Why Natural Thyroid is Better than Synthetic

This article is part one of a series.
For part Two, Click Here
For Part Three Click Here.

by Jeffrey Dach MD

We use exclusively natural thyroid in our office, and a few times every day, I find myself explaining why natural thyroid is superior to Synthroid.  In this article, we will explain why natural thyroid tablets are better than synthetic T4 only tablets, also called Synthroid.

Left Image: Thyroid Gland on Radionuclide Scan Courtesy of Wikimedia Commons.

What is Synthroid? What is in it?

Synthroid contains Thyroxine also called T4,which is identical hormone produced by the thyroid gland.  Levothyroxine is the generic form of Synthroid.  Common brand names include Thyrax, Euthyrox, Levaxin, L-thyroxine, Eltroxin and Thyrax Duotab in Europe; Thyrox in South Asia; Eutirox, Levoxyl and Synthroid in North America.  Strictly speaking, Synthroid is bio-identical, even though it is synthetic.

What is in Natural Thyroid?

Natural Thyroid pills are made from desiccated porcine (pig) thyroid glands which contain Thyroxine (T4), T3, T2, T1 and Calcitonin.

Left Image: courtesy of wikimedia: Natural Thyroid tablets come from this animal, the pig.

Economics of Synthroid

As of 2005, 10 million people in the U.S. take thyroxine. When one considered that  Abbott’s Synthroid is the most popular form of thyroxine, and the second-most prescribed drug in the U.S., one starts to understand the financial rivalry between Synthroid and natural thyroid competitors.

Left image: chemical structure of Tri-Iodothyronine (T3) notice three Iodine molecules.  Add a fourth iodine molecule at the far left ring to make thyroxine, T4.  Image courtesy of wikimedia commons.

What Does Mainstream Medicine Say ?

Here is a typical statement by Mainstream Medicine found on a popular medical information web site called medicine.net. Armour is a natural desiccated porcine thyroid preparation containing T1, T2, T3, T4 and calcitonin.  Synthroid contains only T4.

From Medicine.Net : Answering a Viewer Question

What is your feeling regarding natural vs. synthetic replacement therapy in hypothyroid situations? Armour, for example vs. Synthroid? from L.H.

Doctor’s Answer:  While it is reasonable to assume that synthetic medications are less desirable than natural counterparts, in this case- natural thyroid hormone replacement is definitely not an ideal solution for the vast majority of people.

Here’s why: Armour thyroid is derived from desiccated pig (porcine) thyroid gland. A number of years ago, these natural preparations were our only alternative. Replacement with desiccated thyroid creates dosing problems because there is no way to standardize the exact amount of the dose for each batch. As a matter of fact, these preparations do not report their dosage strength in milligrams, but rather, in grains of thyroid. This is because, they don’t really know the milligram equivalent in each dose. Dosing is also based on the assumptions that each gland has equal amounts of hormones as the next gland, and that the ratio of T4 and T3 (the more active hormone) are similar and constant in each gland from the pigs. There is no way to be certain of this, and patients on these preparations often have fluctuating hormone levels, which may or may not result in symptoms.

Regardless of symptoms, the goal of replacement therapy is to keep the hormone levels as stable as possible. This is much easier to achieve with synthetic preparations such as Levoxyl and Synthroid. These preparations come in a vast number of standardized doses, allowing for minute adjustments in hormone dosing. There is another comment that should be made. With all the issues surrounding “mad cow disease” and other ailments, I personally am reluctant to offer animal based therapy to patients when a safe effective well studied synthetic preparation is widely available.

I hope this helps answer any questions you may have. Thank you for your question.

Medical Author: RM, M.D.

“Natural Thyroid is Not an Ideal Solution” ? !!!!

This nonsense really makes my blood boil and my eyes pop out of head.

Let’s start by doing a little research. If the above statement is true, we should expect to find that the FDAHAS NEVER recalled Synthroid because of problems with stability or potency, and we would expect that the FDA HAS recalled natural thyroid pills because they are unstable, and vary in potency. So let’s ask the FDA about this.  What do we find?  In reality, the FDA says Synthroid is unstable and varies in potency, while natural thyroid from RLC labs HAS NEVER been recalled for instability or variation in potency.

Is Synthroid a Reliable and Stable Drug?

No, Says the FDA.

Synthroid was marketed in 1955, but not FDA approved until July 24. 2002 because of a “history of potency failures…indicates that Synthroid has not been reliably potent and stable.”– United States Food and Drug Administration Letter  to Synthroid Manufacturer, Knoll Pharmaceuticals, April 26, 2001 (link )

Unstable, not of Consistent Potency from Lot to lot

Here is an FDA document  August 14, 1997, Docket No. 97N-0314, which says:

“The drug substance levothyroxine sodium (also called Synthroid) is unstable in the presence of light, temperature, air, and humidity. Unless the manufacturing  process can be carefully and consistently controlled, orally administered levothyroxine sodium products may not be fully potent through the labeled expiration date, or be of consistent potency from lot to lot.

There is evidence from recalls, adverse drug experience reports, and inspection reports that even when a physician consistently prescribes the same brand of orally administered levothyroxine sodium, patients may receive products of variable potency at a given dose. Such variations in product potency present actual safety and effectiveness concerns.

However, no currently marketed orally administered levothyroxine sodium product has been shown to demonstrate consistent potency and stability and, thus, no currently marketed orally administered levothyroxine sodium product is generally recognized as safe and effective. ” end quote source:http://www.gpo.gov/fdsys/pkg/FR-1997-08-14/html/97-21575.htm
FDA Document [Federal Register: August 14, 1997 (Volume 62, Number 157)][Notices][Page 43535-43538]

Armour Thyroid Pill Recall 2005

To be completely fair, there was a recall of Armour thyroid in 2005,  Lots manufactured in 2003 were found to have lost potency 2 years later in 2005, so Forest Labs recalled all tablets made in 2003.  Since it was 2 years later, very little product from these lots was still in distribution, so it was actually a small recall.

Left Image courtesy of wikimedia commons

Change in Armour Formulation

Armour changed their thyroid tablet formulation in 2009, and we have seen reports from patients who are not happy with the new formulation.  To avoid any questions, we use exclusively Naturethroid from RLC labs.  After five years of clinical experience with Naturethroid from RLC labs, I can fully endorse the product as an excellent form of thyroid medication.

Naturethroid Manufacturer Speaks Out: Natural vs Synthetic

The makers of Naturethroid say this :

“In contrast to Naturally Desiccated Thyroid (NDT) containing T3 and T4, most synthetic medications contain T4 (or T3) only. In reality, many patients don’t start to feel normal again until they switch from synthetic to NDT (Thyroid USP). Natural Desiccated Thyroid hormone replacement has been used since the late 1800s, and it is one of the safest drugs available. It contains a full spectrum of thyroid hormones, T4 and T3 and also T2 and T1 as well.

The typical indication by the proponents of synthetic T4 is that NDT is unstable and inconsistent in its dosage. However, under the full USP monograph of both Thyroid USP as an ingredient and Thyroid USP Tablet as a finished product establishing full prescription status, this conventional argument could not be further from the truth. Unlike Nature-Throid™ and Westhroid™, synthetic medications have often been recalled due to batch inconsistencies. Yet most doctors are led to believe that desiccated thyroid is unstable.

To ensure that Nature-Throid™ and Westhroid™ Thyroid USP tablets are consistently potent from tablet to tablet and lot to lot, analytical tests are performed on the raw material (Thyroid USP powder) and on the actual tablets (finished product) to measure actual T4 and T3 activity.”

By the way, contrary to the Medicine.net comment above, natural thyroid tablets are labeled in milligrams. One Grain tablets contain 65 mg .

Left Image courtesy of wikimedia: Conversion of T4 to T3 with IDI Deiodinase enzyme.

Conversion of T4 to T3

A common problem for many patients who don’t feel well on Synthroid is the inability to convert T4 to T3 .  Synthroid contains T4 which is inactive, and must be converted to T3 by the body for it to work.  This conversion is done by the De-Iodinase Enzyme (see image above).  Sometimes this enzyme is deficient or not working, and many patients have an inability to convert T4 to T3.  They feel much better on a natural thyroid medication which contains T3 and T4.  In my experience, most patients feel much better, with more energy, and relief symptoms when switching from synthroid to a natural thyroid such as Naturethroid.

Mary Shomon on Natural Thyroid vs Synthetic

An article by Mary Shoman in the Townsend letter explains why natural thyroid treatment is better, that Synthroid and Levothyroxine are unstable, with dosage varying according to batch, and subjected to multiple recalls.  Natural thyroid from RLC labs has never been recalled and is the preferred solution. Mary Shomon’s blog is an excellent resource on natural thyroid.

Left Image: Courtesy of Mary Shomon

Can I Get Mad Cow Disease from My Pig Thyroid Pill?

Millions of Americans have enjoyed ham sandwiches and pork products for decades without a single case of Mad Cow Disease ever reported.  This essentially invalidates the fear of Mad Cow Disease as an argument.  However, Mary Shomon advises caution with over-the-counter glandular supplements, which may contain unregulated meat products from areas of Europe known to have mad cow infected livestock.

Stop the Thyroid Madness

Another excellent resource is the Stop Your Thyroid Madness Blog and Book by Janie Bowthorpe.  Janie suffered for years with low thyroid symptoms wven while on Synthroid, and had a dramatic recovery after covverting from synthroid to natural thyroid.  With her blog and book, she is one of the strongest advocates for natural thyroid medication.

Left Image: Book Cover, courtesy of Janie Bowthorpe

Our Program:

For diagnosis of low thyroid, we use a lengthy questionnaire which reviews over 70 symptoms of low thyroid, a complete thyroid blood panel including TSH, free T3 and free T4, Thyroid antibodies and a physical examination which includes measurement of reflex time. Also included is a basal body temperature chart filled out by the patient at home.   We also measure selenium and iodine levels and supplement when found low.

Once it has been determined that thyroid hormone is likely to be beneficial, a trial of low dose Nature-Throid from RLC labs is started with a Half Grain (32 mg) tablet every other morning.

A log book is kept by the patient describing benefits of increased energy, clarity of mind, etc, or adverse effects such as palpitations, feeling of warmth, anxiety or insomnia. At the end of a week, the log book is reviewed to determine if the thyroid was of benefit.

We have found that monitoring symptoms with a log book, and the Half Grain gradual increments in thyroid dosage every two to three weeks makes this program very safe. In the event of rapid heart rate or palpitations, the patient is instructed to hold the daily dosage of thyroid medication and inform the physician. This program is also excellent for switching patients from Synthroid to Natural Thyroid with patients invariably reporting dramatic improvement afterwards.

Instead of Natural Thyroid, Why Not Use Cytomel and Synthroid Together?

Cytomel is T3 and Synthroid is T4, so why not use the two together? The Cytomel provides the missing T3 to make a combination that is closer to the Natural Thyroid.  Some patients arrive at my office having been given this combination from the doctor.  The advantage for the prescribing doctor is that both items, Synthroid and Cytomel are available at the corner drugstore, wheras natural thyroid is available from a compounding pharmacy.

Natural Thyroid is still the preferred choice. Among other missing ingredients, the Synthroid and Cytomel lacks Calcitonin which is present in natural thyroid, and usually lacking in patients after thyroidectomy which removes the parathyroid glands.  Giving back the missing calcitonin makes sense, and patients usually feel better.

Update 10/14: New study patient are more satisfied when converted from  Synthroid to Armour: Click here to read the pdf of the study Conversion to Armour Thyroid_endocrinology-2-1055.

This article is part one of a series.
For part Two, Click Here
For Part Three Click Here.

