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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  1. Very Frustrated

    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!!!

    • Michael

      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.

  2. K

    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.

  3. Rose

    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…

  4. mary jane

    I tried T3 supplements and they made me miserably hyper. I would never try it again. I found the reason that I felt bad on thyroid supplements was that I had more wrong with me than just being hypo. But visiting thyroid forums made me think it was all my thyroid when it wasn’t.

    But – it’s important to realize that all thyroid supplements have periodic problems with potency and the generic is a big problem because your pharmacy can change suppliers and it will affect you – go with a name brand if you can afford it. There are a couple of options.

  5. Jessica

    I am a 31yr old woman and had my thyroid removed at 29 and somehow I am still very tired very often you might even say it’s too often . Not a day passes that i’m tired

  6. Reenie

    I was always thin, and then was tested for my thyroid. They said I had a goiter. They put me on thyroid pills. I started gaining weight and couldn’t breathe good and my brain felt like it was going fast.More weight gain. 20 years later, they took my thyroid out saying they suspected thyroid cancer because it came back suspicious.

    More weight gain. No matter what I did or do ,can’t lose weight, just keep gaining. I have no energy, depressed, full of anxiety, hormones wacky, losing hair, moody, and more weight gain, feel full even if I don’t eat.

    Just keep gaining weight no matter if I eat or not. I am reading all this about the T3 and wondering if our own thyroid makes T3 that means we need it, so why do they just give you a thyroid pill and no T3. They work together.

    Seems to me, if they don’t give the T3 then you have other symptoms then they have to treat those and they ALWAYS ALWAYS say you have to lose weight. Well, guess what, it was the pills that put weight on me in the first place. And guess what, we NEED that T3 cause our own bodies made it and that means it should be supplemented to us for our bodies to work normally again.

  7. vic

    i have non of the symptoms associated with low active thyroid but have now been given tablets of Levothyroxine. Has anyone been very active before starting medication. Now I feel foggy and under the weather. Help!

    • Gail

      This is to Vic in Merryside: I too had NO symptoms of underactive thyroid. At 65 years old, I could do yard work, exercises, play with grandkids and felt great – no tiredness. Had blood work done and my doc said I had hypothyroid (she couldn’t believe I had literally none of the symptoms except slightly dry skin – especially on my legs). Put me on Levothyroxine six weeks ago and I feel horrible! After 2 weeks, I could barely do any yard work – would have to work for two minutes and sit to get my energy back. The worst has been the past 2-3 weeks when I’ve had awful indigestion – never had the problem before. Today I ached all day, can’t stand the tightness of my bra (feels like a vice around my chest). Saw my doc today so she could take blood to see if the Levo is working. Told her how awful I feel now that I’m on this and she said, “well it’s bioidentical so it can’t be causing problems”. I’m researching natural remedies and will be switching.

  8. Denise
    Triad NC

    I just got diagnosed with hypothyroidism and my PCP just put me on 50 mcg of levothyroxine a day! It’s been 3 weeks and I feel worse than before I was diagnosed!!!!! I’ve gained weight, have terrible headaches, itchy rash on my face, scalp, arms. I’m walking around like I’m numb and in the fog! My legs are achy, and I’m constipated and very sleepy. I tried taking the medicine at night instead of the morning, and I tried taking half the dose, it hasn’t helped, why am I not feeling better and feeling worse? Someone please help me! My doctor keeps telling me that my body will adjust?

  9. Craycray

    I was diagnosed hypothyroid in 2000. The doctor put me on Synthroid. None of my symptoms, which are all the same as everyone here, have started changed. Now on armour thyroid nothing has changed, so I don’t know what to do. I’m exhausted plus all the symptoms listed. Nothing got better. I used to ask my doctor why am I taking synthroid when nothing has changed? No answer.

  10. Denise

    I had a total thyroidectomy about 3 weeks ago…after recovering from the surgery itself, I actually felt better. The problem started when I began the levothyroxine (125) I have been so utterly exhausted and no appetite. I stopped taking it for 3 days…felt better…took half a tablet for 2 days…fatigue and not appetite again. I am so sad that a medication that I must take makes me feel so bad. A friend suggeted that I may have adrenal fatigue and the levothyroxine…just puts too much stress on the adrenals? What does a person do?

