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The value of the measurements of thyroid uptake andurinary excretion of I131 in assessing thyroid function of normal and congenitally hypothyroid children
T H E V A L U E OF T H E M E A S U R E M E N T S OF T H Y g O I D U P T A K E AND U R I N A R Y E X C R E T I O N OF 1 T M IN A S S E S S I N G T H Y R O I D F U N C T I O N OF NORMAL AND C O N G E N I T A L L Y HYPOTHYROID CHILDREN* WILLIAM A. REILLY, M.D., e~'~ AND DINA I. BAYER, M.D. SAN F~*~ClSCO, CALIF. INTRODUCTION
H E purpose of this study was to the iodine uptake in the thyroid gland a n d its excretion in the urine in normal and hypothyroid children. I T M was given in smaller amounts of radioactivity than usually employed for such measurements in order to avoid serious irradiation effects in the thyroid gland, t and in doses of iodine below the usual daily human requirement for iodine. Small doses of iodine might be better taken up by the gland than larger amounts. The u r i n a r y excretion was measured to note if this could be used indirectly as a measure of thyroid gland uptake. The data presented in this paper indicate that satisfactory measurements of uptake are obtained with the smaller tracer doses. (See Table I.)
T measure
H I S T O R I C A L REVIEW
Previous investigators have not given a tracer dose containing less than the usual daily iodine requirement of the body. This is thought by Salter 4 to be " a b o u t 200 micrograms F r o m t h e U n i v e r s i t y of A r k a n s a s Sehool o~ Medicine, Pediatric Department, Little R o c k , A r k . J o u r n a l S e r i e s No. 966, U n i v e r s i t y of Arkansas. * T h e r a d i o a c t i v e i o d i n e u s e d in t h i s s t u d y was .supplied by the Oak Ridge National L a b o r a t o r i e s , O a k /~.idge, T e n n , , u n d e r a l l o c a tion f r o m t h e U n i t e d S t a t e s A t o m i c E n e r g y Commission. **Present address: Veterans Administration H o s p i t a l , F o r t Miley, S a n F r a n c i s c o 21, Calif. #Private-communication from the Atomic Energy Commission. See p r o c e d u r e in t h i s paper. 714
for adults and growing children. The requirement for infants is probably somewhat less." I n our study we gave 5 or 10/xc of I T M as a test dose, which contained 0.00004 or 0.00008 t~g of inorganic iodine, plus 1 or 2 /~g of carrier inorganic iodine which was added. The dose of thyroid extract given, 65 rag. daily, contained 130 tLg"of iodine. Excluding thyroid extract these amounts of iodine were below the usual daily requirement. The tracer doses in mieroeuries are the smallest to our knowledge at date of writing (Jan. 15, 1952). PROCEDURE
These studies were approved by the Atomic Energy Commission, who also agreed that the test tracer dose for normal children under 6 years of age should be 5 ~e and for older children 10 ]~e. We added enough potassium iodide to the p3~, upon arrival of the shipment, so that there was 1 t~g of inorganic iodine for each 5 tzc of I~% The inorganic iodine thus is a carrier for the radioactive I ~1. It may not:be possible otherwise to quantitate accurately carrier-free I T M for it adheres to glassware, rubber tubing, mueosae, etc. Tile I T M was standardized by evaporating an aliquot to dryness in a planchet and comparing beta ray counts, using a thin window (1.2 mg.
REILLY
AND
BAYER:
113~ IN
per square centimeter) Geiger-Mueller tube, with a known Ra l) and E standard as supplied by the National Bureau of Standards. G a m m a counts with an aluminum-shielded Geiger-M u e 11 e r tube, which excluded all beta particles, were then made f r o m a p h a n t o m to determine the number of counts for ] ~e of the I ~3~. TABLE I.
THYROID
MEASURENII~]NT
7]5
the container were drunk; this step removed adherent vestiges of I ~a~ f r o m the containers, mouth, or esophagus. Measurements were taken over the thyroid gland and over the circumference of the thigh equal to that of the thyroid area of the neck. The thigh counts were subtracted, as background, f r o m the thyroid counts. A Geiger-
I)~EPOI%TEDNOI%MALS WITII VARIOUS 2~IViOUNTS OF IOIIINE ~DMINISTERED WITII I131
I
pose (,e)
I No. ~ES~EP i
ttamilton~ et al.,1 12.5 1943 Quimby and Me20 to 40 Cune,2 1947 (not more t h a n 2 ~g o f inorganic iodine added as carrier) Lowrey, et al.,,~ 20 to 50 1949 Reilly and Bayer, 5 or 10 ]952 (this arti- (1 or 2 ~g of ineIe) organic iodine added as carrier)
!
