Cognitive Impairment & Thyroid (what routine tests miss)

Cognitive Impairment & Thyroid (what routine tests miss)

The number of people living with cognitive impairment in the United States is equal to twice the population of New York City. ~Centers for Disease Control and Prevention (CDC)[1]

Written by Raphael Kellman, MD

You are living with brain fog. You feel that something has changed in your brain, and you are exhausted and lacking energy. Maybe you’ve noticed memory impairment or confusion or lack of focus. Perhaps there are gastrointestinal issues. Or fatigue, anxiety, even depression. Sound familiar?

New research shows that there are multiple interconnected factors that lead to both a healthy or unhealthy brain state. This new research shows that there’s an answer.

Scientists have identified Non-Thyroidal Illness Syndrome (NTIS) as one cause of low thyroid. In NTIS, the problem is not the thyroid itself but in the signals coming from the hypothalamus and the pituitary gland in the brain. In NTIS those signals are diminished. It’s as if the body is going into low gear. This diminished communication results in a thyroid that isn’t producing adequate hormone, and this in turn leads to hypothyroid disease. This occurs in states of protracted health issues such as depression, anxiety, gastrointestinal and microbiome dysfunction or chronic inflammation.

The problem is that routine tests can miss the cause of NTIS.

Scientists have found that the TRH Stimulation test is able to detect NTIS even when routine thyroid tests come back with “normal” results. The TRH Stimulation used to be administered routinely but for various reasons and for lack of appreciation of deeper testing, it’s been limited to research centers.

NTIS can occur in many chronic illnesses, including:

  • Chronic anxiety
  • Depression
  • Colitis
  • Chronic inflammation
  • Chronic microbiome dysfunction (Note: Gut issues, including previous overuse of antibiotics or PPI’s usually indicate chronic microbiome dysfunction)
  • Dementia
  • Alzheimer’s
  • ICU patients
  • Other degenerative disorders

Again, this condition is not uncommon, but lab results can be elusive. Sometimes thyroid lab tests can appear completely normal.

NTIS can only be properly diagnosed through the TRH Stimulation Test.

TRH Stimulation Test

The TRH Stimulation Test is a different, even controversial, test to evaluate thyroid function. Once the gold standard for detecting low thyroid output, this test was abandoned in favor of the routine blood tests that measure T3, T4, and thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Produced in the hypothalamus, TRH, or thyrotropin-releasing hormone, acts on the pituitary to stimulate TSH production. Injecting TRH to stimulate the pituitary allows physicians to see what’s happening in the pituitary gland.

I perform a stimulation test using thyrotropin-releasing hormone (TRH) when I suspect the presence of hypothyroidism in patients, especially older patients, with “normal” TSH levels. The TRH stimulation test is only to be conducted under the direct supervision of a physician. The test involves administering a small amount of TRH intravenously and measuring the changes in TSH level.

A Look at Thyroid Medication

Low levels of T3 thyroid hormone, within the normal range, have been found in patients with Alzheimer’s Disease AD.[2] In 2018, a cross-sectional, case control study evaluated 40 outpatients with mild to moderate AD and 20 normal controls. The patients with AD had worse cognitive function and lower Free T3. Researchers suggested the potential efficacy of adjunctive T3 treatment.[3]

A large number of patients arrive at my office already taking a thyroid prescription, most often Synthroid or another T4 only medication. Unfortunately many of these people haven’t gotten better even though they’ve been taking thyroid medication for years, even decades. After extensive testing, I frequently find there is a need for T3 supplementation as well as T4.

A very quick thyroid hormone lesson will help to explain the issues a bit better. The thyroid secretes 2 hormones that regulate the metabolism and energy levels of the body: triiodothyronine, known as T3, and thyroxine, known as T4. Only 10% to 20% of the hormone produced by the thyroid is T3, the active form. T4 is an inactive hormone that must be converted to T3 before the body can use it.