Articles with Related Content:

New Study Shows Natural Thyroid is Better than Synthetic

Hashimotos Thyroiditis and Selenium Part One

Hashimotos, Selenium and Iodine, Part Two

Ann Nicole Smith and Hypothyroidism

Why Natural Thyroid is Better than Synthetic Part One

Why Natural Thyroid is Better Part Two

The TSH Reference Range Wars – Part One

TSH Wars, Part Two

The Thyroid Nodule Epidemic

The Strange Case of the Autonomous Thyroid  Nodule

Books Recommended:

Hypothyroidism the Unsuspected Illness, by Broda Barnes MD

Iodine, Why You Need It and Why You Cant Live Without It by David Brownstein MD

Hypothyroidism, Type Two by Mark Starr MD

Adrenal Fatigue: The 21st Century Stress Syndrome  by Wilson

jeffrey dach md

Links and References

http://findarticles.com/p/articles/mi_m0ISW/is_2002_Feb-March/ai_82881784/?tag=content;col1

Treating hypothyroidism naturally , in the Townsend Letter for Doctors and Patients, Feb-March, 2002 by Sunny Willmington, Howard Hagglund, Mary Shomon – Natural vs Synthetic Thyroid

http://thyroid.about.com/cs/synthroidlawsuit/a/settlement.htm
The Synthroid Settlement: Fair Payoff or Patient Ripoff?
By Mary Shomon, About.com  December 14, 2003

http://www.wes-throid.com/vs.asp  Natural vs Synthetic

http://pubs.acs.org/cen/coverstory/83/8325/8325thyroxine.html
Chemical and Engineering News
The Top Pharmaceuticals That Changed The World Vol. 83, Issue 25 (6/20/05)
Today, more than 10 million people in the U.S. take thyroxine. Synthroid, manufactured by Abbott Laboratories and the most popular brand of thyroxine, is the second-most prescribed drug in the U.S.

http://www.thecompounder.com/alternative-treatments/hormone-imbalance/thyroid/armour-thyroid-synthroid-a-thyroid-madness
Larry Frieders, the compounder, THYROID MADNESS DEFINITION:

1.Treating hypothyroid patients solely with T4-only meds (synthroid)
2.Dosing solely by the TSH and the total T4, or using the outdated “Thyroid Panel”
3.Prescribing anti-depressants in lieu of evaluating and treating the free T3
4.Telling thyroid patients that desiccated natural thyroid like Armour is “unreliable”, “inconsistent”, “dangerous” or “outdated”.
5.Making lab work more important than the hypo symptoms which scream their presence
6.Failing to see the OBVIOUS symptoms of poorly treated thyroid, and instead, recommending a slew of other tests and diagnoses.

synthroid

Common brand names include Thyrax, Euthyrox, Levaxin, L-thyroxine, Eltroxin and Thyrax Duotab in Europe; Thyrox in South Asia; Eutirox, Levoxyl and Synthroid in North America. There are also numerous generic versions. Synthroid is the most prescribed brand of T4 in the United States. Synthroid was marketed in 1955, but was not FDA approved at that time as it was “generally regarded safe”.[5] In the 1990s, in response to debate as to whether Synthroid was more effective than other levothyroxine preparations, (which ended up concluding that there was little difference between Synthroid and generic brands) all levothyroxine preparations were required to undergo the formal FDA approval process. Synthroid was approved by the FDA on 24 July 2002.[6]

http://www.thyroid-info.com/articles/synthroidproblems.htm
Synthroid Has a Long History of Problems, Says FDA
In Denying Synthroid’s Request for Special Approval Status, FDA’s Scathing Letter Outlines History of Subpotent Product, Inconsistency and Poor Stability
by Mary Shomon

http://www.medicinenet.com/script/main/art.asp?articlekey=17253
Medicine net web site

http://www.naturalthyroidchoices.com/FDANT.html
What’s up with desiccated thyroid
& the FDA?

http://www.life-enhancement.com/article_template.asp?id=907
Between 1991 and 1997, there were ten recalls of synthetic T4, involving over 100 million tablets.9 In nine of these recalls, the tablets had been found to be subpotent, or they were losing their potency before their expiration date; in the tenth recall, the tablets were found to be too potent. For patients, such unreliability means that the synthetic T4 they receive could be either too strong or not strong enough to treat their condition properly
Source: Federal Register 62, No. 157, 14 August 1997, pp. 43535-8.
________________

http://thyroid.about.com/od/thyroiddrugstreatments/a/recall2005.htm
As with all drugs, Armour’s manufacturer, Forest Laboratories, holds back samples from every lot it produces, and periodically tests those samples. When Armour Thyroid is manufactured, it has a 24-month expiration date. That means that Armour Thyroid should maintain its potency for a full two years.
What Forest found in recent sample testing was that there were several lots of Armour Thyroid that were not maintaining full potency. These lots were manufactured between March 2003 and August of 2003, and therefore they were set to expire between March 2005 and August of 2005.

http://www.nature-throid.com/vs.asp
The typical indication by the proponents of synthetic T4 is that NDT is unstable and inconsistent in its dosage. However, under the full USP monograph of both Thyroid USP as an ingredient and Thyroid USP Tablet as a finished product establishing full prescription status, this conventional argument could not be further from the truth. Unlike Nature-Throid™ and Westhroid™, synthetic medications have often been recalled due to batch inconsistencies. Yet most doctors are led to believe that desiccated thyroid is unstable.

http://www.thyroid-info.com/articles/madcow.htm
Is There A Real Risk of Mad Cow Disease from Armour Thyroid?
An Update on Armour Thyroid and Glandulars by Mary Shomon
If you are willing to eat American pork products, you shouldn’t be any more concerned about Armour thyroid, as far as risk of mad cow disease. Caution is encouraged, however, with over-the-counter glandular supplements, which may contain unregulated meat products from areas of Europe known to have mad cow infected livestock.

http://www.altsupportthyroid.org/dt/dtrefs.php
Desiccated Thyroid References

Jeffrey Dach MD
www.jeffreydach.com
www.drdach.com
www.naturalmedicine101.com
www.truemedmd.com

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The Unreliable TSH Lab Test 

by Jeffrey Dach MD

This article is part one of a series, click here for part two,and click here for part three.

A Woman with Low Thyroid Condition

Suzy is a 59 year old post menopausal woman with low thyroid function.  About three months ago, she started her bio-identical hormone program which included natural thyroid pills.  After starting the program, she was doing well with more energy, better sleep, improved appearance of skin and hair, and resolution of her menopausal symptoms of flashes and sweats.  However about 12 weeks into her program, Suzy had a visit with her primary care doctor who did a follow up thyroid panel.  Her primary care doctor informed Suzy that her TSH test result was below the lab normal range, and therefore, her thyroid dose was too high, and should be reduced. (Note: TSH is Thyroid Stimulating Hormone, and is made by the pituitary gland).  Above left image: Thyroid scan courtesy of wikimedia commons.

Too Many Doctors Spoil the Soup

Suzy called me at the office distraught and confused.  Two doctors were telling her two different things and she didn’t know who to believe.  Her primary care doctor was telling her one thing and I was telling her another.  I explained to Suzy that her primary care doctor was incorrect in relying slavishly on the TSH test. Even though her TSH test was 0.15 which is below the lab reference range of 0.3, this was perfectly acceptable and indicated her thyroid medicine was suppressing the TSH to a low level which was perfectly fine.   This test interpretation means she is taking thyroid pills, and the pills are working.  It does not mean she is “hyperthyroid” by any stretch of the imagination.

No Clinical Evidence of Thyrotoxicosis

I also informed Suzy that her Primary Care Doctor is mistakenly relying on the TSH test to determine her thyroid dosage. The TSH test is an indirect measure of thyroid function and can be unreliable to monitor thyroid dosage.  A more accurate indicator of thyroid function is the free T3, which in her case was 375, well within the normal range of 240 to 420. The Free T3 lab test together with the absence of any signs or symptoms of thyroid excess indicates she is using the correct dosage of natural thyroid medication. Symptoms of thyroid excess are rapid heartbeat or palpitations, and Suzy reported no such symptoms.  In fact, Suzy said she felt fine and now that she understands it, she didn’t want to go back to feeling tired, sluggish as before she started the thyroid pills.  Suzy was relieved to find out that the low TSH result was perfectly acceptable and there was nothing to worry about.  This TSH scenario is a recurring event at my office.

Conventional Docs Slavishly Rely on the TSH Test 

Conventional primary care doctors use an older thyroid lab panel which does not include the Free T3 test, the most informative thyroid lab test.  Instead, mainstream endocrinology relies on the TSH test which is not a direct measure of thyroid function, and can, in fact, be unreliable.

Above Left image: Thyroid Gland Anatomy Diagram, courtesy of  National Institute of Health, and wikimedia commons.

Most conventional doctors are unfamiliar with the use of natural thyroid which contains both T3 and T4, and instead use Synthroid which is quite different, containing only T4.   Since the Primary care doctors bill the health insurance for the office visit and payment is only a few dollars, the office visit is brief, 3-5 minutes.  In this short time, Primary care doctors can provide only the most basic care, which is a quick look at the TSH lab test.  If the TSH is below the lab reference range the doctor gives a new prescription for Synthroid with a reduced dosage.  If the TSH is above the reference range, the primary care doctor will increase the Synthroid dosage.

The Cleveland Clinic Chimes In

A few months ago, I found myself talking on the phone with an endocrinologist at the Cleveland Clinic explaining why the TSH blood test can be unreliable. He informed me I was wrong, and that he uses the TSH test as the gold standard. We agreed to disagree and parted company as friends. I have found that, in general, endocrinologists and mainstream doctors rely heavily on TSH to make a diagnosis of low thyroid.

Why Thyroid Blood Testing is Unreliable.

I recommend to you a book by Barry Durrant Peatfield, Your Thyroid and How to Keep It Healthy(1)   After serving as a general practitioner in the British National Health Service,  Peatfield traveled to the US to train at the Broda Barnes Institute.  Peatfield later returned to England to start his own thyroid clinic.  His book was written at the end of his career and contains the wisdom of 25 years of diagnosing and treating thyroid conditions.   One section of the book is devoted to this question.  Here it is quoted from the book: :

1) Anxiety in the medical establishment about rules and dogma has led to a slavish reliance on blood tests, such as the TSH, which are often unreliable and can actually produce a false picture.

2) Very few doctors can accept the fact that a normal, or low TSH, may still occur with low thyroid function.

3) As a result of this test (TSH), thousands are denied treatment for low thyroid condition.

Dr. Peatfield’s Reward After a LifeTime of Service

After a lifetime of work serving his community, you might imagine the honors and accolades for such a knowledgeable thyroidologist as Dr Peatfield,   yet quite the opposite happened.  Dr. Peatfield’s license was suspended in 2001 at the age of 68 by the General Medical Council of England.(5-6)  The GMC ruling was based on “unfavorable testimony” from competing endocrinologists who “slavishly rely on the TSH test” as a measurement of thyroid function to diagnose the low thyroid condition and monitor treatment with thyroxine.  Sadly, this is the sort of “Witch Hunt “which has kept medical science in the “Dark Ages” regarding the treatment of the low thyroid condition.(13)

Broda Barnes and the Low Thyroid Condition

Another useful book recommended to you is written by Broda Barnes MD on the low thyroid condition.   Broda Barnes MD reported 40 years ago on the same problem of his medical colleagues relying too heavily on thyroid blood tests.  The book, Hypothyroidism: The Unsuspected Illnessby Barnes, Broda is a medical classic and should be required reading for every medical student and doctor. (2)  I have read the book many times. The book contains the condensed wisdom of a lifetime of research and clinical experience with the thyroid, and it rings true today as it did in 1976. Thyroid blood tests come and go, yet human physiology remains the same.

Important Point:  The TSH test is unreliable for determining optimal thyroid dosage.  A “below lab range” TSH is routinely encountered when patients are optimally treated with natural thyroid medication and obtain the best clinical results.

Hypothyroidism the Unsuspected Illness, by Broda Barnes MD

Broda Barnes estimated that up to 40% of the population suffers from a low thyroid condition and would benefit from thyroid medication. Of course, Barnes’ opinion differed with that of mainstream medicine of his time which relied dogmatically on thyroid blood tests to make the diagnosis of low thyroid.  Barnes felt the blood tests were unreliable and instead used the basal temperature, history and physical examination. This medical debate regarding unreliability of thyroid blood testing continues today. (3,4)

Being an astute clinician, Dr. Barnes makes a number of observations about the low thyroid condition. Firstly, low thyroid is associated with a reduced immunity to infectious diseases such as TB (tuberculosis). Before the advent of modern antibiotics in the 1940’s, most low thyroid children succumbed to infectious diseases before reaching adulthood. Secondly, low thyroid is associated with a peculiar form of skin thickening called myxedema which causes a characteristic appearance of the face, puffiness around the eyes, fullness under the chin, loss of outer eyebrows, and hair thinning or hair loss.

