CLINICAL VALUE OF SERUM THYROXINE DETERMINATION
V. E. CHESKY, M.D., W. C. DREESE, M.D., B. 0 . DUBOCZKY, M.D., W. II. HALL,
B.S., AND C. A. HELLWIG, M.D.
The Hertzler Clinic and Research Foundation, Halslead, Kansas
In a recent article, Bartels 2 summarized the experience of the Lahey Clinic
on functional tests in disorders of the thyroid gland as follows: "Should one be
limited to one diagnostic test for hyperthyroidism and one for myxedema, the
basal metabolic rate should be selected for the former and plasma cholesterol
for the latter." After 2}4 years of determining blood iodine in all cases of thyroid
disease and in a large number of patients without endocrine disorders, we have
come to the conclusion that in questionable cases the determination of serum
thyroxine is the best single diagnostic test.
M A T E R I A L AND
METHODS
Routine iodine determinations have been made on our goiter patients since
December, 1949. At first we used a modified Salter's 6 ashing method, but since
1950 we have followed Barker's 1 distillation and ashing methods. After performing over 400 tests, we found Barker's ashing method the most practical
and reliable for clinical work. Our method and results of the determination of
protein-bound iodine (PBI) in 96 surgical goiter patients have been published
previously.3 Since 1951, we have determined the serum thyroxine in addition to
the PBI and total iodine in serum. Elmer 5 regards the former as a more sensitive
index of thyroid activity than PBI. According to Danowski and his coworkers,4
in thyroxine estimation there is the additional advantage that administration of
inorganic iodine will raise the PBI and the total iodine content of the serum but
leave the thyroxine level of the serum unchanged. On the other hand, x-ray
dyes containing organic iodine will also increase the values of thyroxine and,
therefore, the thyroxine determination is of no value in these cases.
TECHNICAL
PROCEDURE
The procedure as used in our laboratory combines the principles of Taurog
and Chaikof's7 method for separation of the thyroxine from blood serum and
Barker's ashing method for determination of PBI. Following Taurog and
Chaikof's method for separation of the thyroxine from blood serum, extra care is
taken in washing the precipitate from the serums of patients who have received
Lugol's solution, by a third or fourth washing with the hydroxide solution.
Our procedure for measuring PBI differs slightly from the original method of
Barker. We add 0.5 ml. of 12 per cent glycocoll (aminoacetic acid) to 2 blank
tubes before drying, in order to have the same organic content as that in the
Received for publication September 2, 1952.
Dr. Chesky is Chief Surgeon of the Hertzler Clinic, Dr. Dreese is Attending Surgeon
of the Clinic, Dr. Duboczky is with the Julius Marks Sanitarium in Lexington, Kentucky,
and Dr. Hell wig is Pathologist at the Hertzler Clinic.
41
42
CHESKY ET
AL.
serum tubes. Two blanks are made for every ashing process. For the colorimetric
determinations of the iodine we use a Coleman Junior Spectrophotometer and
15 by 125-mm. colorimeter tubes. The reading and calculation are made on a
linear scale.
RESULTS
One hundred and thirty-four patients with thyroid disease and 79 patients
without endocrine disorders form the basis of the present thyroxine study (Table
1). Fifteen of the patients with thyroid disease were men and 119 were women;
53 had an operation, 81 did not.
Thirty-nine patients had hyperthyroidism. The serum thyroxine level varied
between 2.3 and 10.8 jug- per 100 ml., with an average of 6.7 ng.
Seventy-five patients had nontoxic goiter. For these, the serum thyroxine level
varied from 1.0 to 4.2 jug- per 100 ml. The average thyroxine level was 3 jugTwenty patients had hypothyroidism. Six of these patients had spontaneous
myxedema with serum thyroxine levels varying from 0.0 to 0.5 jug- per 100 ml.
TABLE 1
S E R U M T H Y R O X I N E CONCENTRATIONS IN P A T I E N T S W I T H AND W I T H O U T T H Y R O I D D I S E A S E
CLINICAL DIAGNOSIS
NO. OF
PATIENTS
RANGE OF
THYROXINE
39
75
20
79
1.9-10.8
1.0- 4.2
0 . 0 - 2.3
2 . 0 - 4.3
AVERAGE
THYROXINE
tig. per 100 ml.
Hyperthyroidism
Nontoxic goiter
Hypothyroidism
Euthyroid
6.5
3.0
1.0
3.0
Six patients had postoperative myxedema with serum thyroxine levels varying
from 0.2 to 1.6 jug- per 100 ml. Eight other hypothyroid cases had serum thyroxine
levels varying from 1.3 to 2.4 jug- per 100 ml.
Histologic diagnoses on goiters removed from the 53 patients with operation
were made from paraffin sections stained with hematoxylin and eosin. Thirteen
patients had exophthalmic goiter with serum thyroxine levels varying between
2.5 and 10.8 jug. per 100 ml. The average was 7.1 jug. per 100 ml. Two patients
had fetal adenomas with serum thyroxine levels of 2.4 and 3.0 jug- For 16 patients
with colloid adenomas the serum thyroxine varied between 1.0 and 5.9 jug., with
an average of 3.2 jug- Five patients had mixed colloid and fetal adenomas; the
serum thyroxine varied from 3.0 to 10.1 ng., with an average of 4.8 ng. per 100 ml.
