Letter to the Editor: Revised Nomenclature for Tests of Thyroid Hormones in Serum THE COMMITTEE ON NOMENCLATURE OF THE AMERICAN THYROID ASSOCIATION In 1972, a Nomenclature for Tests of Thyroid Hormones in Serum was proposed by the American Thyroid Association (1). In the intervening years, new tests have been introduced and several of those previously included have fallen into disuse. Also, the terminology for various indices of free thyroxine and free triiodothyronine has become even more laced with confusion than it was in 1972. For these reasons, the original Committee was reactivated and it developed the simplified Nomenclature outlined in Table 1, which has been approved for distribution by the Executive Council of the American Thyroid Association. The revised Nomenclature is intended for as wide use as possible by practicing physicians and clinical laboratories, with the hope that uniformity, and thence improved communication, can be achieved. Although applicable to research, it is not primarily directed at research workers, whose publications are expected to include whatever statement or referencing is required for unambiguous presentation of their methodology. Confusion has arisen in three principal areas. First, some physicians and laboratories fail to distinguish between T4 and T4I, referring to the latter test as a "T 4 ." Since T4I is less than twothirds as great as T4, it clearly has a different normal range. Hence, inaccurate naming of the test can lead to false communication and quite needless errors in diagnosis. Fortunately, tests in which iodine is measured are rapidly falling into disuse, so this source of confusion will probably soon disappear. Meanwhile, the proposed Nomenclature, as in the first edition, recommends the unambiguous designation, thyroxine iodine (chromatographic), or T4I(C), for the test reported as iodine, and T4(C) for the case where the test measures iodine but the result is recalculated to correspond to the whole thyroxine molecule, i.e., by dividing the T4I result by 0.65. A second source of confusion has been the continuing practice, fostered by some manufacturers of test kits, or alluding to T3 uptake tests

as simply "T 3 tests" or "T 3 ." This shorthand was at one time tolerable, but is now utterly unacceptable because of the inevitable uncertainty as to whether a T3(RIA) was really the test the physician intended to request. Since the units and normal ranges are so different, the physician receiving a report can usually deduce what was done, but the more serious problem lies in the operation of ordering the test. Thus, the laboratory is in serious doubt as to which test to perform when a "T 3 " is requested. The Nomenclature, once again, adheres to the uncomplicated distinctions drawn in the first edition. The measurement of the concentration of triiodothyronine in serum is designated "Triiodothyronine (radioimmunoassay)" and abbreviated "T3(RIA)." The estimate of the reciprocal of unsaturated thyroxine-binding sites (which correlates with the free hormonal fraction) is referred to as the "Triiodothyronine uptake" and abbreviated "T 3 U." The latter stands for a group of tests, differing in the inert medium used to absorb non-protein-bound radioactive T3, but identical in physiological significance. It should be emphasized that the result of a T3U test does not depend to any important extent on the concentration of T3 in serum; the only important factors are the serum T4 and thyroxine-binding globulin (TBG). So devastating has been the confusion occasioned by the use of the term "T 3 " that some laboratories are eliminating the T3U test from their order slips. This step is perhaps not absolutely necessary to restore clarity, provided the terms T3(RIA) and T3U are rigidly adhered to and clearly distinguished as in Table 1. As a matter of fact, however, the elimination of T3U from request slips and reports would not be an unreasonable step, since this test is not designed to be used alone as a test for hyperthyroidism or hypothyroidism, and the information it would provide regarding thyroxine-binding activity can be calculated from a report which includes the result of a T4(D) or T4(RIA) and a FT 4 index, using the formula: T3U = FT4 Index/T4. Conversely, if the T3U is reported directly, then it

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FT,

9. Free triiodothyronine

T3U

11. Triiodothyronine uptake ratio

D. Indirect estimates of free hormone concentration

T3U

10. Triiodothyronine uptake

C. Estimate of free hormone fraction*

FT 4

7. Triiodothyronine (radioimmunoassay) T3(RIA)

8. F r e e thyroxine

ng/dl

%

Fraction of normal

Uptake of 131I-T, on a solid phase

ng/dl

T3(RIA) and % FT,

Uptake of m I-T 3 on a solid phase

ng/dl

T 4 (C),T 4 (D)orT 4 (RIA)and % FT4

11. The ratio is the T3U of the patient divided by the T3U of a pool of normal standard reference serum included in the same assay run. This form is strongly preferred over no. 10 and is the only form which should be used in calculating a free thyroxine index. The normal range, although centered on 1.0, is not necessarily identical for each method. The inverted fraction has been used at times. This leads to extreme confusion and should be stopped. As long as tests reported as the inverted fraction remain in use, the result must be divided into the T4 to calculate a free thyroxine index.

10. T3U tests include use of a variety of noncellular absorbing media, such as resins, charcoal, Sephadex, etc.

9. Equal to [(T3) x (% FT3)/100]. The % FT3 is usually estimated by equilibrium dialysis.

8. Equal to [10 x (T4) x (% FT.,)]. The % FT4 is usually estimated by equilibrium dialysis.

6. Although radioimmunoassay is clearly a subtype of displacement assay, it is given a separate designation and abbreviation (RIA) because of its unique characteristics and importance.

T4

6. Thyroxine (radioimmunoassay)

T4(RIA)

5. Thyroxine (displacement)

5. Often called "Thyroxine (Murphy-Pattee)." Displacement refers to the group of methods which have been described as displacement analysis, isotope displacement assays, saturation analysis, competitive protein-binding, and radioligand binding.

T4(C)

4. Thyroxine (chromatographic) T4

2. Rarely used now.

1. Only use now is to establish nonthyroxine PBI.

Comments

T 4 (D)

I

Units*

4. Calculated as TJ/0.65.

T4I(C)

3. Thyroxine iodine (chromatographic)

I

I

Actually measured

I

BEI

2. Butanol-extractable iodine

B. Hormone concentration

PBI

Abbreviation

1. Protein-bound iodine

A. Iodine concentration

Name of test

TABLE 1. Revised nomenclature for tests of thyroid hormones in serum

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