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LifeLabs BC handout reveals thyroid testing policy failure

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This week (as of October 4, 2019), a thyroid patient from British Columbia posted an image of a piece of paper handed to her at a LifeLabs laboratory.

LifeLabs BC was using this paper leaflet to explain to her why “Free T3 and Free T4 will not be tested when the TSH is in reference range.”

The paper says this:

“Thyroid Protocol Changes.

YES: Diagnosis or comments on the requisition include any of the following words or phrases:

All other diagnoses and comments do not qualify as special case.”

In this post, I’m going to show how the leaflet reveals problems in our thyroid healthcare system.

  1. First of all, it shows poor communication strategies.
    • This information is addressed to a physician, but it is being given to a patient. A patient has no reason to celebrate the reduction of 80 conditions to 6. What if they had one of those 80 conditions now disqualified? They may reasonably suspect that the policy is being oversimplified at the expense of their health.
    • It includes 5 synonyms that mean exactly the same health condition (central hypothyroidism), so it is misleading. It makes it look like there are 6 special cases, when in fact, there are 2. This is an inflated vocabulary list, not a health justification.
    • It shows no respect for the struggle of treated, thyroid-disabled patients who are working with compassionate physicians to alleviate their chronic symptoms and improve their health during lifelong thyroid therapy by finding the FT3 and FT4 levels that are optimal for their disabled bodies.
  2. Secondly, the handout reveals the blindness of the “normal TSH” paradigm.
    • The paradigm puts too much faith in the TSH hormone and its reference interval as a proxy for the appropriateness of circulating thyroid hormones. The science in the past decade shows that the HPT axis is not defined by a perfectly log-linear TSH-FT4 relationship. Being “in range” is not synonymous with euthyroidism.
    • This paradigm incorrectly presumes that the outer boundaries of descriptive reference intervals for a population function as physiologically meaningful health risk thresholds for an individual.
    • It presumes that reference range boundaries ought to serve as dose adjustment thresholds for individuals on thyroid treatment. This is the fallacy of making a descriptive statistical range for non-disabled populations into prescriptions and prisons for disabled individuals.

We need exceptions for ALL people whose TSH-FT4-FT3 relationships are likely to be distorted, not just people with suspected central hypothyroidism (hypothalamus or pituitary failure).

At the end, I’ll reveal an easy fix for this failed policy.

We need to listen to the new thyroid science and stop listening to “Choosing Wisely’s” penny-pinching arguments.

Note: This article was revised Jan. 21, 2023 due to a 2nd reader complaining that it was “disparaging the laboratory” (see comments below).

I’m sorry it sounded that way. It was not my intent to disparage LifeLabs staff. I hope that the main point of the title (unchanged) has been clarified. The “LifeLabs BC handout reveals thyroid testing policy failure” …

1) a failure of communication, which can elicit mistrust from patients and frustration from physicians,
2) a failure at a larger scale, since the directives are handed down to labs from people on committees.

The policy failure #2 goes far beyond LifeLabs. The handout is part of a Canada-wide and global FT3 and FT4 cancellation trend that seeks cost savings and efficiency while being ignorant of thyroid treatment guidelines and thyroid science, which I outline here.

Fortunately, long before I revised this post, within “5 months” of its implementation, LifeLabs had changed its policy, likely because it was causing patients and doctors to complain and question it

On July 7, 2020 LifeLabs published a revision of the guideline which includes 3 additional indications for FT3 and FT4 testing when TSH is normal.

Some treated hypothyroid patients in BC will be greatly relieved! “Treatment with T3” has been included as a “special case” for FT3 and FT4 testing as of mid-2020.

Why is this needed? The TSH response to T3 dosing is very different from the TSH response to endogenously-produced T3. It is also very different from the TSH response to LT4 dosing.

During T3 therapy, TSH recovery may be delayed by at least 12h after a dose of 10mcg T3 and 90 hours after a dose of 50 mcg T3. This is a drug-induced TSH-FT3 relationship distortion because TSH recovery occurs long after the FT3 / Total T3 levels have returned close to their pre-dosing baseline (See graphs by Saravanan et al, 2007 and Jonklaas et al, 2015 in our post “Free T3 peaks and valleys in T3 and NDT therapy“).

