Effects of Iodine-131 Thyroid Damage on Lactation and Thyroid Function in the Bovine

J. K. MILLER AND E. W. SWANSON Agricultural Research Laboratory ~

The University of Tennessee, Oak Ridge

Abstract

Partial thyroid destruction was produced in one member of each of nine pairs of identical-twin dairy heifers with single oral doses of ~3~I varying from 99 to 180 ~Ci per kilogram of body weight. Twin pairs were bred beginning two months after treatment. First-calving reproduc- tion was normal in the thyroid-damaged heifers. During lactation the six heifers dosed with 144 to 180 gCi per kilogram av- eraged, as a percentage of their control mates, 7% thyroid iodine uptake, 28% thy- roxine secretion rate, 31% plasma protein- bound iodine, 83% heart rate, and 99% body weight. Three heifers dosed with 99 to 111 FCi averaged for the same values, respectively, 86, 70, 72, 87, and 101% of their control twins. One pair of twins milked only two months; the others all completed 10-month lactations except two thyroid-damaged twins in which lactation ceased after six and seven months. Al- though thyroid-damaged twins initially appeared fatter than the controls, their milk fat tests averaged 82% of control tests during the first two months of lacta-

Received for publication September 5, 1968. This manuscript is published with the per-

mission of the Director of the University of Tennessee Agricultural Experiraent Station, Knoxville.

Operated by the Tennessee Agricultural Ex- periment Statioa for the U.S. Atomic Energy Commission under Contract no. AT-40-l-GEN-242.

tion, after which there was no significant difference. Average measurements for control and thyroid-damaged heifers, re- spectively, were milk yield, 4,000 and 2,042 kg; milk fat, 4.29 and 3.96%; solids-not- fat, 8.77 and 8.66%; and 4% fat- corrected milk, 4,186 and 2,032 kg.

Iodine-131, which is produced in relatively large amounts during reactor operation or processing of fissionable materials, has been considered to be one of the more important fission products from a health-physics aspect. A knowledge of iodine metabolism and effects of 1~1I thyroid damage is important for dairy cattle because of the relationship between thy- roid function and lactation (8). Effects of I'~I irradiation in jury on iodine metabolism, appearance, and reproduction of dairy cattle have been reported (2, 5).

Effects of thyroid damage on thyroid func- tion and milk yield and composition are de- scribed in this report.

Experimenta| Procedures

Nine pairs of identical-twin heifers from 2 to 20 months old were purchased from Ten- nessee dairy farmers. The twins were judged monozygous by similarities in body conforma- tion, hair color, and physical reactions, as well as by determination of identical blood cell anti- gens without evidence of admixtures. The twins were of dairy breeding, including three Jerseys (Pairs 1, 8, and 9--Table 1), two Guernseys (Pairs 2 and 7), two Holsteins (Pairs 5

TABLE 1. Dosing age, body weights, and ~1I doses administered to identical-twin dairy heifers.

Cow no. Body weight Age

Pair no. Control Treated dosed Control Treated ~I dose

(month) (kg) (mCi) (~Ci kg)

1 406 405 25 276 267 48 180 2 469 468 23 332 318 55 173 3 471 470 26 317 301 53 176 4 403 404 23 440 440 70 159 5 464 465 13 259 272 41 151 6 466 467 23 411 430 62 144 7 190 189 39 391 388 43 111 8 473 472 12 180 191 20 105 9 475 474 7 137 141 14 99

95

96 I ~ I L L E R A N D S W A N S O N

and 6), one Brown Swiss (Pair 4), and one Holstein-Jersey cross (Pair 3). Af te r pre- liminaxy iodine metabolism measurements (5), groups of three heifers, each a member of one twin pair, were each given about 105, 150, or 180 ~Ci ~uI per kilogram of body weight as single oral doses in gelatin capsules (Table 1). Cows 189 and 190 of Pair 7 were in the fourth month of gestation at time of ~ I dosing. The others were heifers which had not been bred. The heifers were pasture bred beginning two months after dosing, except Pair 9, bred nine months after dosing.

Each heifer was brought from pasture main- tenance to barn feeding and management as parturition appeared imminent. The cows were confined in covered pens adjacent to the milk- ing barn, with free access to mixed alfalfa hay, water, and noniodized salt. A commer- cial 16% protein concentrate mixture contain- ing noniodized salt was fed, initially at 3.6 kg daily and increasing to 6.4 kg by the sec- ond month of lactation.

