves both levothyroxine together with T3 supplementation (Journal of Clinical Endocrinology and Metabolism (May, 2009).

Old Beliefs Die hard

A few generations of endocrinologists and primary care physicians learned that the only thing that matters when monitoring thyroid function in hypothyroid patients is TSH levels. And the only treatment needed is levothyroxine. Changing such entrenched beliefs is not easy. Although many patients do just fine with such an approach, there appear to be many others who do not. The overview in the Annals of Internal Medicine suggests that a more nuanced, personalized approach may be the wave of the future for people with hypothyroidism.

Patient Stories

Pat says:

“I had blood work done a few months ago for thyroid function. My primary care physician states that the test showed that my TSH was normal…12.9.

“I said, ‘what about the test for t3 and t4 levels?’ The doc stated that further testing wouldn’t be required if the TSH levels were in normal range. From what I have been reading, 12.9 seems to be a high normal. Is there some verification on what the normal range is for TSH?

” have been loosing hair, have dry skin, fatigue, and depression, which could also be attributed to the high blood pressure medication that I’ve been using (amlodipine), which I have titrated off of. My blood pressure is still high, (withdrawal symptoms or the rebound effect). My life is continual stress along with all the other work and effort to maintain a healthy lifestyle.”

Neil in the UK shared this:

“I’m a 55 year old man. I was diagnosed with hypothyroidism in 2011 (TSH 98). I was tarted on levothyoxine and ended up balanced after 6 months. I was still tired with foggy thinking, aches and insomnia.

“They the tested me yearly and I remained within normal limits. I’ve no idea what my T4 and T3 level are as the Dr. won’t tell me. Last autumn my TSH was 9.5 so they increased my dose of levo from 150 mcg to 175. My TSH fell to 0.05 so they cut me back to 125 mcg. My TSH is now 70.

“For the entire time I have been on  levothroxine I’ve felt bad no matter what my TSH levels are. I don’t know what to do in order to feel better. They don’t offer T3 in the UK.”

Other Patient Stories:

My daughter has had hypothyroidism since she was 12. She is now 28 and took Synthroid up until 2 years ago. She felt lousy and was tired and her hair fell out and she had dry skin, even though they said her levels were fine! Well she started to take Armour Thyroid two years ago and there was a huge difference!

“She feels better and was also able to lose 60 lbs over the past 2 years. She couldn’t lose any before, as hard as she worked at it. I highly recommend Armour instead of the Synthroid!” J.F.

I have struggled with thyroid problems since I was 8. At age 57, I’ve had thyroid cancer twice, 2 surgeries & now high dose radiation/ablation. My last surgery was 18 months ago & I have gained 18 pounds since then.

“I have no energy & struggle to stay awake. My hair & nails are falling off. I’ve been getting weekly iron IV infusions yet my red blood cell & ferritin levels as well as thyroid levels remain low.”

“For years I took Armour Thyroid & was happy & healthy. Now I’m told I MUST take Synthroid even though I feel it’s ruining my life. I’m in my doctor’s waiting room now; I plan to show him these articles & ask for Armour. It’s hard to imagine the damage levothyroxine has done to my life unless you have lived it. I urge all people taking Synthroid but feeling poorly to tell their doctor & give Armour a try.” Shasha

“I have taken Armour Thyroid, Synthroid and Levothroid at various times. The ONLY one of the 3 that did not give me major side effects has been the Armour Thyroid. I have much more energy, no headaches and no fatigue like I have with the synthetic products.” Diane

We are not beating the drum for Armour Thyroid or any particular brand of natural or synthetic thyroid hormone. Some doctors prescribe levothyroxine and supplement it with Cytomel (T3) or with a special timed-release T3 formulation that compounding pharmacists can make. This creates more balanced T4 and T3 levels circulating within the body.

If you are intrigued by this thyroid discussion we think you will find our newly revised 25-page Guide to Thyroid Hormones of great interest. Not only does it go into much greater depth regarding treatment options, it provides information about thyroid testing that you may not find anyplace else.

