Sex Hormones for You, Personally

Sex Hormones for You, Personally

The second in a series of talks by Alan McDaniel MD

Let’s take a look at the sensible replacement of an individual woman’s hormones at menopause.  Yes, this is a personal approach for one woman’s needs, not some “one size-fits all” protocol. We start by understanding normal physiology – “how it works” and apply modern science to find the best doses for you personally.  Our goals are success and safety.

To help you understand this better, let’s see what hormones do and what happens when we lose them.  I’ll explain why it is important to consider replacing them at menopause and why sooner is better.  We’ll see how that can – and should – be done.  If we’re going to do this, let’s do it the best way, one woman at a time!

Basics:  Puberty to Menopause

Hormones are little chemical messengers that change the way your body behaves.  Sex hormones transform our bodies from those of children to healthy adults and allow us to reproduce the species.  Glands are collections of cells especially-designed to make particular hormones.  The output of these little hormone-factories is controlled by feed-back to the brain and glands themselves – the body stops making a hormone when it has enough.

What happens at menopause?  Levels of sex hormones fall and a woman’s body starts returning slowly to its original child-like state.  The early symptoms are described by Harvard’s Dr. Altman as “estrogen withdrawal”: Hot flashes; insomnia; mood swings and depression; “brain fog” (cognitive dysfunction), and reduced libido are some of the worst ones.  Some of these, like hot flashes, usually ease-off in time.  Other symptoms get worse: Menopausal women not taking hormones can enjoy an active sex life but according to Yale’s Dr Sarrel, participation falls from 90% at age 50 to only 10% of women aged 60.

After 5-10 years, women progress to what Altman calls “hormone deficiency” and their bodies show serious changes from lack of hormone support.  Their genitals return to a childish state, becoming thin, dry and fragile.  They lose muscle-tone and their waistline and bladder sag, permitting urine leakage as their hourglass figure becomes a bowling-pin.  Cholesterol goes up as does their risks of heart attack and stroke.  They lose bone calcium and risk fractures.  They are more vulnerable to colon cancer and arthritis.  Even the brain suffers: Their risk of dementia is increased and strokes can do more damage.

History of Treatments for Menopause

In the mid-1950s, hormone treatment for menopause became available and women were offered hope and relief from their dreadful symptoms.  There were no lab tests in those days and doctors gave estrogen replacement based solely on symptoms.  It took 20 years before they could see that oral estrogen replacement gave women uterine cancer; their uterine cells had needed progesterone to prevent cancer but hadn’t gotten enough.  This was an early lesson in the importance of balancing hormones!

The modern era of hormone replacement began in 2002 with the Women’s Health Initiative (WHI) study.  The WHI was a flawed study of a flawed practice.  Shockingly, its alarming claim that hormone replacement treatment (HRT) causes breast cancer – trumpeted by all the media – was not true!   In the final data analysis, the increased risk was not statistically significant!  Do you remember hearing that retraction?  Neither do I.

Good came of the WHI, though.  It revealed that our old methods of HRT hadn’t been the best.

• It showed us the synthetically jacked-up progesterone (called “progestin”) we’d been giving to protect the uterus may increase women’s risk of breast cancer.
• It showed us that hormone replacement should be started earlier rather than later.  The longer women wait to begin, the less they may benefit and the greater their risks.
• It proved that women’s HRT had become so political that even scientists were unable to accurately report their data.

The WHI gave us impetus to re-evaluate and to re-invent HRT – and that is a great outcome.  The WHI and other research studies included huge numbers of rather diverse women, all treated exactly the same.  Alert physicians could see clearly that each woman needs to be treated individually.  With modern laboratory tests, we now have great tools to do this.

Individualized Hormone Replacement Treatment

With heightened awareness, then, we ask: “Who needs hormone replacement treatment?”  First, women with symptoms can benefit from treatment.  Their symptoms come from altered feedback and low hormones.  Secondly, we believe women with a family history of hormone-deficiency problems such as bone loss (osteoporosis) are good candidates for HRT.

Thirdly, the laboratory shows us women with lower hormone levels have greater risk for degenerative diseases.  This has become distressingly apparent in women treated for cancer by hormone-deprivation.  Healthy women with low hormones are headed for hormone-deficiency problems and the most specific preventative treatment is to restore those very hormones.