A third observation by Dr. Barnes is that low thyroid is associated with menstrual irregularities, miscarriages and infertility. Barnes treated thousands of young women with thyroid pills which restored cycle regularity and fertility. In his day, the medical system resorted to the drastic measure of hysterectomy for uncontrolled menstrual bleeding. Although today’s use of birth control pills to regulate the cycles is admittedly a far better alternative, Barnes found that the simple administration of desiccated thyroid served quite well. Again, Barnes noted that blood testing was usually normal in these cases which respond to thyroid medication.

A lengthy chapter is devoted to heart attacks and the low thyroid condition. Based on autopsy data from Graz Austria, Barnes concluded that low thyroid patients who previously would have succumbed to infectious diseases in childhood go on years later to develop heart disease. Barnes also found that thyroid treatment was protective in preventing heart attacks, based on his own clinical experience. Likewise for diabetes, Dr. Barnes found that adding thyroid medication was beneficial at preventing the onset of vascular disease in diabetics. Again, blood tests are usually normal.

Important Point:  A low thyroid condition is a serious risk factor for heart disease.

Dr. Barnes devotes separate chapters in the book to discussion of chronic fatigue, migraine headaches and emotional/behavioral disorders all of which respond to treatment with thyroid medication.

The final chapter describes Dr. Barnes work on obesity when he presided over a hospital ward of volunteer obese patients, and monitored everything they ate. He found that the obese patients invariably ate a high carbohydrate diet, and avoided fat. Barnes added fat back into the menu and reduced the refined carbohydrates and found that his obese patients lost 10 pounds a month with no hunger pangs.

Missing from the book are discussions of Iodine supplementation and the role of the Adrenal, both of which are covered in later updated versions of Barnes thyroid book by other authors. See Hypothyroidism Type Two by Mark Starr, and Your Thyroid by Barry Durrant Peatfield. Iodine supplementation is covered by both Derry and Brownstein. The Safe Uses of Cortisol by William McK Jefferies is the companion medical classic devoted to the adrenals and cortisol.

Broda Barnes Institute

Although Broda Barnes has since passed away, his work lives in at the Broda Barnes Institute.  Patricia Puglio is the director and a great resource.  She is available by phone to answer questions and offer suggestions. Here is her contact information: Patricia A. Puglio, Director, Broda O. Barnes, M.D. Research Foundation, Inc. PO Box 110098 Trumbull, CT 06611.

More on the Unreliability of the TSH Lab Test

Thanks to Jonathan Wright’s newsletter for bringing to my attention a recent article in the June 2010 International Journal of Clinical Practice by Dr. O’Reilly which summarizes the medical literature on this question of the reliability of the TSH test. (9)   Essentially, Dr O’Reilly reviews the medical literature and the history thyroid medicine and provides all the medical studies and information showing that Dr Barnes and Dr Peatfield were right all along. (7-12). Here are a few quotes from Dr O’Reilly (9):

The use of the TSH measurement to assess thyroid status in patients on thyroxine (Synthroid) replacement could be considered a classic example of the misapplication of a laboratory test.”

Instead of the TSH measurement, Dr. O’Reilly recommends the T3 test for monitoring treatment with thyroid medication.  He says:

“The adequacy of thyroxine (Synthroid) replacement should be assessed clinically with the serum T3 being measured, when required, to detect over-replacement”

We use the Free T3 measurement which is widely available at any lab.

In spite of the obvious need for a better approach to the low thyroid condition, there has been very little movement to rehabilitate mainstream endocrinology which dogmatically clings to the TSH test and synthetic T4 only medications (levothyroxine).  Here in the state of Florida, we are fortunate that the state legislature passed a Health Freedom Law in 2001.  This “Health Freedom Law” protects doctors and patients from unwarranted abuse or harassment for utilizing “outside of mainstream medical practices”, such as correct diagnosis and treatment of the low thyroid condition based on the wisdom of Drs Broda Barnes, Barry Peatfield, DS O’Reilly, Jonathan Wright, David Brownstein and many others. (14)

This article is part one of a series, click here for part two,and click here for part three.

Articles with Related Interest

TSH Wars Part One

TSH Wars Part Two

References and Links,

(1) Your Thyroid and How to Keep It Healthyby Durrant-Peatfield (2006).  Hammersmith Press, London

(2) Hypothyroidism: The Unsuspected Illnessby Barnes, Broda Otto (1976). Harper Collins.

(3) http://ccpd.ucsf.edu/hypothyroidism.shtml  Pituitary 101, UCSF California Center for Pituitary Disorders at UCSF. Web Site: “TSH is often an unreliable measure of secondary hypothyroidism and should not be used to assess the adequacy of thyroid replacement in these patients. The inappropriate use of TSH levels to determine hormone replacement is one of the more common mistakes that we see in the patients we follow, and patients should be cautious if another physician discusses changing their thyroid hormone dose. Many patients have returned for their one-year follow-up visits having had their doses lowered in response to “low TSH levels.” Most of them feel poorly, but improve after we increase or restart their medication.”

(4) http://www.bmj.com/cgi/content/full/326/7398/1087  BMJ  2003;326:1087 (17 May) Letter- Thyroid function tests and hypothyroidism, A D Toft.

“We have long taken the view that most hypothyroid patients are content with a dose of thyroxine that restores serum concentrations of thyroid stimulating hormone to the low normal range. However, some achieve a sense of wellbeing only when serum thyroid stimulating hormone is suppressed, when we take care to ensure that serum tri-iodothyronine is unequivocally normal.  Until valid evidence shows that such a policy is detrimental we will continue to treat patients holistically rather than insist on adherence to a biochemical definition of adequacy of thyroxine replacement. The issue of whether a little too much thyroxine is dangerous is likely to evaporate when appropriate preparations become available to allow treat.

(5) http://www.drlowe.com/news/drpeatfield/jclletter.htm

In Defense of Dr. Barry Peatfield, letter sent ot Geneeral medical council of England as testimony on behalf of Dr. Barry Peatfield. April 17, 2001 by Dr. John C. Lowe

(6) http://news.bbc.co.uk/2/hi/health/1332644.stm

Thursday, 17 May, 2001 UK Investigation into thyroid doctor. GP Dr Barry Durrant-Peatfield, 64, who has a practice in Purley, Surrey, has been stopped from working for 18 months so that the GMC can complete its investigation.

(7) http://www.ncbi.nlm.nih.gov/pubmed/8200938  J Clin Endocrinol Metab. 1994 Jun;78(6):1368-71. Comparison of second and third generation methods for measurement of serum thyrotropin in patients with overt hyperthyroidism, patients receiving thyroxine therapy, and those with nonthyroidal illness. Franklyn JA, Black EG, Betteridge J, Sheppard MC.  “Undetectable TSH results, even in a third generation assay, are not diagnostic of overt hyperthyroidism, but are also found in subjects with treated thyroid disease and NTI.”

(8) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1341585/

Br Med J (Clin Res Ed). 1986 September 27; 293(6550): 808–810.  Are biochemical tests of thyroid function of any value in monitoring patients receiving thyroxine replacement? W D Fraser, E M Biggart, D S O’Reilly, H W Gray, J H McKillop, and J A Thomson. “These measurements are therefore of little, if any, value in monitoring patients receiving thyroxine replacement. “

(9) http://www.ncbi.nlm.nih.gov/pubmed/20584231

Int J Clin Pract. 2010 Jun;64(7):991-4. Thyroid hormone replacement: an iatrogenic problem.O’Reilly DS.

“Thyroid hormone replacement is one of the very few medical treatments devised in the 19th century that still survive. It is safe, very effective and hailed as a major success by patients and clinicians. Currently, it is arguably the most contentious issue in clinical endocrinology. The current controversy and patient disquiet began in the early 1970s, when on theoretical grounds and without proper assessment, the serum thyrotropin (TSH) concentration was adopted as the means of assessing the adequacy of thyroxine replacement. The published literature shows that the serum TSH concentration is a poor indicator of clinical status in patients on thyroxine. The adequacy of thyroxine replacement should be assessed clinically with the serum T3 being measured, when required, to detect over-replacement.”

(10) http://www.ncbi.nlm.nih.gov/pubmed/3122632

Ann Clin Biochem. 1987 Nov;24 ( Pt 6):614-9. Thyroid stimulating hormone measurement by an ultrasensitive assay during thyroxine replacement: comparison with other tests of thyroid function. Wheatley T, Clark PM, Clark JD, Raggatt PR, Edwards OM.   “A suppressed serum TSH was found in 65% of patients with a normal serum total thyroxine. “

(11) http://www.bmj.com/content/320/7245/1332.extract

BMJ 320 : 1332 doi: 10.1136/bmj.320.7245.1332 (Published 13 May 2000) Education and debate: Thyroid function tests—time for a reassessment. Denis StJ O’Reilly, consultant clinical biochemist

(12) http://www.bmj.com/content/320/7245/1332.extract/reply#bmj_el_8954

Thyroid function tests—time for a reassessment Denis StJ O’Reilly BMJ 2000;320:1332-1334

(13) http://www.independent.co.uk/life-style/health-and-families/health-news/claims-of-acirciquestiquestwitchhuntacirciquesttrade-as-doctor-is-suspended-for-alternative-thyroid-care-685141.html

Claims of witch-hunt as doctor is suspended for alternative thyroid care By Michael Durham Friday, 18 May 2001. Independent UK

(14) http://laws.flrules.org/2001/116

State of Florida Health Freedom Law: CHAPTER 2001-116 Senate Bill No. 1324 An act relating to health care; creating s. 456.41, F.S.; amending s. 381.026, F.S.; Ch. 2001-116 (S.B. 1324) Authorizes provision of and access to complementary or alternative health care treatments; requires specified disclosures by the health care practitioner and the keeping of certain records; conforms the Florida Patient’s Bill of Rights. Effective May 31, 2001.

Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663

TSH Suppression Benefits and Adverse Effects by Jeffrey Dach MD

At a recent medical meeting I attended, “the danger of TSH suppression” was mentioned.  The listening audience of doctors was advised not to suppress TSH with thyroid medication.  We were advised to make sure the TSH always stays within the lab reference range.

Thyroid Excess and Thyrotoxicosis

Of course, we would all agree that too much thyroid medication causing thyroid excess and thyrotoxicosis is to be avoided, as this clearly is the most significant adverse effect of taking thyroid hormone pills.  Taking too many pills is not a good thing, as this will cause a clinical syndrome known as thyrotoxicosis characterized by tachycardia, palpitations, insomnia, anxiety, panic attacks etc.  The arrythmia, atrial fibrillation is the dreaded complication to be avoided.

Take the Time to Go Over Thyroid Excess List of Symptoms

We actually spend 5 or 10 minutes with each patient in the office talking about Thyroid excess signs and symptoms to look for, and we give each patient a print out of this list to take home and post on their bulletin board to read every day.  If the patient experiences any symptoms of thyroid excess they are instructed to stop the thyroid pills.  Patient selection is also a factor here, as a patient with early dementia could not be expected to have the cognitive function to recognize thyroid excess and stop their pill.  The patient must be able and willing to play a role in their health care.  Otherwise, they are not a candidate for natural thyroid treatment, and instead are referred to your local friendly endocrinologist for levothyroxine dosage and TSH in range.

Stop the Thyroid Pills

Thyroid excess is easily avoided by simply stopping the thyroid medication should  signs of rapid resting heart rate occur.   Symptoms will resolve within hours after stopping the natural thyroid pill.  For T4 only levothyroxine, which has a longer half life, it takes longer for symptoms to resolve.

Is a low TSH indicative of Thyroid Excess ?

Mainstream endocrinology makes the assumption that a suppressed TSH indicates thyroid excess, and by definition, thyrotoxicosis.   This is true for Graves disease and Toxic Nodular Goiter.  In Graves disease with thyrotoxicosis, hypercalcemia from rapid bone turnover has been reported. (21,22)

However, for the vast majority of hypothyroid patients taking natural dessicated thyroid (Nature-throid- RLC labs) a suppressed TSH merely indicates adequate treatment dosage with full clinical benefit, and does not correspond with the clinical signs and symptoms (or laboratory findings) of thyroid excess.

