profilaxis y tratamiento de bocio ,peru-ecuador

8/14/2019 Profilaxis y tratamiento de Bocio ,Peru-Ecuador

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1597

THE AM ER ICAN JO URN AL O F CL IN IC AL NU TR IT IO Nvol . 22 , No. 1 2 , D ecem ber, 19 69, p p. 1 59 7-1 60 7

Pr in te d in U. S. A.

Prophy lax is and T reatm en t o f E nd em icG oiter w ith Iod ized Oil inR u ra l E cuador and P eru 1

JOHN KEVANY , 2 M.D. , R0D RIG0 FIERRO -B EN ITEZ ,3 M.D. , EDUARDO A . PR ETELL ,4 M .D .,AND JOHN B . STA NBURY ,5 M .D .

AuTH FEW EXCEPTIO NS endemic goiter con tinues as a m a jo r hea lth p rob lemin those areas o f the w orld w here th edisease has b een know n fo r gene ratio ns.Subs tan tia l und erstand ing o f its p atho -genes is, sim ple an d effec tiv e preven tivem easu re s, an d a ris ing w o rld econ om yhave d one little to reduce its p reva lenceon a w orldw ide sca le . Th is sta te o f a ffa irsis due princ ipa lly to the low p rio r ity ac -co rd ed to the d isease by health au tho ritie sand to the ub iqu ito us co nflicts o f in te re stb etw een the pub lic and p riv ate sec to rs .

O ne of th e m o st ex tensiv e an d sev erefo cu ses o f end em ic g o ite r occu rs in L a tinAm erica . T he d is ea se is w id esp readth roug hou t C en tra l and Sou th Am ericabu t i s c on ce nt ra te d in the m oun tain rang esex tend in g a long the P ac ific coast fromM exico to C h ile. A s an estim ate , ove r 10m illion peop le m ay be affec ted by th iscond it ion . Precise figures cannot be ob-tain ed becau se m o rb id ity sta tis tic s a re in -

1 Supported in pa rt b y U . S . Pub lic H ea lth S erv iceG rants AM 12748 and AM 10992 , T he N ationa lA ssoc iation for R e tard ed C hild ren , Th e Pan Am eri-can H ealth O rgan iza tion , Fondo N ac iona l de Saludy B ien es tar Soc ial and Serv ic io E spec ial de SaludP #{ 25 2} bl ic a o f P eru .

2 Pan A m erican H ea lth O rgan iza tion , W ash ing ton ,D . C . D epartam en to d e R ad io is#{243} topos , E scue laPo lit# {2 33 }cnic a N aciona l, Q uito , E cuad or. D epar ta-m ento de Endo crin o lo g ia , In sti tu to (IC Invest iga-cio ne s de Ia A ltu ra , L im a, Peru . U nit o f E xp eri-mental M edic ine , D epa rtm ent of N u tri tion andFood Sc ien ce, M assach usetts In stitu te of T ech nology ,C am brid ge , M assachu se tts.

com ple te o r u nava ilab le and becau se su r-v eys have been lim ited in geograph ic scopeor to sp ec ia l age g roup s (1 , 2 ) .

If en dem ic g o ite r im p lied o n ly an en-largem en t o f th e thy ro id , it co u ld b e d is-m issed as a triv ia l a fflic tio n . In fac t, severeendem ic go ite r is accom pan ied by a sub-stan tia l in ciden ce of c re tin ism and d eaf-m utism . Furthe rm ore , the re is goo d rea -son fo r su spec ting tha t, in m any cases, tilem en ta l reta rda tion (ap a rt from ove rt c re-tin ism ), neu rom u scu la r d istu rbance , an dsho rt s ta tu re tha t usua lly accom pany se-vere en d em ic goiter m ay in fa ct be causallyre la ted . In add itio n , it ha s been su ggestedtha t th e d isease m ay have an un favorab leeffec t on g en e ra l h ealth and edu ca tion alcapaci ty .

