Unfortunately a misdiagnosis can happen in the management of hypothyroidism and other thyroid disorders. If you go to a doctor with hypothyroid symptoms, you may be given replacement hormones without first determining what’s causing your thyroid issues.
Or, if you have hypothyroid symptoms but your lab tests are normal, your doctor may not realize you’re experiencing thyroid issues in the first place. You may even receive treatment or medication to deal with the symptoms you’re experiencing—like an antidepressant to address depressive symptoms—but you won’t receive anything that will help your thyroid disorder.
The problem with this approach is that thyroid physiology is complex.
The production, conversion, and uptake of thyroid hormone in the body involves several steps. A malfunction in any of these steps can cause hypothyroid symptoms, but may not show up on standard lab tests.
All cases of hypothyroidism do not share the same cause—and, as you might guess, they require different treatments.
In this article, I’ll present five patterns of thyroid dysfunction that may not show up on standard lab tests. If you have one of these patterns, your thyroid isn’t functioning properly and you will have symptoms. But depending on the tests your doctor runs, you may not get a diagnosis of hypothyroidism; and, if that’s the case, you won’t receive the treatment you need.
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A standard thyroid panel usually includes TSH and T4 only (while some panels will also look at free T3, free T4, and check for thyroid antibodies). The ranges for these markers vary from lab to lab, which is one of two main problems with standard lab ranges. The other problem is that lab ranges are not based on research that tells us what a healthy range might be, but on a bell curve of values obtained from people who come to the labs for testing.
Now, follow me on this. Who goes to labs to get tested? Sick people. If a lab creates its “normal” range based on test results from sick people, is that really a normal range? Does that tell us anything about what the range should be for health? (For more on the problems with standard lab ranges, watch this great presentation by Dr. Bryan Walsh)
Are you experiencing hypothyroidism symptoms even though your lab work is normal? You may still have hypothyroidism, though it may not show up on standard labs. Check out this article for more. #functionalmedicine #chriskresser
The Five Thyroid Patterns
1. Hypothyroidism Caused by Pituitary Dysfunction
This pattern is caused by elevated cortisol, which is in turn caused by active infection, blood sugar imbalances, chronic stress, pregnancy, hypoglycemia, or insulin resistance. (1) These stressors fatigue the pituitary gland at the base of the brain so that it can no longer signal the thyroid to release enough thyroid hormone. There may be nothing wrong with the thyroid gland itself. The pituitary isn’t sending it the right messages.
With this pattern, you’ll have hypothyroid symptoms and a TSH below the functional range (1.8 – 3.0) but within the standard range (0.5 – 5.0). The T4 will be low in the functional range (and possibly the lab range too).
2. Under-Conversion of T4 to T3
T4 is the inactive form of thyroid hormone. It must be converted to T3 before the body can use it. More than 90 percent of thyroid hormone produced is T4.
This common pattern is caused by inflammation and elevated cortisol levels. T4 to T3 conversion happens in cell membranes. Inflammatory cytokines damage cell membranes and impair the body’s ability to convert T4 to T3. (2) High cortisol also suppresses the conversion of T4 to T3. (3)
With this pattern you’ll have hypothyroid symptoms, but your TSH and T4 will be normal. If you have your T3 tested, which it rarely is in conventional settings, it will be low.
3. Hypothyroidism Caused by Elevated TBG
Thyroid binding globulin (TBG) is the protein that transports thyroid hormone through the blood. When thyroid hormone is bound to TBG, it is inactive and unavailable to the tissues. When TBG levels are high, levels of unbound (free) thyroid hormone will be low, leading to hypothyroid symptoms. (4)
With this pattern, TSH and T4 will be normal. If tested, T3 will be low, and T3 uptake and TBG will be high.
Elevated TBG is caused by high estrogen levels, which are often often associated with birth control pills or estrogen replacement (i.e. Premarin or estrogen creams). To treat this pattern, excess estrogen must be cleared from the body.