  11. Jackie

    If doctors were given the go ahead to treat hypothyroidism patients with t3 added to their levothyroxine after the proper blood tests full panel rev t3 t3 ferratin,vitamin d,not the bog standard nhs test, etc and they were willing to pay that would help struggling surgerys all over the country and if it turned out that they needed the t3 and even paid for their prescriptions at least that would be a start and I think like myself I would pay it would also put a stop from people self medicating and buying thyroid medications on line where it could be dangerous!

    Because myself and everyone else with thyroid complications think it’s because of pricing also there is irrefutable proof that levothyroxine isn’t for everyone and is cruel to offer no alternatives it’s 2017 this should not be happening I took ndt for the first ten years of my life and was always well until it was changed now I suffer like everyone else ! And if you don’t have thyroid issues don’t be quick to assume what they say about levothyroxine is true it’s not ! If the above option was considered I’m sure there would be thousands of hypothyroid patients happier than they have been for years .????????? please help !!!

  12. Debbie

    I had a partial thyroidectomy when I was 19 yrs old due to a goiter. I wasn’t prescribed any thyroid medication at that time because my doctor said the other half of my thyroid was producing enough, When I was 25 yrs old, I had the other half removed due to another goiter. I was then placed on Synthroid or levothyroxine. I have been on levothyroxine for 23 yrs. My doctor has been trying to adjust the dosage for about a year now. I have fatigue, dry skin, weight gain, brain fog, restless sleep, joint pain, brittle nails and hair, and irritability. I just found out yesterday that he is lowering my dose again. After reading this, I believe I need a T3 supplement along with my levothyroxine since I do not have a thyroid gland to produce any thyroid hormones.

  13. Jane

    I am new to this process. Due to Graves disease I took radioactive iodine. Then started on Levothyroxine. Weight isn’t a problem though I am careful. But I have fatigue, brain fog, dry skin, inconsistent bowel function. I don’t feel good! My doctor has lowered the dose of Levothyroxine twice and we’ll see if there’s improvement. There has been no discussion of adding T3 med. I want my old self back.

  14. Helen
    Alberta, Canada

    I have read all this but not gone into the articles yet. I will do that. I am 72; I have been on T4 medication since I was 15 (57 years!!). Only recently, about 2 years ago, did I find a doctor who tested the T3 and found it consistently low, so I’ve been on cytomel since then. All my life I’ve had issues as reported above in the articles – bone wearying fatigue, constipation like you wouldn’t believe, etc. My big worry now is my head and it is worse when I go to bed. It stings, shivers, is in pain though not as a headache. Certain spots in my head feel as if something is stuck there. The feelings are there in the daytime also but more subdued. Is this the inflammatory response from the basic autoimmune condition which doctors will do absolutely nothing for? That is, the autoimmune chronic inflammation has now entered and is attaching my brain? If there is any help anywhere, please let me know. In advance, Thanks so much.

  15. Teal
    Columbia, Missouri

    I had a total thyroidectomy in 1996. For 13 years I functioned well on levothyroxine with a suppressed TSH at 0.01 – 0.1, though I remember feeling oddly fatigued at times. Then, in 2007, my dose was slowly lowered. I began having “flu-like-with-no-fever” symptoms affecting my entire mind and body. My TSH fluctuated from 0.01 to 7.4, my cholesterol began to rise, my hair got course, straight and began falling out and I had moments when I felt like my body was shutting down. My doctors seemed to suggest I was non-compliant with my dosing.

    Unbeknownst to me, I was labeled a “hypochondriac” which only further complicated my health care.