Of course, there’s more to this than just throwing hormones at women.  As we start to look at the art and science of skillful HRT, I think it goes without saying that we must use only biologically-identical hormones.  Among the many reasons for this, the laboratory can detect only bio-identical hormones and using the lab to evaluate our patients is a “key” to getting good results.

Please understand that “biologically-identical” is not the same thing as “natural.”  Estrogens in pregnant horses’ urine are natural but they are not identical to human hormones – and that makes them undesirable.  On the other hand, plant estrogen that has been modified to make it identical to human estrogen gives us excellent results – because it is identical!

Doctors must consider the age of each woman as well as questions like “do you still have your ovaries” and “when was your last period?”  Such simple things significantly influence our testing strategy and treatment doses.

After we’ve chosen to start HRT, the next obvious question is “with which?”  Some women need only one or another or the third sex hormone in order to achieve balance at desirable levels.  Most women need different amounts of several hormones – and we’ve learned balance is essential.  An important lesson we can infer from the WHI was that doctors shouldn’t recommend “rubberstamp” treatment.

Next, ask “how much?”  The WHI also used “one-size fits all” and showed us that wasn’t so successful.  When women take hormones, their body has to accept them, at least for a while, until it processes and expels them.  The bigger the dose, the more of that hormone the body has to deal with, for better or worse.  Since docs create and control patients’ blood levels by the dose they choose, they must ask: “What blood levels are desirable for this person?”  That’s a darned important question!

The answer to that question should settle a huge debate that’s been raging over 40 years – is HRT is good or harmful?  The “pro” group points to the terrible degenerative changes that follow years of low hormone levels and correctly argues that HRT is good.  Their opponents say HRT is bad, because the more estrogens women take, the greater their risks of cancers, blood clots and gallstones – and they are also correct.  The argument has been so fierce because both sides are right!  How can this be reconciled?

We need to invite a lateral-thinking solution. Just think like Goldilocks: If one extreme is too hot and the other is too cold, is there somewhere in the middle that’s “just right?”

What hormone levels give the best effects at the lowest risks?  We don’t know yet.  Some doctors avoid the question altogether by giving “low-dose” birth control pills or using the Wiley protocol.  Both of these plans move hormones from low to high and back again every month, perpetuating the menstrual flow.

Many Anti-aging and integrative doctors give women robust doses of all the hormones.  Their patients may have every-day blood levels so high they are normal only for the second half of their monthly cycle.  This is called the “proliferative” phase and cancer is uncontrolled proliferation; it concerns me – is cell growth over-stimulated?  Remember, the higher the hormone level, the greater the risks!

It seems safer to use lower doses – the least amount of hormones needed for our patients to feel well.  This begs the question: How much is that?  Perhaps Nature gives us some guidance.

Let’s ask, then: When in the normal monthly cycle do women feel best?  That second phase of the cycle is pre-menstrual, when many women don’t feel well – PMS, right?  Uncomfortable symptoms occur so often at mid-cycle that the Germans gave it a name: mittelschmerz, or “middle-pain.”  Oh, and who feels great when their menstrual flow is just starting?  When you ask lots of women, as I have, nearly all report feeling best in the days after their flow has stopped and before they ovulate – called “mid-follicular.”

First Steps – Progesterone and Testosterone

Delightfully, these follicular blood levels are rather modest and are relatively easy to reproduce.  To most doctors’ surprise, women can make ample amounts of progesterone and testosterone for themselves with a little over-the-counter (OTC) help.

First, we must supply tools (co-factors) to our glands’ enzymes that make sex hormones from cholesterol.  These tools are dietary nutrients but our food may not provide enough.  Supplements called “adrenal glandulars” provide them very effectively.  I’ve given some details at the end of this paper.

Secondly, partly-assembled sex hormones (precursors) called pregnenolone and DHEA can be taken orally to produce progesterone and testosterone.  Their safety – and the reason they are sold OTC – lies in the fact our body doesn’t have to use them.  They are a perfect example of an important principle: Give the body what it needs and it will often do the job for itself.

Both of these precursors bypass a “synthetic bottleneck.”  They replenish those people who by stress, exhaustion and failing or surgically-removed glands are not making enough of their own.  DHEA is two steps away from becoming testosterone and pregnenolone is just one step from progesterone – but whether our body takes those steps is completely its option.  Unless it is biochemically “drowned” with an overdose, it will simply get rid of what it doesn’t want to use.