In v iew of the m agn itud e and seve rityo f the p ro b lem , th e P an Am erican H ealthO rgan izatio n (PAHO ) h as m a in ta ined anactiv e p ro gram of techn ica l as sis tance inth is fie ld d urin g th e p as t 2 d ecades . O f the26 m em ber g ove rnm en ts , 1 7 h av e a de fin edp rob lem o f endem ic go ite r , and end em icc retin ism is kn ow n to ex ist in seve ra l o fthese afflicted areas. Fifteen of the 17 co u n -tries h av e enac ted leg is la tion requ iring th eio d iza tion of sa lt, and the rem ain ing 2have leg isla tio n und er cons id eration . D e-sp ite th is ex press ion of o f fic ia l co ncern ,e ffec tive p rogram s h av e been es tab lishedin less th an ha lf o f the coun tr ies a ffec ted ,an d m any of the m ost se riou s a reas o f en-d em ia a re still w itho u t an y prev en tive


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up to 2 years 01(1:2-6 years old:6-12 SearS old:12 years old and up:

0.2 m l o f iod iz ed o il0.5 m l of iodized oil1.0 m l o f i od i z e d o i l2.0 m l of iodized oil

1598 K e v a n y et al.

illeasures. In view of this, the PA H O de-C i(IC d to look for alternate m ethods of pre.vention of endem ic goiter and cretinism .T his decision in no w ay conflicted w ith thePriority given to salt iodization but rather1VS directed to finding an interim solu-tiO ll. The PA H O also recognized that som eof the m ost severely affected populationsare so isolated from norm al com m ercialcilallnels that the people w ill continue touse prim itive sources of uniodized salte v e n if salt iodization is im plem ented on anational scale.

A m ong various alternative m ethods fors u p p l y i n g d i e t a r y i o d i n e , o n e h a s b e e nprovision of parenteral iodine to establishl o n g - t e r m b o d y s t o r e s . A n u mb e r o f y e a r sago a program of goiter prevention by t h einjection of iodized oil w as begun in N ewG uinea. Inform ation available from thosesurveys ( 3 - 5 ) indicated that prophylacticprogram s w ere effective in r e d u c i n g t h eprevalence of goiter and that tile proced-ure w as practical and safe. The resultsobtained in N ew G uinea, how ever, havenot provided enough inform ation regard-ing the effectiveness of this form of pro-piiylaxis in reducing incidence and havegiven virtually no inform ation regardingprevention of those disabilities that areepidem iologically associated w ith severeendem ic goiter. W ith these considerationsin view , field studies w ere begun in 1966 todeterm ine the feasibility and effectivenessof parenteral adm inistration of iodized oiliii p r even tion and treatm ent of endem icgoiter and the defects that m ay accom panyit.

Tw o neighboring countries of SouthA m erica, Ecuador and Peru, w ere se-lected for study since both presentedareas w ith high prevalence of goiter andcretinism , and no preventive program sw ere being undertaken.

T H E PR O G R A M IN EC U A D O R#{149}w o villages, Tocachi and La Espe-ranza, w ere selected because of their re-

m oteness and because, in both, endem icgoiter is severe and cretinism is com m on-place. They are about 70 km north of Q uito,6 m iles apart, and ethnically, socially, andbiologically com parable (6). The villagershave unusually lim ited social m obility andcontact w ith tile outside w orld, charac-t e r i s t i c s s h a r e d wi t h h u n d r e d s o f o t h e r si n t h e S o u t h Ame r i c a n An d e a n region.

he sociocconom ic situation is precariousin both villages (T able i). Th e r e i s a h i g hinfant m o rtality rate, a high incidence ofillegitim acy, a low level of literacy, and agreat p o v e r t y reflected by the low per capitai n c o me a n d s ma l l p e r c e n t a g e o f a r t i s a n s .C hronic iodine deficiency is severe in bothv i l l a g e s , a n d p r e v a l e n c e of goiter a n d a s s o c i -a t e d defects is high (Table ii). S a l t u s e d b ythe villagers contains 0 . 24 g / g i od i ne .

I o d i n e wa s g i v e n t o the Tocachi pop-ulat 1011 , w hile La Espcranza s e r v e d a s ac o n t r o l v i l l a g e . T h e p r o g r a m wa s s t a r t e di n Ma r c h 1 9 6 6 . The iodized oil w as E thio-(101 (37% iodized poppy seed oil, eachm illiliter containing 475 m g of iodine, ob-tained from E. Fougera, Inc., H icksville,L. I . , Ne w Yo r k ) . Di s p o s a b l e p l a s t i c s y -rillge s w ere used to avoid problem s ofs t e r i l i z a t i on a t h i gh a l t i t ud e s . Th e f o l l o w-i n g d o s a g e s c h e d u l e wa s u s e d :

The o i l wa s adm inistered intram u scu-larly into the gluteal region of sm all chil-dren and into tile deltoid region of adults.Dr a wb a c k wa s p r a c t i c e d to ensure that oilw as not injected intravenously. M erthiolatewas used for skin sterilization.

Th y r o i d s i z e wa s e v a l u a t e d b y a mo d i -fication o f t i l e c l a s s i f i c a t i o n of Perez et aL( 7 ) .