Um'~I~E
~XC~ETIO~
3 adults
20% at 24 hr.
32 children
12% at 48 hr.
12 children
400 to 800% increase Jn comtts at 24 hr. 8.7-29.8% between 55% at 48 hr. 24 and 96 hr. 57% at 96 hr. aver. 16% (average)
25 children
70.1% at 48 hr. in 6 trials
T~BLE IY PLASI~A
e~RoN-
A~E ~'~ r
r
I
/ C~OL~S-
0LOGICAL ONSET OF I BASAL TEROLh{G. AGE SYI~IPTOI~S IIEIGHT I I~ETABOLIC/ PEI%100
.A~I~NT C.K. 92532 P. McK. 84297 U, S. G.W. 106229 J.G.
(Yrs.)
(~0.)
(INCHES) ~AT~ (%)
e.C.
EPIPHYSEAL AGE
I.Q.
ANE~IA (%)
(.i~.)
12
0-6
47
-25
333
Great
59
6~2
13
0-6
441~
-28
146
Great
37
54~2
10/12 4
1 1-2
54 36
N.C. ~ N.C.
150 150
Moderate None
50 65
3
3/12
1/2
23
N.C.
232
Great
55
1~ 8 me. fetal age
*N. C. means "no cooperation." Several patients had received thyroid extract for enough time in their past lives to have removed partially some of their deficiencies. This explains the epiphyseal age of G. W. and C. S. Histories and physical examination revealed at the time of these examinations (when no thyroid substance had been taken for four to six weeks) other characteristics, particularly myxedema. C. I~2. and P. McK. had complete explorations of the neck; no thyroid tissue could be found either grossly or by microscopic study of biopsy fragments.
The chiIdren were oil normal diets and not ingesting extra iodine for weeks before the tests. They were not fasting. The dose was d r u n k from a beaker; for infants, it was given f r o m a glass pipette or through a stomach tube. Three distilled water rinsings of
Mueller thin-walled end-window tube, shielded lateratly with 0.5 inch lead (to reduce background), was held 4 era. f r o m the skin. G a m m a counting alone was done by shielding the end-window with 200 rag. per square centimeter of aluminum, which amount blocks all
~]6
THE JOURNAL OF PEDIATRICS
beta radiations. At this distance the maximum of gamma counts with these uptakes was detected. Counts consisted of background for t h i r t y minutes and over the thigh and thyroid preferably for five minutes; the duration depended on the cooperation of the child. Counts were done at 2, 4, 6, 24, 48, 72, and 96 hours after administration of the dose. A f t e r this time, counting was not feasib!e because of the small amount of tracer dose left in the gland. Urine was collected at the same intervals in jars containing 2 to 4 ml. of s a t u r a t e d potassium iodide solution, again to p r e v e n t adherence of I ~3~ to glass. Quantitative counts were made with a dipper tube 5 within t w e n t y - f o u r hours a f t e r each collection was made. The small dosage and the relatively short hal~-tife of I ~3~ make it desirable to quantitate excretion within 12 to 24 hours after c o l leetion.
Normal C h i 1 d r e n .--Twenty-five euthyroid patients between the ages of 9 months and 15 years were tested once each; there were 14 Negro and 11 white children; 14 were boys and 11 girls. Congenitally Hypothyroid Children. - - F i v e such children were studied, They were either athyreotie or born with an almost total deficiency of functioning gland. Two had explorations (C. K. and P. McK.) of the neck and no normal thyroid gland was found. (Table I1). All five were repeatedly tested when they were taking 65 rag. of thyroid substance daily and again four to six weeks after this medication had been discontinued,
RESULTS
Normal Children.-Thyroid Gland Uptake: Fig. 1 is a composite of alt uptake results. The thyroid gland uptake was in a range of 8.7 and 29.8 per cent, this uptake being- reached usually at 24 hours. maximum as late as 96 hours. The Occasionally some glands trapped the average uptake by 96 hours was 16.9 per cent. Uptake was not influenced by age, sex, color, or season. Urinary Excretion, (Fig'. 2) : This ranged from 29.3 to 70.6 per cent by 96 hours, reaching a peak at 24 horn's in three cases and at 48 hours in the remainder. Excretion was negligible after 48 hours, being less than 3 per cent in sixteen cases. The average total excretion was 54.7 per cent. C.ongenitaZly Hypothyroid Children, Untreated and Treated.-Thyroid Uptake (Figs. 3 and 4 ) : The thyroid gland, when the patients were not taking thyroid substance, took up 1 to 2 per cent of the I~al; this occurred maximally two hours after ingestion of the 1131. That uptake was not increased by thyroid extract therapy. The greatest uptake was 2.2 per cent and this occurred only in one patient. B y 48 or 72 hours, none was detectable in the gland by the GeigerMue]ler tube. Possibly this uptake does not t r u l y represent the gland accumulation. Urinary Excretion: While the patients were off thyroid t h e r a p y the a n n e contained the following ranges of I13~: in the first six hours, 24 to 34 per cent (average 29); between 6 and 24 hours, 28.8 to 32.2 per cent
RE1LLY AND BAYER:
I TM IN
THYROID MEASUREMENT
THYROIDUPTAKEOF 1131IN EUTHYROIDCHILDREN 25 CASES AGES9MO. 15YEARS ~ G R E A T E S T UPTAKE . . . . . LEAST UPTAKE z ; ~ : ~ , 3 MEAN UPTAKE IM
I.IJ
~3o
2,4,6
24
48 HOURS
7?-..
