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THYROID TESTS

SHOULD OUR THYROID HORMONAL ASSESSMENT BE REVIEWED?

Currently, our “system” says that to figure out whether a person’s thyroid balance is satisfactory in terms of keeping our cells working at maximum efficiency, all we need to check is the Thyroid Stimulating Hormone. However TSH is a signal sent by the pituitary gland, to tell the thyroid how much T4 to make: the pituitary is merely ordering Thyroxine, to satisfy itself.
THIS HAS NOTHING TO DO WITH THE REST OF THE BODY!

WHAT OUR MEDICAL SYSTEM IGNORES

Since FT3 is rarely, and rT3 never, measured by family physicians and endocrinologists, they are unaware of the state of thyroid hormonal balance in the cells and organs. The body has no way of expressing its state of satisfaction with the availability of T3 within the cells and other than FT3 /rT3 (which allopathic physicians seem never to have heard of, we don’t have a dedicated test for thyroid balance.

We can, however, resolve the dilemma with minimum civil disobedience
let’s look at FT3 and rT3 results and figure it out!

 METABOLISM OF THYROXINE, THE “T4” HORMONE

T4 is converted preferentially to T3 rather than rT3 (a small amount of rT3 it is naturally produced). However, while TSH and FT4 are only minimally affected when Cortisol output rises due to fasting or any other stress [1,2], T3 production falls and reverse T3 production is boosted. In the serum, FT3 is reduced to a minimum and rT3 increases.

Logical clinical conclusions when FT3 falls in response to stress

If rT3 goes up when T3 goes down, calculating the T3/rT3 and the ratio will provide a measure of the degree of abnormal processing of T4 to rT3. Functional/metabolic medicine practitioners have been utilizing this simple method to assess the state of intracellular Triiodothyronine for decades and it has been observed that hypothyroid symptoms occur when the FT3/rT3 ratio is less than 20.0. We differentiate this Metabolic aberration from true Hypothyroidism, applying a new diagnostic term: “Intracellular Hypothyroidism”. **

Clinical observation confirms that while Hypothyroid symptoms usually indicate a reduction of Thyroxine production (true hypothyroidism), the TSH and T4 are normal in 20%, or more, of hypothyroidism cases.

When this is so, the diagnosis of intracellular hypothyroidism is missed if FT3 and reverse T3 are not tested. Thyroxine (excellent treatment for true hypothyroidism) is prescribed, but the symptoms continue. The result is confusion on the part of the physician and frustration on the part of the patient.

This vexing situation is easily avoided by estimating free T3 and reverse T3 levels, to derive the T3/rT3 ratio, which reliably differentiates between true and Intracellular hypothyroidism (IH). IH is easily and safely treated with Sustained Release Triiodothyronine, the symptoms subside and the patient is happy.

** A.k.a. low T3 syndrome, nonthyroidal illness syndrome, euthyroid sick syndrome and functional hypothyroidism.

TREATING FUNCTIONAL HYPOTHYROIDISM

Treatment with Sustained-Release T3 (SR T3) is safe and side effects (SE) are minimal: compounded, slow-release triiodothyronine is prescribed, beginning with 5 µg per day (taken close to 4 AM, so as to mimic the diurnal surge of T3). The dose is increased in 5 µg increments, following a weekly re-estimation of T3*, to a target T3 of 5.0 – 6.2 pmmol/L. As the serum FT3 rises, the rT3 falls and the symptoms subside.

*When treating true hypothyroidism with thyroxine or its analogue, retesting is done at 6 weeks, because of the long half-life of thyroxine. Retesting can be done weekly when the patient is being treated with triiodothyronine, because the half-life is only 2 – 3 hours.

Usually, FT3/rT3 exceeds 20.0 when the serum FT3 rises above 4.5, but a FT3 of 5.0-6.0 and a ratio of >23 are the targets of choice. Adequate dosage is confirmed by elimination of the patient’s symptoms.

Side effects do not usually occur unless the serum T3 exceeds 6.1: the most frequent side effect is a feeling of being “high”, with enhanced vision and other sensory abilities. However some few subjects have noted a hyper-reactive state, irritability, “antsiness” or increased pulse rate. If SEs ensue the dose is reduced to the previous level.

TSH, FT4, FT3 and rT3 are repeated at a dose of 25mcg, and then, following each dose increase above 25 µg and the dose is modified, to yield a FT3 between 5.0 and 6.0.