The overzealous FT4 and FT3 test cancellation campaign

This 2019 LifeLabs policy was just one local instance of a desire to limit thyroid laboratory testing across Canada and in many countries today.

The campaign called “Choosing Wisely,” richly funded by provincial governments with taxpayer money, is being used to divest taxpayers of access to FT3 and FT4 tests.

Since a campaign to persuade physicians is not very effective, they ask laboratories to enact test cancellations.

Today, according to the way Choosing Wisely Canada testing toolkits and guidelines are being worded, the only justification for testing Free T4 and Free T3 during routine hypothyroid therapy when the pituitary TSH is normal will be based on central hypothyroidism (which causes TSH hyposecretion).

Choosing Wisely materials are an overzealous misinterpretation of thyroid treatment guidelines’ emphasis on TSH normalization.

The American Thyroid Association Guidelines (Garber et al, 2012: Jonklaas et al, 2014) did not forbid FT3 or FT4 tests during the treatment of hypothyroidism.

In fact, the 2012 guidelines gently recommended FT4 testing during levothyroxine (LT4) treatment. There is no way to misinterpret this:

“Assessment of serum free T4, in addition to TSH, should be considered when monitoring L-thyroxine therapy.  Grade B, BEL 1”

(Garber et al, 2012, recommendation 8)

In fact, the 2014 guidelines permitted T3 to be an additional treatment target in patients who lack endogenous thyroid function:

“In some cases, LT4 alone may fail to restore the T3 levels to a value within the reference range in patients who have undergone total thyroidectomy and thus are devoid of residual endogenous production of thyroid hormone (39,41,42). In euthyroid patients undergoing thyroidectomy and not requiring suppressive therapy, if T3 levels are chosen as one of the therapeutic targets, it is reasonable to titrate the therapy to achieve circulating levels of T3 similar to the presurgery values while maintaining the TSH value within the range of normality.”

(Jonklaas et al, 2014, section 1b)

Given the reasoning above, the ATA would permit T3 as a therapeutic target for any person who is “devoid of residual endogenous production of [T3 and T4] thyroid hormone” for any cause, including:

Even if there is no “presurgery” T3 value, the population distribution of FT3 and TT3 is narrowly focused on the middle of the reference interval in untreated healthy subjects.

The ATA’s 2012 prohibition against using T3 to diagnose untreated hypothyroidism (Garber et al, 2012, recommendation 10) does not mean that the concentration of T3 is irrelevant to symptoms or health outcomes during treatment. When the clinical implications of low or low-normal T3 levels were addressed in 2014, the authors admitted ignorance, and no recommendation was given. They did not prohibit T3 testing in 2014.

Years after the 2014 guideline was published, in 2019, Hoermann et al found that thyroidless LT4-treated patients’ symptoms were highly correlated with FT3 levels, and individuals’ symptom-free FT3 levels were found in very narrow ranges within the reference range, and were highly individualized.

It is unfair to condemn a thyroid-disabled individual to a life of perpetual suboptimal-yet-normal FT3 simply because of a refusal to measure it!

Clearly, the guidelines say something very different from Choosing Wisely:

Yet an overzealous cancellation policy is being used by provincial health care systems, pushed onto laboratories and doctors, and reinforced in medical schools.

5 SPECIAL CASES ARE REALLY ONLY ONE

The Life Labs handout seems to be saying to the thyroid patient, “Wow look at all those “special cases” or “diagnoses” or “conditions” you could have that would still justify an FT3 and FT4 test!”

Anyone who understands secondary hypothyroidism will note that items 1-5 are synonyms for of ONE general diagnosis of “Central Hypothyroidism.”

