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Iodine and thyroid disease in Latin America
ENVIRONMENTAL
RESEARCH
Iodine
3, 353-363
and
( 1970)
Thyroid
JOHN B. STANBURY Unit
of
Experimental Medicine, Institute of Technology, Health
Department Cambridge, Organization, Rcceiwd
Disease
in Latin
America
AND JOHN P. KEVANY’ of Nutrition
Massachusetts, Washington, June
and Food Science, Massachusetts and the Pun American D. C.
3, 1970
Available evidence indicates that endemic goiter in Latin America antedated the arrival of the white man, its presence being recorded in the earliest accounts of travels to the inland regions of the South American continent. Today the disease is still a major health problem, for it has been estimated that as many as 10 million persons in Latin America have enlarged thyroid glands (Fig. 1) (1). Precise
statistics arc not available because many regions arc geographically remote, the criteria for diagnosis lack uniformity, and comprehensive surveys or reporting systems are absent. Where the diseaseis severe, as in many scttlcments of the high Andes, one finds endemic cretinism and endemic deafmutism, disorders that inevitably accompany florid endemic goiter and are causally related to it. Less clearly related but often coexisting are short stature, lack of physical and intellectual vigor, and mental retardation and neuromuscular disorders without other evidence of disturbed thyroid f1mction. ’ Present address: Department 2, Ireland.
of Social Medicine, 3.53
Trinity College, DlllAin University, Dublin
354
STANBURY IODINE
AND
AND
KEVANY
ENDEMIC
GOITER
The principal cause of endemic goiter in Latin America is without doubt a deficiency of iodine in food and water. While in some areas there may be other contributing causes, most measurements of available iodine have given values far lower than those found where endemic goiter does not exist. Correction of this deficiency is highly successful in preventing the disease. Iodine is a scarce element in the earth’s crust. Nowhere does it csist naturally in high concentration. It is found most abundantly in the great nitrate deposits of northern Chile, where it may reach a concentration as high as 21, but the average is much lower (2). There arc also rare mineral springs where the water is heavily contaminated with iodine. The element is generally made available to surface plants by the gradual erosion of iodine-containing rocks and is concentrated in the topsoil by recycling through the organic world. Soil may also be enriched by condensation and precipitation of sea mists. Kelp and other seaweeds may selectively take LIP iodine from seawater and may enter the fish cycle and become a human food source with a relatively high iodine value. Soils are depleted of iodine by cropping and by leaching, especially if the water is alkaline, and water draining these areas may bc extremely low in iodine. These considerations suggest that hullran populations subsisting on land that has been depleted of iodine or that has a thin new topsoil produced by recent glaciation may be forced to accept the consequences of a low iodine intake unless iodine is othcrwisc provided. This is the current state of affairs for large populations in Latin ‘4merica. The safety, practicability, and effectiveness of salt iodization as a means of supplementing dietary iodine for prevention of endemic goiter have been well recognized since the classic csperiments of Marine and Kimball in Akron. Ohio, in 1917 (3). Since that time, highly successful programs for iodization of salt have been implcmcntcd in Switzerland, the United States, Guatemala, and elsewhere. Wherever these programs have been carried out, there has been a spectacular reduction in the incidence of goiter and the incidence of defects that accompany severe endemic goiter, such as endemic cretinism and endemic deafmutism. If goiter is endemic in a population, an estimate is necdcd of the amount of iodine available to the population. This may be made by direct measurement of the iodine content of food and water or assay of the mean daily urinary excretion of iodine by members of the population group. or indirectly by a survey for the prevalence of endemic goiter. The last method is based on the assumption of a correlation between available iodine and severity of the goiter endemic. Many investigations have established this association in Latin America, and some of the measurements appear in Table 1. Most values from endemic regions show only a few micrograms of iodine per liter in the drinking water and less than 50 hcg per day in the urine, Since the mean daily iodine in the urine of adults where endemic goiter does not exist is generally in excess of 80 pg/24 hr and the iodine content of drinking water is 10 !Lg or more per liter, one can readily appreciate the severe deficiency of iodine in many regions of Latin America. PROPHYLACTIC
LEGISLATION
IN
LATIK
AMERICA
For a number of years the Pan American Health Organization (PAHO) has been concerned with the health hazard of endemic goiter in Central and South
IODISE
AND
THYROID
TAALK
:3Fj5
DISEASE
1
Ref. 11”. I\lexiw ‘I’epet.lisps ( 196% J ‘I’epet,lixps i 196X i .-irpent,ina Chiquillihllin .Ilisiones hlendoza I1 9il’l Ruenos Aires Bllenos Aires Chile Santiago 1 )ept . .\laipo l>epl. Pedregoso, No Goiter 1 Mutie goiter Nodlllar goit.el Brazil Sao Pa1110 Slatr SIatco c:row, Federal 1 )iafric-1
++ +
4, .i 1
2-i 1 O--L’ .6 2. o-3. I (3)
++ ++ +++ 0 0
+
14
x.5-11
.i
O-X.6
f24)
0.4-“.!I
(14,
!I II 10
10 IO
+ ++ + 0 0
1 .7 + 0. 13 (3Sll
0.3-l.
12 12 12 12
0
+++ 0
0
1.0 0.85 6 .i
0
4.0-liX.!l
++++ ++++
l.6-6.!)
++
++
I1 17 17
I:( 1:; 1:; (111 ilO
14 14
o.:i-1,s
15
0.2
16
2 ‘J-4. :;
16 16
America. In order to define the existing situation regarding the prevention of goiter by salt iodization, the Organization conducted a survey by mail questionnaire to obtain information regarding the existence of legislation, the geographical area covered, the type of iodine compound recommended, and the levels of iodine concentration recommended for the final product. Table 2 presents an analysis of the information gathered. Of the 26 governments surveyed, 17 had defined problems of endemic goiter, at least in certain areas. All of the affected countries have now enacted legislation requiring iodization of salt for goiter prevention, generally within the past 15 years. The regulations on iodization vary widely. In four countrirs the legislation refers
356
THE
STANBURY
STATE
Countries with public health problem Argent.ina Bolivia Brazil Chile Colombia Cotta Rica Ecuador El Salvador Guatemala0 Honduras Mexico Nicaragua Panama Paraguay Peru Uruguay Venezuela
OF GOITER
Year of legislation
PREVENTION
Coverage”
1967 1968 1956 1966 19.5.5 + 1960 1941
G T ? 1 1 H
1961 19.54 1960 196:;
7 r. 1 H r.I
195.5 + 1966 19.58 1940 + 1961 1963 1966 + 1968
H H c; G r.1
1 .i+ L’ -
‘1‘ s H4 G ::
ASD
KEVANY
TABLE 2 PROGRAMS IN LATIN JUNE, 1968
Iodine rompoundb
AMERICA
Responsible in&itilt iond
Concentrat,ion” 30
A+1 .4
20
A4
50
A
10 I5 100 -
I I .4 .4 A .4
1 .i 1-i 1.5 .iO
>30
2.k.iO <%
-
I
- .i - 9
Source of equipmenl and supplies”
HS HS HS HS IN HS -
I’ I G + I’ P G
HS FIS HS HS -
c; + I’ I’
HS r1s HS NS HS A 1:; I :3
AND THE CARI~HEAN,
HS 14 IN 1
Level of program activity!