Monitoring the Other Labs and the Patient

Of course, we always monitor Free T3, Free T4, and Thyroid antibody levels, as well as monitor the patients clinical status.  If the patient has a Free T3 and Free T4 in the normal range, and has no tachycardia at rest or any other symptoms of thyroid excess, then a suppressed TSH indicates adequate thyroid treatment, and by no stretch of the imagination could the patient possibly be in a state of thyroid excess or thyrotoxiciosis.

Adverse Health Effects of TSH Suppression

Another point mentioned at the medical meeting to persuade us clinicians not to suppress the TSH with thyroid mediation was the idea that there are adverse health consequences when the TSH is suppressed.  The major one being loss of bone density, osteoporosis which is a real finding in long standing Graves Disease patients.

However numerous studies have examined this idea in hypothyroid patients treated with thyroid pills and found this to be a medical myth.   In our patient population we see bone density improving, especially in women receiving bioidentical hormone replacement and bone supplements such as Vitamin D3, K2, magnesium and calcium..

As to the idea that there must be some adverse health effects of a suppressed TSH, this has also been examined in two groups of patients on long term TSH suppressive doses of thyroid medication, and this idea found to be false.  In patients after thyroidectomy for papillary thyroid cancer who are commonly treated with TSH suppressive doses of thyroxine, there have been no adverse effects noted in many long term studies.  Similarly in patients with thyroid nodules  treated with TSH suppression, there have no ill effects of TSH suppression.

No Adverse Effects from Low TSH
below Reference Range in Large Scale Study

In 2010, Drs Graham Leese and Robert Flynn from University of Dundee, UK published their large scale study showing no adverse effect of a low TSH in the (.03-.40) range.(24) see Is it safe for patients taking thyroxine to have a low but not suppressed serum TSH concentration? .

Japan to the Rescue

Dr Mitsuru Iti from Japan reported in 2012 that TSH-suppressive doses of levothyroxine are required to achieve  preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy.  Dr Ito found in the post-thyrodiectomy patient, moderately suppressive doses of thyroxine are required to reproduce Free T3 levels found pre-operatively.(25)  In his discussion, Dr Ito quotes Dr Maria Alevizaki Maria who reported in 2005 that “TSH may not be a good marker for adequate thyroid hormone replacement therapy.”

Thierry Hertoghe

Dr Thierry Hertoghe, possibly the most recognized thyroid expert on the planet, suppresses TSH in about 30% of his patients. (personal communication) Left Image courtesy of Thierry Hertoghe.

Thyroid Receptor Mutation Requires TSH Suppressive doses of Thyroid Hormone

Another patient population are those patients with mutations in the Thyroid hormone receptor genes.   The syndrome of peripheral thyroid hormone resistance was predicted and hypothesized twenty years ago, but only recently in 2013 was thegenetic defect in the receptor gene identified.  Patients with peripheral thyroid hormone resistance may require higher Free T3 levels to overcome the receptor defects.(23)

Normal Pregnant Women May Have a Suppressed TSH

During pregnancy, HCG levels rise to very high levels, and there is associated suppression of TSH, not indicative of a hyperthyroid state.  “In up to 10–20% of normal pregnant women, serum TSH concentrations are transiently low or undetectable.” (26)

There are many drugs which suppress TSH.

Hypothalamic Dysfunction in the Chronic Fatigue Fibromyalgia –  Central Hypothyroidism.(27-31)

Both Drs Kent Holtorf and Dr Jacob Teitelbaum have devoted much of their careers to the study and treatment of the chronic fatigue fibromyalgia patient.  One of the keys to understanding the patho-physiology in this disorder is hypothalamic dysfunction which may lead to central hypothyroidism.  One of the pituitary hormones affected by hypothalamic dysfunction is the TSH (thyroid stimulating hormone) which may be paradoxically low even though the patient is in a hypothyroid state with chronic fatigue.  Thus, according to both Drs Holtorf and Teitelbaum, the chronic fatigue patient may have central hypothyroidism with a suppressed TSH.  (27-31)  Again, it would be a clinical error to withhold thyroid hormone treatment from this patient because of a lab finding of a low or “suppressed” TSH.  Left Image courtesy of Jacob Teitelbaum MD.

Chemotherapy during cancer treatment may cause hypothalamic dysfunction in cancer-survivors.  The TSH may be paradoxically low and unreliable in these cases.

Hashimoto’s Thyroiditis Auto-Immune Thyroid Disease

It is common practice among endocrinologist to treat “euthyroid” Hashimotos patients with thyroxine (T4).  “Euthyroid”, of course,  meaning the TSH is in the lab reference range. Studies show benefit with treatment which reduces antibody levels and felt to stabilize the autoimmune process and is recommended as soon as the diagnosis is established.

Conclusion: Long term TSH suppression in the thyroid nodule and thyroid cancer patient is a common practice of  mainstream endocrinology with no adverse effects reported in many published studies.  Since the TSH is a pituitary hormone, the TSH level may not always be an accurate reflection of  peripheral thyroid levels, and may in fact be unreliable in chronic fatigue, fibromyalgia patients with hypothalamic dysfunction.

Articles with Related Interest:

TSH Wars Part One

TSH Wars Part Two

The Unreliable TSH Test

TSH Basics

Above Left Image: Radionulcide Thyroid Scan showing diffuse goiter in patient with TSH receptor mutation and resistance to thyroid hormone courtesy of KIM.

Jeffrey Dach MD
7450 Griffin road Suite 190
Davie, Fl 33314
954-792-4663

Links and References

1) http://www.ncbi.nlm.nih.gov/pubmed/8954028?dopt=Abstract
J Clin Endocrinol Metab. 1996 Dec;81(12):4278-89.
Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis. Uzzan B1, Campos J, Cucherat M, Nony P, Boissel JP, Perret GY.
1Hôpital Avicenne, Centre Hospitale Universitaire Paris Nord, France.
Osteoporosis is the main cause of spine and hip fractures. Morbidity, mortality, and costs arising from hip fractures have been well documented. Thyroid hormones (TH) are widely prescribed, mainly in the elderly. Some studies (but not all) found a deleterious effect of suppressive TH therapy on bone mass. These conflicting data raised a controversy as to the safety of current prescribing and follow-up habits, which, in turn, raised major health-care issues. To look for a detrimental effect on bone of TH therapy, we performed a meta-analysis (by pooling standardized differences, using a fixed effect model) of all published controlled cross-sectional studies (41, including about 1250 patients) concerning the impact of TH therapy on bone mineral density (BMD). Studies with women receiving estrogen therapy were excluded a priori, as were studies with a high percentage of patients with postoperative hypoparathyroidism, when no separate data were available. We decided to stratify the data according to anatomical site, menopausal status, and suppressive or replacement TH therapy, resulting in 25 meta-analysis on 138 homogeneous subsets of data. The main sources of heterogensity between studies that we could identify were replacement or suppressive TH therapy, menopausal status, site (lumbar spine, femoral neck, Ward’s triangle, greater trochanter, midshaft and distal radius, with various percentages of cortical bone), and history of hyperthyroidism, which has recently been found to impair bone mass in a large epidemiological survey. To improve homogeneity, we excluded a posteriori 102 patients from 3 studies, who had a past history of hyperthyroidism and separate BMD data, thus allowing assessment of the TH effect in almost all 25 subset meta-analyses. However, controls were usually not matched with cases for many factors influencing bone mass, such as body weight, age at menarche and at menopause, calcium dietary intake, smoking habits, alcohol intake, exercise, etc. For lumbar spine and hip (as for all other sites), suppressive TH therapy was associated with significant bone loss in postmenopausal women (but not in premenopausal women), whereas, conversely, replacement therapy was associated with bone loss in premenopausal women (spine and hip), but not in postmenopausal women. The detrimental effect of TH appeared more marked on cortical bone than on trabecular bone. Only a large long term prospective placebo-controlled trial of TH therapy (e.g. in benign nodules) evaluating BMD (and ideally fracture rate) would provide further insight into these issues.

2) http://www.ncbi.nlm.nih.gov/pubmed/15278189  J Formos Med Assoc. 2004 Jun;103(6):442-7. Bone mineral density in women receiving thyroxine suppressive therapy for differentiated thyroid carcinoma.  Chen CH1, Chen JF, Yang BY, Liu RT, Tung SC, Chien WY, Lu YC, Kuo MC, Hsieh CJ, Wang PW.

Most patients with well-differentiated thyroid carcinoma have an excellent prognosis and are likely to live long enough to be subjected to osteoporosis. The purpose of this study was to investigate the consequences of treatment with a supraphysiological dose of levothyroxine (l-T4) on bone mineral density (BMD) in Taiwanese women with differentiated thyroid cancer.
METHODS:A total of 69 (44 premenopausal, 25 postmenopausal) Taiwanese women withdifferentiated thyroid cancer were included in this retrospective study. These patients were free of disease recurrence after initial near-total thyroidectomy and I-131 radioablation, and had undergone regular l-T4 suppressive therapy for more than 3 years (mean, 7.3 +/- 3.0 years; range, 3 to 15 years). The degree of thyroid-stimulating hormone (TSH) suppression was determined based on the mean TSH score for each patient which was determined by analysis of all available follow-up TSH data, where 1 = undetectable TSH (< 0.2 mIU/mL); 2 = subnormal TSH (0.2 to 0.39 mIU/mL); 3 = normal TSH (0.4 to 4.0 mIU/mL); and 4 = elevated TSH (> 4.0 mIU/mL). The patients were divided into a full TSH suppression group with a mean TSH score in the range 1.0 to 1.99, and a partial TSH suppression group with a mean TSH score in the range 2.0 to 2.99. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck, Ward’s triangle and total hip. Comparisons between subgroups of patients and controls were performed by unpaired t test. Correlation between BMD and other clinical variables was assessed by Pearson’s correlation analysis.
RESULTS:Postmenopausal patients (aged 57.7 +/- 6.9 years) had significantly higher serum calcium levels and decreased BMD at all sites of the spine and hip as compared with premenopausal patients (aged 38.6 +/- 6.7 years) with similar BMI and duration of TSH suppression. Comparison of BMD between postmenopausal patients and BMI- and age-matched controls revealed that the patient group had decreased BMD at all sites of measurement, although this difference was not significant. This phenomenon was not observed in the premenopausal patients. Furthermore, when BMD was compared between patients categorized as having full and partial suppression of TSH, only patients with full suppression in the postmenopausal group showed a tendency to lower BMD. There was a strong correlation of BMD with age, BMI and serum calcium level. However, no correlation was found between BMD and degree of TSH suppression or duration of l-T4 suppression therapy.
CONCLUSION: Women with differentiated thyroid cancer who had long-term (mean, 7.3 +/- 3.0 years) l-T4 therapy and suppressed TSH levels had no evidence of lower BMD. However, patients with full suppression in the postmenopausal group showed a tendency towards lower BMD. Therefore, careful monitoring of BMD in postmenopausal women during suppression therapy is mandatory.

3) http://www.ncbi.nlm.nih.gov/pubmed/20429634
Endocr Regul. 2010 Apr;44(2):57-63.
Thyrotropin versus thyroid hormone in regulating bone density and turnover in premenopausal women.  Baqi L1, Payer J, Killinger Z, Hruzikova P, Cierny D, Susienkova K, Langer P.

This cross-sectional study aimed to evaluate the interrelations between endogenous TSH level on one side and the status of bone mineral density (BMD) and bone metabolic turnover (BMT) on the other in pooled four groups of premenopausal women either without or with a long-term L-thyroxine treatment.
METHODS:Serum levels of free thyroxine (FT4), thyrotropin (TSH), calcium (Ca), alkaline phosphatase (ALP), osteocalcin OC) and cross linked N-telopeptide of type 1 collagen (NTx) as well as urinary calcium (U-Ca/24h), bone mineral density of lumbar spine L 1-4 (BMD-L) and femoral hip (BMD-F) were estimated in a cohort of 151 premenopausal women (median 36 years) consisting of four groups: Group 1, 40 healthy untreated women, while three other groups consisted of patients previously treated for about 5 years; Group 2, 41 patients with genuine hypothyroidism treated by L-thyroxine (50-100 microg daily); Group 3, 40 patients with genuine hyperthyroidism treated by Carbimazol (10-15 mg daily); Group 4, 30 patients treated by suppressive doses of L-thyroxine (100-150 microg daily) after thyroidectomy for thyroid cancer (n=10) or because of progressively growing benign goitre (n=20).
RESULTS:When using multiple correlation analysis (Pearson’s r) in pooled 151 women, TSH showed significant positive correlation with BMD-L (p<0.01) and BMD-F (p<0.001) and, at the same time, significant negative correlation with serum level of BMT markers such as ALP (p<0.05), OC (p<0.05) and NTx (p<0.01), while the correlation of FT4 with BMD-L, BMD-F was significantly negative (p<0.001 for both) and that with all BMT markers was significantly positive (p<0.05 to <0.001). Thus, it appeared that higher TSH level was associated with increased bone mineral density and, at the same, with decreased bone metabolic turnover. These interrelations were further supported by the findings of significantly lower BMD-F (p<0.01), BMD-L (p<0.001) and significantly higher ALP, OC and NTX (all at p<0.001) in the group of 36 women with TSH level<0.3 mU/l as compared to the group of 115 women with TSH level range of 0.35-6.3 mU/l).
CONCLUSIONS:Irrespectively of thyroid diagnosis and/or previous long term thyroxine treatment in some groups, this cross sectional study showed that, after the pooled group of 151 women has been redistributed according to the actual TSH level, the bone mineral density and the level of bone turnover markers was significantly more favorable in 115 subjects with TSH level range of 0.35-6.3 mU/l than these in 36 women with TSH<0.3 mU/l.