Central hypothyroidism, a condition of TSH hyposecretion, is caused by

  1. Pituitary failure (which causes…)
  2. Secondary hypothyroidism (also more commonly known as “central hypothyroidism” which is strangely omitted from the list),
  3. Hypothalamic or
  4. Hypothalamus failure (which constitutes the same root word with two different endings), and
  5. Tertiary hypothyroidism (which is essentially hypothalamic failure, which causes the pituitary to secrete less TSH per unit of FT4).

This is not a list of 5 DIAGNOSES.

It’s a list of 5 aspects of and synonyms for ONE DIAGNOSIS.

This makes the lab look bad. It denies tests because requisitions don’t have “magic words” on them, and one key magic word is missing.

To the science-informed reader of the leaflet, it makes it seem like the clinical biochemist or lab pathologist at Life Labs, or their superiors in a committee at the health care system level, didn’t realize that these all constitute one disorder now called “central hypothyroidism.”

I recommend this reading list of diagnostic policies for central hypothyroidism.

If you look inside, you will see them talk about hypothalamic and pituitary disorders, and they explain why the “tertiary/secondary” and “pituitary/hypothalamic” distinction is now obsolete. It splits hairs unnecessarily.

The major problem, of course, is this:

The LifeLabs form fails to say “suspected central hypothyroidism.”

It also fails to acknowledge the laboratory data and diagnostic skill needed to suspect it.

Beck-Peccoz’s 2017 article, listed above, is criticizing TSH-first policies like this LifeLabs handout.

Since a normal TSH is common in central hypothyroidism, you have to test more than just TSH before central hypothyroidism can be either diagnosed or suspected! How can you suspect it if FT4 is cancelled?

DID YOU REALLY have A LIST OF 80 unique diagnoses?

The leaflet says this: “Going from 80 diagnoses and conditions that qualified for special case to 6.”

Life Labs BC, and BC healthcare leaders, we have reason to suspect that you may imagine each word in a vocabulary list is a discrete diagnosis.

Were you really making your lab technologists and lab assistants scan a list of 80 words whenever they got a requisition for FT3 and FT4?

Yes, I bet that was an inefficient use of their time and education level.

It makes it seem like patients and their doctors are being denied vital tests just so that the laboratory staff doesn’t have to scan such a long list of synonyms.

What were the 74 health conditions (or vocabulary items) omitted from their list of special cases?

Why was it decided that these 74 no longer have the potential to distort TSH secretion, if someone formerly believed they did?

Where is the justification for their removal from the list? It is not explained in this handout.

Did the human body change? Did today’s scientific understanding of TSH-distorting health conditions and medications change?

In my reading of the scientific literature, the list of TSH-distorting variables has gotten longer over the years, not shorter.

A drug that can “suppress TSH” is also a drug that can make a high TSH become deceptively normal.

Consider the more recent articles:

Can nobody at LifeLabs take the time to defend vulnerable patients, especially patients dosing both LT4 and other drugs that distort TSH, by fact-checking policy decisions?

It would require a hero capable of being a critical thinker who is skeptical of experts and committee decisions. It would require strategic searching in PubMed and medical articles with those 74 words at hand.

Were they omitted for a good enough reason? Or were they omitted because people wanted to save money and time by preventing FT4 and FT3 testing?

Everyone wants to focus on a lab test’s price tag. But no one is capable of judging how much healthcare money a $9 FT3 or $12 FT4 test could have saved, if only it had not been cancelled.

ANALYTICAL INTERFERENCE IS A DIFFERENT ISSUE

The 6th special case in which Free T3 and Free T4 testing may be permitted is “analytical interference.”

“Suspected / Query (?) analytical interference (Requisition MUST indicate that the ordering practitioner has obtained approval by a laboratory physician prior to ordering)”

(LifeLabs Handout, unrevised version)

“Unusual cases where analytical interference is suspected or the TSH result does not match the clinical situation. The requisition must indicate that the ordering doctor has obtained approval from a laboratory physician or clinical biochemist.”

(LifeLabs policy, revised version)

As you can see, the revised version is clearer and elaborated:

This item in the list is not like the others.

“Analytical interference” is not a medical diagnosis or health condition. It is something that could be a problem with ANY lab test.