Conventional medicine tells us that T4 is the best choice medication because it is the one the thyroid gland creates itself in largest quantity. This model ignores the fact that there are many very common conditions that actually block T4 from converting to T3. Inflammation, stress, poor diet, digestive conditions, nutrient deficiencies, liver dysfunction, certain medications, or excessive alcohol use can all interfere with this conversion.

The Thyroid Gland & Cognitive Function

Thyroid status has received considerable attention over recent decades as a potential risk factor for cognitive impairment. This topic has been a hotbed of debate as conflicting results have emerged from research to date.

In 2018, a clinical review found that clinical and subclinical hypothyroidism as well as overt hyperthyroidism in middle-aged and elderly adults are both associated with decreased cognitive functioning.[4]

In a recent study utilizing functional neuroimaging, subjects with subclinical hypothyroidism had abnormal fMRI results in the frontal brain area with impaired verbal and spatial working memory. This study showed that a 6-month treatment with thyroid hormone replacement medication can improve memory impairment and reverse the altered neural activity network.[5] An F-18 FDG PET/CT study suggested that a cortical dysfunction in anterior cingulate and frontal lobes may affect serum values of TSH in Alzheimer’s disease patients.[6]

In a 2018 study titled Cognitive Status in Hypothyroid Patients Before & After Attainment of Euthyroid State, researchers assessed the cognitive status of newly diagnosed overt hypothyroid patients compared with euthyroid controls. They found a significant overall improved performance in hypothyroid patients after they attained a euthyroid state with thyroid hormone replacement treatment.[7]

That these types of cases are largely reversible with proper thyroid diagnosis and treatment is of considerable importance. A reasonable approach would be to conduct a full evaluation of thyroid status in every case of cognitive impairment.

About Raphael Kellman, MD

Raphael Kellman, MD, graduate of Albert Einstein College of Medicine, pioneered a groundbreaking new branch of medicine and healing, seamlessly integrating holistic and functional medicine with his visionary understanding of bacteria, the world and nature, the root of who we are and its connection to health. Founder of “Microbiome Medicine”, Dr. Kellman is recognized internationally as a leader in the field of microbiome medicine, and lectures frequently on the topic.

As medical director of the Kellman Center in New York City, Dr. Kellman specializes in thyroid disorders, gastro concerns, chronic fatigue, fibromyalgia, autism, anxiety, Lyme disease, cancer treatments, infertility, weight management, and unexplained malaise.


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About Dana Trentini

Dana Trentini founded Hypothyroid Mom October 2012 in memory of the unborn baby she lost to hypothyroidism. This is for informational purposes only and should not be considered a substitute for consulting your physician regarding medical advice pertaining to your health. Hypothyroid Mom includes affiliate links including the Amazon Services LLC Associates Program.


  1. I also suffered with some of your issues. The main thing that helped my symptoms was to go on a gluten free diet and to take a liquid iodine supplement. Reduce sugar in your diet as much as possible and mild exercise such as walking 20 minutes a day. I had brain fog,trouble with vision, and slurred speech. After a few months my symptoms were gone and I was able to loose some weight.

  2. I suggest that everyone take a look at a book by Anthony William, Medical Medium Thyroid Healing. If the so called medication is not working, then there may be some other ways to address it. I for one will be taking 600 mg of Ashwagandha and starting on Red Clover in my morning smoothies. Our diet and our environments are toxic and there is build up. We have to be pro active in our health. A pill is not going to cure you. It may produce temporary relief, while you find your body’s path to healing. After reading some threads on here, I will not be taking the medication prescribed. It appears to be barely effective.

  3. Maria joplin says

    Extreme fatigue following after any exertion labs are “normal”. What additional test should I get back to bring myself again

  4. Brenda Robbins says

    If a person has had thyroid surgery because of goiter and been diagnosed with hashimoto thyroid, do I need more than levothyroxin. I started with tinnitus after this surgery and I am thinking the absence of harmones might be reason. Thank you for your time.