Recording of all milk weights began on the third day after calving, considered the be- ginning of lactation. Milking was twice daily at 7- and 17-hr intervals. A one-day composite milk sample was tested monthly for milk fat (Babcock) and total solids (oven drying at 100 C). Although some cows milked longer, lac- tation records were stopped at 44 weeks for experimental comparisons. Two thyroid-dam-

TABLE 2. Comparison of thyroid activity and heart tical-twin cows during lactation.

aged heifers (468 and 470) dried off at 32 and 26 weeks, and one control (190) aborted at 36 weeks. Since the lactation of Cow 190 had appeared otherwise normal until two weeks before she aborted, it was extended from 34 to 44 weeks, using a semilogarithmic extrapola- tion of the lactation curve. Twins 472 and 473 failed to lactate normally; consequently, their lactations were terminated at ten weeks. Firs t lactations of Twins 474 and 475 are incom- plete at this writing.

Body weights, heart rates, and plasma pro- tein-bound iodine (4) were determined at monthly intervals. Thyroid radioiodine up- take (11) and thyroxine secretion rate (6) were determined both before dosing and twice dur- ing lactation.

Results

All heifers conceived for first-lactation com- parisons after dosing. Two heifers receiving high 1~I doses were not observed in estrus, but about six months after dosing they were found by rectal palpation to be pregnant. Four ~ I thyroid-damaged heifers (189, 467, 470, and 474) calved during the same week as their identical-twin controls. The remaining thyroid- damaged heifers calved 257 days before (472), 54 days before (405), 52 days after (404), 93 days after (465), and 222 days after (468) their control twins. Time after dosing at which par- turition occurred averaged 56 weeks for the

rate in normal and ~ I irradiation-damaged iden-

Thyroid Thyroxine Plasma laI secretion protein-bound uptake rate" iodine b

Pair and dose level Control Treated Control Treated

Heart rate"

Control Treated Control Treated

(% of dose) - - ( r a g / d a y ) - - -(mg/100 ml) - - - ( p e r min) - - 176 t~Ci ~ I / k g

1 20.0 3.0 1.15 0.50 4.0 1.8 84 72 2 24.6 1.0 1.50 0.24 3.7 1.0 76 61 3 33.0 1.8 1.00 0.36 3.8 0.8 82 65 Avg 25.9 1.9 1.22 0.37 3.8 1.2 81 66

151 t~Ci ~ I / k g

4 30.0 1.7 1.15 0.19 4.5 0.9 74 60 5 25.7 1.8 1.05 0.27 3.7 1.2 71 62 6 ] 8.8 1.2 1.14 0.34 3.9 1.5 74 62 Avg 24.8 1.6 1.11 0.27 4.0 1.2 73 61

105 t~Ci 13'I/kg

7 28.1 16.2 1.02 0.76 3.9 3.1 77 72 8 17.6 5.6 0.59 0.32 3.9 2.2 104 66 9 9.8 16.5 1.10 0.91 4.4 3.5 85 89 Avg 18.5 12.8 0.90 0.66 4.1 2.9 89 76

a Average of two determinations per cow. b Average of two to ten (monthly) determinations per cow.

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T H Y R O I D D A M A G E AND L A C T A T I O N 97

irradiated heifers and 57 weeks for controls. Calf birth weights averaged 30 kg for both groups. The average birth weights include the total weight of twins born to Cow 404. Calv- ing difficulty was not experienced with thyroid- damaged heifers any more than with control heifers.

Thyroid radioiodine uptake, thyroxine secre- tion rate, plasma PBI, and heart rates mea- sured during lactation are presented in Table 2. The higher dose rates decreased thyroid uptake of a tracer dose of ~ I below control level more than the other measures of thyroid function (thyroxine secretion rate, plasma PBI,

5 4 0

500

~ 4 8 0 t THYROID DAMAG

440 I I

4 2 0 .MONTHS PRERARTUM,I, LACTATION MONTS

-5 -4 -3 -2 - I I 2 5 4 5 6 7 8 9 I0

Fro. 1. Body weight changes in ~3~I thyroid irradiation-damaged cows and their identical- twin controls four months before and through lactation. Standard error of the mean differen£e was 4 kg.

and heart rate). These measurements were impaired about equally with the two higher 1~1I dose levels, but considerably less by the lowest level (Table 2).