  1. Pre-analytical interferences are not the responsibility or fault of the laboratory. They involve factors beyond the control of the lab:
    • “Generally, TSH-independent states are observed when the disorder affects primarily the thyroid gland, but there are non-thyroid conditions that can alter the interaction and confound the diagnosis, such as trophoblastic tumors, struma ovarii, and generalized resistance to thyroid hormone or selective organ resistance to thyroid hormone. Besides, there are TSH-dependent variables due to inappropriate TSH secretion or lack of secretion such as pituitary adenoma, resistance states to thyroid hormone (generalized or pituitary), psychiatric states, smoking, and malabsorption. Besides, there are physiological variables, as follows: circadian rhythm, seasonal influences, environmental influences, exercise, posture, and pregnancy.” (Caruso et al, 2021)
  2. Analytical interferences (sometimes called the “intra-laboratory” phase) are due to human error or procedural mistakes in laboratory handling of samples or equipment, or the fault of the assay technology itself.

According to peer-reviewed articles, analytical aspects of lab testing involve:

In this context, the LifeLabs item #6 makes it seem like a physician with only a TSH result, without a set of distorted TSH, FT3, and FT4 results in hand could have enough grounds to suspect an analytical interference.

Quality control is a high priority for labs. Requiring the test-ordering physician to have the prior approval of the laboratory physician is like asking a head chef to go through his kitchen looking for contaminants just because one customer got sick. Not likely to happen.

Getting the lab to approve the questioning of their own lab test is suspicious. This final “special case” permits the “laboratory physician” to have veto power over the test-ordering physician when laboratory test technologies and procedures are in question.

Why isn’t an unbiased third party carrying out the checking?

Any genuine suspicion of analytical interference would justify going to at least one different laboratory, if not two, to use their test based on different assay manufacturers. Ideally, you would test a single blood sample on several brands of assays (Roche, Abbott, and on) to see the degree to which the test results are discordant with each other.

Even more ideally, you’d get it tested by a gold-standard “liquid chromatography tandem mass spectrometry” TSH, FT4, or FT3 test.

Certain manufacturers’ FT3 and FT4 tests have problems. Certain LifeLabs branches may use the untrustworthy Abbott assay and suspicious methods of determining the FT3 reference range.

Test quality concerns should be carefully investigated and fixed rather than making them too difficult to question.

Is it “ANALYTICAL INTERFERENCE” or TSH paradigm interference?

This final item on the LifeLabs BC handout indirectly reveals the deeper failure of our current thyroid testing policy.

What physicians are probably observing when TSH is inconsistent with FT3 and FT4 is not in fact analytical interference, but pre-analytical and post-analytical “TSH-paradigm interference.”

The standard TSH paradigm teaches clinicians to expect that TSH will be consistent with FT3 and FT4 and even a patient’s clinical status.

In fact, age, sex, thyroid diseases, nonthyroidal diseases, thyroid peroxidase antibodies, and dosing various medications can distort TSH-FT4 hormone relationships.

This paradigm, this false expectation of alignment and consistency, will “interfere” with thyroid test interpretation.

For example, doctors who expect TSH to have perfectly log-linear behavior during thyroid therapy may be puzzled when a patient is dosing T3 and their TSH is normal while FT4 is below range. Puzzling over the inconsistency of a low TSH and low FT4, the doctors suspected either analytical interference or central hypothyroidism. Perhaps some have tried to use this reason to justify their request for FT3 and FT4 testing (or re-testing).

Extreme overconfidence in TSH will make doctors suspect the FT3 and/or FT4 test is untrustworthy and that the TSH is so “sensitive and specific” that its judgment is always “more correct” than the direct measurement of thyroid hormones!

Blind faith in TSH is maintained by physician ignorance and inexperience.

A policy that denies FT3 and FT4 whenever TSH is normal won’t let physicians gain experience with interpreting conflicting results.

This leads to physician ignorance and blind faith in TSH. It is a vicious cycle.

Because of FT4/FT3-blinding policies, physicians rarely get the chance to observe TSH misbehavior when TSH is normal.