4) http://www.ncbi.nlm.nih.gov/pubmed/3295553
N Engl J Med. 1987 Jul 9;317(2):70-5.
Suppressive therapy with levothyroxine for solitary thyroid nodules. A double-blind controlled clinical study. Gharib H, James EM, Charboneau JW, Naessens JM, Offord KP, Gorman CA.
Thyroid nodules are present in up to 50 percent of adults in the fifth decade of life. Patients are often treated with thyroxine in order to reduce the size of the nodule, but the efficacy of thyrotropin-suppressive therapy with thyroxine remains uncertain. In this study, 53 patients with a colloid solitary thyroid nodule confirmed by biopsy were randomly assigned in a double-blind manner to receive placebo (n = 25) or levothyroxine (n = 28) for six months. Before treatment, pertechnetate-99m thyroid scanning showed that 22 percent of the nodules were functional, 25 percent hypofunctional, and 53 percent nonfunctional. High-resolution (10-MHz) sonography was used to measure the size of the nodules before and after treatment. Suppression of thyrotropin release was confirmed in the levothyroxine-treated group by the administration of thyrotropin-releasing hormone; thyrotropin release was normal in the placebo group. Six months of therapy did not significantly decrease the diameter or volume of the nodules in the levothyroxine group as compared with the placebo group. We conclude that the efficacy of levothyroxine therapy in reducing the size of colloid thyroid nodules is not apparent within six months, despite effective suppression of thyrotropin.

5) http://www.ncbi.nlm.nih.gov/pubmed/12414852
J Clin Endocrinol Metab. 2002 Nov;87(11):4928-34.
Effects of thyroid-stimulating hormone suppression with levothyroxine in reducing the volume of solitary thyroid nodules and improving extranodular nonpalpable changes: a randomized, double-blind, placebo-controlled trial by the French Thyroid Research Group.  Wémeau JL1, Caron P, Schvartz C, Schlienger JL, Orgiazzi J, Cousty C, Vlaeminck-Guillem V.
The efficacy of suppressing TSH secretion with levothyroxine (L-T(4)) in reducing solitary thyroid nodule growth is still controversial. In this prospective multicenter, randomized, double-blind, placebo-controlled trial, 123 patients with a single palpable benign nodule were included and randomly allocated to an 18-month treatment with L-T(4) or placebo. Individual dose was adjusted to allow a serum TSH level below 0.3 mIU/liter. Clinical and ultrasonographic nodule characteristics were assessed before treatment and 3, 6, 12, and 18 months thereafter. The largest mean nodule size assessed on palpation and largest volume, assessed by ultrasonography, decreased in the L-T(4) group and increased slightly in the placebo group [size, -3.5 +/- 7 mm vs. +0.5 +/- 6 mm (P = 0.006); volume, -0.36 +/- 1.71 ml vs. +0.62 +/- 3.67 ml (P = 0.01), respectively]. The proportion of clinically relevant volume reduction (> or =50%) rose significantly in the L-T(4) group [26.6% vs. 16.9% (P = 0.04)]. The proportion of patients with a reduced number of infraclinical additional nodules was significantly higher in the L-T(4) group [9.4% vs. 0 (P = 0.04)]. It is concluded from this study that suppressive L-T(4) therapy is effective in reducing solitary thyroid nodule volume and improving infraclinical extranodular changes.

6) http://www.ncbi.nlm.nih.gov/pubmed/1366242
Ir J Med Sci. 1992 Dec;161(12):684-6. TSH as an index of L-thyroxine replacement and suppression therapy. Igoe D1, Duffy MJ, McKenna TJ.
When hypothalamic-pituitary function is normal, serum TSH levels measured by ultrasensitive assay yield bioassays of endogenous thyroid action and thus provide an ideal index of thyroid secretion and its relationship to fluctuating endogenous thyroid levels. It is theoretically possible that patients receiving exogenous L-thyroxine for primary hypothyroidism should have suppressed TSH levels if physiological needs are constantly met. To examine this possibility free thyroxine, FT4 and TSH were measured in 90 clinically euthyroid patients receiving treatment with L-thyroxine for primary hypothyroidism. TSH levels were normal in 44, suppressed in 16 and elevated in 30 patients. FT4 levels were normal in 68, elevated in 13 and suppressed in 9 patients. Normal TSH levels were associated with normal FT4 levels in 79.5% of patients, elevated FT4 levels in 13.6% and low FT4 in 6.8%. Suppressed TSH levels were associated with elevated FT4 levels in 37.5% of patients and normal FT4 levels in 62.5%. When FT4 levels were normal, however, TSH levels were normal in only 51.5% and abnormal in 48.5%. We also examined the possibility that FT4 levels may remain within normal range when TSH is suppressed during L-thyroxine treatment for goitre or cancer. FT4 and TSH were measured in 45 patients on L-thyroxine as TSH suppression treatment. TSH was suppressed in 23 patients(51.1%), normal in 20 (44.4%) and elevated in 2 (4.5%). When TSH was suppressed, FT4 was elevated in 30.4% but normal in 69.6% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

7) http://press.endocrine.org/doi/full/10.1210/jcem.83.11.5215

Suppressive Therapy with Levothyroxine for Solitary Thyroid Nodules: A Double-blind Controlled Clinical Study and Cumulative Meta-analyses
Flávio Zelmanovitz 2 , Sandra Genro, and Jorge L. Gross
JCEM July 01, 2013

The data obtained in this study do not suggest any significant decrease in BMD after 1 yr of treatment with suppressive doses of T4. However, a meta-analysis of related studies, performed by Uzzan et al., demonstrated that suppressive therapy decreased the BMD in 409 postmenopausal patients after an average of 9.6 yr (11).

8) http://www.ncbi.nlm.nih.gov/pubmed/12803168
Ann Intern Med. 2001 Apr 3;134(7):561-8.
Risk for fracture in women with low serum levels of thyroid-stimulating hormone.
Bauer DC1, Ettinger B, Nevitt MC, Stone KL; Study of Osteoporotic Fractures Research Group.
Biochemical evidence of hyperthyroidism may be associated with low bone mass, particularly in older postmenopausal women, but no prospective studies of thyroid function and subsequent fracture risk have been done.
OBJECTIVE:To examine the association between low levels of thyroid-stimulating hormone (TSH) and fracture in older women.
DESIGN:Prospective cohort study with case-cohort sampling.
SETTING:Four clinical centers in the United States.
PATIENTS:686 women older than 65 years of age from a cohort of 9704 women recruited from population-based listings between 1986 and 1988.
MEASUREMENTS:Baseline assessment of calcaneal bone mass, spine radiography, and history of thyroid disease. Spine radiography was repeated after a mean follow-up of 3.7 years; nonspine fractures were centrally adjudicated. Thyroid-stimulating hormone was measured in sera obtained at baseline from 148 women with new hip fractures, 149 women with new vertebral fractures, and a subsample of 398 women randomly selected from the cohort.
RESULTS:After adjustment for age, history of previous hyperthyroidism, self-rated health, and use of estrogen and thyroid hormone, women with a low TSH level (0.1 mU/L) had a threefold increased risk for hip fracture (relative hazard, 3.6 [95% CI, 1.0 to 12.9]) and a fourfold increased risk for vertebral fracture (odds ratio, 4.5 [CI, 1.3 to 15.6]) compared with women who had normal TSH levels (0.5 to 5.5 mU/L). After adjustment for TSH level, a history of hyperthyroidism was associated with a twofold increase in hip fracture (relative hazard, 2.2 [CI, 1.0 to 4.4]), but use of thyroid hormone itself was not associated with increased risk for hip fracture (relative hazard, 0.5 [CI, 0.2 to 1.3]).
CONCLUSIONS:Women older than 65 years of age who have low serum TSH levels, indicating physiologic hyperthyroidism, are at increased risk for new hip and vertebral fractures. Use of thyroid hormone itself does not increase risk for fracture if TSH levels are normal.

9) http://www.ncbi.nlm.nih.gov/pubmed/1286519
Clin Endocrinol (Oxf). 1992 Dec;37(6):500-3.
Morbidity in patients on L-thyroxine: a comparison of those with a normal TSH to those with a suppressed TSH. Leese GP1, Jung RT, Guthrie C, Waugh N, Browning MC.

Patients on L-thyroxine with a ‘suppressed’ TSH (< 0.05 mU/l) were compared to those in whom TSH was detectable but not elevated (0.05-4.0 mU/l), with regard to morbidity data.
DESIGN:Biochemical data from Tayside Thyroid Register was matched to hospital admissions data obtained from Health Board Statistics.
PATIENTS:The patients were identified from those registered on the computerized Tayside Register.
MEASUREMENTS:Serum T4 and TSH assays, clinical assessment scores, and admission records with regard to ischaemic heart disease, overall fractures, fractured neck of femur and breast carcinoma.
RESULTS:Over one year, 1180 patients on thyroxine replacement had clinical and biochemical assessment; 59% had a suppressed TSH and 38% ‘normal’ TSH. Patients with a suppressed TSH exhibited higher median serum thyroxine levels (146 nmol/l, range 77-252 vs 119 nmol/l, 58-224; P < 0.001). Patients under the age of 65 years on L-thyroxine had an increased risk of ischaemic heart disease compared to the general population (female 2.7 vs 0.7%, P < 0.001; male 6.4 vs 1.7%, P < 0.01), but the risk was no different between those with suppressed and normal TSH. There was no increase in risk for overall fracture, fractured neck of femur or breast carcinoma in those on thyroxine with suppressed or normal TSH.
CONCLUSION:Patients under the age of 65 years on L-thyroxine had an increased risk of ischaemic heart disease. There was no excess of fractures in patients on L-thyroxine even if the TSH is suppressed.

10) http://www.ncbi.nlm.nih.gov/pubmed/0009284722
J Clin Endocrinol Metab. 1997 Sep;82(9):2931-6.
Low thyrotropin levels are not associated with bone loss in older women: a prospective study.  Bauer DC1, Nevitt MC, Ettinger B, Stone K.

The relationship between excess thyroid hormone and bone loss is controversial. To determine whether low TSH levels, indicating excessive thyroid hormone, are associated with low bone mass or accelerated bone loss in older women, we performed a prospective cohort study of 458 women over age 65 yr participating in the multicenter Study of Osteoporotic Fractures. Three hundred and twenty-three women were randomly selected from the entire cohort of 9704; an additional 135 randomly selected thyroid hormone users were studied. Medical history, medication use, and calcaneal bone mineral density (BMD) were assessed at the baseline visit. Serum was collected and stored at -190 C. Hip and spine BMD were measured approximately 2 yr later, and follow-up calcaneal and hip BMD measurements were obtained after mean follow-up periods of 5.7 and 3.5 yr, respectively. TSH levels were determined in baseline serum samples using a third generation chemiluminescent assay. After adjustment for age, weight, previous hyperthyroidism, and use of estrogen, bone loss over 4-6 yr was similar in women with low, normal, or high TSH. For example, femoral neck bone loss was -0.3%/yr (95% confidence interval, -0.8%, 0.3%) among women with low TSH (< or = 0.1 mU/L) and -0.5%/yr (95% confidence interval, -0.7%, -0.3%) in those with normal TSH (0.1-5.5 mU/L). There were no statistically significant differences in baseline bone mass of the calcaneus, spine, or femoral neck or trochanteric hip subregions. Baseline total hip BMD was 6% lower (P = 0.01) in women with low TSH. Similar results were obtained in analyses confined to women not taking estrogens. We found no consistent evidence that low TSH, a sensitive biochemical marker of excess thyroid hormone, was associated with low BMD or accelerated bone loss in older ambulatory women.
conclusion, in this prospective study of thyroid function and skeletal health in older women, we found no consistent evidence that low TSH was associated with low bone mass or accelerated bone loss.

