Main navigation

Thyroid Hormone Replacement: Part I

Thyroid Hormone Replacement: Part I
pexels.com/fotografierende

I commonly see hypothyroidism and the need for thyroid hormone replacement in my patient population.

Our body’s hormonal symphony requires balanced thyroid hormones. The thyroid gland, a butterfly-shaped hormone at the base of the neck, builds these hormones. This gland responds to stimulation from the hypothalamus and pituitary glands, which are located in the center of the brain.

Thyroid hormone production and signaling

We all know of the thyroid-related pituitary hormone TSH. This is short for Thyroid Stimulating Hormone. Under the influence of TSH from the pituitary, the thyroid gland begins to assemble thyroid hormone.

Thyroid is built upon the amino acid tyrosine. Enzymes in the thyroid gland then add four iodine molecules. The bloodstream circulates thyroid hormone throughout the body.

Every cell has a receptor for thyroid hormone, so it is pretty important for all of our organs and tissues.

You may be familiar with the hormone T4. This is shorthand for the tyrosine molecule (T) with four iodine molecules attached. T3 has a similar arrangement, but with three iodine molecules.

  • T4 is the amino acid tyrosine bound to four iodine molecules
  • T3 is the amino acid tyrosine bound to three iodine molecules
  • Reverse T3 is the mirror image of T3. It lacks a different iodine molecule from T3, and inhibits the activity of the thyroid receptor.

In general, it is thought that the T4 has little to no biologic activity. The vast majority of thyroid hormone activity is through T3, the active form. I review the biologic and clinical effects of thyroid hormone here.

Reverse T3 (RT3) is the doppelganger of its mirror image T3. It is T3’s evil twin; it is the Jekyll to the T3 Hyde.

When the body is healthy, the T4 converts to its active form, T3. Optimal levels of T3 allow the body’s metabolism to churn along nicely.

In time of stress, inflammation, or starvation T4 converts to RT3. With higher levels of RT3, our body goes into hibernation mode.

Practical strategies to measure and modify thyroid hormone

The purpose of this post is to offer some practical strategies to help you to work alongside your doctor to correctly manage this critical hormone. To understand optimal thyroid replacement, we will first need to review the concept of a negative feedback loop.

Our body utilizes negative feedback in several systems. Thyroid function and feedback explain this most clearly.

This is the general relationship between thyroid hormones and TSH:

This relationship is maintained through negative feedback, which we will cover later in this blog.

Hypothyroidism typically presents with low free hormones and an elevated TSH, as shown in the diagram above. Here we see negative feedback in its simplest form. One hormone goes up, the other goes down.

In Hashimoto’s Thyroiditis, the thyroid gland is damaged by antibodies and inflammation. Typically patients present with the relationship shown above: low free hormones and an elevated TSH.

Scar tissue from the inflammation replaces normal thyroid tissue. A scarred thyroid gland generally isn’t able to make enough thyroid hormone. Individuals with this condition may need thyroid hormone replacement for the rest of their lives.

For this reason it is important to measure and replace thyroid hormone correctly.

How a negative feedback loop regulates your thyroid hormone

Let’s start with a review of a feedback loop, focusing on the one that involves the hypothalamus, pituitary and thyroid glands. Several hormonal systems in the body utilize this feedback. Today we will just focus on the thyroid.

By studying this negative-feedback loop, you will understand what all those numbers mean on your thyroid hormone testing. This insight and knowledge will allow you to become a better advocate for your thyroid health.

A negative feedback loop, is an automatic shut-off system to regulate hormone levels in the body

The principle is simple. But first, let’s define a hormone. A hormone is a molecule that carries a biochemical signal from one part of the body to another. That’s it. This signal tells the recipient organ, muscle or gland how to work.

The brain sends a signal (via a hormone or nerve) to a gland instructing it to make its hormone. This increasing hormone production feeds back to the brain. In response to the elevated hormone levels, the brain makes less of the signal. The gland then lowers its production of the hormone. 