Note that logically, there is no need for a “normal range” for reverse T3, since rT3 is not a metabolite. Its only value is as a marker for reduced conversion of T4 to T3.

rT3 “normal”, according to our laboratories, is “5 – 25 nanograms/DL”, but the range is grossly overestimated. For maintenance of a functionally euthyroid state, the serum rT3 should be between 7 and 13 ng/DL.
The level usually falls below 13 Nanograms/Decilitre when T3 exceeds 5.0 pM/Litre.

EFFECT OF THERAPY WITH TRIIODOTHYRONINE

The endpoint of therapy is elimination, or suppression, of hypothyroid symptoms, as judged by the patient.
Successful therapy reduces the perception of stress, whether or not the individual’s stressors are lessened and relapse is unlikely as long as treatment continues. However SRT3 can be discontinued if the stress is eliminated, but hypothyroidism will relapse if it recurs.

CAVEATS:

(1) Elimination of Intracellular hypothyroidism results in up-regulation of brown adipose tissue (BAT), with resulting improvement in glucose and cholesterol management: if long-term prescription of triiodothyronine is considered, A1c and cholesterol profiles should be seriously repeated, with a view to discontinuation of antidiabetic and anticholesterol medications if indicated.

(2) Weight loss may occur and is of benefit, but SRT3 MUST NOT BE PRESCRIBED FOR WEIGHT CONTROL.

(3) Successful therapy eliminates, or suppresses, hypothyroid symptoms, as judged by the patient.

(4)Successful therapy reduces the perception of stress, whether or not the individual’s stressors are lessened. However relapse is unlikely as long as treatment continues.

(5) SRT3 can be discontinued if stress is eliminated, but hypothyroidism will relapse if it recurs.

(6) If the serum T3 exceeds 6.2, the T3 dose should be reduced, to avoid hyperthyroidism, but if the FT3 is less than 4.5, stress-related recurrence of intracellular hypothyroidism becomes more likely.

Reducing or discontinuing Ancillary prescriptions

DHEA, and progesterone are often necessary because they decline after age 25.
Iodine and Selenium supplements may help if the patient has true hypothyroidism.
Successful prescription of Triiodothyronine does not affect the patient’s requirement for other supportive hormone replacements or prescribed medications. However the body’s Glucose and Cholesterol control will improve, rendering antidiabetic and anti-cholesterol medications unnecessary.
Further, antihypertensives, cognitive support, soporifics and psychoactive drugs can often be stopped or reduced as the patient’s condition and symptoms improve.

REGARDING THE “NORMAL” RANGES OF T3, REVERSE T3 AND TSH

TSH: (1) the upper limit of “normal” (4) is much too high: it should be 2.5. (2) the idea of “age-related normal values” is a logical, obfuscatory and should be jettisoned.

T3: the lower limit of “normal” is too low: it should be 4.0 picomoles per litre.

rT3: there is no “normal range” for reverse T3 and the currently accepted range, 5–25, Is unrealistic.
If reverse T3 is 20 or more nanograms/DL, the FT3 needs to exceed 6.1, to avoid a diagnosis of IH. Put another way, Intracellular hypothyroidism exists if rT3 exceeds 20.


Notes

  • Patients given Eltroxin or Synthroid during an episode of functional hypothyroidism, while T4 is being preferentially converted to rT3, experience worse hypothyroid symptoms.
    This is because the T4 is converted to rT3, which forces Deiodinase 3 to convert any normal T3 remaining in the cell, into T2, which is “garbage”.
    Therefore the T3 level goes even lower and the hypothyroid symptoms get worse.
  • Patients on treatment for intracellular hypothyroidism, may relapse in response to a stressful episode, if their T3 dose is too low.
  • Dessicated Thyroid (DT) should not be used to treat stress-related intracellular hypothyroidism, because desiccated thyroid is 70% T4 and 30% T3. The T4 in DT may increase symptoms, As Eltroxin does.
  • Patients taking T3 (slow-release) often reduce rT3 production to < 9 Ng/DL.
  • Since T3 usually penetrates the Pituitary and since the Pituitary actually uses its level of T3, not T4, to gauge its TSH output, TSH can go below 1.0.
  • Reduced TSH results in minimum T4 production by the thyroid, so sometimes we see a T4 of 8 or less during SRT3 treatment. This simply means that the supply of thyroid hormone to the pituitary is adequate. IT IS NOT A CAUSE FOR CONCERN.
  • Most often, T3 taken by mouth enters the pituitary easily and TSH falls to a minimum. However in a few people, the T3 entry into the pituitary is blocked, so the pituitary calls for more T4 by increasing its TSH production. When this happens, the tests show a high-normal T3 and very low rT3, which is weird, but the solution is simple: a low dose of T4 (Eltroxin or Synthroid), is all that is needed to keep the pituitary gland happy: a small amount of it may be converted to reverse T3, but not enough to cause a problem.
  • The T3 range, currently skewed because a large, unrecognised percentage of our population is functionally hypothyroid, should be reviewed and a new “normal” scale should be proposed.