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4. Hypothyroidism Caused by Decreased TBG
This is the mirror image of the pattern above. When TBG levels are low, levels of free thyroid hormone will be high. You might think this would cause hyperthyroid symptoms. But too much free thyroid hormone in the bloodstream causes the cells to develop resistance to it. So, even though there’s more than enough thyroid hormone, the cells can’t use it and you’ll have hypothyroid—not hyperthyroid—symptoms.
With this pattern, TSH and T4 will be normal. If tested, T3 will be high, and T3 uptake and TBG will be low.
Decreased TBG is caused by high testosterone levels. (5) In women, it is commonly associated with PCOS and insulin resistance. Reversing insulin resistance and restoring blood sugar balance is the key to treating this pattern.
5. Thyroid Resistance
In this pattern, both the thyroid and pituitary glands are functioning normally, but the hormones aren’t getting into the cells where they’re needed. This causes hypothyroid symptoms.
Note that all lab test markers will be normal in this pattern, because we don’t have a way to test the function of cellular receptors directly.
Thyroid resistance is usually caused by chronic stress and high cortisol levels. It can also be caused by high homocysteine and genetic factors. (6)
Thyroid Treatment Depends on the Right Diagnosis
The five patterns above are only a partial list. Several others also cause hypothyroid symptoms and don’t show up on standard lab tests. If you have hypothyroid symptoms, but your lab tests are normal, it’s likely you have one of them.
Not only do these patterns fail to show up on standard lab work, they don’t respond well to conventional thyroid hormone replacement. If your body can’t convert T4 to T3, or you have too much thyroid binding protein, or your cells are resistant, it doesn’t matter how much T4 you take; you won’t be able to use it.
Unfortunately, if you have one of these patterns and tell your doctor your medication isn’t working, all too often the doctor’s response is to simply increase the dose. When that doesn’t work, the doctor increases it yet again.
As I said at the beginning of this article, the key to a successful treatment is an accurate diagnosis. Without understanding precisely what’s causing the problem, you may end up with a treatment that isn’t well-suited to your specific situation.
The good news is that, once the correct diagnosis is made, patients respond very well to treatment.
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Hi Chris. Thanks for the great info. I have had nearly every symptom on the extensive hypo symptom list for 20 years. Labs, which includeTSH, T3 and 4 as well as Free T3 and 4 are almost always normal, with an occasional low normal over the years. My mom was hypo with nodules, as well as possibly her mom. I have been treated with the smallest doses of Armour in the past but reacted horribly to it. I also have AF, low cortisol in morning and high at night. I also have MTHFR, Lyme and Epstein-Barr and I think the unresolved AF is what made my reaction so severe. I meet the criteria on many of the 5 you have listed above. My question is, can any of my health issues be contributing to the false negative thyroid results at all? Are there any further tests you could recommend to get a more accurate answer? I am absolutely miserable. So tired of being sick and tired, bloated, anxious, overweight and watching my hair fall out. Thanks.
I’m 41 years old and im sufre ring from high TSH and high testosterone and have suffered in the past from ovarían cists, Im not currently on any medication yet. Everything that I’ve read that says that hypothyroidism caused by high testosterone caused by PCOS or even just hypothyroidism caused by high testosterone will show a normal TSH and T4 but that is not my case; all my thyroid test came back normal only my TSH is high and my testosterone. Have you come across this scenario? What would be the cause?
Chris,
I am an active 55 year old female who has always enjoyed good health. Over the past year or so, I have developed a lot a joint pain in shoulders, neck, hips, knees. So much pain it has affected my tennis and exercise classes. ( heck just getting my sports bra on and off takes my breath from the pain). Even if I get through the classes, the recovery of the next two days makes me feel like an old lady. I can hardly get up and down. I went to a rheumatologist, he ordered a thyroid ultrasound. I learned that I have several thyroid nodules, and in fact only have half of a thyroid. Referred to an endocrinologist, my blood work (TSH and T4 ) are normal. They did not do a T3. Anyway, they just told me to monitor it and come back in a year. I didn’t really complain about the arthritis to the Endo because I never related it to thyroid. IS IT related to thyroid??? What is the best most comprehensive next step?