11) http://www.ncbi.nlm.nih.gov/pubmed/7848399
JAMA. 1994 Apr 27;271(16):1245-9.
Thyroid hormone use and bone mineral density in elderly women. Effects of estrogen. Schneider DL1, Barrett-Connor EL, Morton DJ.

To determine the effect of long-term use of thyroid hormone on bone mineral density (BMD) in elderly women and the potential mitigating effects of estrogen replacement therapy.
DESIGN:Cross-sectional, community-based study.
SETTING:Rancho Bernardo, Calif.
PARTICIPANTS:A total of 991 white women aged 50 to 98 years who participated in a study of osteoporosis.
MAIN OUTCOME MEASURES:Bone mineral density at the ultradistal radius and midshaft radius using single-photon absorptiometry and at the hip and lumbar spine using dual-energy x-ray absorptiometry.
RESULTS:A total of 196 women taking thyroid hormone for a mean duration of 20.4 years were compared with 795 women who were not using thyroid hormone. Women taking daily thyroxine-equivalent doses of 200 micrograms or more had significantly lower BMD levels at the midshaft radius and hip compared with those taking less than 200 micrograms. Daily doses of 1.6 micrograms/kg and greater were associated with lower bone mass at all four sites compared with nonuse, whereas doses less than 1.6 micrograms/kg were not associated with lower BMD levels. These associations were independent of age, body mass index, smoking status, and use of thiazides, corticosteroids, and estrogen. Women taking both estrogen and a thyroid hormone dose of 1.6 micrograms/kg or greater had significantly higher BMD levels at all four sites than women taking the same thyroid hormone dose alone. Women taking both thyroid hormone and estrogen had BMD levels comparable with those observed in women taking only estrogen.
CONCLUSIONS:Long-term thyroid hormone use at thyroxine-equivalent doses of 1.6 micrograms/kg or greater was associated with significant osteopenia at the ultradistal radius, midshaft radius, hip, and lumbar spine. Estrogen use appears to negate thyroid hormone-associated loss of bone density in postmenopausal women.
Women taking both thyroid hormone and estrogen had BMD levels comparable with those observed in women taking only estrogen.

12) http://www.ncbi.nlm.nih.gov/pubmed/9240728
J Bone Miner Res. 1997 Jan;12(1):72-7.
Skeletal integrity in men chronically treated with suppressive doses of L-thyroxine. Marcocci C1, Golia F, Vignali E, Pinchera A.
We measured bone mineral density (BMD) (lumbar spine, femoral neck, Ward’s triangle, and trochanter) in 34 men given suppressive doses of levothyroxine (L-T4) for a mean of 10.2 years. Indications for treatment were nontoxic goiter (n = 5) or thyroidectomy for differentiated thyroid cancer (n = 6) or nontoxic goiter (n = 3). Patients were followed at our institution and treated with the minimal amount of L-T4 able to suppress thyroid-stimulating hormone (TSH). At the time of evaluation, free T3 was normal in all cases, whereas free T4 was increased in 14 men (41.2%). The mean daily dose of L-T4 was 172 +/- 6 microg, and the cumulative dose of L-T4 was 673 +/- 71 mg. We found no significant difference between patients and age- and weight-matched controls in BMD (g/cm2) at any site of measurement (lumbar spine 1.144 +/- 0.12 vs. 1.168 +/- 0.15; femoral neck 0.979 +/- 0.13 vs. 1.001 +/- 0.13; Ward’s triangle 0.854 +/- 0.17 vs. 0.887 +/- 0.15; and trocanther 0.852 +/- 0.13 vs. 0.861 +/- 0.13). BMD was not correlated with the duration of therapy, cumulative or mean daily dose of L-T4, serum levels of free T4, free T3, osteocalcin, and bone alkaline phosphatase. Serum calcium and osteocalcin were slightly but significantly elevated in patients compared with controls, whereas there was no difference in intact parathyroid hormone, bone alkaline phosphatase, and sex hormone-binding globulin (marker of thyroid hormone action). Our data suggest that L-T4 suppressive therapy, if carefully carried out and monitored, using the smallest dose necessary to suppress TSH secretion, has no significant effects on bone metabolism and bone mass in men.

13) http://www.ncbi.nlm.nih.gov/m/pubmed/8157704/
Carefully monitored levothyroxine suppressive therapy is not associated with bone loss in premenopausal women. Marcocci C, et al. J Clin Endocrinol Metab. 1994.
We measured total body and regional (lumbar spine, femoral neck, Ward’s triangle, and trochanter) bone mineral density (BMD) in 47 premenopausal women chronically treated with suppressive doses of levothyroxine (L-T4). Treatment was administered to 7 patients with nontoxic goiter or, after thyroidectomy, to 38 patients with differentiated thyroid cancer and 2 with nontoxic goiter. Patients were followed at our institution and treated with the minimal amount of L-T4 necessary to suppress TSH. At the time of evaluation, free T3 was normal in all cases, whereas free T4 was increased in 17 (36.2%). The mean daily dose of L-T4 was 154.3 +/- 5 micrograms, and the mean duration of treatment was 10.1 yr. We found no significant difference between patients and age- and weight-matched controls in BMD at any site of measurement. BMD was not correlated with duration of therapy, cumulative or mean daily dose of L-T4, serum levels of free T4, free T3, and osteocalcin. There was no difference between patients and controls in serum total calcium, intact PTH, osteocalcin, or carboxy-terminal cross-linked telopeptide of type I collagen or in the concentrations of two markers of thyroid hormone action (sex hormone-binding globulin and amino-terminal propeptide of type III procollagen). Our data suggest that L-T4 suppressive therapy, if carefully carried out and monitored, using the smallest dose necessary to suppress TSH secretion has no significant effect on bone metabolism or bone mass.

13) http://www.ncbi.nlm.nih.gov/pubmed/7647577
Thyroid. 1995 Apr;5(2):81-7. Possible limited bone loss with suppressive thyroxine therapy is unlikely to have clinical relevance. Müller CG1, Bayley TA, Harrison JE, Tsang R.
To determine the effect of suppressive doses of thyroxine (T4) on bone mass, we studied 50 women on suppressive doses of T4 for 3-27 years (mean of 11 years). Twenty-five had nontoxic goiter and 25 had well-differentiated thyroid carcinoma. Fifty controls were matched for age, menopausal status, and body mass index. Bone mineral density (BMD) was measured in the lumbar spine (LS), femoral neck (FN), trunk (TK), and extremities (EXT) by dual-energy X-ray absorptiometry (DXA). In addition, the trunk area was measured by neutron activation analysis and recorded as a calcium bone index (CaBI). Twenty-one patients were restudied with DXA measurements at a mean of 1.5 +/- 0.5 (1 SD) years. The total population of 50 patients showed no difference in bone mass from controls. In patients with nontoxic goiter, there was no evidence of any loss in bone mass. Cancer patients showed insignificant reductions of 2-5% in BMD of LS, FN, and TK and a significant 5% reduction in BMD of EXT, compared to controls, and a 12% reduction in CaBI compared to goiter patients. Cancer patients had a slightly higher (p < 0.001) mean daily dose of T4 than goiter patients (0.23 vs 0.15 mg/day) but had a similar degree of TSH suppression. BMD and CaBI values did not correlate with free T4 index) with the daily T4 dose, accumulative dose, or with duration of T4 therapy. There were no significant changes in bone mass in either goiter or cancer patients restudied after a mean of 1.5 years.

14) http://www.ncbi.nlm.nih.gov/pubmed/7787427
Thyroid. 1995 Feb;5(1):13-7.Suppressive doses of thyroxine do not accelerate age-related bone loss in late postmenopausal women.
Fujiyama K1, Kiriyama T, Ito M, Kimura H, Ashizawa K, Tsuruta M, Nagayama Y, Villadolid MC, Yokoyama N, Nagataki S.
To examine whether suppressive doses of thyroxine have any adverse effects on bone, we evaluated various bone metabolic markers (lectin-precipitated alkaline phosphatase, osteocalcin, carboxyl-terminal region of type I collagen propeptide, tartrate-resistant alkaline phosphatase, and urinary excretion of hydroxyproline and pyridinium crosslinks), incidence of vertebral deformity, total body and regional (lumbar spine and radius) bone mineral densities (BMDs), and rates of bone loss in 24 late postmenopausal (more than 5 years after menopause) women who were treated with levothyroxine (L-T4) after total thyroidectomy for differentiated carcinoma. Depending on the clinical records, including serum TSH levels measured by immunoradiometric assay, these patients were divided into two groups. One group of patients was given suppressive doses of L-T4 (TSH < 0.1 mU/L, n = 12) and the other group was given nonsuppressive doses of L-T4 (TSH > 0.1 mU/L, n = 12). There was no difference in bone metabolic markers and incidence of vertebral deformity between the groups. In patients with TSH suppression, Z-scores of BMDs calculated from age-matched healthy women (n = 179, aged 55 to 80) were nearly in the zero range of values (0.077 at total body, 0.228 at lumbar spine, and -0.117 at trabecular region of lumbar spine). The rate of bone loss in TSH-suppressed patients (-0.849 +/- 0.605%/year) was not significantly different from that of nonsuppressed patients (-0.669 +/- 0.659). These prospective and cross-sectional data suggest that long-term levothyroxine therapy using suppressive doses has no significant adverse effects on bone.

15) http://www.ncbi.nlm.nih.gov/pubmed/8252740
Clin Endocrinol (Oxf). 1993 Nov;39(5):529-33.
Suppressed TSH levels secondary to thyroxine replacement therapy are not  associated with osteoporosis.  Grant DJ1, McMurdo ME, Mole PA, Paterson CR, Davies RR.
Recent studies have suggested that patients receiving thyroxine are at increased risk of osteoporosis. We set out to measure bone mineral densities in two groups of post-menopausal women receiving thyroxine replacement therapy (those with serum TSH levels persistently suppressed or non-suppressed) and to compare the results in both groups with those of the local control population.
DESIGN:Cross-sectional study.
PATIENTS:Seventy-eight post-menopausal women who had been treated with thyroxine for primary autoimmune or idiopathic hypothyroidism for a minimum of 5 years, 44 with TSH persistently suppressed and 34 non-suppressed. One hundred and two control subjects.
MEASUREMENTS:Forearm bone mineral density at proximal and distal sites as measured by single-photon absorptiometry.
RESULTS:Results were expressed as Z-scores, i.e. number of standard deviations from the mean of a 5-year age-band from the local control population. Mean Z-scores at proximal and distal sites for the non-suppressed patients were -0.03 and -0.07 and for the suppressed patients were -0.20 and -0.25, representing a decrease in bone mineral density of at most 5% in the suppressed patients. The differences between the three groups were not statistically significant.
CONCLUSION:In this patient population, the reduction in bone mineral density due to thyroxine is small. It is unlikely to be of clinical significance and should not on its own be an indication for reduction of thyroxine dose in patients who are clinically euthyroid.