How do we know we’ve given enough – and that the body has chosen to use it?  Right; we test the blood for hormones.  It is surprising how few women need to take progesterone or testosterone once they’ve started these OTC precursors.  I was even disappointed to learn that nearly all menopausal women need prescription estrogen.  At menopause, the particular enzymes that make estradiol just don’t work well (let’s skip that biochemistry, OK?).

Prescription Estrogen

Giving estrogens raises two key questions: Of the three kinds of estrogen, which should we give and how should it be taken?  My goodness, these simple issues provoke arguments!  Here are my answers.

To the first question: We should use estradiol, in the smallest amount needed to achieve our goals.  Estradiol is the most active form of estrogen and most efficiently gives us the effects we desire.  Why is there any debate?  There have been undesirable side effects of HRT.  Before blood tests showed us most of these ill-effects come from excessive dosing and high blood levels or unbalanced hormones, some doctors had worried that estradiol might be too strong.

These concerned physicians hoped the other two estrogens might add a mellowing influence.  In the name of balance, they advocated treatment with all three, as “Tri-Est,” in the proportions normally found in healthy people’s blood.  That turns out to have been unnecessary, even unwise.

One of them, estrone, is not harmless.  In fact, research shows a version of estrone (16 alpha-hydroxyestrone) is often associated with cancer and other trouble.  So, estrone was pulled out and Tri-Est became Bi-Est.  Recently, the FDA withdrew its permission to use the third estrogen, estriol and now, the continued use of Bi-Est is challenged.

Is the loss of Bi-Est a terrible shame?  Not at all; our body converts estradiol to estrone and that to estriol.  When you take estradiol, you’ll make the rest… and if estradiol is taken correctly, all three will balance.

So, when we use estradiol, how should it be taken?  For years, some compounding pharmacists had given us the right answer but it took the French to prove it: Estrogens should be absorbed through the skin.  What an odd way to take something into our body – why not by mouth, as we did for decades?

When we swallow estradiol, it is absorbed from the small intestine and travels in the blood to the liver.  Our liver normally disposes of unwanted hormones and it “chews up” the great majority of what we’ve swallowed.  Worse are the undesirable byproducts it “spits out”; these include that bad actor we just met, 16 alpha-hydroxyestrone.  These byproducts also competitively interfere with estradiol, so the 10% or so that has gotten in past the liver doesn’t work as well as it could.

Absorbing estradiol through the skin gets it into the bloodstream without first passing through the liver.  Women get the same blood levels of estradiol with just one-tenth the dose – and they get far fewer unwanted and possibly risky estrogen-breakdown products.  They get better results from taking far less estrogen and that is proven to be safer.

Risky Business

With this information, you are now ready to consider some difficult issues: Does even perfectly-crafted hormone replacement involve any risks?  Also, is there any person who ought not to take HRT?  Let’s take a careful look at the risks of cancer.

First, women who choose not to take HRT and are willing to accept the degenerative changes of “hormone deficiency” can still get cancer of the breast, uterus and other estrogen-responsive tissues.  In fact, about 10% of women who take no hormone replacement will even-so develop breast cancer.

Secondly, estradiol does not cause cancer.  Estrogen may encourage cancer growth, though.  Our body occasionally produces cancer cells and our immune system kills them, the way a gardener pulls up weeds.  A tumor forms if cancer cells proliferate and grow faster than the immune system can destroy them.  Estradiol increases the chance of a tumor by “fertilizing” some cancer cells and speeding up their growth.  So, yes: People taking estrogen replacement are slightly more likely to get breast cancer.  But wait: Estradiol does something more – with a protective effect!

Estradiol causes breast cells to mature and assume their adult form.  Estradiol has the same effect on breast cancer cells, making them better-differentiated and therefore easier to cure.  This really adds to the complexity of assessing the risk of HRT.  Women who take no estrogen replacement get comparatively fewer cancers – but those they produce are more likely to have anaplastic or primitive cell types with a worse outcome.

There is a final cancer trade-off that must be mentioned.  Women who are not treated with HRT get significantly more colon cancer.  What’s worse, colon cancer is more often fatal than breast cancer.  Because breast cancer is more common, it is a bigger killer of women but colon cancer is definitely the deadlier of the two.  A woman’s risk of colon cancer should be a factor in her decision about using HRT.

Who Should Not Be Treated With HRT?