I G P P
F I P I F P P F F P F P P I’ P F I
I’ 8 c4 I 2
F6 I 3 P8
P
a ‘I’, Total coverage, i.e., all salt, produced and imported is iodized; H, o111y salt, for human consumption is iodized; G, only salt in areas of endemic goiter is iodized. * I, Potassium iodide; .4, potassium iodate. c Thousands of parts of salt to one part of iodine. Figures given represent nini~~?r~ levels established by law. d HS, Health service; lN, Instit,ut,e of Nutrition. e G, Government,; I, international assistance; P, private sector. i F, Fully active; I, being implemented: P, problems encountered. g Problem now reduced below I()(,‘$ level.
only to salt destined for human consumption, leaving that for animals and industrial use uniodized. In eight, total available salt for all purposes must be iodized, an d in three countries, only that salt destined for use in the areas of endemic goiter is covered by law. In 13 countries potassium iodate is the additive prescribed, whereas in the others potassium iodide is used; in one country the choice is left to the individual state government. The concentration of iodine varies from 1 in 100,000 to as high as 1 in 10,000. The figures generally refer to the concentration at the time of processing. It is well known that the iodine level available to the consumer may not be the same as that at the time of processing because of losses due to sublimation. Iodate is considerably more stable than iodide and is the preferred form of the supplement although it is slightly more expensive. In situations where iodide has been used, analysis of commercial salt at the con-
IODIXE
AND
THYROID
357
DISEASE
sumer level has shown substantial losses or even virtual absence due to sublimation. This fact has accounted for the failure of some prophylactic programs. The authority responsible for implementation of the programs of salt iodization has been the national health service in all but one of the Latin American countries. In some countries the manufacturer has been required to purchase the equipment and supplies for iodization, while in others the government has provided these resources. In some instances the costs are shared by the government and the manufacturer. While it is gratifying that 17 of the 26 countries in Latin America have enacted legislation requiring salt iodization, in many instances the legislation has not been effectively implemented. There are many reasons for this, both social and technical. In several countries where entirely adequate legislation has been enacted, the only iodized salt available for consumption is imported as a luxury item. There has been resistance to the program on the part of manufacturers who find iodization inconvenient or economically disadvantageous. Elsewhere action has been delayed due to concern lest the distribution of iodized salt cause a rise in the incidence of toxic goiter (Jod-Basedow). In other instances health authorities do not give goiter a high priority for action since the condition is not generally rcported and thus does not appear in official morbidity and mortality statistics. Prophylactic programs have not been instituted in many remote and iuaccessiblr regions because of a genuine difficulty in the distribution of iodized salt or because-\ supplementation of salt with iodide is not practical. This is illustrated in Fig. 2. In this cottage industry on the w&em slope of the Andes, salt is prepared by digging topsoil from the bed of an ancient lake. This is transported a few hundred yards by mule to the hoppers shown in the photograph. Water is then poured through the soil to leach out the salt. The filtrate collects in pans beneath the hopper and is dried over an open fire. The reddish brown, bitter-tasting product is distributed throughout the countryside as salt, Clearly. iodization is scarcely possibk under such circumstances, and economic development will be required before salt distribution through large suppliers will occur. To the east of the Andes, there arc salt flats where salt of sufficiently high purity for human cons~~mption can simply be scraped from the surface. SOCIAL
AND POLITICAL
ASPECTS
OF ENDEMIC
GOITER
Economic development, quite apart from enabling widespread USCof iodized salt, may reduce the incidence of goiter and increase the availability of iodine by introducing exogenous foods and by improving the mobility of the population. This has been well illustrated by the studies of Maisterrena et ab. (4) in a town of rural Mexico. Construction of a major highway through a village with a high incidence of goiter seemingly resulted in a gradual but substantial fall in goiter over the succeeding several years (Fig. 3). This was coupled with a rise in the mean daily excretion of iodine in the population. The correlation of goiter with economic status in a community is doubtless related to the availability of cxogenous food and to travel by the economically privileged. The economic and political impact of endemic goiter on a population must be considered if one is to put the importance of the diseasein perspective. So far, it
358
FIG.
STANBURY
2.
Production
of salt in a rural
.-\ndenn
AND
KEVAR’Y
community.
The
crude
nkwxl
is surface-mind
hy, bro&t hy mule, and deposited in the hopper. The salt is leached by pouring mater throtlgh and collecting the liquid in a pan. This liquid is then evaporated to dryness over an open fire and the crllde salt is tlistrihlltrd locally. close
has been impossible to untangle the complex interactions between endemic goiter and such associated findings as short stature, deafmutism, mental retardation, physical apatl 1\;, and economic unproductivity. All of these customarily occur together to a greater or lesser degree, but other factors such as protein deficiency, caloric deficiency, a high prevalence of infectious discasc, and hostile climatic conditions complicate interpretations. Generally, the cretinism and deafmutism associated with endemic goiter occur to a greater extent in isolated rural areas. The affected populations have a low level of social development and limited sociopolitical importance in comparison to the more highly organized and vocal groups of urban communities. As a consequence, there is little social pressure on governmental agencies to resolve the problem; it is not surprising that implementation of legislation for salt iodization has not received the desirable priority.