When the brain senses low thyroid hormone, the hypothalamus releases TRF, Thyrotropin Releasing Factor.

TRF travels down a short stalk to the pituitary gland, which sits just below the hypothalamus.

Stimulated by TRF, the pituitary then sends TSH to the thyroid gland. The TSH programs the cells in the thyroid to make more T4 and T3.

Not all thyroid hormone is created equally

The majority of the hormone made in the thyroid gland is T4. A small amount is T3.

In the tissues, an iodine molecule is then removed from the T4 to make the active thyroid hormone, T3.

Increased production of the thyroid hormones T4 and T3 feeds back to the hypothalamus. As the hormone levels rise, the hypothalamus decreases the production of TRF. The downstream TSH decreases as well.

Here we see negative feedback at work.

The diagram above shows how the higher levels of thyroid free hormones then inhibit the hypothalamus. With increasing amounts of free hormones the TSH decreases through negative feedback.

A low TSH almost always correlates with high levels of circulating thyroid hormone

An extremely low or suppressed TSH is most apparent in Graves’ disease, which is a hyperthyroid state. Unlike Hashimoto’s, which over time destroys the gland, Graves’ disease produces antibodies that overstimulate the thyroid gland.

In the presence of these stimulatory auto-antibodies, the thyroid makes high levels of thyroid hormone. In Graves’, the high level of thyroid hormone is not made in response to signals received from the brain.

One of the first laboratory signs of Graves’ is a suppressed TSH.

The brain senses that there is too much hormone around, and knows not to send signals to the thyroid gland to make even more hormone. The pituitary gland stops making TSH.

The Relationship in Graves’ looks like this.

How to talk to your doctor about your thyroid hormone health

The primary question to ask your doctor is whether he or she believes that you should be following only the TSH, or the TSH in addition to the free hormones (T3 and T4).

Knowing only the TSH does not show how much thyroid hormone is being seen by the target cells.

I clearly recall a lecture from a thyroid “expert” while I was in medical school. He said, and I quote.

“Managing thyroid health is easy. You only have to measure TSH.”

“A normal TSH means you are done. The patient has fully normal thyroid function.”

Case closed.

We are taught to this day in medical school that a “full” thyroid assessment can be made with only the TSH.

With more than two decades of clinical practice under my belt, I can tell you that this lesson couldn’t have been more wrong.

Measuring TSH alone does not represent the thyroid activity at the tissue level

In my patient population, I follow TSH in addition to T3 and T4. For years I have seen that TSH alone does not correlate with the patient’s clinical symptoms. I frequently see patients with a “normal” TSH whose free hormones are horribly low. Usually these patients have thyroid-related symptoms.

A doctor who only checks TSH is not assessing the levels of the active hormones

If you never stop to look for something, rest assured that you will never find it. This particularly applies in thyroid hormone management.

Follow this road map to thyroid health

First: Start with TSH (Normal lab range between .4-4.5; ideal .5-1.5.)

This is a good starting point, but not a good ending point. If you have absolutely no thyroid symptoms, and a TSH that is between .5 and 1.5, you probably have normal thyroid function. But that’s not the typical person in my medical practice.

And that probably is not you, if you are reading this blog.

A TSH greater than 4 is always abnormal, and is frequently associated with Hashimoto’s antibodies.

Second: Add Free T3 and Free T4. Do not settle for any other measurements of thyroid function.

These free hormones represent the level of thyroid hormone seen at the level of the cells. Many doctors contract with labs that offer “panels” with markers such as total T4, Free Thyroxine Index and T3 uptake.

Don’t settle for these tests. They will not give you a complete picture of your thyroid health.

Only free hormone levels identify the actual concentration of thyroid hormone seen at the cellular level

Third: Consider measuring Reverse T3.

I tend to add on this lab test on occasion, but not with everybody.