Breast cancer runs in some families.  While Science has identified some “cancer-genes,” these explain less than 20% of family-related cancers.  Women with a strong family history of breast cancer ought to seriously consider avoiding HRT.  What’s strong?  Well, one patient, her mother, her sister and her son had all had breast cancer; that’s “strong!”  However, if your grandmother got breast cancer at 80, your risk is probably not increased.  I’ve heard a Smart Guy say that breast cancer is so common in the US that you may be at no greater statistical risk even if your aunt gets it.

A woman’s decision to start HRT should be the result of counseling with her physician or practitioner.  There can be no guarantees.  If you feel too anxious about the risks to take it with peace of mind or a true sense of comfort, then don’t start it!  Follow your feelings as an “inner guide” and respect them.

Final Thoughts

Well, let’s say that taking nutrition and precursors and a little dinky bit of transdermal estradiol have achieved normal blood levels – you and your Doc ought to be in hog heaven now!  But – what if you are not feeling fantastic?  Here are a few considerations for menopausal-age women:

Lots of other problems appear during our forties and fifties, when menopause sets in.  Thyroid trouble is one of these; up to 20% of menopausal women have thyroid trouble.  Insulin resistance also becomes a really big problem at this age and the hormone changes of menopause just seem to make it worse.

Insulin resistance alters women’s enzymes and they make too much dihydrotestosterone (DHT) – the strongest masculinizing hormone.  When this happens, even modest amounts of DHEA or testosterone can “go wrong” and cause acne, hair growth on the face and body and male-pattern baldness.  Saw palmetto in rather big doses can give excellent relief for this particular form of hormone imbalance.

The combined effects of menopause, thyroid trouble and insulin resistance can result in prodigious weight gain.  This significantly predisposes a person to the sleep apnea syndrome.  However, even without obesity, sleep apnea becomes rather common at mid-life.  It can steal our vitality while we sleep and we may never realize what is causing the problem.

Hormone replacement can alter thyroid hormone activity – and vice-versa.  Estrogen and thyroid hormones have “cross-talk” in the cell nucleus.  Occasionally, thyroid treatment must be adjusted after starting HRT – just as we may need to increase estrogen doses after going on thyroid treatment.

Estradiol is broken down to estrone, as we’ve seen.  Estrone can be metabolized to harmless versions or that trouble-maker 16alpha-hydroxyestrone.  Your practitioner can order a blood test to monitor this through LabCorp and it’s usually covered by insurance.  If an imbalance is found, the nutritional supplement Indole 3 Carbinol  may correct it – Metagenics makes a good one.

Summary

Sixty years ago, researchers made hormones available to relieve the suffering of menopausal women.  We are now learning how to use these with precision and skill.  We are guided by research, which has provided important data and fostered new concepts.  We are aided by newly-available and remarkable laboratory technology.  This “new endocrinology” helps us maintain the health and restore the joy of life to an amazing number of people with a minimum of risk.

After Word:

The best adrenal “glandular” to support adrenal and gonadal function is Cytozyme AD, made by Biotics Research.   It is available on the internet, at Gordon Medical and at Health First Pharmacy in Windsor, CA among others.  It is packed with nutrients necessary for the enzymes that turn cholesterol into sex hormones.  Because it comes from cows, it may cross-react with people’s milk or beef allergies.  Alternative products include Metagenics’ Cortico-B5B6, which is vegetarian but with B-vitamins derived from yeast and Biotics’ ADHS, which seems less potent but is quite hypoallergenic.

The levels of adrenal and ovarian hormones are highest when we wake and lowest when we go to bed.  Since the “glandular” supplies co-factors (“tools”) to the enzymes that make hormones, we should take it as those enzymes are getting to work – last thing at night and first thing in the AM.  About half my patients benefit from adding one at noon, also.

The surest pregnenolone is compounded by skilled pharmacists.  Currently, “tried and true” pregnenolone is also made by Source Natural, Biotics Research, Pure Encapsulations and Ortho-Molecular Products.  As a caution, good products have gone bad in the past and were removed from my list; check your blood levels at least once a year and sooner if your brand changes the size or shape of its capsules or tablets.

The same is true for DHEA.  For now, it is reliably supplied by DeeCee Labs, Biotics Research, Pure Encapsulations and Ortho-Molecular Products.  I am sure other good companies sell reliable product but I can’t vouch for them.  I hate to list makers with whom I’ve had trouble.