IODINE
AND
THYROID
MEAN MEDIAN
B’
1962
63
64
65
359
DISEASE
1
l
66
67
100
68
Evidently the problems associated with the wide distribution of iodized salt are insurmountable at the present time in some countries. Therefore, alternative methods for prcvi-ntion of endemic goiter and cretinism have been sought to offer interim protection for affected populations until such time as their salt SUPplicas arc iodized. These methods could also provide permanent protection for isolatc,d communities having little contact with normal commercial channels for salt distribution, An acceptable altc?rnatise method must meet specific criteria. It must be effective, safe, and cheap. It must be easily applied through local health scrviccs or extension agencies. It must not require frequent doses or close clinical supervision, and it must be acceptable to the recipient population. Thcsc criteria were substantially met by a group of Australian investigators in a prc’\Tc,nti\,c program in New Guinea that began in 1957 ( 18. 19. 20). Iodized poppyseed oil was injected into a large number of subjects. The effectiveness of the program has since been studied by several investigators. There appeared to be an effective correction of iodine deficiency for as long as 4 years after the initial administration and a sharp reduction in the rate of visible goiters. A similar and highly effective program has been carried out by Melange et al. (21) on the island of Idwji in the Republic of the Congo. They gave an injection of iodized oil, in doses ranging from SO to 1000 mg of iodine, to 90% of the 1379 inhabitants of two villages. The prevalence of goiter fell from 49 to 16.3% in the injected group. Marked improvement occurred in 80% of those injected, and no secondary reactions were observed. Similar programs have now been carried out in rural Ecuador and Peru, and preliminary results have hecn reported (13, 23). As in the Nc~l Guinea and Idwji Island studies, these results have shown a gratifying drop in the incidence of goiter among injected persons as compared to control popalations, either neighboring or interspersed. There have been virtually no unwanted side reactions. In the Ecuadorian study, among approximately 900 injected subjects 3 older ~omcn with large nodular goiters developed thyrotoxicosis, which \vas
360
STANBURY
ASD
KFXANY
readily controlled by routine medical management. Results to date indicate a complete absence of cretinism in the protected group and the appearance of seven newborns with severe developmental retardation in the control population. Administration of iodized oil to growing children seemed to cause no acceleration of statural growth or bony development, but there was indication of enhanced intellectual performance in the injected group. On the basis of results obtained from the studies in Ecuador, Peru, and other regions, PAHO has made recommendations for the prophylactic use of iodized oil in regions where it is not technically or economically feasible to prevent endemic goiter by salt iodization programs. FeasibiZity. Currently available knowledge indicates that intramuscularly injected iodized oil is a useful means of combatting endemic goiter and cretinism in areas where salt iodization is not employed. The method is cheap. long acting, relatively free from side effects, and can easily be applied through local health services with existing facilities. Con&ions of use. In areas where public health problems of endemic goiter and endemic cretinism exist and are known to be due to dietary iodine deficiency and where there is no program of salt iodization or iodine supplementation in any other form. Under these conditions the use of iodized oil is recommended until an effective salt iodization program has been established. In the cast of isolated communities beyond the reach of normal commercial channels, the use of iodized oil may be recommended indefinitely. Iodized oil should be administered by the local health service under medical supervision. Recipients. The entire population of the goitrous areas, from 0 to 45 years of age, of both sexes, with no exclusions even for persons with nodular goiters. Dosage scheclubes. The ethyl ester of the fatty acid of poppyseed oil, containing 475 mg of iodine per milliliter (37% by weight), has been used in the basic studies. The recommended dosages are given in Table 3. Administration. Intramuscular, in the &teal region in small children and the deltoid region in adults. Drawback should be practiced to ensure that oil is not injected intravenously. The skin at the injection site should be cleaned carefully to avoid the formation of abscesses. Merthiolatc or a similar colored antibacterial agent is useful because it acts as a marker and reduces the risk of a double injection in a mass treatment. Extra care should be taken in sterilizing equipment, especially at high altitudes. Disposable syringes and needles are preferred.
Iodine, mg
Age O-6 mo. 6-12 mtr. 6 mo.4 yr. 6 yr.-45 yr. * For all persons with dosage should be reduced
Quantity
95 142 a z?a. .i 47.5.0 nodular goiters to 0.2 ml.
(including
single
(375
I),
ml 0. a 0.3 0. .i
1.0 t,hyroid
nodules
wit.hout
goiter),
the
IODIh-E
AND
THYROID
DISEASE
361
Surveillance. If possible, a medical follow-up of all persons injected should be made 3-6 months later to determine if any cases of thyrotoxicosis have occurred. This medical examination should be a simple screening procedure testing for pulse and respiratory rate, tremor, edema, weight loss, and exophthalmos. If this screening cannot be carried out by a physician, a public health nurse or specially instructed auxiliary can perform it. Any cases of suspected thyrotoxicosis should be removed to hospital, if possible, and a definitive diagnosis made and treatment instituted. If hospitalization is impossible, ambulatory treatment should be prescribed, but only after diagnosis is established. Repeat dosage. A minimum of 2 years is recommended between the original and the repeat dose. Specific dosage schedules for repeat injections will depend on the residual iodine levels in blood and urine and on the anatomical and metabolic thyroid response of the population. The possible occurrence of undesirable side effects such as thyrotoxicosis is acknowledged. The low incidence of such side effects, and the feasibility of effective therapeutic control, makes them a minor limitation. Furthermore, the recommended dose for subjects with nodular goiter is reduced tenfold below that administered in the pilot studies. When compared with the continued risk of cretinism and associated neurological defects in a given population, the significance of side effects appears to be minor. A prophylaxis program of iodized oil should be considered only as a temporary measure where a regional or federally controlled program of salt iodization cannot be effectively mounted. Iodized oil programs are only recommended on a permanent basis where a fully implemented salt iodization program cannot reach remote and isolated communities for economic or geographic reasons. In those instances where the distribution and administration of iodized oil is used for prevention of goiter and its allied disorders, existing public health machinery can be effectively employed. SUhlM4RY