96
J~'ig. 1.
EXCRETION OF I TM IN EUTHYROID CHILDREN 7 6O z
50
50
z2
N /1~
,~I~Y/
~
~
~
HOURS F i g , 2.
LEAST EXCRETION
~3ME~. EXOR~T,ON
717
71~
THE JOURNAL OF PEDIATRICS
UPTAKE AND EXCRETION OF1151 IN CRETINS TEATED
2C
f -- -
URINARY EXC,RETION -THYROIDUPTAKE
u
I
:46
24
48 HOURS
72
9"6
Fig. 3.
UPTAKE AND EXCRETION OF" IBI IN CRETINS UNTREATED BC
t-.-
~-
L~
7O
6Q
:t 5C
MRINARY EXCRETION ,,.,,.__._.THYROID UPTAKE
,~ H~S
i~'ig, 4.
Fig's. ,3 and 4 . - - C h a r t s showing averages of all data.
REILLk" AND B A Y E R :
I TM
.(average 30); and during the entire 96 hours, 73.5 to 92.4 per cent (average 79.5). Tile maximal excretion occurred between 24 and 48 hours. While the patients were being treated, the ranges of I T M in p e r cent were: 6 hours, 14.5 to 22.6 per cent (average 18.6); 6 to 24 hours, 10.3 to 24.2 per cent (average 23.7); during 96 hours, 35.8 to 84.5 per cent (average 55). The maximal time of excretion occurred at 48 hours. (Figs. 3 and 4.) D I S C U S S I O N OF R E S U L T S
Normal Children.--The radioactivity in 5 or 10 t~c of I T M is readily detectable in tile normal thyroid gland, especially in the early hours after ingestion. I t is known that careful measurements show I T M in tile gland fifteen minutes a f t e r ingestion 6 because absorption is r a p i d - - m s u a l l y the gland is avid for iodine .and the Geiger-Mueller tube is sensitive enough to detect such small quantities of radioactivity. F o r practical purposes, since the maximal uptake is reached within 24 to 48 hours, one could stop measurements at 48 hours. There was a definite lowering of I T M in the gland a f t e r 48 to 96 hours. H a m i l t o n 6 found that even with small test doses the gland still retained small amounts of 1131 for some weeks. Fig. 2 shows that I T M was present in the urine at two hours and in the thyroid at two hours, the first time of measurements. One cannot "judge by this method how much of the excretion between 24 and 48 hours comes from I T M unabsorbed by the thyroid f r o m the blood. I n general, a f t e r 24 to 48 hours, the u r i n a r y excretion represents mainly thyroid turnover of I ~a~ and this excretion figure might be used indirectly as a measure of thyroid up-
IN THYROID MEASUREMENT
719
take. Iodine is stored in the body elsewhere than in the t h y r o i d - - p a r ticularly in the liver, small intestines, kidney, adrenals, muscles, skin, and blood as P e r l m a n and associates 7 have shown in tile rabbit, so that u r i n a r y excretion also measures indirectly I T M f r o m these stores as well as those f r o m the thyroid gland. N a t u r a l l y the uptake in the thyroid gland is best measured at the glandl Some have suggested the possibiiity of this indirect measure of thyroid uptake by the measurement of u r i n a r y excretion. Since there is no exact method for measuring in h u m a n beings the uptake in other depots t h a n in the thyroid, we cannot agree with such a thesis. Our present results of uptake with 5 to 10/~e test doses compare f a v o r a b l y with those of Hamilton and co-workers 1 using 12.5 /xe in 1938 and 1939, and those of Quimby and McCune 2 in 1947, using' 20 to 40/xe of I T M Our figure of 53 per cent excretion at 48 hours is much lower than the 70.1 per cent excretion of Quimby and McCune. They accounted for 82 per cent of their dose (12 per cent in gland plus 70 p e r cent in urine) on the average at 48 hours. We accounted for 69.9 per cent (16.9 per cent in gland plus 53 per cent in the urine) at the same time. When finishing our measurements at 96 hours, we could account for 71 per cent. Assuming' that there is a 5 to 10 p e r cent error in our method and that some I T M is retained in the body for some weeks, this discrepancy becomes less. H a m ilton a states that there is a negligible a m o u n t of excretion in feces, lungs, skin, and hair2 The addition of 25 /~g of carrier inorganic iodine to the tracer dose just before it was ingested did not alter the uptake or excretion figures. This was
720
THE JOURNAL OF PEDIATRICS
tested once on each of twenty euthyroid children.