Anecdote

In 2014, two of my patients, a man and wife, aged about 50, stopped their T3 and subsequently presented to an ER with FT3 of 1.7: both had myxoedema and heart failure.

THIS TABLE WAS DEVISED FOR A PREVIOUS ITERATION:
I INCLUDE IT HERE, “JUST FOR FUN”
T3
(in Pm/L)
 T3,Ng/DL rT3,Ng/DL T3/rT3 DIAGNOSISCOMMENT
2.8 (Lo N)181.81018.2Mild IHIncludes endemic hypothyroidism
3.2
(old LowN)
207.81118.9Mild IHNeed rT3 <11,
to be Euthyroid
5.0
(Opt. LoN)
324.725 (Lab High N)13.0Severe IHNeed rT3 < 16
to be Euthyroid
5.0324.720 (Lab High Mid)16.2Moderate IHNeed rT3 < 16
to be Euthyroid
5.0324.717 (Lab Low Mid)19.1Mild IHNeed rT3 < 16
to be Euthyroid
5.8(New HiN376.61919.8Mild IHNeed RT3 <19
to be Euthyroid
6.2 (Opt Hi N402.621 (Lab Mid-High)19.2Borderline IHNeed rT3 < 20
to be Euthyroid
6.2
(Opt Hi N)
402.625 (Lab High N)16.1Moderate IHNeed rT3 < 20
to be Euthyroid
7.6 (Hi++)493.52519.7Still has IHIf rT3 = 25, Need T3 > 7.6 to be Euthyroid
rT3 corresponds to T4 level and state of stress. there is no “normal” rT3.
REGARDING TSH

In 2005 Leonard Wartofsky and Richard A Dickey wrote, (paraphrased, for brevity):
“It has become clear that our reference ranges are no longer valid.”
We have more sensitive TSH tests and also, we now realise that previous reference populations included people with (low) thyroid dysfunction, whose high TSH levels led to a spuriously high reference range for TSH in the group.
Recent laboratory guidelines from the National Academy of Clinical Biochemistry indicate that more than 95% of normal individuals have TSH levels below 2.5 mU/liter.”

In 2007 Martin I. Surks and Joseph G. Hollowell said as follows (paraphrased, for brevity)……
“The TSH median, 97.5 centile and prevalence of subclinical hypothyroidism increase progressively with age.
Age-adjusted reference ranges would include many people with TSH greater than 4.5 mIU/liter.” *
They continued: ”Without thyroid disease, 10.6% of 20- to 29-yr-olds had TSH greater than 2.5 mIU/liter.” *
In 80+ year-olds, “Without thyroid disease”, 14.5% had TSH greater than 4.5 mIU/liter. *
TSH frequency distribution curves of the 80+ year-old group showed higher TSH:
The 97.5 centiles for TSH in the 20–29 and 80+ year-olds were 3.56 and 7.49 mIU/litre, respectively.

Then, they said “70% of older patients with TSH greater than 4.5 mIU/liter were within their age-specific range (up to 7.49)**(!!!).
In spite of these findings (almost 100% of) our medical doctors preferred to think like Surks and Hollowell and the reference range for TSH has remained unchanged. ***

However to me, the implications are clear:
· Wartofsky and Dickey were correct: the upper limit of normal TSH should be 2.5.
· Surks and Hollowell would have done better to label the older folks hypothyroid, rather than concluding that “high TSH is normal for the older population”.
What their findings mean is that 70% of the 80+-year-olds were hypothyroid, not “age – specific normal”!
In addition,they should have realised that 10.6% of their 20-29-year-olds were also hypothyroid and should have excluded them. ****


* AGE-SPECIFIC NORMAL, or “NATURAL NORMAL”, makes no sense.