Endemic goiter continues to be a major health problem of Latin America despite legislation in most countries requiring the iodization of salt for human consumption. In many instances this legislation has not been fully implemented or has been entirely neglected. As a result, endemic goiter and its consequences, endemic cretinism and deafmutism and possibly other related disadvantageous states, continue in many communities of Central and South America. Salt iodization programs have not been fully implemented for a variety of reasons, including failure to appreciate the economic and social disadvantages of goiter, apathy on the part of officials charged with the responsibility, the slight economic disadvantage of adding iodide or iodate to salt prepared for human consumption, and the real difficulties of introducing iodized salt into areas that are remote and severely deprived economically. When prophylactic programs employing iodized salt are not possible, for whatever reasons, the population group may be injected with iodized poppyseed oil
362
STANBURY
AKD
EEVASY
as an alternative preventive measure. Programs employing this method have proved to be effective, economically sound, and acceptably free of medical risk. REFERENCES 1. KELLY. F. C., AND SXEDDEN, W. W. (1966). Prevalence and geographical distribution of endemic goitre. In “Endemic Goitre,” p. 27. World Health Organization, Geneva. 2. “Geochemistry of Iodine.” Chilean Iodine Educational Bureau, London, 1956. 3. MARINE, D., AND KI~~BALL, 0. P. (1920). P revention of simple goiter in man. Arch. Intern. Med. 25, 661. 4. MAISTERRENA, J. A., TOVAH, E., AND CHAVEZ, A. ( 1969). Endemic goiter in Mexico and its changing pattern in a rural community. In “Endemic Goiter,” (J. B. Stanbury, ed.), p. 397. World Health Organization, Washington, D. C. 5. MAISTERREXA, J. A., TOVAR, E., CANCINO, A., AND SERRANO, 0. ( 1964). Nutrition and endemic goiter in Mexico. J. Clin. Endocrinol. Metab. 24, 166. 6. DEGROSSI, 0. J., WATANABE, T., ALTSCHULER, N., PECORINI, V., AND SANTILLAN, C. ( 1969). Characteristics of endemic goiter in a Mapuche Indian tribe in Chiquillihuin, El Malleo, Province of Neuquen, Argentine Republic. II. Iodine kinetic studies. In “Endemic Goiter” (J. B. Stanbury, ed.), p. 159. World Health Organization, Washington, D. C. 7. SOTO, R. J., CODEVILLA, A. H., WEINSTEIN, M., ROZADOS, I., RABINOVICH, L., AND GOLDBEHC., D. ( 196S). Adaptive mechanisms to iodine deficiency in endemic goiter in Misiones, Argentina. Metabolism 17, 326. 8. STANBURY, J. B., BROWNELL. G. L., Rmcs, D. S., PERINETTI, H., ITOIZ, J., AYD DEL CasTILLO, E. B. ( 1954 ). “Endemic Goiter.” Harvard University Press, Cambridge, Mass. 9. PAK. N., ZANZI, I., AND DONOSO, G. ( 1962 ). Contenido de yodo y dureza en agua de bebida y su relation con el bocio endemico. Nutr. Bromato!. Toricol. 1, 135. 10. BECKERS. C., BARZELATTO, J., SrEvENsoii, C., GIAXETTI, A., PARDO, A., BOBADILL.~, E., AND DE VISYCHER, M. ( 1967 ). Endemic goitre in Pedregoso (Chile ). II. Dynamic studies on iodine metabolism. Actu Endocrinol. 54, 591. 11. CARDOSO, F. A., GANDFLA, Y. R., AND NAZARIO, G. da relacao ( 1957). D a inconsistencia entre o grau de dureza e o teor de iodo em aguas de abastecimento puhlico. Arq. FUC. Hig. Suude Publica Univ. Sao Parr/o 2, 1. Algunos estudios recientes sobre el bocio endemico. Acta Cient. 12. GAEDE, K. (1963). Vene.2. Suppl. 1, 58. 13. FIERRO-BENITEZ, R., RAMIREZ, I., ESTRELLA, E., JARAAIILLO, C., DIAZ, C., AND URRESTA, J. ( 1969 ). Iodized oil in the prevention of endemic goiter and associated defects in the Andean region of Ecuador. I. Program design. effects on goiter prevalence, thyroid function, and iodine excretion. In “Endemic Goiter” (J. B. Stanbury, ed.), p. 306. World Health Organization, Washington, D. C. 14. CERVINO, J. M., MAGGIOLO, J., DE BAYLZ~, E. J., ASD AVELLAXAL, R. (1964). Endemia bociosa en el Uruguay. Ann. Fat. Med. Mowteaideo 49. 591. 15. ALTSCHULER, N., DEGROSSI, 0. J., CERIA~YI, R., FOIXHEH, H., MAyon, \‘., AND EXRIORI, C. L. (1969). Endemic goiter in the Republic of Paraguay. In “Endemic Goiter” (J. B. Stanbury, ed.), p. 168. World Health Organization, Washington, D. C. E. ( 1969). Thyroid function in adolescents from the 16. WAHNEH, H. W., AND GAITAS, goiter endemic of the Cauca Valley, Colombia, South America. In “Endemic Goiter” (J. B. Stanbury, ed. ), p. 291. World Health Organization. Washington, D. C. 17. ROSENTHAL, D., LOBO, L. C. G., REBELLO, M. A., AND FRIDMAK, J. (1969). Studies on endemic goiter and cretinism in Brazil. 3. Thyroid function studies. In “Endemic Goiter” (J. B. Stanbury, ed.), p. 217. World Health Organization, Washington, D. C. 18. CLARKE, K. H., MCCULLAGH. S. F., AND WIXIKOFF, D. (1960). The use of an intramuscular depot of iodized oil as a long-lasting source of iodine. Med. J. Aust. 1, 89. IQ. HENNESSEY, W. B. (1964). Go&e prophylaxis in New Guinea with intramuscular injections of iodized oil. Med. J. A&. 1, 505.
IODINE
THYROID
DISEASE
363
H., AND HEIZEL, B. S. (1969). E n d emit goiter in New Guinea and the prophylactic program with iodinated poppyseed oil. In “Endemic Goiter” (J. B. Stanbury, ed. ), p. 132. Woild Health Organization, Washington, D. C. 21. MELANGE, F., THILLY, C., POURBAIX, P., AND ERMANS, A. M. ( 1969). Treatment of Idjwi Island endemic goiter by iodized oil. In “Endemic Goiter” (J. B. Stanbury, ed.), p. 118. World Health Organization, Washington, D. C. 22. PHETELL, E. A., MONCLOA, F.. SALINAS,R., GUERRA-GARCIA, R., KAWANO,A., GUTIERREZ, L., PRETELL, J., ANDWAN, M., ( 1969). Endemic goiter in rural Peru: Effect of iodized oil on prevalence and size of goiter and on thyroid iodine metabolism in known endemic goitrous populations. In “Endemic Goiter” i J. B. Stanbury, ed.), p. 419. \1’orld Health Organization, Washington, D. C. 20.