Thyroid hormones are essential for normal body functioning. Getting the balance adjusted is a little like Goldilocks and the porridge; not too hot, not too cold, not too much and not too little. We want you to get it just right. Here is a link to our new guide.

If your physician wants a more authoritative resource, suggest she check out the article in the Annals of Internal Medicine. The authors are endocrinologists. And if you really want to understand this complex story, take some time to listen to our extended interview with one of the authors, Antonio Bianco, MD, PhD. It is free and your doctor may wish to listen as well. Here is a link.

Please share this information with anyone you think would be interested. Comment below in the “Add My Thoughts” section and please vote on this article at the top of the page. We appreciate the feedback. We hope our Guide to Thyroid Hormones will also provide an in-depth understanding of this complex topic.

Revised: 1/12/17

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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As I read all of these experiences with Levothyroxine, I am frightened to death over the fact that I am scheduled to have my thyroid gland removed next month due to compression symptoms.
Am I putting myself on death row???
I am so confused. I don’t want to regret removing it, but in the meantime, I do need to breathe!!

Lisa, most people who have thyroid surgery do pretty well after some adjustment. They don’t write comments online because they are feeling well. So, talk to your doctor about your concerns and make sure you have an endocrinologist who will work with you on the replacement thyroid medicine so that you feel good. Best of luck!

Recently I was diagnosed with thyroiditis and people with thyroiditis can experience the symptoms of hypothyroidism. I feel tired all time and no energy, I get dizzy and lightheaded, I feel like my equilibrium is out of whack. When I’m walking I feel like I’m leaning to one side, feels like I could fall over.

I have muscle aches and pain, especially in my legs sometimes. My doctor is supposed to set me up an appointment with a thyroid specialist. I will be so glad when she does cause I am sick and tired of feeling this way, it sucks when you feel lousy 24/7.

I have been like this for a very long time now, but I never said anything cause I was too afraid and I didn’t want nobody to worry. It’s my own fault why I waited this long to say something, but I am so glad I am getting something done about it now. I do not wish thyroid problems on nobody.

I tried to take Levoxyl and it made me feel terrible, so we switched to Tirosint. I was doing okay on it until recently. In Feb 2018 I was on 100mcg and my TSH was 2.05 so we increased my dose to 112mcg and shortly after, I began to feel lousy. I tried skipping a day or two, then taking 100mcg and I feel horrible. So now I’m inclined to skip it all together and leave my endocrinologist for my regular MD and ask to start a low dose of Armour; I’ve never taken this medication, however, I’m willing to try it, if in fact, it’s necessary to bring my levels into range and will make me feel better than this. – I’m exhausted — depressed — frustrated — overwhelmed — irritated by the whole thing.

I need help… my TSH is at 36 due to a compounding pharmacist giving me the wrong medication. I’m now taking 39.5 micrograms of Tirosint per day, the only medication I can currently take. I need to take more thyroid medication but my body, for some reason, is blocking my taking any more medication. If I take 1 more microgram a week I get extreme hyper symptoms. It’s physiological. I’m on high doses of blood pressure medication and beta-blockers. I had my thyroid removed many years ago. Five doctors have tested everything and can’t come up with an answer. Top doctors in San Diego and Los Angeles tell me that if I can’t get more medication in me there is strong possibility I could die.

To make things worse, in October 2017 I was diagnosed with lung cancer and need surgery but with my TSH number so high doctors have said I would not wake up after the surgery.

Has anyone had a problem like this and has found an answer?

I’m a woman age 67 soon to be 68. The doc put me on levo which lasted a week. Then told doc that I had pain in my back and under breast area. Now for 4 days on armor I feel better but did you know hypothyroidism is 90% diet? 10 % stress? I’m cleaning up my diet which was poor. I now eat NO WHEAT or sugars, use green stevia; eat carrots, celery, asparagus, avocado 3 times a week, at least oils like coconut and olive. I use almond flour and almond or coconut milk.
People can feel depressed and suicidal with thyroid problems and mood changes. Good luck.