“Normal” should be understood to mean the status of healthy humans aged 20-25 with no abnormal results for any test: any abnormal finding should disqualify the candidate for all estimates of “normal”.

** Any result >2.5 suggests hypothyroidism, so this implies that more than 14.5% of the 80+ year olds were hypothyroid.
Including them in the “normal” group means that 15+% of 80-yr-olds won’t get the treatment they need.

***
We should apply fair logic to every scientific paper, so as to exclude glaring errors and prejudices like these from your belief systems.

Maybe all our tests are wrong

**** Think about it – if I am right, since the thyroid hormone dictates the efficiency level of every cell and system in the body, and if 10.6% (or more) of the thyroid test study population should have been excluded from the calculation of “normal” thyroid hormone levels, then
The parameters for our other tests could be wrong: maybe a lot of tests are invalid!

MESSAGE

· Many other hormones suffer the same fate as DHEA: Melatonin, Progesterone, Allopregnanolone, Testosterone and Thyroid hormone all go down over time, mostly by slow, gradual loss of production.

· In some people several hormone levels can “crash” suddenly, causing various symptoms of deficiency depending on which hormones are involved.
This can happen with Melatonin in the “teens”, Progesterone and Allopregnanolone in the twenties, Testosterone in the thirties or earlier and particularly Oestrogen, which disappears naturally in the early fifties but can fall to almost zero in the late thirties or early forties and to absolute zero, if the ovaries are surgically removed.

· Thus calculating “normal” is impossible, if you include “natural age-related hormonal change”!

· To give medical investigators their due, an effort is always made to include only the fittest individuls in the group evaluated. However unknown or ignored factors can lead to a “curve ball” situation and unreliability of an accepted “normal” range.

· IN SUMMARY, aberrations of hormonal production are pervasive and there is a delicate interdependence of hormonal systems.

Test subjects should be
BETWEEN AGE 20 AND 25 YEARS and ALL THEIR OTHER RESULTS SHOULD BE 100% NORMAL
If not, they should be excluded from studies to calculate a “normal” reference range.
This should apply for whatever test is to be evaluated.

  REFERENCES

[1] Opposite effects of dexamethasone on serum concentrations of 3,3′,5′-triiodothyronine (reverse T3) and 3,3’5-triiodothyronine (T3),I J ChopraD E WilliamsJ OrgiazziD H Solomon, J Clin Endocrinol Metab, 1975Nov;41(5):911-20, doi: 10.1210/jcem-41-5-911, PMID: 1242390. DOI: 10.1210/jcem-41-5-911,

[2] Diversion of peripheral thyroxine metabolism from activating to inactivating pathways during complete fasting, A G VagenakisA BurgerG I PortnaryM RudolphJ R O’BrianF AziziR A ArkyP NicodS H IngbarL E Braverman, PMID: 1150863, DOI: 10.1210/jcem-41-1-191 J Clin Endocrinol Metab, 1975 Jul;41(1):191-4. doi: 10.1210/jcem-41-1-191. https://pubmed.ncbi.nlm.nih.gov/1150863/

(3) The evidence for a narrower thyrotropin reference range is compelling
Leonard Wartofsky 1 Richard A Dickey, J Clin Endocrinol Metab, 2005 Sep; 90(9):5483-8 PMID: 16148345 DOI: 10.1210/jc.2005-0455 .https://pubmed.ncbi.nlm.nih.gov/16148345/

(4) Age-Specific Distribution of Serum Thyrotropin and Antithyroid Antibodies in the U.S. Population: Implications for the Prevalence of Subclinical Hypothyroidism:
Martin I. Surks, Joseph G. Hollowell, The Journal of Clinical Endocrinology & Metabolism, Volume 92, Issue 12, 1 December 2007, 4575–4582, https://doi.org/10.1210/jc.2007-1499 01 Dec. 2007.
https://academic.oup.com/jcem/article/92/12/4575/2596923?login=true

(5) A new prognostic index in surgery and parenteral feeding: the ratio of triiodothyronine to reverse triiodothyronine in serum A new prognostic index in surgery and parenteral feeding: the ratio of triiodothyronine to reverse triiodothyronine in serum (T3/rT3 ratio) H.D. Calvey, W.J. Marshall, P.D. Marsden M. Davis
Front Endocrinol (Lausanne). 2018; 9: 97.Volume 5, ISSUE 3, P145-149, August 01, 1986:OI:https://doi.org/10.1016/0261-5614(86)90003-8 Published online 2018 Mar 20. doi: 10.3389/fendo.2018.00097 PMCID: PMC5869352 PMID: 29615976