RUTTFIELD, I.
Ah-D
RESEARCH
Iodine
3, 353-363
and
( 1970)
Thyroid
JOHN B. STANBURY Unit
of
Experimental Medicine, Institute of Technology, Health
Department Cambridge, Organization, Rcceiwd
Disease
in Latin
America
AND JOHN P. KEVANY’ of Nutrition
Massachusetts, Washington, June
and Food Science, Massachusetts and the Pun American D. C.
3, 1970
Available evidence indicates that endemic goiter in Latin America antedated the arrival of the white man, its presence being recorded in the earliest accounts of travels to the inland regions of the South American continent. Today the disease is still a major health problem, for it has been estimated that as many as 10 million persons in Latin America have enlarged thyroid glands (Fig. 1) (1). Precise
statistics arc not available because many regions arc geographically remote, the criteria for diagnosis lack uniformity, and comprehensive surveys or reporting systems are absent. Where the diseaseis severe, as in many scttlcments of the high Andes, one finds endemic cretinism and endemic deafmutism, disorders that inevitably accompany florid endemic goiter and are causally related to it. Less clearly related but often coexisting are short stature, lack of physical and intellectual vigor, and mental retardation and neuromuscular disorders without other evidence of disturbed thyroid f1mction. ’ Present address: Department 2, Ireland.
of Social Medicine, 3.53
Trinity College, DlllAin University, Dublin
354
STANBURY IODINE
AND
AND
KEVANY
ENDEMIC
GOITER
The principal cause of endemic goiter in Latin America is without doubt a deficiency of iodine in food and water. While in some areas there may be other contributing causes, most measurements of available iodine have given values far lower than those found where endemic goiter does not exist. Correction of this deficiency is highly successful in preventing the disease. Iodine is a scarce element in the earth’s crust. Nowhere does it csist naturally in high concentration. It is found most abundantly in the great nitrate deposits of northern Chile, where it may reach a concentration as high as 21, but the average is much lower (2). There arc also rare mineral springs where the water is heavily contaminated with iodine. The element is generally made available to surface plants by the gradual erosion of iodine-containing rocks and is concentrated in the topsoil by recycling through the organic world. Soil may also be enriched by condensation and precipitation of sea mists. Kelp and other seaweeds may selectively take LIP iodine from seawater and may enter the fish cycle and become a human food source with a relatively high iodine value. Soils are depleted of iodine by cropping and by leaching, especially if the water is alkaline, and water draining these areas may bc extremely low in iodine. These considerations suggest that hullran populations subsisting on land that has been depleted of iodine or that has a thin new topsoil produced by recent glaciation may be forced to accept the consequences of a low iodine intake unless iodine is othcrwisc provided. This is the current state of affairs for large populations in Latin ‘4merica. The safety, practicability, and effectiveness of salt iodization as a means of supplementing dietary iodine for prevention of endemic goiter have been well recognized since the classic csperiments of Marine and Kimball in Akron. Ohio, in 1917 (3). Since that time, highly successful programs for iodization of salt have been implcmcntcd in Switzerland, the United States, Guatemala, and elsewhere. Wherever these programs have been carried out, there has been a spectacular reduction in the incidence of goiter and the incidence of defects that accompany severe endemic goiter, such as endemic cretinism and endemic deafmutism. If goiter is endemic in a population, an estimate is necdcd of the amount of iodine available to the population. This may be made by direct measurement of the iodine content of food and water or assay of the mean daily urinary excretion of iodine by members of the population group. or indirectly by a survey for the prevalence of endemic goiter. The last method is based on the assumption of a correlation between available iodine and severity of the goiter endemic. Many investigations have established this association in Latin America, and some of the measurements appear in Table 1. Most values from endemic regions show only a few micrograms of iodine per liter in the drinking water and less than 50 hcg per day in the urine, Since the mean daily iodine in the urine of adults where endemic goiter does not exist is generally in excess of 80 pg/24 hr and the iodine content of drinking water is 10 !Lg or more per liter, one can readily appreciate the severe deficiency of iodine in many regions of Latin America. PROPHYLACTIC
LEGISLATION
IN
LATIK
AMERICA
For a number of years the Pan American Health Organization (PAHO) has been concerned with the health hazard of endemic goiter in Central and South
IODISE
AND
THYROID
TAALK
:3Fj5
DISEASE
1
Ref. 11”. I\lexiw ‘I’epet.lisps ( 196% J ‘I’epet,lixps i 196X i .-irpent,ina Chiquillihllin .Ilisiones hlendoza I1 9il’l Ruenos Aires Bllenos Aires Chile Santiago 1 )ept . .\laipo l>epl. Pedregoso, No Goiter 1 Mutie goiter Nodlllar goit.el Brazil Sao Pa1110 Slatr SIatco c:row, Federal 1 )iafric-1
++ +
4, .i 1
2-i 1 O--L’ .6 2. o-3. I (3)
++ ++ +++ 0 0
+
14
x.5-11
.i
O-X.6
f24)
0.4-“.!I
(14,
!I II 10
10 IO
+ ++ + 0 0
1 .7 + 0. 13 (3Sll
0.3-l.
12 12 12 12
0
+++ 0
0
1.0 0.85 6 .i
0
4.0-liX.!l
++++ ++++
l.6-6.!)
++
++
I1 17 17
I:( 1:; 1:; (111 ilO
14 14
o.:i-1,s
15
0.2
16
2 ‘J-4. :;
16 16
America. In order to define the existing situation regarding the prevention of goiter by salt iodization, the Organization conducted a survey by mail questionnaire to obtain information regarding the existence of legislation, the geographical area covered, the type of iodine compound recommended, and the levels of iodine concentration recommended for the final product. Table 2 presents an analysis of the information gathered. Of the 26 governments surveyed, 17 had defined problems of endemic goiter, at least in certain areas. All of the affected countries have now enacted legislation requiring iodization of salt for goiter prevention, generally within the past 15 years. The regulations on iodization vary widely. In four countrirs the legislation refers
356
THE
STANBURY
STATE
Countries with public health problem Argent.ina Bolivia Brazil Chile Colombia Cotta Rica Ecuador El Salvador Guatemala0 Honduras Mexico Nicaragua Panama Paraguay Peru Uruguay Venezuela
OF GOITER
Year of legislation
PREVENTION
Coverage”
1967 1968 1956 1966 19.5.5 + 1960 1941
G T ? 1 1 H
1961 19.54 1960 196:;
7 r. 1 H r.I
195.5 + 1966 19.58 1940 + 1961 1963 1966 + 1968
H H c; G r.1
1 .i+ L’ -
‘1‘ s H4 G ::
ASD
KEVANY
TABLE 2 PROGRAMS IN LATIN JUNE, 1968
Iodine rompoundb
AMERICA
Responsible in&itilt iond
Concentrat,ion” 30
A+1 .4
20
A4
50
A
10 I5 100 -
I I .4 .4 A .4
1 .i 1-i 1.5 .iO
>30
2.k.iO <%
-
I
- .i - 9
Source of equipmenl and supplies”
HS HS HS HS IN HS -
I’ I G + I’ P G
HS FIS HS HS -
c; + I’ I’
HS r1s HS NS HS A 1:; I :3
AND THE CARI~HEAN,
HS 14 IN 1
Level of program activity!