Thanks for this very interesting discussion. I’m 61 and have been on 300mcg of a synthetic thyroid supplement since a demi thyroidectomy in 1998. Despite this massive dose I am frequently exhausted, have extremely dry, ridged nails, joint pain, and tinnitus. My concern at taking such a large dose has always been quashed by the medical profession however my cholesterol has now reached unacceptably high levels and I am losing bone density, despite an excellent diet, moderate excercise and the fact that I’m not at all overweight (5ft 2 & 8st 4lbs).
My recent test results showed TSH right up at the top end of normal, & T4 & T3 both at the lower end of normal. Ferritin, & Vit D were low &, white blood cells and neutrophils were below the normal acceptable range. Everything else was fine.
I’ve never participated in something like this before but I would be grateful to hear your comments on my situation. Thanks.
Hello Di,
Have you had your Adrenal glands & DHEA levels tested, not by your GP as they only offer the Synacthen test for the adrenals ( this only shows up anything if you have addisons disease).
The reason I say that is your on a high level on synthetic thyroid but it doesn’t sound like it is being taken up properly. Have you ever tried other forms of thyroid medication like the natural product – some people feel a lot better on that.
Best wishes
Debbie
1. YOU NEED TO SEE A GENERALIST FIRST. You need to have all of your symptoms evaluated. I went to three endocrinologists all gave the same response after seeing the same test results. Unfortunately, the medication prescribed I was allergic to. They all prescribed a higher dosage, which made the reaction even worse. I finally returned to see a generalist doctor at a free clinic. The first response was… you are allergic to the meds. I was put on the natural alternative and am now “normal”. (After one month.)
2. HAVE YOUR OWN TESTS performed. I used the internet to find a lab and had ALL the tests done. (applied costs on taxes). When I showed to a general doctor who also was a holistic doc. I learned that it was more than hypothyroidism.
The tests cost about $200. Including the saliva, and hair test. Blood and urine tests were done locally.
3. Trust yourself, research, and ask questions. If not, write them all down, and give the list to a medical advisor.
4. By the way, between the medicine and silkense volume shampoo, my hair is growing back.
I forgot to mention in my previous post that my T4 was 1.2 & TSH was 1.75
I’m a 37 year old male who has been type 1 diabetic for 21 years. I’ve also been recently diagnosed with Hashimoto’s. I was told that I wouldn’t be a candidate for synthetic thyroid treatment until it progressed to hypothyroidism despite having fatigue, muscle pain, joint swelling, weight gain, & depression. The mention of hypothyroidism related to pituitary dysfunction struck a chord with me due to the fact that I have endured several severe hypoglycemic episodes over the years. I was wondering if you could give any guidance with how to proceed, and possibly refer me to someone in or near Las Vegas?
Hi there, I found your article very interesting. I am a 29 year old female, and I synthroid until 18 when the endocrognologist took me off to see if my thyroid would kick back in, and it did, supposedly, but I have been suffering with fatigue since. I have had my thyroid checked yearly, but it always comes back as normal. My bloodwork has shown that I am deficient in Vitamin D and B12. I also have enlarged red blood cells, which the hematologist never found an explanation for. I also had problems with hypogyclemia as a teenager. I also have had migraines since I was a child. I have GERD, IBS and lactose intolerance, and a history of endometriosis. I also have red blood cells in my urine, which the urologist can not pin point a cause for. For over a year now I have had a severe case of plantar fasciitis which is not responding to treatment. I read about how people with hypothyroidism can develop connective tissue disorders like plantar fasciitis. I feel like I have been passed around from specialist to specialist but no one can seem to fix me. I have been to the neurologist, gastroentrologist, gynocologist, podiatrist, hematologist, urologist, chiropractor, ENT.
Between the foot problems, frequent migraines, fatigue and some weight gain I was concerned something was wrong with my thyroid, so I scheduled an appointment with and endocrinologist. I referenced your post, but she “doesn’t believe that you can be hypothyroid if you have normal lab results”, and she told me there is nothing she can do for me.
Free T3 was 3.1
TSH was 0.67
Free T4 was 1.1
Thyroglobulin Antibodies <20
Thyroid Peroxidase Antibodies <10
I know you aren't taking new patients right now, but any advice you can give would be most appreciated!