I have been on levothyroxine 75mcg for 3 years. I still feel like crap and don’t really live life. The levothyroxine really helped for a few weeks but then the symptoms came back. Since my levels are better, my doctor thinks that I’m fine. I’ve tried convincing him to add cyntomel or switch me to armour. He’s only looking at blood tests and not listening to how bad I feel. I think he thinks it’s all in my head. I just want my life back.

I was on levrothyroxine for years – still felt terrible and couldnt think clearly. It was hard to do my job. I kept going to the doctor and told her how bad I felt all the time and the terrible brain fog. It was hard to hold a conversation! Anyway, finally the doctor said she would try me on liothyronine in addition to my levrothyroxine. It has changed my life! I feel normal again for the first time in 14 years. Please have your doctor consider this option.

I had a sub thyroidectomy over 30 years ago for graves, they said i had normal bloods after it for years! but to be honest I never ever felt 100%, my hair never grew longer than shoulders it snapped off at that lengh, my skin was dry and I had not the normal energy of a 20 yrs old.

I tried to have a baby when 27 yrs old, but just couldn’t fall pregnant so i am guessing thyroid must of been to low for many years my thyroid was tested at the time but only the TSH which I should of had T3. T4 as well as i had a thyroidectomy .I have no children thanks to the TSH test

Tt the age of 40 I was diagnosed with hypothyroidism , I hadn’t put any weight on but was extremely tired i had slept solid for 2 weeks, I was put on Levothyroxine and i have slowly been falling to pieces on it,
I never once felt well on it and was only put on a dose of 50mgs and left I was never told to go have bloods , so eventually I ended up in a mental hospital for hearing things.

I am guessing this was my under treated thyroid that done this as no thyroid test was taken when it happened !
, I put my dosage up myself to 100mgs as was falling asleep again and was a bit better with raise I again a few year later raised it again up to 150mgs as again coma like sleeps, all levothyroxine seemed to do was stop me falling asleep 24/7 I was still aching all over, bad heart burn, fibromyalgia pains all over, extremely itchy shins , my hair was thin and i had been putting on loads of weight since taking Levothyroxine, the GP who was quite useless thinking back on how he treated me always told me it was because I wasn’t exercising ( I had a dog and walked over an hour per day so it wasnt that at 1st later i couldn’t walk due to pain ) and i was eating too much, I hardly ate a thing as i don’t like being fat as was only a size 8 and i had crept up to a size 16-18 uk size thats huge I was wearing tents not nice clothes.

I crash dieted all the time just so I didn’t pile even more weight on! I also stopped my periods about a month after starting Levothyroxine to which I was glad as all my life I had suffered with heavy periods and endometriosis, then I started to blow up with huge amount of water retention which I was given diuretics for and used to spend from 7 am to 2pm sitting on the toilet getting rid of fluid every day, I asked for HRT at 41 yrs but was told i couldn’t have it as i was prone to water retention. I was given anti-depressants on numerous occasions through out my life but they made me so spaced out they really did not agree with me I wasnt depressed I was fed up of how my body was feeling not fed up with life!

Every time I tried AD I felt even worse so I stopped them (which GP was never happy about I think he wanted me so spaced out I would or couldn’t be bothered to complain how i was feeling and thought I would go home sleep all time and leave him alone I feel like suing him for loss of my life as he should of spotted all my symptoms were hypothyroid but he chose to blame everything but, I was never told their were other drugs available for hypo ..anyway on AD felt even worse and lazier on them, I was given several different ones and none of them worked, I tried to explain to the GP what i was feeling was tired, no energy. Aching, brain was haggled, memory was not what it was again this was what everyone felt like its my age get used to it as it will worsen is what he said!