I G P P
F I P I F P P F F P F P P I’ P F I
I’ 8 c4 I 2
F6 I 3 P8
P
a ‘I’, Total coverage, i.e., all salt, produced and imported is iodized; H, o111y salt, for human consumption is iodized; G, only salt in areas of endemic goiter is iodized. * I, Potassium iodide; .4, potassium iodate. c Thousands of parts of salt to one part of iodine. Figures given represent nini~~?r~ levels established by law. d HS, Health service; lN, Instit,ut,e of Nutrition. e G, Government,; I, international assistance; P, private sector. i F, Fully active; I, being implemented: P, problems encountered. g Problem now reduced below I()(,‘$ level.
only to salt destined for human consumption, leaving that for animals and industrial use uniodized. In eight, total available salt for all purposes must be iodized, an d in three countries, only that salt destined for use in the areas of endemic goiter is covered by law. In 13 countries potassium iodate is the additive prescribed, whereas in the others potassium iodide is used; in one country the choice is left to the individual state government. The concentration of iodine varies from 1 in 100,000 to as high as 1 in 10,000. The figures generally refer to the concentration at the time of processing. It is well known that the iodine level available to the consumer may not be the same as that at the time of processing because of losses due to sublimation. Iodate is considerably more stable than iodide and is the preferred form of the supplement although it is slightly more expensive. In situations where iodide has been used, analysis of commercial salt at the con-
IODIXE
AND
THYROID
357
DISEASE
sumer level has shown substantial losses or even virtual absence due to sublimation. This fact has accounted for the failure of some prophylactic programs. The authority responsible for implementation of the programs of salt iodization has been the national health service in all but one of the Latin American countries. In some countries the manufacturer has been required to purchase the equipment and supplies for iodization, while in others the government has provided these resources. In some instances the costs are shared by the government and the manufacturer. While it is gratifying that 17 of the 26 countries in Latin America have enacted legislation requiring salt iodization, in many instances the legislation has not been effectively implemented. There are many reasons for this, both social and technical. In several countries where entirely adequate legislation has been enacted, the only iodized salt available for consumption is imported as a luxury item. There has been resistance to the program on the part of manufacturers who find iodization inconvenient or economically disadvantageous. Elsewhere action has been delayed due to concern lest the distribution of iodized salt cause a rise in the incidence of toxic goiter (Jod-Basedow). In other instances health authorities do not give goiter a high priority for action since the condition is not generally rcported and thus does not appear in official morbidity and mortality statistics. Prophylactic programs have not been instituted in many remote and iuaccessiblr regions because of a genuine difficulty in the distribution of iodized salt or because-\ supplementation of salt with iodide is not practical. This is illustrated in Fig. 2. In this cottage industry on the w&em slope of the Andes, salt is prepared by digging topsoil from the bed of an ancient lake. This is transported a few hundred yards by mule to the hoppers shown in the photograph. Water is then poured through the soil to leach out the salt. The filtrate collects in pans beneath the hopper and is dried over an open fire. The reddish brown, bitter-tasting product is distributed throughout the countryside as salt, Clearly. iodization is scarcely possibk under such circumstances, and economic development will be required before salt distribution through large suppliers will occur. To the east of the Andes, there arc salt flats where salt of sufficiently high purity for human cons~~mption can simply be scraped from the surface. SOCIAL
AND POLITICAL
ASPECTS
OF ENDEMIC
GOITER
Economic development, quite apart from enabling widespread USCof iodized salt, may reduce the incidence of goiter and increase the availability of iodine by introducing exogenous foods and by improving the mobility of the population. This has been well illustrated by the studies of Maisterrena et ab. (4) in a town of rural Mexico. Construction of a major highway through a village with a high incidence of goiter seemingly resulted in a gradual but substantial fall in goiter over the succeeding several years (Fig. 3). This was coupled with a rise in the mean daily excretion of iodine in the population. The correlation of goiter with economic status in a community is doubtless related to the availability of cxogenous food and to travel by the economically privileged. The economic and political impact of endemic goiter on a population must be considered if one is to put the importance of the diseasein perspective. So far, it
358
FIG.
STANBURY
2.
Production
of salt in a rural
.-\ndenn
AND
KEVAR’Y
community.
The
crude
nkwxl
is surface-mind
hy, bro&t hy mule, and deposited in the hopper. The salt is leached by pouring mater throtlgh and collecting the liquid in a pan. This liquid is then evaporated to dryness over an open fire and the crllde salt is tlistrihlltrd locally. close
has been impossible to untangle the complex interactions between endemic goiter and such associated findings as short stature, deafmutism, mental retardation, physical apatl 1\;, and economic unproductivity. All of these customarily occur together to a greater or lesser degree, but other factors such as protein deficiency, caloric deficiency, a high prevalence of infectious discasc, and hostile climatic conditions complicate interpretations. Generally, the cretinism and deafmutism associated with endemic goiter occur to a greater extent in isolated rural areas. The affected populations have a low level of social development and limited sociopolitical importance in comparison to the more highly organized and vocal groups of urban communities. As a consequence, there is little social pressure on governmental agencies to resolve the problem; it is not surprising that implementation of legislation for salt iodization has not received the desirable priority.