I look for an elevated RT3 in:

  • A person who has persistent thyroid symptoms, and a “normal” TSH or T4 on Levothyroxine or Synthroid (prescription T4). In this case, a well-intended physician may be continually upping the dose of the prescription T4. The higher T4 suppresses the TSH, but the T4 may be converting to the “evil twin” RT3 and not the active thyroid hormone, T3.
  • A person who has recently undergone significant stressors, weight changes (up or down), or is inflamed. RT3 is our survival hormone. It lowers our metabolism. Fad diets and unending stress tell our body retreat to survival mode. Our body does this to save energy, preserve our resources and stay alive.

Fourth: Look for autoimmunity. Consider Hashimoto’s and Graves’ disease.

  1. Graves’: Measure Thyroid Stimulating Antibodies (TSIs)
  2. Hashimoto’s: Measure anti-thyroglobulin (Anti-TG) and anti-Thyroid Peroxidase (anti-TPO)
  3. Autoimmune thyroid disease is present in up to 5% of the population

Review of autoimmune thyroid conditions

These two autoimmune conditions are generally on different ends of the thyroid spectrum.

Graves disease is a hyperthyroid state where autoimmune antibodies stimulate the thyroid gland to make more hormone. The list below shows the associated clinical signs:

  1. Sweating
  2. Nervousness
  3. Palpitations
  4. Weight loss
  5. In advanced cases, patients present with proptosis, bulging eyes where the whites of the eyes are seen between the pupils and lids

In Graves the TSH is suppressed and I will commonly see a low TSH <.01. The antibodies are independently driving the thyroid gland. The thyroid stops listening to the pituitary. It is marching to a different drum, that of abnormal antibodies, rather than the normal signals sent from the brain.

Hashimoto’s Thyroiditis can present with both a hyper and hypothyroid state. Patients almost always present in a hypothyroid state with a high or high normal TSH, and low free hormones.

Hashimoto’s is similarly an antibody-driven autoimmune condition. But in this case the antibodies attack and destroy our own thyroid gland. Our body basically attacks itself.

Hashimoto’s Thyroiditis can present with either hyperthyroidism or hypothyroidism

Early in the condition, Hashimoto’s can look like Grave’s disease as the inflammation actively progresses. Inflammation initially turns the thyroid gland on, and thyroid hormone spills out as the gland is damaged.

Over time the gland burns out. Scar tissue replaces normal thyroid cells. It seems like this is when the vast majority of Hashimoto’s patients present to the doctor. Their fatigue, and progressive low thyroid hormone levels have become too prominent.

Hashimoto’s is frequently missed in the early stages of the disease. I have seen numerous patients with early Hashimoto’s presenting with a TSH of 3.5-4.5, and hormones in the “normal” range.

In many autoimmune conditions, antibodies to the tissue can be present for 3-7 years before diagnosis

The individual with early Hashimoto’s often unnecessarily suffers with fatigue for years before the condition is discovered.

Conclusion

In conclusion, you will need to check labs to fully evaluate the function of the thyroid gland. Be sure to measure the TSH in addition to the free hormones.

Additionally, consider looking for evidence of autoimmunity with a strong family history, and either a very high or very low TSH on initial laboratory screening.

If your doctor insists on only checking a TSH, look into direct-to-consumer testing on the Internet to better understand your thyroid function with the testing listed above.

In a subsequent post, I will review how I like to actually replace thyroid hormone. You can use these tips to work with your doctor to get your thyroid function, your energy, and your health spot on.

 

Join the Conversation

Join my mailing list to receive a complimentary copy of my ebook, Think Different. In it you will learn to reignite your energy by changing your perspective on health.

  • This field is for validation purposes and should be left unchanged.

Reader Interactions

Comments

  1. Scott! Thank you so much for posting your Thyroid 101. I’ve skimmed through it just now and realize I need this information for improving my care of patients. It’s super helpful and my practice has just now changed when it comes to all the women with complaints of fatigue. I hear it every day. I appreciate you sharing your knowledge.
    I’m excited to apply it, starting now, and having more success in helping female patients get appropriately diagnosed, and treated. Thanks Scott!