Congenitally Hypothyroid Children. - - T h e low uptake of 1 to 2 per cent is to be expected if the function of the thyroid gland is f a r below normal. All five children had very low or practically no functioning gland. Exploration and biopsy of C. K. and P. McK. did not reveal any thyroid gland. U r i n a r y excretion of 73.5 to 92.4 per cent of I T M within 96 hours when these cretins were not being treated (Fig. 4) was greater than that of our normals and is in keeping with low function of the thyroid gland. I t will be noted that during treatment, excretion of 35.8 to 84.5 per cent (Fig. 3) was lower than when the patients were not being treated. We have no direct proof but only possible explanations for this lowered excretion. Among possibilities are the following two: (1) uptake of the I T M by the protein of the thyroid extract ingested, which may have been unsaturated with iodine. In general protein compounds take up iodine by chemical reaction. (2) Chapman s in 1941 suggested that the extrathyroidal depots for iodine possibly produce a thyroxine-like substance which could then trap I ~3~. Only two other groups, using carrier-free I T M in small tr.acer doses, have data which can be used ~or comparison. The eases of Hamilton, and associates ~ and Quimby and MeCune 2 took up to 1 per cent, which is practically the same as ours. U r i n a r y excretion was measured in only one ease2; that was 70 per cent at 48 hours, which is practically the same as our figures. Although only five cretins were tested (the repetition oi the test al-
ways gave practically the same resuits), we feel that uptake of I T M is a reliable diagnostic test of the presence of vestiges of thyroid gland. Some general clinical laboratories in offices, hospitals, and clinics may become equipped within the next few years to carry out these tests; we feel that they may become quite practical. SUMMARY
1. I T M in doses of 5 to 10 t~c was used to measure quantitatively both iodine uptake in the thyroid gland and u r i n a r y excretion in twenty-five cathyroid children and in five congenitally h y p o t h y r o i d children (cretins). 2. Over a 96-hour period the thyroid of the normal children took up between 8.7 and 29.8 per cent with the maximum between 24 and 96 hours. During 96 hours their u r i n a r y excretion ranged from 29.3 to 70.6 per cent; the maximal excretion occurred between 24 and 48 hours. 3. Repeated tests showed I T M uptake in the cretins to be negligible. It was between 1 and 2 per cent and it was not appreciably influenced by thyroid therapy. The u n t r e a t e d cretins excreted 73.5 to 92.4 per cent of I ~ within 96 hours, while the same cretins when treated excreted between 35.8 and 84.5 per cent within the same length of time. The authors acknowledge the valuable technical help of l~. t~. Edwards, Ph.D., nuclear chemist, Institute of Science and Technology, University of Arkansas~ leayetteville~ Ark. REFERENCES 1. t~amilton~ 3. G., Soley, M. /{., Reilly~ W. A., and Eichorn, I4. ]3. : Radioactive Iodine Studies in Childhood ttypothyroidism, Am. J. Dis. Child. 66: 495, 1943.
REILLY AND BAYER:
113z IN THYROID MEASUREMENT
2. Quimby, E. I-L, and McCune, D. J. : Uptake of Radioactive Iodine by the Normal and Disordered Thyroid Gland in Children, Radiology 49: 201, 1947. 3. Lowrey, G. H., Beierwalters, W. tI., Lampe, I., and Gomberg, H. J.: Radio-Iodine Uptake Curve in Humans, Pediatrics 4: 6277 1949. 4. Salter, T. S.: The Endocrine Function of Yodine, Cambridge, Mass., 1940, Harvard University Press, p. 186. Also recent personal communication. 5. Edward% R. R., Reilly, W. A., and Holmes, 1%. G.: Determination of Iodinelal in Urine, Proe. Soe. Exper. Biol. & Med. 72: 158, 1949.
721
6. Hamilton, J. G.: Summary of Iodine Physiology and Metabolic Studies Using Radioactive Isotopes o:f Iodine, U.S. Atomic Energy Commission, MDDC'-1060~ J u n e 25, 1947. 7. Perlman, I., ChMkoff, I. L., and Morton, M.E.: R,adioactive Iodine as an Indicator of the Metabolism of Iodine. L The Turnover of Iodine in the Tissues of the Normal AnimM, With Particular Reference to the Thyroid~ J. Biol. Chem. 139: 433, 1941. 8. Chapman, A.: The ]~elation of the Thyroid and the P i t u i t a r y Glands to Iodine Metabolism, Endocrinology 29: 680, 1941.