IODINE
AND
THYROID
MEAN MEDIAN
B’
1962
63
64
65
359
DISEASE
1
l
66
67
100
68
Evidently the problems associated with the wide distribution of iodized salt are insurmountable at the present time in some countries. Therefore, alternative methods for prcvi-ntion of endemic goiter and cretinism have been sought to offer interim protection for affected populations until such time as their salt SUPplicas arc iodized. These methods could also provide permanent protection for isolatc,d communities having little contact with normal commercial channels for salt distribution, An acceptable altc?rnatise method must meet specific criteria. It must be effective, safe, and cheap. It must be easily applied through local health scrviccs or extension agencies. It must not require frequent doses or close clinical supervision, and it must be acceptable to the recipient population. Thcsc criteria were substantially met by a group of Australian investigators in a prc’\Tc,nti\,c program in New Guinea that began in 1957 ( 18. 19. 20). Iodized poppyseed oil was injected into a large number of subjects. The effectiveness of the program has since been studied by several investigators. There appeared to be an effective correction of iodine deficiency for as long as 4 years after the initial administration and a sharp reduction in the rate of visible goiters. A similar and highly effective program has been carried out by Melange et al. (21) on the island of Idwji in the Republic of the Congo. They gave an injection of iodized oil, in doses ranging from SO to 1000 mg of iodine, to 90% of the 1379 inhabitants of two villages. The prevalence of goiter fell from 49 to 16.3% in the injected group. Marked improvement occurred in 80% of those injected, and no secondary reactions were observed. Similar programs have now been carried out in rural Ecuador and Peru, and preliminary results have hecn reported (13, 23). As in the Nc~l Guinea and Idwji Island studies, these results have shown a gratifying drop in the incidence of goiter among injected persons as compared to control popalations, either neighboring or interspersed. There have been virtually no unwanted side reactions. In the Ecuadorian study, among approximately 900 injected subjects 3 older ~omcn with large nodular goiters developed thyrotoxicosis, which \vas
360
STANBURY
ASD
KFXANY
readily controlled by routine medical management. Results to date indicate a complete absence of cretinism in the protected group and the appearance of seven newborns with severe developmental retardation in the control population. Administration of iodized oil to growing children seemed to cause no acceleration of statural growth or bony development, but there was indication of enhanced intellectual performance in the injected group. On the basis of results obtained from the studies in Ecuador, Peru, and other regions, PAHO has made recommendations for the prophylactic use of iodized oil in regions where it is not technically or economically feasible to prevent endemic goiter by salt iodization programs. FeasibiZity. Currently available knowledge indicates that intramuscularly injected iodized oil is a useful means of combatting endemic goiter and cretinism in areas where salt iodization is not employed. The method is cheap. long acting, relatively free from side effects, and can easily be applied through local health services with existing facilities. Con&ions of use. In areas where public health problems of endemic goiter and endemic cretinism exist and are known to be due to dietary iodine deficiency and where there is no program of salt iodization or iodine supplementation in any other form. Under these conditions the use of iodized oil is recommended until an effective salt iodization program has been established. In the cast of isolated communities beyond the reach of normal commercial channels, the use of iodized oil may be recommended indefinitely. Iodized oil should be administered by the local health service under medical supervision. Recipients. The entire population of the goitrous areas, from 0 to 45 years of age, of both sexes, with no exclusions even for persons with nodular goiters. Dosage scheclubes. The ethyl ester of the fatty acid of poppyseed oil, containing 475 mg of iodine per milliliter (37% by weight), has been used in the basic studies. The recommended dosages are given in Table 3. Administration. Intramuscular, in the &teal region in small children and the deltoid region in adults. Drawback should be practiced to ensure that oil is not injected intravenously. The skin at the injection site should be cleaned carefully to avoid the formation of abscesses. Merthiolatc or a similar colored antibacterial agent is useful because it acts as a marker and reduces the risk of a double injection in a mass treatment. Extra care should be taken in sterilizing equipment, especially at high altitudes. Disposable syringes and needles are preferred.
Iodine, mg
Age O-6 mo. 6-12 mtr. 6 mo.4 yr. 6 yr.-45 yr. * For all persons with dosage should be reduced
Quantity
95 142 a z?a. .i 47.5.0 nodular goiters to 0.2 ml.
(including
single
(375
I),
ml 0. a 0.3 0. .i
1.0 t,hyroid
nodules
wit.hout
goiter),
the
IODIh-E
AND
THYROID
DISEASE
361
Surveillance. If possible, a medical follow-up of all persons injected should be made 3-6 months later to determine if any cases of thyrotoxicosis have occurred. This medical examination should be a simple screening procedure testing for pulse and respiratory rate, tremor, edema, weight loss, and exophthalmos. If this screening cannot be carried out by a physician, a public health nurse or specially instructed auxiliary can perform it. Any cases of suspected thyrotoxicosis should be removed to hospital, if possible, and a definitive diagnosis made and treatment instituted. If hospitalization is impossible, ambulatory treatment should be prescribed, but only after diagnosis is established. Repeat dosage. A minimum of 2 years is recommended between the original and the repeat dose. Specific dosage schedules for repeat injections will depend on the residual iodine levels in blood and urine and on the anatomical and metabolic thyroid response of the population. The possible occurrence of undesirable side effects such as thyrotoxicosis is acknowledged. The low incidence of such side effects, and the feasibility of effective therapeutic control, makes them a minor limitation. Furthermore, the recommended dose for subjects with nodular goiter is reduced tenfold below that administered in the pilot studies. When compared with the continued risk of cretinism and associated neurological defects in a given population, the significance of side effects appears to be minor. A prophylaxis program of iodized oil should be considered only as a temporary measure where a regional or federally controlled program of salt iodization cannot be effectively mounted. Iodized oil programs are only recommended on a permanent basis where a fully implemented salt iodization program cannot reach remote and isolated communities for economic or geographic reasons. In those instances where the distribution and administration of iodized oil is used for prevention of goiter and its allied disorders, existing public health machinery can be effectively employed. SUhlM4RY