    • Sandy, Thanks for the note. I am publishing “Part II” later today; this will mirror the first half. I am so glad that this is helping your clinical practice. You made my day!

      SAR

  2. All of this seems so confusing. However, Dr. Resnick has a great way of explaining all of this in his office. It especially makes sense when he is talking about your own results.

    I’ve felt bad for the past four years. I’ve put all of my trust in him to get to the bottom of my problems and make me feel better. One of the things I most admire about Dr. Resnick is he tries to find the cause of the problem. Most physicians just ask you what’s wrong and get their pad out to write a prescription. Not Dr. Resnick. I love the fact that he gets excited about talking to me about my health. I’m on my way to feeling better thanks to Dr. Resnick and his staff.

    • Lisa,

      Thanks you for your comment. We really do our best here to help people to get well. I’m posting a follow up to this blog sometime today, so be sure to check it out.
      All my best,

      SAR

Leave a Reply

Your email address will not be published. Required fields are marked *

Address Book Address Card adjust align-center align-justify align-left align-right ambulance American Sign Language Interpreting Anchor Angle Double Down Angle Double Left Angle Double Right Angle Double Up angle-down angle-left angle-right angle-up Archive Alternate Arrow Circle Down Alternate Arrow Circle Left Alternate Arrow Circle Right Alternate Arrow Circle Up Arrow Circle Down Arrow Circle Left Arrow Circle Right Arrow Circle Up arrow-down arrow-left arrow-right arrow-up Alternate Arrows Alternate Arrows Horizontal Alternate Arrows Vertical Assistive Listening Systems asterisk At Audio Description backward Balance Scale ban barcode Bars Baseball Ball Basketball Ball Bath Battery Empty Battery Full Battery 1/2 Full Battery 1/4 Full Battery 3/4 Full Bed beer bell Bell Slash Bicycle Binoculars Birthday Cake Blind bold Lightning Bolt Bomb book bookmark Bowling Ball Braille Briefcase Bug Building bullhorn Bullseye Bus Calculator Calendar Alternate Calendar Calendar Check Calendar Minus Calendar Plus Calendar Times camera Retro Camera Car Caret Down Caret Left Caret Right Caret Square Down Caret Square Left Caret Square Right Caret Square Up Caret Up Shopping Cart Arrow Down Add to Shopping Cart certificate Area Chart Bar Chart Line Chart Pie Chart Check Check Circle Check Square Chess Chess Bishop Chess Board Chess King Chess Knight Chess Pawn Chess Queen Chess Rook Chevron Circle Down Chevron Circle Left Chevron Circle Right Chevron Circle Up chevron-down chevron-left chevron-right chevron-up Child Circle Circle Notched Clipboard Clock Clone Closed Captioning Cloud Cloud Download-alt Cloud Upload-alt Code Code Branch Coffee cog cogs Columns comment Alternate Comment comments Compass Compress Copy Copyright Credit Card crop Crosshairs Cube Cubes Cut Database Deaf Desktop Dollar Sign Dot Circle Download Edit eject Horizontal Ellipsis Vertical Ellipsis Envelope Envelope Open Envelope Square eraser Euro Sign Alternate Exchange exclamation Exclamation Circle Exclamation Triangle Expand Alternate Expand Arrows Alternate External Link Alternate External Link Square Eye Eye Dropper Eye Slash fast-backward fast-forward Fax Female fighter-jet File Alternate File Archive File Audio File Code File Excel File Image File PDF