I was only 42ys which isn’t old its quite young life begins at 40 they say mine stopped completely! I was feeling 90yrs old even my mother who was 70 at time had more energy than me,, my voice was deep and husky I couldn’t think straight, I was sent to a psychiatrist and they diagnosed me with ADHD I was put on Dexamfetamine I did feel a bit better I lost a little weight, i could think better and I thought that was what the problem was and was better but still not right, hair was still thinning skin bad and my aches and pains were still happening and getting worse,
I put myself back in a mental hospital as was hearing things again, spent a few days in hospital ate properly and was out with in days I was taken off the ADHD drugs as they blamed them for me hearing things I knew it wasnt them as at times before though I heard things, but was only after being prescribed Levothyroxine not before that! I think was def my under treated hypothyroid. and seemed to be if i was under stress when i lost love ones etc that the voices happened. but the last time it happened and they took ADHD meds off me was in the middle of moving to a new area, I then lost all my energy I was even more brain fogged.

I managed the move somehow with help from a friend or would of still been sitting staring into space , but never un packed in new house as I just couldn’t get out of bed and ached so much my memory was bad I spent a year in bed and eventually made it to a new dr I wrote a list of symptoms, he said it was my hormones and put me on HRT (I had finished periods well over 10 yrs ago and over the hot flushes so think that was a bit late) the HRT made me have more water retention but i had a tiny but of energy I could walk to the shop but was back in bed after 40 mins as was worn out.

I also got sent to a NEW ADHD clinic which took them another year of deciding I could go back on tablets again, I got them but a pro drug Vyvanse, this time which didn’t work as well as old tablets, but they worked for 2 hours so most days but not all days, this gave my mind 2 hrs to sort things out like paper work but i had zero energy to get up etc.. I don’t think I do well on pro drugs…

So another 2 years pass I am now 54yrs old and still struggling with weight, hair getting thinner, aching like a 90 yr old. My back has been causing me vast amounts of problems I lost use of left leg due to sciatica and my shoulder was hurting for no reason, macro tests showed that I had anything wrong, so again I was made to feel it was all in my head, TBH at times I did think of ending it all, if this is all life had to offer what was the point on living a life of pain and staying in beds most days.

I managed to get my ADHD drugs put back to dexampfetamine, yes I could think again so I took to seriously researching hypothyroid and found that I was not the only person feeling this way, Was now freezing cold this was summer and my body temp was constantly under 35.0 and i was shivering in the summer, I thought I was going to die of hyperthermia at times . my blood pressure was extremely low my ears kept popping I couldn’t hear anyone but my self talking, I kept going dizzy I was feeling so ill, my gums were always bleeding and i was getting constant pain in my teeth.

I read on T3 and asked GP who arranged to see an Endocrinologist as she was unable to prescribe T3 for me and she said i would probably benefit from it by my symptoms, At last a GP who didnt think it was all in my head ! Hooray at last 13 years later I get listened to, it took 6 months to see Endo and he said would I like to try T3 , of course I did, he reduced my levothyroxine, which I was 150 at this point to 100mgs and he added 20mgs Liothyronine take 2x 10mgs per day
I woke the next morning really excited about taking a drug that may help me at last, I was not disappointed It took around half an hour to work, I instantly felt so much happier everything went brighter it was like i had been in black and white for years, colours were vibrant, I suddenly had energy I jumped of the bed and didnt screech in pain I felt
free from pain, I was like wow why did no one give me this 13 years ago, why was I left to suffer for 13 years, been put on some serious ADHD tabs dead amphetamines quite high dosage as well 70mgs per day, when all i had needed was T3..
I had also done a genetic gene test whilst acting for the End appointment which the results came back 2 days after Endo had prescribed me T3,, so he had prescribed me on my symptoms not my results…

My results of Dio2 gene test were Deiondinase Iodathyyranine Type II Dio2 (T92A) 225014 Heterozygous variant genotype TA. I am told it means I will feel better with T3 added to levothyroxine…

I must agree with it as since i had T3 added in Dec 2017 I have decorated 3 rooms since taking it, so something is giving me energy and making me feel better I am now not bed bound, I have the occasional back pain but think that is damaged through years of pain, my shoulder pain went completely.. I am a different person now or should i say more like before I became hyperthyroid when i was in my teens as I have spent over 35 yrs of not feeling normal and I’ll I got told I look more relaxed and that I’m not about to kill someone they said i was looking well I had colour at last in my cheeks.