Great articles. My name i Darek i’m from Germany i am specially interested in the 5. point. What may I do if in case of thyroid resistance ? How may i renew my receptors to be able to absorb more ft3 and ft4 ? Besides of reducing stress in my life. I am suffering for a long time actually and i am giving armour a chance know. I would be really glad for an answer.
Darek,
I am in Germany, too. I posted to ask for confirmation of what my levels were in German, lol.
Just wondering if you were able to find a doctor that listened to you. I cannot find anyone in Frankfurt. I have “normal” levels but I have a high level of TPO Antibodies. But I have an assortment of hypo symptoms. Worst is zero energy and weight gain of 9kg in the last year. I have gained tons of weight in my stomach. I cannot lose a single pound. Nothing. A year ago, I could do this with one small change if I needed to. I am irritable and have no patience. My hair is breaking all the time, I am cold, I am short of breath, I have allergies and asthma I didn’t used to have. And I am just exhausted all.the.time now which is a big change and gotten progressively worse for me in the last 3-6 months.
I have the same trouble as I always do here. They want to do every test and it takes me about 8-12 weeks between appointments and then they want to schedule a separate appointment to discuss the results and meanwhile, my life is falling apart because I can barely function and deal with work, my son, get any exercise. Anything. And in the last couple months, I have gotten depressed. My doctor was trying to tell me I was always depressed and I was like, “No, I was not always depressed.” How can I have been a person that had fun, participated in and appreciated my life, enjoyed every minute with my son, laughed all the time be depressed?! NOW I feel depressed. I cannot get anyone to listen to how my entire quality of life has disappeared.
I am starting to really dread the coming years which is really bad. If I can’t get this resolved and I just continue to gain weight and be tired all the time? And don’t have energy to do anything with my son? But I don’t know who to talk to. No one is listening.
Tina
Great article. I’m glad someone has their head on straight! Thyroid resistance sounds like the worst of all these conditions–is their any treatment? Can these conditions ever be fully corrected?!
Great post. Can you point us in a good direction for more information on #5: Thyroid Resistance? Would like more information on how this one would be diagnosed and/or treated.
Thank you so much! After reading this article, I printed a copy for my Doctor. We discovered I have Thyroid resistance due to chronic stress. We are working on adjusting my dosage and lowering my stress and supporting my adrenals. I feel so hopeful!
After years of working with the :best” in the world (D.C.), I still was mis prescribed. pay for the tests from your pocket. do your own research. and ask for second, third, and fourth opinions. Try to find a doctor who listens to ALL of your ailments. After looking at my blotchy calves. I was told that I was allergic to the synthetic thyroid medicine. and I needed to go to Armour thyroid. Drs get kick back from Abbott labs thats why they prescribed the synthetic. I also found out it was my adrenal gland as well affected. Consider looking for a doctor that is an MD as well as a homeopathic.
you know you……. trust yourself.
Good luck with finding these docs. The one’s that seem to know this stuff, interrupt test properly, etc seem to be a precious few, (and or) charge outrageous fee’s. And that doesn’t mention the cost for the testing, supplements, trial and error, and so on.
Perhaps it would be useful if people start making recommendations in their area’s of these “rare” docs. List their experiences. As Chris said the immune system is very complex. It’s very difficult for a layman to sort through all this clutter by theirself.
My daughter has had problems since she was in high school with her periods, very severe cramps. She seems to me to have symptoms of mild hypothyroidism, very sluggish and fatigue. At times, we thought maybe she was hypoglycemic. Nothing has ever tested out. She is 30 now and experiences infertility and yeast infections and bladder infections. She did get pregnant after 4 rounds of AI. Her tests show no signs of hypothyroidism but I am not convinced. I have hypo and hyperthyroidism in our family on both my mother and fathers side. My daughters doctor says her tests are fine. She is not fine and cannot get pregnant. Where do we go to find a doctor that will treat her old school? Should she go to a nutritionist? I am thinking this could be the reason she isn’t getting pregnant. In 8 years and 10 AI’s she has had one pregnancy. Any advice?