H E purpose of this study was to the iodine uptake in the thyroid gland a n d its excretion in the urine in normal and hypothyroid children. I T M was given in smaller amounts of radioactivity than usually employed for such measurements in order to avoid serious irradiation effects in the thyroid gland, t and in doses of iodine below the usual daily human requirement for iodine. Small doses of iodine might be better taken up by the gland than larger amounts. The u r i n a r y excretion was measured to note if this could be used indirectly as a measure of thyroid gland uptake. The data presented in this paper indicate that satisfactory measurements of uptake are obtained with the smaller tracer doses. (See Table I.)
T measure
H I S T O R I C A L REVIEW
Previous investigators have not given a tracer dose containing less than the usual daily iodine requirement of the body. This is thought by Salter 4 to be " a b o u t 200 micrograms F r o m t h e U n i v e r s i t y of A r k a n s a s Sehool o~ Medicine, Pediatric Department, Little R o c k , A r k . J o u r n a l S e r i e s No. 966, U n i v e r s i t y of Arkansas. * T h e r a d i o a c t i v e i o d i n e u s e d in t h i s s t u d y was .supplied by the Oak Ridge National L a b o r a t o r i e s , O a k /~.idge, T e n n , , u n d e r a l l o c a tion f r o m t h e U n i t e d S t a t e s A t o m i c E n e r g y Commission. **Present address: Veterans Administration H o s p i t a l , F o r t Miley, S a n F r a n c i s c o 21, Calif. #Private-communication from the Atomic Energy Commission. See p r o c e d u r e in t h i s paper. 714
for adults and growing children. The requirement for infants is probably somewhat less." I n our study we gave 5 or 10/xc of I T M as a test dose, which contained 0.00004 or 0.00008 t~g of inorganic iodine, plus 1 or 2 /~g of carrier inorganic iodine which was added. The dose of thyroid extract given, 65 rag. daily, contained 130 tLg"of iodine. Excluding thyroid extract these amounts of iodine were below the usual daily requirement. The tracer doses in mieroeuries are the smallest to our knowledge at date of writing (Jan. 15, 1952). PROCEDURE
These studies were approved by the Atomic Energy Commission, who also agreed that the test tracer dose for normal children under 6 years of age should be 5 ~e and for older children 10 ]~e. We added enough potassium iodide to the p3~, upon arrival of the shipment, so that there was 1 t~g of inorganic iodine for each 5 tzc of I~% The inorganic iodine thus is a carrier for the radioactive I ~1. It may not:be possible otherwise to quantitate accurately carrier-free I T M for it adheres to glassware, rubber tubing, mueosae, etc. Tile I T M was standardized by evaporating an aliquot to dryness in a planchet and comparing beta ray counts, using a thin window (1.2 mg.
REILLY
AND
BAYER:
113~ IN
per square centimeter) Geiger-Mueller tube, with a known Ra l) and E standard as supplied by the National Bureau of Standards. G a m m a counts with an aluminum-shielded Geiger-M u e 11 e r tube, which excluded all beta particles, were then made f r o m a p h a n t o m to determine the number of counts for ] ~e of the I ~3~. TABLE I.
THYROID
MEASURENII~]NT
7]5
the container were drunk; this step removed adherent vestiges of I ~a~ f r o m the containers, mouth, or esophagus. Measurements were taken over the thyroid gland and over the circumference of the thigh equal to that of the thyroid area of the neck. The thigh counts were subtracted, as background, f r o m the thyroid counts. A Geiger-
I)~EPOI%TEDNOI%MALS WITII VARIOUS 2~IViOUNTS OF IOIIINE ~DMINISTERED WITII I131
I
pose (,e)
I No. ~ES~EP i
ttamilton~ et al.,1 12.5 1943 Quimby and Me20 to 40 Cune,2 1947 (not more t h a n 2 ~g o f inorganic iodine added as carrier) Lowrey, et al.,,~ 20 to 50 1949 Reilly and Bayer, 5 or 10 ]952 (this arti- (1 or 2 ~g of ineIe) organic iodine added as carrier)
!
Um'~I~E
~XC~ETIO~
3 adults
20% at 24 hr.
32 children
12% at 48 hr.
