This abstract says little or nothing about the utility of rT3 testing - despite its title. All it appears to do is identify test numbers and, to some extent, who is doing the ordering.
Maybe the full text would actually fulfil the promise of the title? (No, I really don't believe it will, either.)
Thyroid. 2018 May 14. doi: 10.1089/thy.2017.0645. [Epub ahead of print]
Does Reverse Triiodothyronine Testing Have Clinical Utility? An Analysis of Practice Variation Based on Data from a National Reference Laboratory.
1 University of Utah, Pathology , 15 N Medical Drive East , Salt Lake City, Utah, United States , 84112.
2 ARUP Laboratories, 33294, Salt Lake City, Utah, United States ; robert.schmidt@hsc.utah.edu.
3 USC School of Medicine , 1200 N State St , # 18415 , Los Angeles, United States , 90033.
4 United States ; JLoPresti@socal.rr.com.
5 University of Colorado Hospital, Endocrinology , 1635 N Ursula Street , Rm OP-6620 , Aurora, Colorado, United States , 80010 ; Michael.mcdermott@ucdenver.edu.
6 University of Michigan, Department of Family Medicine and Department of Nutritional Sciences, Ann Arbor, Michigan, United States ; szick@med.umich.edu.
7 University of Utah, Department of Pathology , 500 Chipeta Way , Mail Code 115 , Salt Lake City, Utah, United States , 84108 ; joely.a.straseski@aruplab.com.
Abstract
BACKGROUND:
Clinical laboratories are under pressure to increase value by improving test utilization. The clinical utility of reverse triiodothyronine (rT3) is controversial. We conducted a study to identify order patterns that might suggest inappropriate utilization of reverse triiodothyronine.
METHODS:
We reviewed all orders for thyroid tests placed over a period of one year at a national reference laboratory. We analyzed order patterns by client (hospital) and by provider. We conducted a Pareto analysis to determine the percentage of orders placed as a function of the percentage of providers. We conducted a systematic review of the indexed literature and an informal review of the web to identify indications for rT3 testing.
RESULTS:
There were 402,386 orders for 447,664 thyroid tests including 91,767 orders for rT3. These orders were placed by 60,733 providers located at 1139 different organizations. Only 20 percent of providers who ordered thyroid tests placed an order for rT3. Of those who placed an order for rT3, 95% placed two or less orders for rT3. One hundred providers (0.1% of the 60,733 providers who placed orders for thyroid tests) accounted for 29.5% of the orders for rT3. Sixty of the 100 providers with the highest order volumes for rT3 were classified as practitioners of functional medicine. A systematic review of Medline found little evidence to support the high volumes of orders for rT3. A survey of web sites for functional medicine suggest that rT3 is useful for the diagnosis of rT3 dominance and can be used to direct triiodothyronine replacement therapy.
CONCLUSIONS:
There is wide practice variation in rT3 testing. A high proportion of tests are ordered by a relatively small proportion of providers. There is little evidence to support high volumes of rT3 testing placed by some practitioners.
This excerpt is also about RT3 I looked at earlier today. I cannot find link at present but this is an excerpt:
"Dr. Lowe: Some readers will not be familiar with reverse-T3, and I know from experience that many others harbor misconceptions about the molecule. Because of this, I have summarized in the box below what we know about reverse-T3. I've answered your question below the summary.
Conversion of T4 to T3 and Reverse-T3: A Summary
The thyroid gland secretes mostly T4 and very little T3. Most of the T3 that drives cell metabolism is produced by action of the enzyme named 5'-deiodinase, which converts T4 to T3. (We pronounce the "5'-" as "five-prime.")
Without this conversion of T4 to T3, cells have too little T3 to maintain normal metabolism; metabolism then slows down. T3, therefore, is the metabolically active thyroid hormone. For the most part, T4 is metabolically inactive. T4 "drives" metabolism only after the deiodinase enzyme converts it to T3.