Endemic goiter continues to be a major health problem of Latin America despite legislation in most countries requiring the iodization of salt for human consumption. In many instances this legislation has not been fully implemented or has been entirely neglected. As a result, endemic goiter and its consequences, endemic cretinism and deafmutism and possibly other related disadvantageous states, continue in many communities of Central and South America. Salt iodization programs have not been fully implemented for a variety of reasons, including failure to appreciate the economic and social disadvantages of goiter, apathy on the part of officials charged with the responsibility, the slight economic disadvantage of adding iodide or iodate to salt prepared for human consumption, and the real difficulties of introducing iodized salt into areas that are remote and severely deprived economically. When prophylactic programs employing iodized salt are not possible, for whatever reasons, the population group may be injected with iodized poppyseed oil
362
STANBURY
AKD
EEVASY
as an alternative preventive measure. Programs employing this method have proved to be effective, economically sound, and acceptably free of medical risk. REFERENCES 1. KELLY. F. C., AND SXEDDEN, W. W. (1966). Prevalence and geographical distribution of endemic goitre. In “Endemic Goitre,” p. 27. World Health Organization, Geneva. 2. “Geochemistry of Iodine.” Chilean Iodine Educational Bureau, London, 1956. 3. MARINE, D., AND KI~~BALL, 0. P. (1920). P revention of simple goiter in man. Arch. Intern. Med. 25, 661. 4. MAISTERRENA, J. A., TOVAH, E., AND CHAVEZ, A. ( 1969). Endemic goiter in Mexico and its changing pattern in a rural community. In “Endemic Goiter,” (J. B. Stanbury, ed.), p. 397. World Health Organization, Washington, D. C. 5. MAISTERREXA, J. A., TOVAR, E., CANCINO, A., AND SERRANO, 0. ( 1964). Nutrition and endemic goiter in Mexico. J. Clin. Endocrinol. Metab. 24, 166. 6. DEGROSSI, 0. J., WATANABE, T., ALTSCHULER, N., PECORINI, V., AND SANTILLAN, C. ( 1969). Characteristics of endemic goiter in a Mapuche Indian tribe in Chiquillihuin, El Malleo, Province of Neuquen, Argentine Republic. II. Iodine kinetic studies. In “Endemic Goiter” (J. B. Stanbury, ed.), p. 159. World Health Organization, Washington, D. C. 7. SOTO, R. J., CODEVILLA, A. H., WEINSTEIN, M., ROZADOS, I., RABINOVICH, L., AND GOLDBEHC., D. ( 196S). Adaptive mechanisms to iodine deficiency in endemic goiter in Misiones, Argentina. Metabolism 17, 326. 8. STANBURY, J. B., BROWNELL. G. L., Rmcs, D. S., PERINETTI, H., ITOIZ, J., AYD DEL CasTILLO, E. B. ( 1954 ). “Endemic Goiter.” Harvard University Press, Cambridge, Mass. 9. PAK. N., ZANZI, I., AND DONOSO, G. ( 1962 ). Contenido de yodo y dureza en agua de bebida y su relation con el bocio endemico. Nutr. Bromato!. Toricol. 1, 135. 10. BECKERS. C., BARZELATTO, J., SrEvENsoii, C., GIAXETTI, A., PARDO, A., BOBADILL.~, E., AND DE VISYCHER, M. ( 1967 ). Endemic goitre in Pedregoso (Chile ). II. Dynamic studies on iodine metabolism. Actu Endocrinol. 54, 591. 11. CARDOSO, F. A., GANDFLA, Y. R., AND NAZARIO, G. da relacao ( 1957). D a inconsistencia entre o grau de dureza e o teor de iodo em aguas de abastecimento puhlico. Arq. FUC. Hig. Suude Publica Univ. Sao Parr/o 2, 1. Algunos estudios recientes sobre el bocio endemico. Acta Cient. 12. GAEDE, K. (1963). Vene.2. Suppl. 1, 58. 13. FIERRO-BENITEZ, R., RAMIREZ, I., ESTRELLA, E., JARAAIILLO, C., DIAZ, C., AND URRESTA, J. ( 1969 ). Iodized oil in the prevention of endemic goiter and associated defects in the Andean region of Ecuador. I. Program design. effects on goiter prevalence, thyroid function, and iodine excretion. In “Endemic Goiter” (J. B. Stanbury, ed.), p. 306. World Health Organization, Washington, D. C. 14. CERVINO, J. M., MAGGIOLO, J., DE BAYLZ~, E. J., ASD AVELLAXAL, R. (1964). Endemia bociosa en el Uruguay. Ann. Fat. Med. Mowteaideo 49. 591. 15. ALTSCHULER, N., DEGROSSI, 0. J., CERIA~YI, R., FOIXHEH, H., MAyon, \‘., AND EXRIORI, C. L. (1969). Endemic goiter in the Republic of Paraguay. In “Endemic Goiter” (J. B. Stanbury, ed.), p. 168. World Health Organization, Washington, D. C. E. ( 1969). Thyroid function in adolescents from the 16. WAHNEH, H. W., AND GAITAS, goiter endemic of the Cauca Valley, Colombia, South America. In “Endemic Goiter” (J. B. Stanbury, ed. ), p. 291. World Health Organization. Washington, D. C. 17. ROSENTHAL, D., LOBO, L. C. G., REBELLO, M. A., AND FRIDMAK, J. (1969). Studies on endemic goiter and cretinism in Brazil. 3. Thyroid function studies. In “Endemic Goiter” (J. B. Stanbury, ed.), p. 217. World Health Organization, Washington, D. C. 18. CLARKE, K. H., MCCULLAGH. S. F., AND WIXIKOFF, D. (1960). The use of an intramuscular depot of iodized oil as a long-lasting source of iodine. Med. J. Aust. 1, 89. IQ. HENNESSEY, W. B. (1964). Go&e prophylaxis in New Guinea with intramuscular injections of iodized oil. Med. J. A&. 1, 505.
IODINE
THYROID
DISEASE
363
H., AND HEIZEL, B. S. (1969). E n d emit goiter in New Guinea and the prophylactic program with iodinated poppyseed oil. In “Endemic Goiter” (J. B. Stanbury, ed. ), p. 132. Woild Health Organization, Washington, D. C. 21. MELANGE, F., THILLY, C., POURBAIX, P., AND ERMANS, A. M. ( 1969). Treatment of Idjwi Island endemic goiter by iodized oil. In “Endemic Goiter” (J. B. Stanbury, ed.), p. 118. World Health Organization, Washington, D. C. 22. PHETELL, E. A., MONCLOA, F.. SALINAS,R., GUERRA-GARCIA, R., KAWANO,A., GUTIERREZ, L., PRETELL, J., ANDWAN, M., ( 1969). Endemic goiter in rural Peru: Effect of iodized oil on prevalence and size of goiter and on thyroid iodine metabolism in known endemic goitrous populations. In “Endemic Goiter” i J. B. Stanbury, ed.), p. 419. \1’orld Health Organization, Washington, D. C. 20.
RUTTFIELD, I.
Ah-D