Eight patients had multinodular colloid goiters in which the serum thyroxine
levels varied between 2.3 and 4.4 jug. per 100 ml., with an average of 3.5 jug. per
100 ml. Five patients had diffuse colloid goiters, the serum thyroxine value
varying from 2.8 to 7.9 jug. per 100 ml., with an average of 4.3 /ig. Two patients
had lymphadenoid goiters with serum thyroxine concentrations of 2.3 and 2.5
jug. per 100 ml. Two patients had cancer of the thyroid gland, one had a solid
adenocarcinoma in one lobe and the other had a Hiirthle-cell tumor in the isthmus.
SERUM THYROXINE
43
Their serum thyroxine values were 1.8 and 8.6 Mg- per 100 ml., respectively.
Of the 79 patients without endocrine disorders, 19 were men and 60 were
women. The serum thyroxine level of this entire series varied from 2.0 to 4.3 /jg.
per 100 ml., the average being 3.0 ng. Thirty patients were receiving medication
for thyroid disease at the time of the thyroxine determinations. Of these 30
patients, 12 had toxic goiter treated with propylthiouracil only, 4 had toxic
goiter treated with Lugol's solution only, 4 had nontoxic goiter treated with
LugoPs solution or inorganic iodide, and 7 had hyperthyroidism treated with
thyroid extract.
For the first 12 patients, the duration of propylthiouracil medication varied
from 2 weeks to 1 year, with an average of 17 weeks. The duration of medication
with Lugol's solution varied from 1 to 8 weeks, with an average of 3 weeks.
The PBI values varied from 6.4 to 22.4 fig. per 100 ml., with an average of 12.0
ng., while the serum thyroxine was relatively much lower, varying from 1.6 to
7.6 jug per 100 ml., with an average of 3.4 ng.
The 4 patients with toxic goiter receiving Lugol's solution only, had PBI values
varying from 7.4 to 18.0, with an average of 13.9 jug.; while the thyroxine varied
from 2.9 to 6.8 /jg. per 100 ml., with an average of 5.2 jug- The 4 patients with
nontoxic goiter receiving Lugol's solution only were treated from 2 to 3 weeks,
with an average of 2^2 weeks. Their PBI concentration varied from 7.2 to
50.0 jug. per 100 ml., with an average of 19.2 ^g. The thyroxine values did not
show the same increase as the PBI, but varied from 2.1 to 5.1 jug- per 100 ml.,
with an average of 3.5 ng.
Three patients with mild hypothyroidism receiving thyroid extract had serum
thyroxine levels varying from 2.1 to 3.8 ng. per 100 ml., with an average of
2.8 Mg.
Three patients with pronounced myxedema receiving thyroid extract had
PBI concentrations varying from 2.5 to 4.2 jug. per 100 ml. and thyroxine values
varying from 1.8 to 2.0 ng. per 100 ml., with an average of 1.9 ng. The duration
of treatment varied from 14 days to 5 months, with an average of 2 % months.
From these observations it is apparent that the thyroxine determination
gives more reliable indication of the functional state of the thyroid gland than
does determination of the PBI. Its greatest advantage, in our opinion, lies in the
fact that thyroxine in the serum is not increased by giving inorganic iodine by
mouth. We believe, therefore, that the determination of total iodine can be
dispensed with in most cases.
CONCLUSIONS
The results of serum thyroxine determinations of 134 goiter patients and 79
controls have been presented. Our technic is a combination of Taurog and
Chaikof's butyl alcohol extraction of the serum thyroxine and Barker's ashing
method for determination of protein-bound iodine.
After comparison of our chemical results with the clinical findings in 214
patients, it seems justifiable to conclude that determination of thyroxine in
the blood serum is a practical and reliable laboratory procedure. In our opinion
44
CHESKY ET AL.
it offers much greater diagnostic aid than does determination of the basal
metabolic rate or of the plasma cholesterol.
REFERENCES
1. B A R K E R , S. B . : Determination of protein bound iodine. J . Biol. Chem., 173: 715-724,
1948.
2. BARTELS, E . C . : Basal metabolic rate and plasma cholesterol as aids in t h e clinical s t u d y
of thyroid disease. J . Clin. Endocrin., 10: 1126-1134, 1950.
3. C H E S K Y , V. E . , D R E E S E , W. C , DUBOCZKY, B . 0 . , AND H E L L W I G , C. A.: H i s t o l o g y of
goiter and blood iodine. Arch. Surg., 64: 64-73, 1952.
4. D A N O W S K I , J . S., JOHNSTON, S. Y., AND G R E E N M A N , J . H . : Alterations in serum iodine
fractions induced by the administration of inorganic iodide in massive dosage. J .
Clin. Endocrin., 10: 519-531, 1950.
5. E L M E R , A. W . : Iodine metabolism a n d thyroid function. London: Oxford Univ. Press.,
1938, p p . 190-194.
6. SALTER, W. J., BASSETT, A. M., AND SAPPINGTON, J. S.: Protein-bound iodine in blood:
VL. I t s relation t o thyroid function in 100 clinical cases. Am. J . M . S c , 202: 527-542,
1941.
7. TAUROG, A., AND CHAIKOP, J. L . : Relation of the thyroxine content of t h e thyroid gland
and of the level of protein-bound iodine of plasma to iodine i n t a k e . J . Biol. Chem., 165:
217-222, 1946.