Another enzyme called 5-deiodinase continually converts some T4 to reverse-T3. Reverse-T3 does not stimulate metabolism. It is produced as a way to help clear some T4 from the body.
Under normal conditions, cells continually convert about 40% of T4 to T3. They convert about 60% of T4 to reverse-T3. Hour-by-hour, conversion of T4 continues with slight shifts in the percentage of T4 converted to T3 and reverse-T3. Under normal conditions, the body eliminates reverse-T3 rapidly. Other enzymes quickly convert reverse-T3 to T2 and T2 to T1, and the body eliminates these molecules within roughly 24-hours. (The process of deiodination in the body is a bit more complicated than I can explain in this short summary.) The point is that the process of deiodination is dynamic and constantly changing, depending on the body's needs."
If anyone's interested I got hold of the paper and print below the Discussion which is the only worthwhile bit. Sorry it's a bit drawn-out:
DISCUSSION
We found that orders for rT3 are concentrated among relatively few providers and
clients. Among providers who ordered thyroid-related tests, one tenth of a percent (0.1%)
of providers account for 29% of rT3 orders. Similarly, approximately one percent of clients
accounted for 56% of orders for rT3. Further, we found that providers who order high
volumes of rT3 tend to be clustered within clients. We found that results from providers
who order high volumes of rT3 tend to have a lower clinical yield (i.e., a lower rate of
abnormal findings) than orders from providers who placed relatively few orders for rT3.
Finally, we found that specialists in functional medicine are highly represented among the
providers who order the highest volumes of rT3.
The highly skewed distribution of rT3 test utilization suggests that there is
significant practice variation with respect to rT3 measurements. The wide practice
variation suggests misutilization. Given the lack of evidence to support the usefulness of
high volumes of rT3 testing, our data suggests that rT3 testing is over-utilized by a small
proportion of practitioners.
In conventional practice, rT3 is considered an inactive metabolite of the thyroid
hormone thyroxine (T4), as opposed to the conversion of T4 into the active T3. The
inability of rT3 to exert the same energy and metabolism-related effects as T3 supports its
definition as an inactive hormone representative of the catabolic state. It has been
proposed that favoring the alternative rT3 metabolic pathway may serve as a mechanism
to conserve energy in times of severe illness or starvation(19-21). Elevated
concentrations of rT3 are the norm in nonthyroidal illness (NTI or sick euthyroid syndrome)
and “low T3 syndrome” (decreased T3 and elevated rT3 concentrations); therefore, its
measurement is rarely useful in hospitalized patients (22). In most laboratories, rT3 is sent
to a referral testing site and the long turnaround time may further limits its utility,
particularly in inpatient settings. The indications for rT3 testing in ambulatory care are
very limited. For example, rT3 measurements can be helpful in the diagnosis of thyroid
hormone cell membrane transport defects (THCMTD), thyroid hormone metabolism
defects, and consumptive hypothyroidism(23-25).
It has been reported that rT3 concentrations increase with age, proposedly due to
diminished renal metabolism and eventual degradation of rT3 in the liver (26, 27). This rise
in rT3 may, in part, reflect underlying illness or malnutrition in the aging population,
similar to that described in hospitalized patients. Elevations in free T4 and rT3 hormone
concentrations have been associated with lower physical and mental functionality scores
in elderly men (28), but the strong correlation between the T4 and rT3 values is consistent
with the notion of concurrent illness which may explain these lower scores.
One situation where rT3 testing may be helpful is to distinguish central
hypothyroidism from non-thyroidal illness (NTI) in hospitalized patients; while other
thyroid tests, like TSH and free T4, may be similarly low in these two conditions, rT3 is
usually also low in central hypothyroidism and high in patients with NTI. Even here,
however, a good clinical evaluation by an experienced clinician will usually provide the
accurate diagnosis in the absence of a rT3 measurement. The distinction between primary
hypothyroidism and NTI is much more straightforward since the serum TSH is elevated in
primary hypothyroidism and usually low in NTI until the recovery phase when it is
transiently mildly elevated. A seasoned clinician and even less experienced providers
usually have no problem making this distinction without the added expense of a rT3
measurement. There are also some rare conditions such as consumptive hypothyroidism,
MCT8 mutations, and SBP2 mutations where rT3 measurements can be helpful in
characterizing the phenotype and the underlying mechanism of disease (23, 29, 30).