I can’t accurately recommend doses but few people need any more than 40 mg combined pregnenolone and DHEA.  For women, pregnenolone seems best taken at bedtime, while DHEA often feels best taken in the morning.  Women must be careful about taking more than 10 mg DHEA daily if they have any degree of insulin resistance.

Alan McDaniel, MD will be speaking at the Biotoxin Illness weekend, on Non -Ige Mold Allergy and Inflammation. He is a Board-certified Ear, Nose & Throat specialist with two sub-specialties.  His work with dizziness and allergy in the 1980s led him to seek solutions for Chronic Fatigue Syndrome.  Since 2003, Dr. McDaniel has taught physicians practicing on five continents to effectively employ nutrition and hormones for this and other issues in his two-day course titled “The New Endocrinology.”  Dr. McDaniel has been a visiting physician at Gordon Medical Associates in Santa Rosa, California.

Treat Your Thyroid Right: Straight Talk for Regular People

Treat Your Thyroid Right: Straight Talk for Regular People

by Alan B. McDaniel MD

A talk originally presented at Whole Foods Market, Coddington Center, Santa Rosa on 8/18/11. Use this link to see the schedule of other talks Dr. McDaniel will be giving.

Let me introduce myself.  I am board-certified in Ear, Nose and Throat with two subspecialties in that field.  However, I found my true calling was treating patients who had fallen through the cracks – those people for whom the standard treatments were not effective.  That’s why I work with patients who need help with their thyroid, adrenals, sex hormones, and other endocrine problems.

Everyone has heard about thyroid trouble.  Low-thyroid is so common that thyroid hormone pills are the second most-frequently filled prescription in the US.  At this moment, about 15% of all Americans have diseased thyroid glands.  Many of them are not being treated.  Sadly, many people who are treated for thyroid trouble are not fully restored to normal and they are often quite dissatisfied with their results.  Since our thyroid glands are so much at risk and so often a persistent problem, it is good to learn more about what they do and how best to deal with their problems.

The thyroid gland releases hormones into our blood, on “orders” from the brain and pituitary gland, which together regulate its production.  The brain “measures” thyroid hormones in the blood and signals the pituitary when more is needed.  The pituitary responds by releasing thyroid-stimulating hormone (TSH) into the blood.  True to its name, TSH stimulates the thyroid to produce hormones.  These thyroid hormones set the rate of our metabolism, the way our body makes and uses energy.   This fact was discovered by observing people whose thyroid glands produced too much hormone – and too little.

The main purpose of this talk is to explain why the treatment now established as “the standard of care” for people with low thyroid is imperfect for so many.  Before we get there, let’s review a few other thyroid problems so you can feel more at home with the workings of this complex system.

 Goiters

Any enlargement of the thyroid gland is called a goiter.  “Endemic (prevalent in a particular location) goiter” is caused by a nutritional deficiency of iodine: The gland gets bigger and bigger as it keeps trying to make hormones – which it cannot do without iodine!  Goiters can also be caused by all sorts of inflammation, tumors, cysts and excessive iodine intake but the most common type found in the US is a “multi-nodular goiter.”

Multinodular goiters are often the result of the gland’s efforts to repair itself after it has been damaged.  Inflammation of the gland (“thyroiditis”) kills thyroid cells, which can be replaced.  However, the immediate response to the injury leaves scar tissue, or fibrosis woven throughout the area.  The regenerating thyroid cells must crowd in between the scarred areas.  Packing new cells into these small spaces makes nodules.  Despite their alarming appearance on ultrasound imaging, these lumpy, bumpy thyroids are usually quite harmless.

Hyperthyroidism

Hyperthyroidism means the body has too much thyroid hormone.  Around 1830, several physicians described this condition: Their patients had abnormally large thyroid glands and were hyperactive; hot and sweaty; had a rapid pulse and lost weight despite eating everything in sight (we give credit to the Irishman, Graves).  It was later learned these people’s metabolism had been put into overdrive by a great excess of thyroid hormone, coming from an overactive thyroid gland – but why?  We’ve seen that the brain and pituitary should control the thyroid output; what goes awry to cause hyperthyroidism?

The immune system is most often to blame for causing hyperthyroidism.  It makes an immune globulin that acts just like TSH, an effect called “molecular mimicry.”  As the immune system makes more of this improper and unregulated thyroid-stimulating globulin, the more the thyroid gland is driven to over-produce its hormone (http://en.wikipedia.org/wiki/Graves%27_disease).  This auto-immune disease is the most common cause of spontaneous hyperthyroidism.