16) http://erc.endocrinology-journals.org/content/12/4/973.long
Lack of deleterious effect on bone mineral density of long-term thyroxine suppressive therapy for differentiated thyroid carcinoma
J L Reverter, S Holgado1, N Alonso, I Salinas, M L Granada2 and A Sanmartí
Department of Endocrinology and Nutrition, Germans Trias i Pujol Hospital, Carretera de Canyet s/n. 08916, Badalona, Barcelona, Spain
1Department of Rheumatology, Germans Trias i Pujol Hospital, Badalona, Barcelona, Spain
2Hormone Laboratory, Germans Trias i Pujol Hospital, Badalona, Barcelona, Spain

The effect of subclinical hyperthyroidism on bone mineral density is controversial and could be significant in patients with differentiated thyroid carcinoma who receive suppressive doses of levothyroxine (LT4). To ascertain whether prolonged treatment with LT4 to suppress thyrotropin had a deleterious effect on bone mineral density and/or calcium metabolism in patients thyroidectomized for differentiated thyroid cancer we have performed a cross-sectional study in a group of 88 women (mean ± SD age: 51 ± 12 years) treated with LT4 after near-total thyroidectomy and in a control group of 88 healthy women (51 ± 11 years) matched for body mass index and menopausal status. We determined calcium metabolism parameters, bone turnover marker N-telopeptide and bone mass density by dual-energy X-ray absorptiometry. No differences were found between patients and controls in calcium metabolism parameters or N-telopeptide except for PTH, which was significantly increased in controls. No differences were found between groups in bone mineral density in femoral neck (0.971 ± 0.148 gr/cm2 vs 0.956 ± 0.130 gr/cm2 in patients and controls respectively, P = 0.5). In lumbar spine, bone mineral density values were lower in controls than in patients (1.058 ± 0.329 gr/cm2 vs 1.155 ± 0.224 gr/cm2 respectively, P<0.05). When premenopausal (n = 44) and postmenopausal (n = 44) patients were compared with their respective controls, bone mineral density was similar both in femoral neck and lumbar spine. The proportion of women with normal bone mass density, osteopenia and osteoporosis in patient and control groups was similar in pre- and postmenopausal women. In conclusion, long-term suppressive LT4 treatment does not appear to affect skeletal integrity in women with differentiated thyroid carcinoma.

17) http://www.ncbi.nlm.nih.gov/pubmed/21247815
Endocrinol Nutr. 2011 Feb;58(2):75-83. doi: 10.1016/j.endonu.2010.09.007. Epub 2011 Jan 17.
[Potential risks of the adverse effects of thyrotropin suppression in differentiated thyroid carcinoma].
[Article in Spanish]
Reverter JL1, Colomé E.
In patients with differentiated thyroid carcinoma, long-term inhibition of thyrotropin (TSH) secretion through levothyroxine administration is required when there is evidence of persistent or recurrent disease. In these cases, levothyroxine doses should be monitored to achieve the objectives of inhibiting TSH and avoiding clinical hyperthyroidism. The possibility that suppressive therapy may produce deleterious effects is still controversial, mainly in elderly patients. There are many studies on the potential harmful effects of suppressive therapy on various organs and systems with discrepant results. However, there is no scientific evidence that the clinical impact of these effects is significant.

18) http://www.ncbi.nlm.nih.gov/pubmed/20494634
Endocrinol Nutr. 2010 Oct;57(8):350-6. doi: 10.1016/j.endonu.2010.03.015. Epub 2010 May 24.
[Clinical endocrinologists’ perception of the deleterious effects of TSH suppressive therapy in patients with differentiated thyroid carcinoma].
[Article in Spanish]
Reverter JL1, Colomé E, Puig Domingo M, Julián T, Halperin I, Sanmartí A.
To explore the opinion of clinical endocrinologists as to the deleterious effects of thyrotropin (TSH) suppressive therapy in patients with differentiated thyroid carcinoma (DTC).
MATERIALS AND METHODS:
A self-administered survey was sent by e-mail to a group of endocrinologists with expertise in the treatment of patients with differentiated thyroid carcinoma. The questionnaire consisted of three questions related to: 1) the possible adverse effects of this therapy on different organ systems, 2) the clinical significance of these effects and 3) the usefulness of treatment guidelines for DTC.
RESULTS:A total of 91 endocrinologists responded with a wide divergence of opinions. No question had more than 80% of answers in a particular option. Of the possible side effects of suppressive therapy, a high degree of ignorance to three of them (increased left ventricular mass, reentrant tachycardia and diastolic dysfunction). Most respondents felt that the seven items, dementia and Alzheimer, decreased quality of life, decreased bone mineral density (BMD) in premenopausal women and men, thromboembolic disease, signs and symptoms of hyperthyroidism and increased risk of fractures were not affected by suppressive therapy, while most responded positively to two items (increased heart rate and decreased BMD in postmenopausal women). Eighty percent of the respondents felt that in any case these effects were not clinically significant and 33% considered that treatment guidelines should be reviewed.
CONCLUSIONS:Clinical endocrinologists seem to have a very heterogeneous opinion regarding the potential harmful effects of TSH-suppressive therapy for DTC.

19) http://www.townsendletter.com/Jan2011/ltrpub0111.html
Criminalizing Doctors Who Diagnose Hypothyroidism
The State of Oregon v. John E. Gambee, MD
John Gambee, MD is a physician practicing in Eugene, Oregon,
Letter from the Publisher
by Jonathan Collin, MD

20) http://thyroid.about.com/library/news/blderry2.htm
Dr. Derry Medical License Suspended

21)  Case Reports in Endocrinology Volume 2015 (2015), Article ID 684648, 5 Life-Threatening Hypercalcemia due to Graves’ Disease and Concomitant Adrenal Failure: A Case Report and Review of the Literature
Hande Mefkure Ozkaya, Fatma Ela Keskin, Ozlem Asmaz Haliloglu, Tugba Elif Senel, and Pinar Kadioglu  Endocrinology and Metabolism, Cerrahpasa Medical School, University of Istanbul, 34098 Istanbul, Turkey

22) Hyperthyroidism an overlooked cause of severe hypercalcaemia Clark 2010 Abdul Mohammedb, Anita Pillaib, Angelos Klotsasb,
Paul Mastersa and Nigel Lawsona Grand Rounds Volume 10 2010

free full

23) Biochim Biophys Acta. 2013 Jul;1830(7):3987-4003.
The syndromes of reduced sensitivity to thyroid hormone.
Dumitrescu AM1, Refetoff S. Department of Medicine, The University of Chicago, Chicago, IL, USA.

24) Endocrine Abstracts (2010) 21 OC5.6
Is it safe for patients taking thyroxine to have a low but not suppressed serum TSH concentration?  Graham Leese & Robert Flynn
University of Dundee, Tayside, UK.

We aimed to examine the safety of having a TSH which was either suppressed (≤0.03 mU/l), low (0.04–0.4 mU/l), ‘normal’ (0.4–4.0 mU/l) or raised (>4.0 mU/l) in a population-based cohort of patients all of whom were treated with thyroxine.

There were a total of 16 426 patients on thyroxine replacement (86% female, mean age 60 years) with a total follow-up of 74 586 years. Cardiovascular disease, dysrhythmias and fractures were increased in patients with a high TSH (adjusted hazards ratio 1.95 (1.73–2.21), 1.80 (1.33–2.44) and 1.83 (1.41–2.37) respectively), and patients with a suppressed TSH (1.37 (1.17–1.6), 1.6 (1.1–2.33) and 2.02 (1.55–2.62) respectively), when compared to patients with a TSH in the laboratory reference range. Patients with a low TSH did not have an increased risk of any of these outcomes (HR: 1.1 (0.99–1.123), 1.13 (0.88–1.47) and 1.13 (0.92–1.39) respectively.

25) Ito, Mitsuru, et al. “TSH-suppressive doses of levothyroxine are required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy.” European Journal of Endocrinology 167.3 (2012): 373-378.

26) Soldin, Offie P., Sarah H. Chung, and Christine Colie. “The Use of TSH in Determining Thyroid Disease: How Does It Impact the Practice of Medicine in Pregnancy?” Journal of Thyroid Research 2013 (2013): 148157. PMC. Web. 21 May 2015.

(27) Effective Treatment of Chronic Fatigue Syndrome and Fibromyalgia: A Comprehensive Medicine Approach by Jacob Teitelbaum, MD Townsend Letter December 2011

28) Chronic Fatigue Syndrome Fibromyalgia Jacob Teitelbaum 2001

29) Effective Treatment of Chronic Fatigue Syndrome and
Fibromyalgia—A Randomized, Double-Blind, Placebo-
Controlled, Intent to Treat Study  Jacob E. Teitelbaum, MD*1; Barbara Bird, M.T.,C.L.S.*; Robert M. Greenfield, MD1; Alan Weiss, MD1; Larry Muenz, Ph.D2; Laurie Gould, BS*3  Published in the Journal of Chronic Fatigue Syndrome Vol. 8, No. 2, 2001. PP3-28.

30) treating-thyroid-despite-normal-labs Kent Holtorf JAcob Teitelbaum

31) Holtorf, Kent. “Diagnosis and treatment of hypothalamic-pituitary-adrenal (HPA) axis dysfunction in patients with chronic fatigue syndrome (CFS) and fibromyalgia (FM).” Journal of Chronic Fatigue Syndrome 14.3 (2007): 59-88. hypothalamic-pituitary-adrenal HPA dysfunction chronic fatigue syndrome fibromyalgia Holtorf 2007

32) Effective Treatment of Chronic Fatigue Syndrome JAcob Teitelbaum 2005 Integrative Medicine

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33) Nuklearmedizin. 1999;38(5):144-9.
[Effect of iodine and thyroid hormones in the induction and therapy of Hashimoto’s thyroiditis].  [Article in German] Rink T1, Schroth HJ, Holle LH, Garth H.
The effect of an iodine prophylaxis on the induction of Hashimoto’s thyroiditis as well as the influence of various therapeutic approaches on the course of antithyroglobulin (TgAb) and antiperoxidase (TPOAb) antibodies in manifest diseases are evaluated.
METHOD:  A collective of 375 euthyroid subjects without relevant goiter received daily doses of 200 micrograms iodide, weekly doses of 1.53 milligrams iodide, or no medication. A second group of 377 patients suffering from Hashimoto’s thyroiditis was treated with a non-suppressive hormone medication, a suppressive hormone administration, a combination of a non-suppressive hormone therapy with low dose iodide (50-150 micrograms/day), mere iodide in doses of 200 micrograms/day, or received no therapy. The mean observation period in these two groups was 860 and 848 days, respectively.
RESULTS:

There was no significant increase of the antibody levels in the subgroup with 200 micrograms iodide/day and in the non-treated subjects of the first collective. However, the group that received 1.53 milligrams iodide/week presented a distinct increase of the TgAb as well as the TPOAb, and the incidence of Hashimoto’s thyroiditis was 4-fold higher than in the two other subgroups. The patients of the second collective revealed a significant decrease of the TgAb in the subgroups treated with up to 200 micrograms iodide/day, while the reduction of the TPOAb depended on the thyrotropin level(TSH) and was most significant in the suppressed group (p < 0.0001).
CONCLUSION:

To lower the incidence of autoimmune thyroid diseases in predisposed subjects, a daily iodine supplementation seems to be superior to high-dose weekly administrations. A hormone therapy combined with a daily, low-dose iodine medication is able to reduce the TgAb and the TPOAb levels even in patients with Hashimoto’s thyroiditis.

34) Effects of prophylactic thyroid hormone replacement in euthyroid Hashimoto’s thyroiditis  Aksoy DY, Kerimoglu U, Okur H, Canpinar H, Karaağaoğlu E, Yetgin S, Kansu E, Gedik O Section of Endocrinology and Metabolism, Department of Internal Medicine, Hacettepe University, Ankara, Turkey.
Endocrine Journal [2005, 52(3):337-343]

Hashimoto’s thyroiditis is the most frequent autoimmune thyroid disease. L-thyroxine therapy can reduce the incidence and alleviate the symptoms of this disease. The aim of this study was to evaluate the effects of prophylactic L-thyroxine treatment on clinical and laboratory findings of patients who were euthyroid at the time of diagnosis.

Thirty-three patients who had diagnosis of euthyroid Hashimoto’s thyroiditis were randomized to two groups, one group received prophylactic L-thyroxine treatment and the other was followed-up without treatment. Initial thyroid function tests, autoantibodies, ultrasonography, fine needle aspiration biopsy and peripheral blood lymphocyte subsets were similar in the two study groups. After 15 months of L-thyroxine treatment, there was a significant increase in free T4 and a significant decrease in TSH and anti-thyroglobulin antibody anti-thyroid peroxidase antibody levels. CD8+ cell counts increased in both groups, CD4/CD8 levels decreased significantly because of the increase in CD8+ cell count levels. Though there was no change in cytological findings, ultrasonography showed a decrease in thyroid volume in L-thyroxine receiving patients whereas an increase was detected in patients who were followed without treatment. In conclusion, prophylactic thyroid hormone therapy can be used in patients with Hashimoto’s thyroiditis even if they are euthyroid.