    Finally, in 2016, I convinced my doctor to start me on T3. I have had remarkable results and felt as though I’d been given my life back when my TSH was at 0.1 and normal feeeT4 and freeT3. Then, my doc lowered my dose again to raise my TSH and I am feeling sick again.
    At this time my TSH is 0.4 with free T4 and Free T3 in the low-normal range. Sometimes I feel fine but about 30% of the time I feel like lead, sluggish with brain fog.
    If anything I have a tremendous appreciation for the power of these hormones, but I also have a tremendous concern for the limitations a doctor can have due to prejudice, preconceptions and suspicions and an inability by some to get beyond lab results when communicating with their patient.
    I have lost much of the past eight years of my life.
    Good news: When they found my thyroid cancer, a routine pregnancy test put off treatment for nine months; that baby is about to graduate from Stanford University.

    • JP

      I felt the same way when they added T3 to my regimen. And as time went by it got worse. I started getting severe migraine with aura dizzy spells and sometimes it felt like I was having a stroke although I didn’t. My body is way to sensitive to t3 and I can’t take it. I was on Name brand Synthroid for 30 years and was fine until they kept upping my dose and added t3.

  16. Isha

    I have been living in US since 2013. Thats when i started putting on weight and feeling tired all the time.
    I thought its just the home sickness. I used to weigh 105 lbs and i am 5 feet 1 inch tall. I started going to gym regularly and eating healthy. No change! I tried to do this for 6 months or so and then went to the Doctor, she told me its PCOS and put me on birth control medication. No change! More weight gain, tiredness, hair loss,constipation. I changed my doctor till then i was 140 lbs. She said everything is fine (she thought so). She said continue taking birth control. 2 years passed by. My condition worsened. I now weighed 165 lbs and i have tried getting a personal trainer eat healthy. Follow all the no junk nothing diet.

    No change! I changed my Doctor again twice. Same! Then in 2016 i changed my Doctor again and she did my thyroid test. She said she will put me on Levothyroxine and it should help me get back to track. No change!!!!

    Its one year i have been taking Levothyroxine. No change in my symptoms.

    Why is it so hard for Doctors to understand that there is something wrong and look into this. It was the 5th Doctor that i had changed that i got to know i have hypothyroid. Other never tested me for that. So symptoms are all that point to thyroid. I never knew this till i got to know i have thyroid.

    Can someone please help me and suggest some Doctor in the Rochester,NY area or anywhere nearby who actually can see whats wrong and why my T4 levels are in range and i see no change.

    Please Help!

    • Terry Graedon

      Isha, TSH levels may be more telling than T4. You need a doctor who will look at how you are feeling as well as what your tests say.

  17. Crystal
    Waldorf, MD

    I had thyroid surgery in 2007 I had a goiter and they removed the goiter and my right thyroid. My doctor told me that I would be on the medication the rest of my life. Before my surgery I had mood changes unhappy one day sad another or crying, I had out flashes and my hair came out at the top of my head and my stylist suggest that I take the prenatal pills to grow it back and it did. After surgery I felt a good change in me then a couple months later, I was back feeling depress and irritable. My doctor had tool me off my medication after surgery then when I told him how I was feeling he put me back on the synthorid and then off again now I am taking a antidepressant and I really don’t think I need it. I need to be put back on synthorid even if my test comes out normal. I been on almost every antidepressant you can name Lexapro ,Paxil Depakote, Zoloft, Cymbalta. Lately I have been feeling very tired, no energy at all. Somebody pleas help me

  18. CJ

    I had goiter since childhood and my TSH level come out normal. By the age of 22, the symptoms is kind of full blown, that it impacts my study in dental school. No one in my family had such illness and it took my years (with Levothyroxine) to actually feel lesser joint pains, dry skin. However, I had difficulty to accept that I have hypothyroid and it affects my studies profoundly that I was later diagnosed having Major Depressive Disorder, and my life turns upside down.

    I was started on multiple antidepressants and feel super sluggish, super sleepy and fatigue despite having enough rest. I have changed my antidepressant many times to actually lessen the memory problem and fatigue but it does not seem to improve. I begin to realize last month that my current symptoms seem to remind me of the symptoms of hypothyroid before i was diagnosed. I took TSH blood test and usual it came out normal. This is just driving me mad. I can’t afford to risk my current study (I have drop the previous degree), and start from zero again. I’m 28 but act like my 60+ year old mother.

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