Therefore, for the conventional medical community, the clinical indications for use of rT3
testing are very limited, and it remains an unusual request. Its use is not referred to or
supported in routine clinical practice guidelines related to thyroid disease testing or
management (31). This is presumably due to minimal evidence of rT3 utility found in the
primary literature.
The functional medicine community believes that tissue concentrations of T3 are
the key determinant of thyroid function and that serum concentrations of T3 are sometimes a poor indicator of thyroid hormone concentrations at the tissue level (32, 33).
Functional medicine hypothesizes that rT3 competes with T3 at binding sites so that
elevated rT3 can cause hypothyroid symptoms when T3 concentrations are normal (34,
35). This is known as rT3 dominance. It is proposed that a number of conditions such as
liver disease, kidney disease, stress, chronic alcohol abuse or other drug abuse, and simple
aging can lead to increases in rT3 which, in turn, leads to rT3 dominance. These
practitioners recommend the use of the rT3/T3 ratio to diagnose rT3 dominance. When
the rT3/T3 ratio is elevated in the setting of hypothyroid symptoms and normal TSH, T3
and FT4, these practitioners suggest therapy with thyroid hormone supplementation (34).
However, the affinity of T3 for the T3 receptor is 100 fold higher than the affinity of rT3;
therefore the notion that rT3 can compete with T3 for occupancy of the T3 receptor is not
consistent with current scientific data (36). Moreover, we found no studies in the
conventional literature that recommend interventions based on rT3 concentrations.
Functional medicine practitioners treat patients with a rT3 dominance profile
(hypothyroid symptoms, elevated rT3 and normal T4) with hormone supplementation
(liothyronine or dessicated thyroid hormone preparations). Functional medicine
practitioners sometimes prescribe co-factors for enzymes involved in thyroid metabolism
or nutrients that are considered important for thyroid health such as selenium, zinc, iron,
iodide, and vitamins C, D and E. These nutrients are thought to enhance the conversion of
T4 to T3 rather than rT3 and provide an alternative to T3 supplementation (37); however,
according to conventional medicine, the only known intervention that increases T4 to rT3
conversion is the administration of glucocorticoids (38). There is little or no published
evidence to support the rT3 dominance hypothesis or the interventions based on the
theory.
Is the rT3 dominance hypothesis plausible? There is evidence that many diseases
and medications lead to changes in thyroid hormone concentrations (39, 40). It is
theoretically possible that rT3 might compete for T3 receptors; however, the evidence
suggests that this is not case. One study, from almost 30 years ago suggested that rT3
had an had an affinity for placental nuclear binding sites that was 40 times greater than
thyroxine and 63 times greater than triiodothyronine (41). Another study suggested that
rT3 represses thyroid-regulated genes in mice (42). However, in contrast, another study
showed that the relative affinity of rT3 to T3 for solubilized nuclear T3 receptors was 0.01
(36). In addition, T3 is present in much higher concentrations than rT3. The reference
range for the T3/rT3 ratio is 4.2 – 11.0 (43). The T3/rT3 ratio remains above 1.0 even in
illness (3). Because of the transient function of the placenta and its unique deiodinase
profile, it is certainly questionable whether T3 receptor binding in this tissue is
representative of the rest of the body’s tissues. In contrast, studies of T3 receptors in
human liver and kidney have demonstrated that the affinity of T3 for the T3 receptor is
100 fold higher than that for rT3 (34). This certainly casts doubt on the ability of rT3 to
compete with T3 for receptor occupancy and therefore of the validity of the concept of rT3
dominance.