12 children
400 to 800% increase Jn comtts at 24 hr. 8.7-29.8% between 55% at 48 hr. 24 and 96 hr. 57% at 96 hr. aver. 16% (average)
25 children
70.1% at 48 hr. in 6 trials
T~BLE IY PLASI~A
e~RoN-
A~E ~'~ r
r
I
/ C~OL~S-
0LOGICAL ONSET OF I BASAL TEROLh{G. AGE SYI~IPTOI~S IIEIGHT I I~ETABOLIC/ PEI%100
.A~I~NT C.K. 92532 P. McK. 84297 U, S. G.W. 106229 J.G.
(Yrs.)
(~0.)
(INCHES) ~AT~ (%)
e.C.
EPIPHYSEAL AGE
I.Q.
ANE~IA (%)
(.i~.)
12
0-6
47
-25
333
Great
59
6~2
13
0-6
441~
-28
146
Great
37
54~2
10/12 4
1 1-2
54 36
N.C. ~ N.C.
150 150
Moderate None
50 65
3
3/12
1/2
23
N.C.
232
Great
55
1~ 8 me. fetal age
*N. C. means "no cooperation." Several patients had received thyroid extract for enough time in their past lives to have removed partially some of their deficiencies. This explains the epiphyseal age of G. W. and C. S. Histories and physical examination revealed at the time of these examinations (when no thyroid substance had been taken for four to six weeks) other characteristics, particularly myxedema. C. I~2. and P. McK. had complete explorations of the neck; no thyroid tissue could be found either grossly or by microscopic study of biopsy fragments.
The chiIdren were oil normal diets and not ingesting extra iodine for weeks before the tests. They were not fasting. The dose was d r u n k from a beaker; for infants, it was given f r o m a glass pipette or through a stomach tube. Three distilled water rinsings of
Mueller thin-walled end-window tube, shielded lateratly with 0.5 inch lead (to reduce background), was held 4 era. f r o m the skin. G a m m a counting alone was done by shielding the end-window with 200 rag. per square centimeter of aluminum, which amount blocks all
~]6
THE JOURNAL OF PEDIATRICS
beta radiations. At this distance the maximum of gamma counts with these uptakes was detected. Counts consisted of background for t h i r t y minutes and over the thigh and thyroid preferably for five minutes; the duration depended on the cooperation of the child. Counts were done at 2, 4, 6, 24, 48, 72, and 96 hours after administration of the dose. A f t e r this time, counting was not feasib!e because of the small amount of tracer dose left in the gland. Urine was collected at the same intervals in jars containing 2 to 4 ml. of s a t u r a t e d potassium iodide solution, again to p r e v e n t adherence of I ~3~ to glass. Quantitative counts were made with a dipper tube 5 within t w e n t y - f o u r hours a f t e r each collection was made. The small dosage and the relatively short hal~-tife of I ~3~ make it desirable to quantitate excretion within 12 to 24 hours after c o l leetion.
Normal C h i 1 d r e n .--Twenty-five euthyroid patients between the ages of 9 months and 15 years were tested once each; there were 14 Negro and 11 white children; 14 were boys and 11 girls. Congenitally Hypothyroid Children. - - F i v e such children were studied, They were either athyreotie or born with an almost total deficiency of functioning gland. Two had explorations (C. K. and P. McK.) of the neck and no normal thyroid gland was found. (Table I1). All five were repeatedly tested when they were taking 65 rag. of thyroid substance daily and again four to six weeks after this medication had been discontinued,
RESULTS
Normal Children.-Thyroid Gland Uptake: Fig. 1 is a composite of alt uptake results. The thyroid gland uptake was in a range of 8.7 and 29.8 per cent, this uptake being- reached usually at 24 hours. maximum as late as 96 hours. The Occasionally some glands trapped the average uptake by 96 hours was 16.9 per cent. Uptake was not influenced by age, sex, color, or season. Urinary Excretion, (Fig'. 2) : This ranged from 29.3 to 70.6 per cent by 96 hours, reaching a peak at 24 horn's in three cases and at 48 hours in the remainder. Excretion was negligible after 48 hours, being less than 3 per cent in sixteen cases. The average total excretion was 54.7 per cent. C.ongenitaZly Hypothyroid Children, Untreated and Treated.-Thyroid Uptake (Figs. 3 and 4 ) : The thyroid gland, when the patients were not taking thyroid substance, took up 1 to 2 per cent of the I~al; this occurred maximally two hours after ingestion of the 1131. That uptake was not increased by thyroid extract therapy. The greatest uptake was 2.2 per cent and this occurred only in one patient. B y 48 or 72 hours, none was detectable in the gland by the GeigerMue]ler tube. Possibly this uptake does not t r u l y represent the gland accumulation. Urinary Excretion: While the patients were off thyroid t h e r a p y the a n n e contained the following ranges of I13~: in the first six hours, 24 to 34 per cent (average 29); between 6 and 24 hours, 28.8 to 32.2 per cent
RE1LLY AND BAYER:
I TM IN
THYROID MEASUREMENT
THYROIDUPTAKEOF 1131IN EUTHYROIDCHILDREN 25 CASES AGES9MO. 15YEARS ~ G R E A T E S T UPTAKE . . . . . LEAST UPTAKE z ; ~ : ~ , 3 MEAN UPTAKE IM
I.IJ
~3o
2,4,6
24
48 HOURS
7?-..