What happens to people with Graves’ disease?  At least 40% of them get better on their own.  It is too bad that we can’t predict who that will be!  Doctors have evolved several treatment strategies, using anti-thyroid drugs; operations to remove some or all of the gland and the use of radioactive iodine.  Thyroid cells are specially equipped to take up iodine, an essential ingredient of thyroid hormone.  Because of this, the thyroid gland can be killed by a dose of the deadly ¹³¹I* isotope that should be safe for all other cells.

In Europe, newly-diagnosed hyperthyroid patients are given anti-thyroid drugs to slow down the runaway gland.  Doctors stop the treatment after 18 months, hoping the disease has gone into remission.  If the thyroid once again starts racing, it is killed and the patient must take replacement hormone for the rest of her life.  A second option for initial treatment described as “block and replace” can be more satisfactory, though the process is quite “high-maintenance” and requires close patient follow-up and frequent lab tests.

Because Graves’ disease is notoriously unpredictable and prone to relapses and remissions without warning, most American physicians now tell patients to kill the gland outright.  Before they do this, patients should insist that their doctor prove the hyperthyroidism is due to Graves’ disease.  There are many other reasons for hyperthyroidism that can be dealt with more simply.  It can be caused, for instance, by taking too much iodine; from taking too much thyroid hormone; from an easily removed benign tumor; or by the release of stored hormones due to injury, infection or inflammation.

Sometimes, doctors simply misinterpret the results of laboratory tests and make an incorrect diagnosis.  People often come to me for a second-opinion before they take their doctors’ advice to kill their thyroid glands.  Lately, several needed only to stop taking iodine, with complete resolution in a matter of months.  A member of my wife’s family was operated for disk disease in her neck.  It seems retractors damaged her multinodular thyroid gland, because she promptly became hyperthyroid.  The blood levels returned to normal in six months – but for the whole time, she had to fend off her doctor’s urgent referrals to radiation therapists and neck surgeons.  I am sorry to report that I’ve also reviewed medical malpractice cases in which glands were destroyed for the wrong reasons, including a missed pituitary gland tumor.

Hypothyroidism

Hypothyroidism means the body has too little thyroid hormone.  This is the most common thyroid problem.  Despite physicians’ descriptions of goiters for several thousand years, we didn’t really understand the problem until the 1870s.  That’s when the invention of anesthesia and sterile technique allowed surgeons to remove giant goiters that had choked their owners.  Postoperatively, these people – now completely lacking thyroid glands – became cold, sluggish and mentally impaired (“cretinism”).

Observing these patients led scientists to understand that thyroid hormone sets the thermostat of our metabolism. When the thyroid gland cannot make enough hormones, the cells of our body get too little energy.  They cannot efficiently do their jobs and nothing works very well.

Here’s a short list of what happens when low-thyroid fails to support our metabolism: We feel tired.  We become depressed and have difficulty learning, remembering, thinking and making decisions.  We don’t sleep well and wake up feeling poorly-rested.  We feel cold and our hands and feet are icy; we hate the winter and love the summer but dislike air-conditioning.  We’re prone to headaches, allergy trouble and infections.  We get heart palpitations, muscle aches and joint stiffness.  Menstrual cycles can be irregular and first-trimester miscarriages commonly cause infertility.  Our gut is effected and constipation, sometimes alternating with diarrhea, is common.  Our hair thins out and our fingernails grow slowly and are flakey.  We gain weight.  Our death rate is significantly increased!

This problem is now diagnosed by a blood test for thyroid-stimulating hormone (TSH).  As the failing thyroid gland falters, the brain and pituitary “whip” it harder with more and more TSH – confusing some of our patients (why do you say my thyroid is low when my test is high?).  Before this blood test became available, doctors at first diagnosed hypothyroidism just by their patients’ symptoms and physical appearance; then by a series of increasingly sophisticated tests leading up to our present technology.

We usually can determine what caused this hypothyroidism – and we should make the effort.  Sometimes it is easy: Most people know when they’ve had thyroid surgery or have been treated with destructive doses of radioactive iodine.  Otherwise, some tests are needed.