Much of the evidence from the functional medicine practitioners appears to be
based on anecdotal evidence that patients with symptoms and laboratory values
consistent with rT3 dominance experience symptom relief with T3 therapy. From the
perspective of conventional medicine, such evidence is suggestive, but could also be
explained by a placebo effect. Also, some of the effect of T3 supplementation might be
explained by the fact that supra-physiologic doses of T3 can work as a mood-enhancer in
depressed patients (44). The symptoms of hypothyroidism (fatigue, trouble thinking, and
weight gain) are very nonspecific and are frequently experienced by healthy people. rT3
concentrations are also elevated in chronic illness/malnutrition. The T4/rT3 ratio generally
remains constant and glucocorticoids are the only factors know to alter this ratio (38).
Thus, nutritional interventions are unlikely to be effective. Overall, it appears that there is
no published evidence to support the rT3 dominance theory; however, it is important to
bear in mind that “absence of evidence is not evidence of absence”(45).
What types of studies are needed to determine whether measurement of rT3 has
clinical utility? Functional medicine believes that patients with an rT3 dominance profile
(hypothyroid symptoms, elevated rT3, and normal T4) can be treated with thyroid
hormone supplementation; however, to our knowledge this hypothesis has never been
tested in a clinical trial. Therefore, a double-blinded randomized trial with patients fitting
the rT3 dominance profile (arm 1) and patients with normal rT3 profile (arm 2) and
treatment with placebo or T3 supplementation could verify the claims that patients with
an rT3 dominance profile benefit from T3 supplementation. Similarly, double-blinded
placebo-controlled randomized trials to determine whether nutritional interventions
provide symptomatic relief for patients with an rT3 dominance profile might be
illuminating. Studies on competitive binding of rT3 and T3 could rule out the rT3
dominance theory if rT3 did not interfere with T3 binding. Results showing that rT3
competes with T3 would be consistent with the rT3 dominance theory but would not be
conclusive. Experimental studies showing that exogenous rT3 has an impact on basal
temperature and other physiological parameters mediated by T3 would also support the
rT3 dominance theory; however, it has been shown that administration of rT3 does not
change serum TSH concentrations (46). If rT3 were active, it would be expected to alter
TSH concentrations. These studies would be relatively inexpensive and could provide data
to guide the use of rT3 testing.
Our study found that our laboratory received approximately 91,000 orders for rT3
in one year. On a national basis, we suspect that the order volume for rT3 is at least 1
million. Each rT3 test costs about $20 (average list price of commercial laboratories, range:
$7.00 to $46.25). It is unclear whether these orders provide value. If rT3 measurement
provides no value, there could be an opportunity for significant savings at sites with high
order rates for rT3. Given the current emphasis on laboratory utilization, it seems that
studies on the utility of rT3 are warranted and would most likely be cost-effective. Since
the evidence suggests no utility for rT3, the burden of proof is on the functional medicine
community to design scientific studies that support its clinical utility.
Our study has several limitations. Practice variation suggests misutilization but is
not conclusive. Our study only identified order patterns but did not determine the reason
why individual orders were placed. A survey or interviews of users might identify the
reasons for test orders and identify hypotheses that could be tested. rT3 is generally
performed by reference laboratories, but routine thyroid tests are performed at most
hospitals. Thus, our estimate of the percentage of physicians who order rT3 is likely to be high because most thyroid testing would be performed locally. Our review of the
conventional literature was systematic; however, our review of the web literature was informal. Finally, our study found a lack of evidence to support rT3 testing; however, a
lack of evidence does not prove a lack of effect. Additional studies are needed to
determine the clinical utility of rT3.
In summary, our study shows significant practice variation in rT3 testing. A high
proportion of tests are ordered by a relatively small proportion of providers and much of
the use of rT3 testing appears to be driven by functional medicine. At present, there is
little evidence to support the high volume of rT3 testing requested by this community.
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Elevated Reverse T3 
British Thyroid Foundation - ?
RT3 in urine too low, meaning?