  5. I’ve been taking levothyroxine for 44 years and I can count on 1 hand the so called good days I’ve had. I suffer with anxiety, weight gain, hair loss, fatigue, brain fog, fibromyalgia etc. seeing different doctors over the years they would adjust my meds once in awhile, but I’ve been on the same dose for probably 7 years now. I try to exercise but my whole body aches terribly bad and I have neuropathy in my feet so it’s painful to walk, which I used to love to go for walks. Doctors today will absolutely not listen to their patients needs. It’s all about money now. Ive been trying very hard to lose weight because I’m overweight and I have lost 38 pounds but it doesn’t seem to be helping much as far as how I feel even though the pounds are dropping off. I pray that doctors will be more sufficient in doing these special tests on patients with thyroid disease. Good luck to all those who suffer daily with this health problem.

  6. Lily Rice
    I habe had Hypo. . For many many years along with ALL the symptoms. .However, my experience as a Large woman Doctors always told me “lose weight” it will all go away…..It did not. …Have been on Levothyroid for close to 20 yrs always at the very lowest end of normal….Still it helps, One Doctor actually listened to me…..

  7. Cheryl Pitts says

    I Belueve I May Have This Issue With My Memory And It’s Getting Worse And very frustrating anyone got any suggestions on how to get a doctor who will do these tests for someone on Medicare and Medicad?

  8. Thank you for sharing this interesting article. I have question a after reading it. Are they suggesting T3 hormone replacement therapy? I’m curious as a 62 year old who has been on levothyroxine for 22 years. I’ve been monitoring my TSH, Free T3 and Free T4 levels. I function better when my TSH is on the low range and T3 is on the high range. Currently, my T3 is in the lowest range of normal. Dr says that’s fine. I don’t feel as good as I used to when my T3 was higher. Any suggestions?

    • Logan Smith says

      Switch from Levo to Armour Thyroid. Has definitely helped me out – still suffer from majority of symptoms (fatigue, brain fog, anxiety) but u has helped control these a bit. Armour thyroid is derivative from a pigs thyroid and releases both T3 and T4. Try it out

      • I switched from armor to natur-throid to NP thyroid while taking levothyroxine and I feel 1000% better than I did taking just synthroid or just levothyroxine by themselves. I lost abl to loose and keep 20lbs off. I changed by diet to NSNG (no sugar no grain) and I lost a total of 60lbs. And I have no bloat, heartburn, gas, swelling in my face or legs or neuropathy. If I fall off the wagon everything comes back. Diet is a major culprit to these symptoms. I’ve done WW, keto, Atkins, etc. And this pill combo and way of eating is the ONLY thing that has worked for me.

  9. I was diagnosed with hypothyroidism a year ago. I have been on levothyroxine 50. I have lots of anxiety and memory problems.. I eat healthy most of the time. I have weight gain .I exercise, but its really hard I have lots of muscle aches. I have hair loss and fingernails and toe nails crack and even fell off. I take vitamins they help some. Is Hypothyrodism the cause of all this,?

    • Yes unfortunately thyroid affects everything I have been on Synthroid since I was 22yrs Old hypothyroidism affects hair growth nails menstrual cycle it really affects so much

    • Cheryl Pitts says

      Yes It Is, and More, now if we could just get the Medical Professionals To Get On Board With All These Studies We All Might Be Better Off Now Doctors Only Look For Their Next Dollar So They Keep You Coming Back Instead Of Cure You☮️🤩

    • Mamata Sudeepsaami says

      Hi.. I m from India. I have been living with hypothyroid from past 20years. Many of you told about muscle pain during exercise and after exercises. Using of ginger in everyday diet helps you reduce muscle pain and weight training is must in 3days a week.

  10. I have thyroid issues for years depression and anxiety. What do I look to tell the doctor for a test

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