Thyroid-damaged heifers averaged 8% heav- ier (P < .05) than their identical-twin con- trols at five months prepartum (Fig. 1). During later gestation they failed to maintain their heavier weight and dropped to 95% of controls one month before calving. After parturit ion both groups were nearly equal in body weight. Heifers in the thyroid-damaged group aver- aged 2% heavier than controls through the sixth month of lactation and were about equal through the ninth month. During the tenth month they averaged 93% of control weight, a nonsignificant difference (P > .10). Differ- ences in appearance were greater than weight difference (Fig. 2). Coats of thyroid-damaged cows were rougher and some failed to shed in the spring. Skeletal growth was subnormal in the hypothyroid cows.

Lactation curves of thyroid-damaged cows and their identical-twin controls are shown in Fig. 3. Pair 8, failing to lactate normally, and Pair 9 which has not completed the first lactation, were not included in this comparison. Init ial milk yields of cows with damaged thy- roids averaged 76% of control, and declined to 26% at 44 weeks. During the first month of lactation, milk fat tests of thyroid-damaged and control groups, respectively, averaged 3.7 and 4.9% (P < .05) (Fig. 4). Corresponding fat tests during the remaining lactation aver-

FIG. 2. Thyroid-damaged cow alld her identlcal-twin control showing reduced skeletal growth and rougher coat of the thyroid-damaged twin.

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9 8 M I L L E I ~ A N D S W A N S O N

17

~, io

D

' " ; . . . . Io . . . . , ; . . . . i o " " ~ ; . . . . i o ' " ; ~ ' " ' ; o ' " , ~ , WEEK OF LACTATION

FIG. 3. Averaged lactat ion curves o f thyro id- daanaged cows and their identical-twin controls showing the lower ini t ial milk and reduced per- sistency of the thyroid-damaged twins. Standard error of the mean difference was 0.2 kg.

aged 4.1 and 4.2%. Al though so l ids -not - fa t pe rcen tages of t hy ro id -damaged cows were s l ight ly lower d u r i n g the first two months (Fig . 4) , averages f o r the comple te lac ta t ion did no t differ s ignif icant ly (Tab le 3). Total 44-week milk yields of t hy ro id -damaged cows averaged 50% of controls (Table 3).

Since p e r f o r m a n c e of each t hy r o i d - dam aged an ima l in r e l a t i on to the control tw in is the most sensi t ive compar ison , thy ro id ac t iv i ty mea- su rement s and mi lk yields of the t h r ee i r r ad ia - t ion levels are p re sen ted as pe rcen tages of control values in Table 4. Thyro id ac t iv i ty p a r a m e t e r s of the two h ighes t dose levels av- e raged nea r ly the same, and milk yield depres- s ion was comparab le fo r the h ighes t dose levels.

TABLE 3. Effect of thyroid i rradiat ion damage on

iif :==-oo

f MONTH OF LACTATION

FI~. 4. Percentages o f mi lk f a t and solids-net- f a t in milk of thyroid-damaged cows mud their identical-twin controls. S tandard error of the mean difference was 0.12% for f a t and 0.08% for solids- not-fat .

Milk yields were not decreased nea r ly as much in the h ighes t dose g r o u p s as was the t hy ro id secret ion ra te . I n the lowest dose groups , p a r a m e t e r s of t hy ro id func t i on showed only 15 to 30% damage, and milk yields were de- p ressed abou t 15%.

Discussion

Effects of surgical thy ro id removal on re- p roduc t ion and lac ta t ion have been descr ibed (8, 9) . I t was expec ted t h a t the h ighes t doses used in this e x p e r i m e n t would not comple te ly des t roy the t hy ro id gland. The objec t ive was to p roduce a r ange of pa r t i a l t hy ro id damage resu l t ing f r o m g raded 1~1I doses. The va lue of ident ical twins fo r pa i r ed compar i sons has

reproduction, milk yield, and composition.

Pa i r IlO.