File Powerpoint File Video File Word File Film Filter fire fire-extinguisher flag flag-checkered Flask Folder Folder Open font Football Ball forward Frown Futbol Gamepad Gavel Gem Genderless gift Martini Glass Globe Golf Ball Graduation Cap H Square Lizard (Hand) Paper (Hand) Peace (Hand) Hand Pointing Down Hand Pointing Left Hand Pointing Right Hand Pointing Up Pointer (Hand) Rock (Hand) Scissors (Hand) Spock (Hand) Handshake Hashtag HDD heading headphones Heart Heartbeat History Hockey Puck home hospital Hourglass Hourglass End Hourglass Half Hourglass Start I Beam Cursor Identification Badge Identification Card Image Images inbox Indent Industry Info Info Circle italic key Keyboard Language Laptop leaf Lemon Level Down-alt Level Up-alt Life Ring Lightbulb Link Turkish Lira Sign list list-alt list-ol list-ul location-arrow lock Lock Open Alternate Long Arrow Down Alternate Long Arrow Left Alternate Long Arrow Right Alternate Long Arrow Up Low Vision magic magnet Male Map map-marker Map Marker-alt Map Pin Map Signs Mars Mars Double Mars Stroke Mars Stroke Horizontal Mars Stroke Vertical medkit Meh Mercury Microchip microphone Microphone Slash minus Minus Circle Minus Square Mobile Phone Alternate Mobile Money Bill-alt Moon Motorcycle Mouse Pointer Music Neuter Newspaper Object Group Object Ungroup Outdent Paint Brush Paper Plane Paperclip paragraph Paste pause Pause Circle Paw Pen Square Alternate Pencil Percent Phone Phone Square Phone Volume plane play Play Circle Plug plus Plus Circle Plus Square Podcast Pound Sign Power Off print Puzzle Piece qrcode Question Question Circle Quidditch quote-left quote-right random Recycle Redo Alternate Redo Registered Trademark Reply reply-all Retweet road rocket rss RSS Square Ruble Sign Indian Rupee Sign Save Search Search Minus Search Plus Server Share Alternate Share Alternate Share Square Share Square Shekel Sign Alternate Shield Ship Shopping Bag Shopping Basket shopping-cart Shower Alternate Sign In Sign Language Alternate Sign Out signal Sitemap Horizontal Sliders Smile Snowflake Sort Sort Alpha Down Sort Alpha Up Sort Amount Down Sort Amount Up Sort Down (Descending) Sort Numeric Down Sort Numeric Up Sort Up (Ascending) Space Shuttle Spinner Square Square Full Star star-half step-backward step-forward Stethoscope Sticky Note stop Stop Circle Stopwatch Street View Strikethrough subscript Subway Suitcase Sun superscript Sync Alternate Sync table Table Tennis tablet Alternate Tablet Alternate Tachometer tag tags Tasks Taxi Terminal text-height text-width th th-large th-list Thermometer Empty Thermometer Full Thermometer 1/2 Full Thermometer 1/4 Full Thermometer 3/4 Full thumbs-down thumbs-up Thumbtack Alternate Ticket Times Times Circle tint Toggle Off Toggle On Trademark Train Transgender Alternate Transgender Trash Alternate Trash Tree trophy truck TTY Television Umbrella Underline Undo Alternate Undo Universal Access University unlink unlock Alternate Unlock Upload User User Circle user-md Add User User Secret Remove User Users Utensil Spoon Utensils Venus Venus Double Venus Mars Video Volleyball Ball volume-down volume-off volume-up Wheelchair WiFi Window Close Window Maximize Window Minimize Window Restore Won Sign Wrench Yen Sign 500px Accessible Icon Accusoft App.net Adversal affiliatetheme Algolia Amazon Amazon Pay Amilia Android AngelList Angry Creative Angular App Store iOS App Store Apper Systems AB Apple