96
J~'ig. 1.
EXCRETION OF I TM IN EUTHYROID CHILDREN 7 6O z
50
50
z2
N /1~
,~I~Y/
~
~
~
HOURS F i g , 2.
LEAST EXCRETION
~3ME~. EXOR~T,ON
717
71~
THE JOURNAL OF PEDIATRICS
UPTAKE AND EXCRETION OF1151 IN CRETINS TEATED
2C
f -- -
URINARY EXC,RETION -THYROIDUPTAKE
u
I
:46
24
48 HOURS
72
9"6
Fig. 3.
UPTAKE AND EXCRETION OF" IBI IN CRETINS UNTREATED BC
t-.-
~-
L~
7O
6Q
:t 5C
MRINARY EXCRETION ,,.,,.__._.THYROID UPTAKE
,~ H~S
i~'ig, 4.
Fig's. ,3 and 4 . - - C h a r t s showing averages of all data.
REILLk" AND B A Y E R :
I TM
.(average 30); and during the entire 96 hours, 73.5 to 92.4 per cent (average 79.5). Tile maximal excretion occurred between 24 and 48 hours. While the patients were being treated, the ranges of I T M in p e r cent were: 6 hours, 14.5 to 22.6 per cent (average 18.6); 6 to 24 hours, 10.3 to 24.2 per cent (average 23.7); during 96 hours, 35.8 to 84.5 per cent (average 55). The maximal time of excretion occurred at 48 hours. (Figs. 3 and 4.) D I S C U S S I O N OF R E S U L T S
Normal Children.--The radioactivity in 5 or 10 t~c of I T M is readily detectable in tile normal thyroid gland, especially in the early hours after ingestion. I t is known that careful measurements show I T M in tile gland fifteen minutes a f t e r ingestion 6 because absorption is r a p i d - - m s u a l l y the gland is avid for iodine .and the Geiger-Mueller tube is sensitive enough to detect such small quantities of radioactivity. F o r practical purposes, since the maximal uptake is reached within 24 to 48 hours, one could stop measurements at 48 hours. There was a definite lowering of I T M in the gland a f t e r 48 to 96 hours. H a m i l t o n 6 found that even with small test doses the gland still retained small amounts of 1131 for some weeks. Fig. 2 shows that I T M was present in the urine at two hours and in the thyroid at two hours, the first time of measurements. One cannot "judge by this method how much of the excretion between 24 and 48 hours comes from I T M unabsorbed by the thyroid f r o m the blood. I n general, a f t e r 24 to 48 hours, the u r i n a r y excretion represents mainly thyroid turnover of I ~a~ and this excretion figure might be used indirectly as a measure of thyroid up-
IN THYROID MEASUREMENT
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take. Iodine is stored in the body elsewhere than in the t h y r o i d - - p a r ticularly in the liver, small intestines, kidney, adrenals, muscles, skin, and blood as P e r l m a n and associates 7 have shown in tile rabbit, so that u r i n a r y excretion also measures indirectly I T M f r o m these stores as well as those f r o m the thyroid gland. N a t u r a l l y the uptake in the thyroid gland is best measured at the glandl Some have suggested the possibiiity of this indirect measure of thyroid uptake by the measurement of u r i n a r y excretion. Since there is no exact method for measuring in h u m a n beings the uptake in other depots t h a n in the thyroid, we cannot agree with such a thesis. Our present results of uptake with 5 to 10/~e test doses compare f a v o r a b l y with those of Hamilton and co-workers 1 using 12.5 /xe in 1938 and 1939, and those of Quimby and McCune 2 in 1947, using' 20 to 40/xe of I T M Our figure of 53 per cent excretion at 48 hours is much lower than the 70.1 per cent excretion of Quimby and McCune. They accounted for 82 per cent of their dose (12 per cent in gland plus 70 p e r cent in urine) on the average at 48 hours. We accounted for 69.9 per cent (16.9 per cent in gland plus 53 per cent in the urine) at the same time. When finishing our measurements at 96 hours, we could account for 71 per cent. Assuming' that there is a 5 to 10 p e r cent error in our method and that some I T M is retained in the body for some weeks, this discrepancy becomes less. H a m ilton a states that there is a negligible a m o u n t of excretion in feces, lungs, skin, and hair2 The addition of 25 /~g of carrier inorganic iodine to the tracer dose just before it was ingested did not alter the uptake or excretion figures. This was
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THE JOURNAL OF PEDIATRICS
tested once on each of twenty euthyroid children.