The most common cause of low-thyroid is again the immune system, in this case by making antibodies that destroy the thyroid gland as though it were a transplanted organ being rejected.  How common is this?  A CDC study showed 15% of Americans have some degree of autoimmune thyroiditis (AIT).  Hypothyroidism due to iodine deficiency is rare and a simple overnight urine test will tell that tale.  This test also detects people with high TSH from taking too much iodine – over 1 mg daily is risky).  Tumors or other pituitary problems causing hypothyroidism are rare – hence the malpractice case!

Treatment for hypothyroidism was routinely and successfully established by 1900 – even before the word “hormone” had been coined.  Dried sheep thyroid glands were taken three times-daily and patients’ results were considered miraculous.  This worked because the healthy thyroid gland uniquely stores a large amount of the hormones it makes – about a 3-months’ supply.

Over the following decades, research revealed there are a variety of thyroid hormones!  The most abundant type (90%) carries four iodine atoms, so is called T4 (tetra-iodothyronine, levothyroxine or L-thyroxine).  The second-most abundant version (9%) of thyroid hormone has only three iodine atoms and is called – right, “T3” (tri-iodothyronine or liothyronine).  T3 is the most potent form of thyroid hormone.  We are just learning to appreciate a third form of thyroid hormone, which is sparse (1%).  It too has three iodine atoms but they are arrayed differently, which greatly alters its activity.  It is called reverse T3 (RT3) and we will soon visit it again.

Throughout this time of discovery, patients were treated with dried animal thyroid glands (“desiccated thyroid, USP”), as they had been since the 1890s.  Then in 1957, a biologically-identical, synthetic version of T4 was introduced and skillfully marketed, addressing fears about the safety and quality of animal thyroid.  This synthetic thyroid, Synthroid® (T4, levothyroxine) rose to dominate the market.

By 1970, scientists and physicians had realized T4 is converted to T3 within the cells of our body – and that T3 is indeed the active form of thyroid hormone.  So, the major product of our thyroid gland, T4 is a rather weak pre-hormone.  Why does the gland release a pre-hormone?  For the same reasons Campbell’s soup is put into cans at the factory – ease of transportation and a long shelf-life.  When they “need” energy, our cells activate T4 by converting it to T3.  This step was thought to be “automatic” until the 1980s.  That is not the case, which explains why “standard treatment” with T4 fails to help many people.

Non-thyroidal Illness (Low-T3 Syndrome, Euthyroid Sick Syndrome, Wilson’s Thyroid Syndrome)

In the 1980s, intensive care specialists discovered many of their sickest patients had low levels of T3, the active thyroid hormone.  Those people’s thyroid glands were perfectly healthy and their TSH was not elevated but they died at a significantly greater rate.  The explanation came when researchers found these people had abnormally large amounts of reverse T3 (RT3).  This was a “new” kind of thyroid problem.

We vertebrates are “programmed” to adapt to life-threatening situations by slowing our metabolism to become very fuel-efficient.  Under stress of all kinds, from injuries to infections, to low-temperatures, to starvation – to just taking examinations – the human body refuses to activate T4 to T3.  Instead, T4 is converted to RT3, which blocks T3 and slows down our metabolism.  Only in 2005 did scientific papers explicitly state this is a second “level” at which our thyroid function is regulated.  Problems can certainly come from this level, but doctors do not usually test for this.

Dennis Wilson was correct when he called our attention to RT3 and postulated a milder form of the ICU-syndrome exists, due to various types of life stresses.  His suggestion that this causes symptoms of hypothyroidism even though TSH and T4 blood levels are normal is valid; it commonly makes patients chronically fatigued.  The inappropriate conversion of T4 to RT3 instead of T3 gives us the same results as driving with the parking brake on.  This also explains why many patients and a few doctors had objected to using synthetic thyroid hormones (e.g. Mary Shomon, Dr. Broda Barnes).  How can we diagnose it?

Measuring RT3 levels alone proved unreliable.  Many doctors turned to old methods of diagnosis using symptoms and body temperature.  Subsequently, a seemingly obvious fact showed us how we can use the laboratory to identify people with this problem: The vast majority of RT3 in our blood comes from T4.  Since T4 is converted to either T3 (active hormone) or RT3 (a blocking hormone), the ratio of T3 to RT3 is all that’s needed to make the diagnosis of Non-Thyroidal Illness.