Apple Pay Asymmetrik, Ltd. Audible Autoprefixer avianex Aviato Amazon Web Services (AWS) Bandcamp Behance Behance Square BIMobject Bitbucket Bitcoin Bity Font Awesome Black Tie BlackBerry Blogger Blogger B Bluetooth Bluetooth BTC Büromöbel-Experte GmbH & Co. KG. BuySellAds Amazon Pay Credit Card American Express Credit Card Apple Pay Credit Card Diner's Club Credit Card Discover Credit Card JCB Credit Card MasterCard Credit Card Paypal Credit Card Stripe Credit Card Visa Credit Card Centercode Chrome cloudscale.ch Cloudsmith cloudversify Codepen Codie Pie Connect Develop Contao cPanel Creative Commons CSS 3 Logo Alternate CSS3 Logo Cuttlefish Dungeons & Dragons DashCube Delicious Logo deploy.dog Deskpro deviantART Digg Logo Digital Ocean Discord Discourse DocHub Docker Draft2digital Dribbble Dribbble Square Dropbox Drupal Logo Dyalog Earlybirds Edge Browser Elementor Ember Galactic Empire Envira Gallery Erlang Ethereum Etsy ExpeditedSSL Facebook Facebook F Facebook Messenger Facebook Square Firefox First Order firstdraft Flickr Flipboard Fly Font Awesome Alternate Font Awesome Font Awesome Flag Fonticons Fonticons Fi Fort Awesome Alternate Fort Awesome Forumbee Foursquare Free Code Camp FreeBSD Get Pocket GG Currency GG Currency Circle Git Git Square GitHub Alternate GitHub GitHub Square GitKraken GitLab Gitter Glide Glide G Gofore Goodreads Goodreads G Google Logo Google Drive Google Play Google Plus Google Plus G Google Plus Square Google Wallet Gratipay (Gittip) Grav Gripfire, Inc. Grunt Gulp Hacker News Hacker News Square Hips HireAHelper Hooli Hotjar Houzz HTML 5 Logo HubSpot IMDB Instagram Internet-explorer ioxhost iTunes Itunes Note Jenkis Joget Joomla Logo JavaScript (JS) JavaScript (JS) Square jsFiddle KeyCDN Kickstarter Kickstarter K KORVUE Laravel last.fm last.fm Square Leanpub Less Line LinkedIn LinkedIn In Linode Linux lyft Magento MaxCDN MedApps Medium Medium M MRT Meetup Microsoft Mix Mixcloud Mizuni MODX Monero Napster Nintendo Switch Node.js Node.js JS npm NS8 Nutritionix Odnoklassniki Odnoklassniki Square OpenCart OpenID Opera Optin Monster Open Source Initiative page4 Corporation Pagelines Palfed Patreon Paypal Periscope Phabricator Phoenix Framework PHP Pied Piper Logo Alternate Pied Piper Logo Pied Piper PP Logo (Old) Pinterest Pinterest P Pinterest Square PlayStation Product Hunt Pushed Python QQ QuinScape Quora Ravelry React Rebel Alliance red river reddit Logo reddit Alien reddit Square Rendact Renren replyd Resolving Rocket.Chat Rockrms Safari Sass SCHLIX Scribd Searchengin Sellcast Sellsy Servicestack Shirts in Bulk SimplyBuilt SISTRIX skyatlas Skype Slack Logo Slack Hashtag Slideshare Snapchat Snapchat Ghost Snapchat Square SoundCloud Speakap Spotify Stack Exchange Stack Overflow StayLinked Steam Steam Square Steam Symbol Sticker Mule Strava Stripe Stripe S Studio Vinari StumbleUpon Logo StumbleUpon Circle Superpowers Supple Telegram Telegram Plane Tencent Weibo ThemeIsle Trello TripAdvisor Tumblr Tumblr Square Twitch Twitter Twitter Square Typo3 Uber UIkit Uniregistry Untappd USB us-Sunnah Foundation Vaadin Viacoin Viadeo Viadeo Square Viber Vimeo Vimeo Square Vimeo Vine VK VNV Vue.js Weibo Weixin (WeChat) What's App What's App Square WHMCS Wikipedia W Windows WordPress Logo Wordpress Simple WPBeginner WPExplorer WPForms Xbox Xing Xing Square Y Combinator Yahoo Logo Yandex Yandex International Yelp Yoast YouTube YouTube Square