My TSH shot up through the roof and I was heading into thyroid storm. Be very careful when playing with the thyroid.
I am sure my thyroid issue is an autoimmune and felt I could heal through diet and natural supplementation, did not work. Just my own personal experience.
We really need to be very cautious when dealing with the thyroid. I went off off of my levothyroxine cause I felt I was feeling betterwith special focus on diet. My TSH ahot through
I have number 1 elevated cortisol levels from being pregnant. I have all the symptoms of hypothyroidism but all my test come back great except for my cortisol and B12 levels. I felt as if my doctor blew me off, she stated we would watch it. I definately feel different sometimes I have no energy and other times I feel extremly energtic, but not good energy. I never feel normal. What to do?
OK, Let’s cut through this mess.
1. What tests should be taken to determine the type and severity of hypothyroidism?
2. Is there a list of doctors that could act as advisors?
Every Endocrine doc I have seen just looks at former tests. I paid out of pocket for the 4 X a day saliva test. Then they started to take me seriously.
I have been seen by 3 of the best docs in the world when I lived in the Washington DC area.
The Synthetic stuff makes me higher than a kite after one dose. I am now living out of my truck and on food stamps because this illness has caused me to lose DoD contractor jobs. I need help! I am tired of being mollified and patronized by young and older male doctors and older women doctors, as well as LPN and interns.
So again what tests should I take and how do I find a doc that will correct my situation quickly.
thanks for being there
My husband is 66 years old and was diagnosed with a tumor on his pituatary gland about 22 years ago. He seems to have all of the symptoms that you describe in the 1st dysfunction. They just recently tested his thyroid and of course the test showed nothing. He is on a lot of medications including testostorone injections, anti depressants, acid reflux medicine and sleep medicine just to name a few. He has been tested for everything under the sun and no one has been able to really help him. Physically he is in great shape. Although it is a struggle he works out just about everyday. He recently has had a lot of trouble urinating and his bowels are irregular and have been for a while. He will be seeing his doctor next week. Do you think we should bring you article to the Doctor?
I am 43, normal weight, reasonably healthy eater, work full time. I have a problem with my spine that restricts me from a very high level of physical activity, but I am not ‘dormant’ and I move about as much as I can every day, moderately active. I have had serious depression in the past dealing with a particular problem, and overcome this with CBT and I am now good at managing any mood difficulties. For the last four years I have noticed a deterioration in my energy levels and general feeling of fitness and well-being. My mood also deteriorated, and for the last 12 months depression crept up on me and I am on antidepressants again for the last three months, although this feels very different to previous depression – there is nothing I am depressed about, I just feel all the symptoms. My mood has improved, however. But I am exhausted so much of the time and I cannot trace it to anything in my lifestyle – I seem far more tired than I should be for my age and health and activity. I have never needed more than 5-6 hours sleep, but in the last 12 months seem to need more and more, and after significant activity fall asleep within minutes and can sleep for 15 hours at a time, so deeply that I miss alarm clocks and people trying to wake me – this is absolutely out of character for me. Even after little or moderate activity I am physically exhausted, not necessarily sleepy, and have to sit or lie down. My concentration is appalling, although a bit better since taking the antidepressants. I am always freezing cold, with cold extremities and cold skin all over most of the time – I wear layers and layers of clothes whilst those around me are in shorts and t-shirts. In the last 3 months I have started having headaches, and I have never suffered from headaches.
I have had blood tests and I have low iron and now take an iron supplement and have that monitored frequently. I also have had thyroid blood tests, and they are in normal range. Every female on the maternal side of my family has under-active thyroid, my mother, her sister, my grandmother, and 4 female cousins. My GP said I have raised TSH but normal thyroxine.
I feel like a fraud when I talk to the GP about how I feel, because I am told ‘everything is normal’, and especially because I had depression previously and I think GPs automatically think it can account for everything, whereas on this occasion I feel like the depression is a symptom of something else, rather than is the central problem.
I don’t know what to do, but I am becoming unreliable and I think my job might be at risk.
I would actually like to think this is not a thyroid problem and work out what else it might be, but I am running out of explanations. I don’t know how to proceed. Thanks for any advice