It is unbelievable this tiny hormone made me feel well again..
And more to the point its unbelievable that the GPs ignore your symptoms and that pharma are telling everyone that Levothyroxine works for everyone IT CLEARLY DOES NOT IN MY CASE IT LEFT ME ILL FOR 13 yrs. I have lost my best parts of my life because they state it works for all. I do feel very bitter as I am 54 now and i have not had a good life and my life on Levothyroxine made me sicker…

Please everyone if when on Levothyroxine you feel still hypothyroid still, go and find a sympathetic Endo and get treated with T3 as i wasted my life with GPS blaming my age hormones , depression etc you know the excuses for your illness DO NOT BELIEVE THEM GET YOUR LIFE BACK!

It was all the time me getting the wrong treatment Levothyroxine No way can work for everyone we are all built different. GOOD luck all the who are still trying to get T3 prescribed.

I have a question: my endocrinologist just started me on a low dose of Levo today and has only given me one refill, and I won’t see her until next week. Is this normal for a doctor to do this? I am new on this hypothyroid thing so I just wanted to know.

After reading many peoples comments here, plus I have been on many thyroid forums, and websites, reading about how all of these people just want help…. including myself. I just can’t stand it anymore !!! This is just so frustrating to watch and deal with. This is a silent disease that completely make existance miserable sometimes, even though you can’t see it on the outside. There are SO MANY OF US that are just suffering because doctor’s who think they flippin know it all with their “PHd’s” won’t open their dang minds to look beyond that stupid pill that is supposed to be a cure all!! NOT!

What is it going to take for medical schools to start retraining the doctor’s to not only relearn thyroid/endocrine physiology but also that just because they have a PHd does not make them god and savior, and if they want to truly be as smart and educated as they think they are they would KNOW that and OPEN MIND is one of the most important things you can learn anywhere…. period! LISTEN TO YOUR PATIENTS!!!

Totally agree with your comments. It took 14 years before my doctor said she would try another thyroid medicine. Liothyronine has been a life saver!!

it is the same in the UK as well !

Agree. I was diagnosed with hypothyroidism 2 years ago after feeling tired all the time, and as is the norm they put me on Levothyroxine. Immediately after starting treatment I felt great. For the first time in years I had a spring in my step and an alert mind. It was a wonderful feeling. But I should have known it was too good to be true. That great feeling only lasted a few weeks, then all the symptoms came back. That was 2 years ago, and even though my blood tests show normal levels I have felt like crap non-stop since then. Clearly T4 replacement is NOT the answer, or at least not the complete answer.

I have extreme fatigue fibromyalgia (cause they can’t find anything else), gastroparesis, hiatal hernia, depression, anxiety,s and now heart palpitations. The Drs throw their hands up and use the word hypochondriac. Currently on levoxyl. Oh yeah, 75 lbs overweight and had radioactive iodine in 1981. No one will dig deeper because my labs come back normal. I just want someone to say, “Oh yeah, this is what we have to do to get you feeling good.” I’m only 54 not 84.

I had my thyroid removed 12 years ago (cancer). Was sent home after surgery with a prescription of T4 and a script for a month of T3. Was feeling okay until the T3 ran out. Several days after being off the cytomel, I began feeling horrible. I literally wanted to kill myself. That´s how depressed I was. I went to see my endo (now ex endo) and informed him of the situation and asked him to prescribe T3, which he refused.

I wasn´t happy with his reply and told him that if he wasn´t interested in helping me, that I would have to leave his care and find someone that wanted to help. He began verbally listing all his `credentials`… How he knew better than I did, and that I should be put on antidepressants. I said “hell no”, left his office and never went back to see him. My GP stood up and helped… Was lucky there… I just want to state that doctors need to listen to what their patients are telling them and not assume that you know better of how the patient is feeling than the patient… That time in my life was pure hell…

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