Congenitally Hypothyroid Children. - - T h e low uptake of 1 to 2 per cent is to be expected if the function of the thyroid gland is f a r below normal. All five children had very low or practically no functioning gland. Exploration and biopsy of C. K. and P. McK. did not reveal any thyroid gland. U r i n a r y excretion of 73.5 to 92.4 per cent of I T M within 96 hours when these cretins were not being treated (Fig. 4) was greater than that of our normals and is in keeping with low function of the thyroid gland. I t will be noted that during treatment, excretion of 35.8 to 84.5 per cent (Fig. 3) was lower than when the patients were not being treated. We have no direct proof but only possible explanations for this lowered excretion. Among possibilities are the following two: (1) uptake of the I T M by the protein of the thyroid extract ingested, which may have been unsaturated with iodine. In general protein compounds take up iodine by chemical reaction. (2) Chapman s in 1941 suggested that the extrathyroidal depots for iodine possibly produce a thyroxine-like substance which could then trap I ~3~. Only two other groups, using carrier-free I T M in small tr.acer doses, have data which can be used ~or comparison. The eases of Hamilton, and associates ~ and Quimby and MeCune 2 took up to 1 per cent, which is practically the same as ours. U r i n a r y excretion was measured in only one ease2; that was 70 per cent at 48 hours, which is practically the same as our figures. Although only five cretins were tested (the repetition oi the test al-
ways gave practically the same resuits), we feel that uptake of I T M is a reliable diagnostic test of the presence of vestiges of thyroid gland. Some general clinical laboratories in offices, hospitals, and clinics may become equipped within the next few years to carry out these tests; we feel that they may become quite practical. SUMMARY
1. I T M in doses of 5 to 10 t~c was used to measure quantitatively both iodine uptake in the thyroid gland and u r i n a r y excretion in twenty-five cathyroid children and in five congenitally h y p o t h y r o i d children (cretins). 2. Over a 96-hour period the thyroid of the normal children took up between 8.7 and 29.8 per cent with the maximum between 24 and 96 hours. During 96 hours their u r i n a r y excretion ranged from 29.3 to 70.6 per cent; the maximal excretion occurred between 24 and 48 hours. 3. Repeated tests showed I T M uptake in the cretins to be negligible. It was between 1 and 2 per cent and it was not appreciably influenced by thyroid therapy. The u n t r e a t e d cretins excreted 73.5 to 92.4 per cent of I ~ within 96 hours, while the same cretins when treated excreted between 35.8 and 84.5 per cent within the same length of time. The authors acknowledge the valuable technical help of l~. t~. Edwards, Ph.D., nuclear chemist, Institute of Science and Technology, University of Arkansas~ leayetteville~ Ark. REFERENCES 1. t~amilton~ 3. G., Soley, M. /{., Reilly~ W. A., and Eichorn, I4. ]3. : Radioactive Iodine Studies in Childhood ttypothyroidism, Am. J. Dis. Child. 66: 495, 1943.
REILLY AND BAYER:
113z IN THYROID MEASUREMENT
2. Quimby, E. I-L, and McCune, D. J. : Uptake of Radioactive Iodine by the Normal and Disordered Thyroid Gland in Children, Radiology 49: 201, 1947. 3. Lowrey, G. H., Beierwalters, W. tI., Lampe, I., and Gomberg, H. J.: Radio-Iodine Uptake Curve in Humans, Pediatrics 4: 6277 1949. 4. Salter, T. S.: The Endocrine Function of Yodine, Cambridge, Mass., 1940, Harvard University Press, p. 186. Also recent personal communication. 5. Edward% R. R., Reilly, W. A., and Holmes, 1%. G.: Determination of Iodinelal in Urine, Proe. Soe. Exper. Biol. & Med. 72: 158, 1949.
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6. Hamilton, J. G.: Summary of Iodine Physiology and Metabolic Studies Using Radioactive Isotopes o:f Iodine, U.S. Atomic Energy Commission, MDDC'-1060~ J u n e 25, 1947. 7. Perlman, I., ChMkoff, I. L., and Morton, M.E.: R,adioactive Iodine as an Indicator of the Metabolism of Iodine. L The Turnover of Iodine in the Tissues of the Normal AnimM, With Particular Reference to the Thyroid~ J. Biol. Chem. 139: 433, 1941. 8. Chapman, A.: The ]~elation of the Thyroid and the P i t u i t a r y Glands to Iodine Metabolism, Endocrinology 29: 680, 1941.