35) One-year prophylactic treatment of euthyroid Hashimoto’s thyroiditis patients with levothyroxine: is there a benefit?

Padberg, Heller K, Usadel KH, Schumm-Draeger PM
Medica Clinic l, Endocrinology, Center of Internal Medicine, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.  Thyroid : Official Journal of the American Thyroid Association [2001, 11(3):249-255]

Studies in animal models of spontaneous Hashimoto’s autoimmune thyroiditis (HT) show that prophylactic treatment with levothyroxine (LT4) can reduce incidence and degree of lymphocytic infiltration in HT. The aim of the present study was to clarify whether there is a benefit of prophylactic treatment with LT4 in patients with euthyroid HT with respect to the progression of the autoimmune process. Twenty-one patients with euthyroid HT were checked for thyroid function (thyrotropin [TSH], free triiodothyronine [FT3], free thyroxine [FT4]), thyroid volume, antibodies (thyroglobulin [Tg-Ab], thyroid peroxidase [TPO-Ab]), and lymphocyte subsets. Peripheral (PBL) and thyroid-derived lymphocytes (TL) were analyzed by triple color flow cytometry. One-half of the patients with euthyroid HT were treated with LT4 for 1 year (n = 10). The other half (n = 11) were never treated with LT4. TL were obtained by fine-needle aspiration biopsy (FNAB). Thirteen healthy subjects (C) without medical history of thyroid disease served as controls concerning PBL, and patients with non-toxic nodular goiter (NG; n = 10) served as controls concerning TL. Thyroid-derived T-helper cells were found more frequently in euthyroid patients with HT compared to patients with NG (p < 0.01). After 1 year of therapy with LT4, TPO-Abs and B lymphocytes decreased significantly only in the treated group of euthyroid patients with HT (p < 0.05). In contrast, TPO-Abs levels did not change or even increased in untreated euthyroid patients with HT. Thyroid volume did not differ before and after therapy. Prophylactic treatment of euthyroid patients with HT reduced both serological and cellular markers of autoimmune thyroiditis. Therefore, prophylactic LT4 treatment might be useful to stop the progression or even manifestation of the disease. However, the long-term clinical benefit of prophylactic LT4 therapy in euthyroid patients with HT is yet to be established.

36) http://www.ncbi.nlm.nih.gov/pubmed/18631004
Schmidt, Matthias, et al. “Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) treated with levothyroxine.” Thyroid 18.7 (2008): 755-760.

Thyroid. 2008 Jul;18(7):755-60. doi: 10.1089/thy.2008.0008.
Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) treated with levothyroxine.
Schmidt M1, Voell M, Rahlff I, Dietlein M, Kobe C, Faust M, Schicha H.

A number of studies show that the serum levels of antithyroid peroxidase antibodies (TPO-Ab) in patients with Hashimoto’s thyroiditis decline during levothyroxine treatment, but do not provide quantitative data or report the fraction of patients in whom test for TPO-Ab became negative (“normalization percentage”). The objective of the present study was to provide this information.
METHODS:

This was a retrospective study of TPO-Ab concentrations in 36 women and 2 men (mean age 51 +/- 16 years; range 19-81 years) with Hashimoto’s thyroiditis as defined by the following criteria: elevated plasma TPO-Ab and typical hypoechogenicity of the thyroid in high-resolution sonography at first presentation or during follow-up and low pertechnetate uptake in thyroid scintigraphy. When first studied 17 women and 1 man were not yet taking levothyroxine. The remaining 20 patients were receiving levothyroxine. At initial examination 18 patients had serum thyroid-stimulating hormone (TSH) concentrations above normal. Results of up to eight (mean = 5.8) measurements obtained over a mean period of 50 months while patients were receiving levothyroxine were analyzed. In addition, serum TSH, free triiodothyronine (fT3), and free thyroxine (fT4) were measured, and ultrasound of the neck was performed at each follow-up examination.
RESULTS:  In terms of TPO-Ab levels, 35 of 38 patients (92%) had a decrease, 2 patients had undulating levels, and 1 patient had an inverse hyperbolic increase in her TPO-Ab levels. In the 35 patients in whom there were decreasing TPO-Ab values, the mean of the first value was 4779 IU/mL with an SD of 4099 IU/mL. The mean decrease after 3 months was 8%, and after 1 year it was 45%. Five years after the first value, TPO-Ab levels were 1456 +/- 1219 IU/mL, a decrease of 70%. TPO-Ab levels became negative, < 100 IU/mL, in only six patients, a normalization percentage of 16%. There were no correlations between changes in thyroid volume and changes in TPO-Ab.
CONCLUSION:

Serum TPO-Ab levels decline in most patients with Hashimoto’s thyroiditis who are taking levothyroxine, but after a mean of 50 months, TPO-Ab became negative in only a minority of patients.

37)  Clin Endocrinol (Oxf). 1991 Sep;35(3):235-8.
Influence of thyroxine treatment on thyroid size and anti-thyroid peroxidase antibodies in Hashimoto’s thyroiditis.
Hegedüs L1, Hansen JM, Feldt-Rasmussen U, Hansen BM, Høier-Madsen M.

It has been postulated that a decrease in thyroid size can be achieved by thyroxine treatment in patients with goitrous Hashimoto’s thyroiditis but no objective data are available. We have therefore investigated the influence of thyroxine treatment on ultrasonically determined thyroid size. We also measured serum antithyroid peroxidase antibodies.
DESIGN:  Consecutive patients with goitrous Hashimoto’s thyroiditis was studied.
PATIENTS:  Thirteen women participated; all had goitrous thyroiditis.
TREATMENT:  To render them euthyroid thyroxine was given for 24 months.
MEASUREMENTS: Thyroid size was measured ultrasonically and antithyroid peroxidase antibodies were measured using a commercial radioimmunological method.
RESULT:  Concomitant with the gradual increase in serum free thyroxine and free triiodothyronine index values and a fall in serum thyrotrophin level, a gradual decrease in thyroid volume from 50.4 +/- 6.8 ml (mean +/- SEM) to 34.1 +/- 5.7 ml (32%), P less than 0.001 was demonstrated. Antithyroid peroxidase antibodies were present in high concentrations in all subjects but the mean serum level was not significantly changed at 24 months after initiation of treatment.
CONCLUSION:  A clinically significant reduction in thyroid volume related to normalization of thyroid function but unrelated to changes in antithyroid peroxidase antibody can be achieved during L-thyroxine treatment of hypothyroid goitrous Hashimoto’s thyroiditis.

38) Exp Clin Endocrinol Diabetes. 1999;107 Suppl 3:S84-7.
Prophylactic levothyroxine therapy in patients with Hashimoto’s thyroiditis.
Schumm-Draeger PM1, Padberg S, Heller K.
1Medical Clinic I, Endocrinology, Center of Internal Medicine, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany. Schumm-Draeger@em.uni-frankfurt.de

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39) Breast Cancer Res Treat. 2007 Jul;103(3):303-11. Epub 2006 Sep 29.
Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy.
Silverman DH1, Dy CJ, Castellon SA, Lai J, Pio BS, Abraham L, Waddell K, Petersen L, Phelps ME, Ganz PA.

Purpose To explore the relationship of regional cerebral blood flow and metabolism with cognitive function and past exposure to chemotherapy for breast cancer.

Patients and methods Subjects treated for breast cancer with adjuvant chemotherapy remotely (5–10 years previously) were studied with neuropsychologic testing and positron emission tomography (PET), and were compared with control subjects who had never received chemotherapy. [O-15] water PET scans was acquired during performance of control and memory-related tasks to evaluate cognition-related cerebral blood flow, and [F-18] fluorodeoxyglucose (FDG) PET scans were acquired to evaluate resting cerebral metabolism. PET scans were analyzed by statistical parametric mapping and region of interest methods of analysis.

Results During performance of a short-term recall task, modulation of cerebral blood flow in specific regions of frontal cortex and cerebellum was significantly altered in chemotherapy-treated subjects. Cerebral activation in chemotherapy-treated subjects differed most significantly from untreated subjects in inferior frontal gyrus, and resting metabolism in this area correlated with performance on a short-term memory task previously found to be particularly impaired in chemotherapy-treated subjects. In examining drug-class specific effects, metabolism of the basal ganglia was significantly decreased in tamoxifen + chemotherapy-treated patients compared with chemotherapy-only breast cancer subjects or with subjects who had not received chemotherapy, while chemotherapy alone was not associated with decreased basal ganglia activity relative to untreated subjects.

Conclusion Specific alterations in activity of frontal cortex, cerebellum, and basal ganglia in breast cancer survivors were documented by functional neuroimaging 5–10 years after completion of chemotherapy.

40)
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de Ruiter, Michiel B., et al. “Cerebral Hyporesponsiveness and Cognitive Impairment 10 Years After Chemotherapy for Breast Cancer.”

Hum Brain Mapp. 2011 Aug;32(8):1206-19. Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer.
de Ruiter MB1, Reneman L, Boogerd W, Veltman DJ, van Dam FS, Nederveen AJ, Boven E, Schagen SB.

Chemotherapy is associated with cognitive impairment in a subgroup of breast cancer survivors, but the neural circuitry underlying this side effect is largely unknown. Moreover, long-term impairment has not been studied well. In the present study, functional magnetic resonance imaging (fMRI) and neuropsychological testing were performed in breast cancer survivors almost 10 years after high-dose adjuvant chemotherapy (chemo group, n = 19) and in breast cancer survivors for whom chemotherapy had not been indicated (control group, n = 15). BOLD activation and performance were measured during an executive function task involving planning abilities (Tower of London) and a paired associates task for assessment of episodic memory. For the chemo group versus the control group, we found hyporesponsiveness of dorsolateral prefrontal cortex in the Tower of London, and of parahippocampal gyrus in the paired associates task. Also, the chemo group showed significantly impaired planning performance and borderline significantly impaired recognition memory as compared to findings in the control group. Whole-brain analyses demonstrated hyporesponsiveness of the chemo versus the control group in very similar regions of bilateral posterior parietal cortex during both the Tower of London and the paired associates task. Neuropsychological testing showed a relatively stable pattern of cognitive impairment in the chemo group over time. These results indicate that high-dose adjuvant chemotherapy is associated with long-term cognitive impairments. These impairments are underpinned by (a) task-specific hyporesponsiveness of dorsolateral prefrontal cortex and parahippocampal gyrus, and (b) a generalized hyporesponsiveness of lateral posterior parietal cortex encompassing attentional processing.

41) Hum Brain Mapp. 2011 Mar;32(3):480-93. doi: 10.1002/hbm.21033.
Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients.
Deprez S1, Amant F, Yigit R, Porke K, Verhoeven J, Van den Stock J, Smeets A, Christiaens MR, Leemans A, Van Hecke W, Vandenberghe J, Vandenbulcke M, Sunaert S.

A subgroup of patients with breast cancer suffers from mild cognitive impairment after chemotherapy. To uncover the neural substrate of these mental complaints, we examined cerebral white matter (WM) integrity after chemotherapy using magnetic resonance diffusion tensor imaging (DTI) in combination with detailed cognitive assessment. Postchemotherapy breast cancer patients (n = 17) and matched healthy controls (n = 18) were recruited for DTI and neuropsychological testing, including the self-report cognitive failure questionnaire (CFQ). Differences in DTI WM integrity parameters [fractional anisotropy (FA) and mean diffusivity (MD)] between patients and healthy controls were assessed using a voxel-based two-sample-t-test. In comparison with healthy controls, the patient group demonstrated decreased FA in frontal and temporal WM tracts and increased MD in frontal WM. These differences were also confirmed when comparing this patient group with an additional control group of nonchemotherapy-treated breast cancer patients (n = 10). To address the heterogeneity observed in cognitive function after chemotherapy, we performed a voxel-based correlation analysis between FA values and individual neuropsychological test scores. Significant correlations of FA with neuropsychological tests covering the domain of attention and processing/psychomotor speed were found in temporal and parietal WM tracts. Furthermore, CFQ scores correlated negatively in frontal and parietal WM. These studies show that chemotherapy seems to affect WM integrity and that parameters derived from DTI have the required sensitivity to quantify neural changes related to chemotherapy-induced mild cognitive impairment.

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