44-weeks Milk f a t Calving age milk yield test

Con- Treat- Con- Treat- Con- Treat- trol ed tro] ed tro] ed

4% Fat- Solids-not-fat corrected tes t milk yield

Con- Treat- Con- Treat- trol ed trol ed

- ( m o n t h ) - - - - ( k g ) - -

1 41 39 3,048 2,604 4.15 4.73 2 34 41 3,182 916 c 4.18 3.71 3 36 36 4,066 1,128 d 4.58 3.97 4 36 38 3,416 ],817 3.77 3.28 5 25 28 4,879 2,418 4.39 4.26 6 37 37 5,684 2,678 4.32 3.60 7 44 ~ 44" 3,719 b 2,731 4.65 4.17 8 34 25 1196 162 e 6.45 4.10 9 25 25 1,451 f 1,363 ~ 4.00 3.92

( % ) - - ( k g )

9.02 9.26 3,109 2,887 9.36 8.23 3,268 876 8.75 8.86 4,416 1,126 8.56 8.56 3,301 1,627 8.62 8.49 5,162 2,512 8.39 8.40 5,964 2,511 8.69 8.84 4,082 2,802 9.20 8.71 163 164 8.98 8.92 1,451 1,347

" Second lacta£ion for Pa i r 7. b Extended to 44 weeks following abort ion at 250 days. eDried off a t 292 days. d Dried off a t 224 days. e Dried off at 70 days due to abnormally low lactation.

F i r s t lactation incomplete. Values presented axe for 21 weeks.

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THYI~OID DAMAGE AND L A C T A T I O N 99

TABLE 4. Thyroid activity, heart rate, and milk yield of ~azI irradiation-damaged cows expressed as percentages of their control identical twins.

Average dose, gCi/Z~I kg body weight

Cows 176 151 105

- - - - ( % of c o n t r o l ) - Thyroid aa~I uptake 8.2 6.4 85.9" Thyroxine secretion rate 31.8 24.0 70.5 b

Plasma PBI 31.0 30.3 71.8 b Heart rate 81.8 84.1 87.2 Milk yield 47.3 50.0 83.6 b'¢ 4% FCM yield 48.4 46.7 80.1 b'~

~.b Differs from other values in the same line : a, P ~ . 1 0 ) ; b, P ~ .01. Other values do not differ (P ~ .25) from values in the same line not bear- ing a superscript.

¢ Excludes Pair 8 with abnormal lactations.

been established for comparing thyroid activ- ity (11). Differences between treated and con- trol twins can be considered due to ~31I irradia- tion damage.

Although there was some difficulty in detect- ing estrus, reproduction in thyroid-damaged cows was not adversely affected. Spielman ct a]. (9) reported that outward manifestations of estrus were absent in cows after surgical thyroidcctomy, but Garner et al. (2) stated this was not so in cows receiving total doses up to 140 mCi ~~I. Williams and Stott (12) found that 12 of 15 first services during two breeding periods for eight thyroidectomized cows resulted in pregnancies, although cows also parathyroidectomized were unable to carry their calves to term. All of our ~I- treated cows delivered normal calves and one (404) had twins. In a second parturition, another thyroid-damaged cow (405) gave birth to twins. Garner et al. (2) also reported twins born to a cow dosed with 140 mCi ~3~I before breeding. Ragan et al. (7) reported that re- productive performance of 17 ewes rendered hypothyroid by ~ I was inferior to that of six control ewes.

Eight of the nine control cows have produced at commercially acceptable levels (Table 3, Fig. 3). Lower yields of thyroid-damaged cows resulted from a combination of lower initial yield and reduced persistency (Fig. 3). Spiel- man et al. (8) observed that surgical thyroid- ectomy caused a complete cessation of lactation in about 180 days. Garner et al. (2) reported lactation periods of only 77 and 203 days for two cows which during the previous lactation had each received 10 mCi ~ I daily over a two- week period. Total milk yields averaged only

19 and 49% of respective yields during the last lactation before dosing. Total 1SlI doses of 70 tLCi and less did not measurably reduce either milk yield or lactation period (2). In contrast, a single 43 mCi dose lowered produc- tion of Cow 189 to 73% that of her control twin (Table 3), but a comparable dose to a seven-month-old heifer (474) resulted in only about 10% reduction of first-lactation yield (incomplete). Low initial milk yields of cows with thyroid damage indicate that the thyroid influences lactogenesis as well as lactation maintenance.

The lower milk fat percentage in milk of thyroid-damaged cows (Fig. 4) is a logical effect, in view of the thyroid's involvement in lipid metabolism (1). Greenbaum et al. (3) found that thyroidectomy decreased the content of short-chain fat ty acids and increased the content of long-chain fat ty acids in the mam- mary glands of lactating rats.

I t was apparent (Table 3) that milk yield was affected differently in different cows by the same ~1I dose level on a body weight basis.