As often the case, the idea of comparing T3 to RT3 came to many people at the same time.  I began looking at the ratio in the late 1990s and shortly after, Genova Lab offered the test.  Groups in Brazil, Holland and England studied the ratio and by 2005, a Dutch-Belgian report showed the T3/ RT3 ratio was the single most significant indicator of which ICU patients would live and which would die.  How’s that for validation?

Treatment of hypothyroidism, revisited

Now we can understand why thyroid treatment with T4 alone might not be successful.  Many patients, ill and stressed, are not able to efficiently activate T4 to T3.  For best results, treatment should include T3.  Because of its short half-life, T3 must be given at least twice-daily.  This is true for all preparations that contain T3, including Armour thyroid.

What of the people with Non-Thyroidal Illness (NTI)?  Prescription T4 does not correct the problem – indeed, it worsens it.  Wilson again was correct when he suggested giving them twice-daily treatment with T3; it works!

A professional golfer has different clubs in his bag and knows when to use them.  Similarly, a skilled physician should know how to use the different thyroid hormone preparations and in which situations.  While our scope here is limited, a few observations are in order.

Synthetic T4 is bio-identical but often disappoints its user.  USP “natural” thyroid is relatively rich in T3 but still contains 80% T4.  That is enough T4 to occasionally give hypothyroid patients poor results – and rather often disappoint NTI patients – sometimes leading to quite large doses being taken, that might become harmful.

The best treatment for NTI patients is prescription T3 taken twice-daily.  Even better, T3 can be given along with T4 or Armour “natural” thyroid to get the mixture of T4 and T3 “just right” for each patient.  Please note: T3 doesn’t have to be expensively compounded; standard T3 tablets work very well (Cytomel®, Paddock liothyronine).  I’ve observed the compounding material doesn’t delay absorption so much as blocks it – many patients’ blood levels have shown their uptake was reduced by about 50%.

Other considerations in giving thyroid hormone treatment

Always remember we are treating the whole patient, not just the thyroid gland.  When we reactivate a person’s metabolism, we influence virtually their entire body.  If the adrenal gland is stressed-out and depleted from “working overtime,” it may not be able to keep up!  I give most of my patients some excellent over-the-counter nutrition to enable their adrenal glands to perform their jobs efficiently.  Although low-thyroid may cause low blood sugar, occasionally fixing the thyroid may exaggerate the effects of a bad diet and some patients may have worse symptoms after indiscreet snacks.  Hormones also effect each other and taking thyroid can increase the need for estrogen, sometimes worsening symptoms of menopause (and taking the Pill or hormone replacement may worsen a thyroid problem!).

There’s an important consideration which is not found in any book (but my own).  Caffeine and other stimulants may cause problems on starting thyroid hormone treatment.  Most of my hypothyroid patients have a pretty big caffeine habit – their failing energy called for a boost and caffeine is legal and tasty!  When I began treating my thyroid disease, my caffeine intake was two pots of coffee daily (pots!).  On all that, a little pediatric dose of Armour made my hands shake!  As you build your thyroid dose, it is necessary to wean off all caffeine and stimulants that may interact with thyroid hormone.  Once we’ve found the ideal dose, enjoy some caffeine – but you’ll need very little.

Summary

Thyroid problems are common.  Symptoms of hypothyroidism and hyperthyroidism are similar to each other and to a variety of other hormonal disorders as well.  Modern doctors are fortunate to be able to employ brilliant laboratory tests – but we must understand how to apply them.  Our “standard’ methods of diagnosis do not reveal Non-Thyroidal Illness.  My 25 years of working with chronically fatigued people has convinced me that many of them indeed have NTI.  They have been denied a diagnosis – and the treatment that would have restored them to health.

Applying our new knowledge and determining how T4 is processed by measuring the T3/ RT3 ratio will give our patients much better results.  Those with NTI can be diagnosed and successfully treated.  Indeed, all hypothyroid patients can benefit from making certain they are receiving the right forms of replacement hormones in the right proportions.

Alan McDaniel, MD is a Board-certified Ear, Nose & Throat specialist with two sub-specialties.  His work with dizziness and allergy in the 1980s led him to seek solutions for Chronic Fatigue Syndrome.  Since 2003, Dr. McDaniel has taught physicians practicing on five continents to effectively employ nutrition and hormones for this and other issues in his two-day course titled “The New Endocrinology.”  Dr. McDaniel has been a visiting physician at Gordon Medical Associates in Santa Rosa, California.