It is futile to judge a TSH, or an FT4 or a FT3 on the basis of whether each analyte in isolation from the other is normal, high, or low. Most results will be within or close to the reference interval, which gives a sense of false assurance to the uninformed physician that “everything is fine.” The opposite may be true if you look at hormone relationships.

During thyroid treatment, whenever values are within or close to the reference range, no single analyte in isolation has diagnostic veto power. For example, a low-normal TSH may occur when FT4 is low or undetectable and T3 dosing makes FT3 from high-normal to high. Is the patient hypothyroid due to their low FT4, or hyperthyroid for the hours when their FT3 is high?

Whenever TSH is responding to abnormal FT3:FT4 ratios induced by thyroid diseases and their therapies, TSH is not a proxy or predictor of the precise position of the other two hormones.

Fortunately, both FT3 and FT4 have the diagnostic power to reveal that a TSH level is inappropriate:

Many doctors are utterly ignorant of the larger potential for distorted TSH-FT4-FT3 relationships during thyroid diseases and their therapy. They have no clue that a patient with Hashimoto’s can also acquire pituitary failure, or that a low titer of Graves’ disease antibodies may interfere with therapy. All they are trained for is how to diagnose thyroid conditions in isolated and simple cases BEFORE thyroid therapy distorts the hormone relationships in a different direction.

Doctors will never learn how to interpret abnormal TSH-FT4-FT3 relationships if they rarely see a full set. When all three are normal, or only one is abnormal, and if they lack training, they won’t be able to “see”

Physicians should be learning how to interpret TSH-FT4-FT3 relationships by experience over the years.

DIAGNOSE THE POLICY FAILURE

We need to observe TSH inconsistency with FT3 and FT4 and clinical presentation.

Collecting the inconsistent data is necessary to correctly diagnose not only the laboratory test quality and the patient’s thyroid hormone status. But first, we have to diagnose this deeper issue …

The critical FAILURE of this TSH-centric thyroid testing policy in the context of thyroid therapy.

Our most popular blog post shows patients how to use science to adjust their own TSH results: “7 ways to raise TSH without reducing thyroid dose.”

Consider all the ways in which normalized TSH fails to give enough information to guide effective thyroid therapy:

Consider the years of suffering these test-cancellation policies cause thyroid patients whose TSH does not reflect their hypothyroid symptoms during treatment, whose physicians refuse a dose increase or T3 treatment “because the TSH is normal.”

A QUICK FIX FOR THE POLICY FAILURE

How many citizens in your healthcare region are on lifelong thyroid hormone replacement at doses higher than 88 mcg/day? A very small percentage of your population.

The lifelong health and welfare of vulnerable thyroid patients is worth a few dollars extra per test.

For thyroid patients who are symptomatic on levothyroxine (LT4) despite a normal TSH, there is no reason why they should not obtain FT3 and FT4 tests, since their TSH-FT3 relationship will be abnormal and their FT3:FT4 ratio will usually be low. Testing just our TSH is not going to provide enough information about how normal their FT3 and FT4 are.

For thyroid patients on T3-inclusive thyroid medication, FT3 and FT4 should be the norm, and the FT3 should be tested >12h post-dose, during the 2nd “slow clearance” phase. Testing just our TSH is not going to provide enough information.

Add a couple of checklist items to the laboratory requisition:

“X = On levothyroxine (LT4) thyroid hormone replacement > 50 mcg/day.”

“X = On liothyronine (LT3) or desiccated thyroid (test >12h post-dose)”

“X = Other clinical indications, i.e. suspected central hypothyroidism.”

This should cover all the necessary, valid conditions for FT3 and FT4 testing.

Instead, you can implement algorithms like SPINA-Thyr in your lab reports to help doctors see even mild subclinical cases of central hypothyroidism before they get worse. We see central hypothyroidism causing thyroid hormone underdose in patients undergoing treatment for primary thyroid failure, and that is why we have a post about “Screening for central hypothyroidism during thyroid therapy.”

You can advocate for workshops that help physicians make better use of FT4 and FT3 lab data, such as

– Tania S. Smith

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