This effect could result from any one or a combination of factors. Dosing the heifers on a body weight basis was based on the assump- tion that thyroid size was proportional to body size, whereas, in reality, thyroid mass in the living animal was an unknown variable. Degree of irradiation damage resulting from a given amount of 1~I would Mso vary with amount concentrated by the thyroid and re- tention time in the gland. The latter two fac- tors would be influenced by individual animal variation, age, season, and stable iodine in- take (11). Also, level of thyroid function could be more critical in some individuals than in others. After radioiodine treatment of 348 cases of human hyperthyroidism, Yang (13) stated that two factors make selection of an appropriate dose difficult: inaccuracy in esti- mation of gland weight, and unpredictability of individual thyroid sensitivity to irradiation.

Spietman et al. (8) reported that subtotal removal of the thyroid resulted in only a temporary decline in milk secretion. This in- dicated either adaptation of the cow or re- generation of the gland. On the other hand, following 1~1I treatment of human hyperthy- roidism, some patients may later lapse from an initial euthyroid condition into myxedema. lV[edieal surveys reviewed by Stanbury and De Groot (10) reveal that nearly one-third of the individuals who have received ~ I for Grave's disease is destined to become hypo- thyroid. Whether the partially damaged bovine thyroid is capable of regeneration after ~ I

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100 MILLER AND SWANSON

i r r ad ia t ion or would even tua l ly de ter iora te f u r - ther is yet to be demons t ra t ed .

Acknowledgment

Blood cell ant igens of the twins were determined by Dr. W. H. Stone, Universi ty of Wisconsin Genetics Department. Appreciation is also ex- pressed to B. R. Moss and C. L. Pankey for technical assistance and to L. D. Elliott, g. E. Ridenour, E. E. ¥ insan t , and H. C. Weaver for care of the animals.

References

(1) Fain, J. N., and A. E. Wilhelmi. 1962. Ef- fects of adrenalectomy, hypophysectomy, growth hor~none and thyroxine on f a t ty acid synthesis in vivo. Endocrinology, 71:541.

(2) Garner, R. J., B. F. Sansom, H. G. Jones, and L. C. West. 1961. Fission products and the dairy cow. 5. The radiotoxicity of iodine-131. J. Comp. Pathol., 71: 71.

(3) Greenbaum, A. L., E. Walters, and P. Me- Lean. 1967. The effect of thyroidectomy on the pat tern of fa t ty acids synthesized by mammary gland from lactat ing ra.ts. Biochem. J., 103: 720.

(4) Lennon, H. D., Jr., and J. P. Mixner. 1957. Some factors affecting the deternlination of plasma protein-bound iodine, using the al- kaline fusion-eerie sulfate nlethod. J . Dairy Sci., 40 : 351.

(5) Miller, J. K., and E. W. Swanson. 1967. Performance and iodine metabolism of

dairy cattle with iodine T M irradiation in- jury. J. Dairy Sci., 50: 90.

(6) Post, T. B., and J. P. Mixner. 1961. Thy- roxine turnover methods for determining thyroid secretion rates in dairy cattle. J. Dairy Sci., 44: 2265.

(7) Ragan, H. A., W. J. Clarke, R. O. Mc- Clellan, V. G. Horstman, and L. K. Bustad. 1963. Effect of I ~l on reproduction per- formance i1~ ewes. Heal th Physics, 9: 1343.

(8) Spielman, A. A., W. E. Peterson, and J. B. Fitch. 1944. The effect of thyroidectomy on lactation in the bovine. J. Dairy Sci., 27 : 44].

(9) Spiehnan, A. A., W. E. Peterson, J. B. Fitch, and B. S. Pomeroy. 1945. General appearance, growth, and reproduction of thyroldeetom~zed bovine. J. Dairy Sci., 28 : 329.

(10) Stanbury, J. B., and L. J. De Groot. 1964. Problem of hypothyroidism af ter I TM ther- apy of hyperthyroidism. New England J. Med., 271: 195.

(11) Swanson, E. W., F. W. Lengemann, and R. A. Monroe. 1957. Factors affecting the thyroid uptake of I ~3~ in dairy cows. J. Anita. Sci., 16: 318.

(12) Williams, R,. J., and G. H. Stott. 1966. Reproduction in thyroidectomized and thyro- parathyroidectomized cattle. J. Dairy Sci., 49 : 1262.

(13) Yang, H. F. 1964. I TM t reatment of hyper- thyroidism: Analysis of 346 cases treated with the initial dose of 7 me or less. J. Formosml Med. Ass., 63:234.

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