(6) Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study
Begoña Ruiz-Núñez,1,2,* Rabab Tarasse,1 Emar F. Vogelaar,3 D. A. Janneke Dijck-Brouwer,1 and Frits A. J. Muskiet1 Front Endocrinol (Lausanne). 2018; 9: 97, Published online 2018 Mar 20. doi: 10.3389/fendo.2018.00097, PMCID: PMC5869352 PMID: 29615976 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869352/

(7) Opposite effects of dexamethasone on serum concentrations of 3,3′,5 triiodothyronine (reverse T3) and 3,3’5 triiodothyronine (T3): IGA chopper, DE Williams, JR get C, DH Solomon,
PM ID 124-2390, DOI 10.110/jcem-41- 5- 911
HT to//pub med.and CBI.nim.nih.gov/124-2390/

(8) Effect of 3:5:3′-L-triiodothyronine in myxoedema, GROSS J, PITT-RIVERS R, TROTTER WR. Lancet. 1952 May 24;1(6717):1044–1045.

(9) A radioimmunoassay for measurement of 3,3′,5′-triiodothyronine (reverse T3). Chopra IJ. J Clin Invest. 1974 Sep;54(3):583–592. [PMC free article] [PubMed] [Google Scholar]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC301591/

(10) Diversion of peripheral thyroxine metabolism from activating to inactivating pathways during complete fasting.Vagenakis AG, Burger A, Portnary GI, Rudolph M, O’Brian JR, Azizi F, Arky RA, Nicod P, Ingbar SH, Braverman LE. J Clin Endocrinol Metab. 1975 Jul;41(1):191–194. https://pubmed.ncbi.nlm.nih.gov/1150863/

(11) Concentrations of 3,3′,5′-triiodothyronine (reverse T3) and 3,3′-triiodothyronine (T3)
IJ chopra, DE Williams,J Orgiazzi, DH Solomon.
PM ID: 124-2390, DOI: 10.121 0/jcem–41–5–911 the(11) https://pubmed.ncbi.nlm.nih.gov/1242390/

(12) Diversion of peripheral thyroxine metabolism from activating to inactivating pathways during complete fasting, A G VagenakisA BurgerG I PortnaryM RudolphJ R O’BrianF AziziR A ArkyP NicodS H IngbarL E Braverman, PMID: 1150863, DOI: 10.1210/jcem-41-1-191 J Clin Endocrinol Metab, 1975 Jul;41(1):191-4. doi: 10.1210/jcem-41-1-191. https://pubmed.ncbi.nlm.nih.gov/1150863/

G. A. Harry, MB, BS (London), LMCC, FRCSC (urology), ABAARM (A4M, 2014).

I am a Toronto-trained Urologist. I practiced in downtown Toronto, from 1977 to 1997, when I went to Saudi Arabia as chief of Urology at the Armed Forces (teaching) hospital in Tabuk. Returning to Toronto in Y2000, I switched to family practice. In 2007, began to prescribe Hormone Restoration Therapy and in 2012, I became a member of the American Academy of Antiaging Medicine [A4M]. I successfully wrote the A4M's written examination in December, 2013 and In May, 2016 I passed the oral examination, for accreditation as a BHRT consultant. In 2014 I began BHRT practice in Collingwood, Ontario and in January, 2017, joined the Stone Tree Naturopathic Clinic. Now I am 82 and have retired, but it seems wasteful to jettison my learning and experience: the medical establishment knows nothing of BHRT / Functonal medicine and I feel obliged to offer my knowledge in the interest of those who are willing to think outside the box. MY QUALIFICATIONS: MB, BS, (from UWI), 1964. LMCC 1969. FRCSC (Urology), 1974. ECFMG 1984. Florida license 1998 [inactive], ABAARM Certification [A4M], 2016. I am a Member of CSAMM [the Canadian Society for Aging and Metabolic Medicine], the OMA&CMA, SUSO, CUA, RCP&S/C. PRACTICE TO DATE: Consultation in Functional Medicine, including assessment of Chronic Fatigue Syndrome, Fibromyalgia, Andropause, Menopause, Teenage and Postpartum Depression/Panic Attacks, Thyroid Hormone malfunction, Infertility, Sexual Dysfunction and “the Undiagnosable”. ALL ARE WELCOME to read, comment or question!