G rade O a:n ot p alp ab le

G rade O b:palpable, but not visible w ith the headraised


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less than 1 year old:from 1 to 5 years old:O V C 1 6 y ears o l d :

0.5 m l1.0 m l2.0 m l

1600 K evany et al.

Tarm a, a nearby tow n equipped w ithlaboratory and hospital facilities, servedas headquarters for the field w ork. M oredetailed laboratory w ork w as carried outin Lim a, about 5 hr aw ay by autom obile.

Iodized oil or a placebo w as injectedi n t o 1 , 77 1 s u b j e c t s . Th e p l a c e b o wa s p o p p yseed oil w ithout iodine. N ine hundredand tw enty-three subjects in the threevillages w ere injected w ith iodized oil(G rI) and 848 w ith the placebo (G rP). In-jections w ere done in fem ales up to 45years of age and in m en up to 1 8 . Am ongthe schoolchildren, groupings for the pla-cebo and the iodized oil w ere predeter-m ined at random w ithin a given age. C arew as taken to m atch the size of goiter. Inother groups random ization w as accom -plished by consecutive alternation of io-(line and placebo injection. The dosesused w ere the follow ing:

In adult w om en w ith nodular goiter thec l o s e wa s r e d u c e d t o 0 . 2 m l. A ll injectionsw ere perform ed in the 1st w eek of O ctober1966.

Surveys w ere also m ade for bone andn e u r o l o g i c a l ma t u r a t i o n . Re e v a l u a t i o n o fthe prevalence of goiter w as m ade at 6,12, and 18 m onths after injection. A t thetim e of reevaluation, the exam iners w ereignorant of both the prior estim ated glandsize and the type of injection. C linical as-sessm ent w as m ade by m em bers of the sam eteam throughout the program .

Particular attention has been paid tothe fem ales in the child-bearing age (16-45years old). A s m any pregnancies as possi-ble occurring in both the G rP and G rIgroups w ere follow ed throughout gesta-tion. N ew borns w ere recorded for the pur-pose of future evaluation. In addition,serum levels of thyroid horm one w ere in-v e s t i g a t e c l i n p r e g n a n t wo me n , a s we l l a siodine content in m ilk from lactatingw omen.

G oiter P reva len ceR E S U L T S

A dm inistration of iodized oil in Tocachicaused a regular and consistent fall in theprevalence of goiter for 20 m onths, bothin the total population and in m en andw o m e n taken separately. The ratio ofgoiter in w om en to that in m en increasedw hile the prevalence of goiter in the totalpopulation decreased (Fig. 1). A fter the20th llT lOIlth the prevalence began to riseagain.

A t the tim e of the survey 6 m onths afteriodization, nodular goiter had increasednoticeably w hile diffuse goiter had de-creased, but in tile follow ing surveys (upt o the 2 0 t h mo n t h ) n o d u l a r i t y a l s o stead-ily decreased. T he Ethiodol produced adistinct decrease of t h e i n c i d e n c e o f g r ad eII goiters and larger, and th is d ecreasecontinued into the survey conducted 25m onths after iodization. A lthough t h e d e -crease ill size of large goiters w as achieveda t the e x p e n s e o f a n i n c r e a s e i n t h e mc i -dence of gr a d e I goiters, after the surveyat 12 m ontlls grade I goiters also tended todim inisll. T his trend persisted after 20m onths. Af t e r t h e 2 0 t h - mo n t h s u r v e y , h o w-ever, this type of goiter (but not those oflarger size) tended to increase in the totalp o p u l at i o n . l t s e e ms c e r t a i n t h a t t h e s h a r pincrease of nodular goiter found 6 m o nthsafter iodization w as a result of involutionof hyperplastic thyroid tissue.

Th e d e g r e e o f r e d u c t i o n i n g o i t e r d i -illinished as age increased. Tile m axim umr e d u c t i o n wa s s e e n during tile first 1 8y e a r s o f l i f e . Th e r e w as mi n i ma l r e d u c t i ona f t e r 40 years of age. R eduction at 25mo n t h s a f t e r i o d i z a t i o n wa s 3 6 % f o r t h etotal population. There w as not a singleinstance of palpable thyroid in childrenb o r n i n To c a c h i t o i od i z e d mo t l l e r s . Ei gh t -e e n p e r c e n t o f t h e c h i l d r e n o f La Es p e -ranza up to 2 years of age w ho w ere exam -ined at t h e t i me o f t h e 2 5 t h - mo n t h s u r v e yp r e s e n t e d p a l p a b l e g l a n d s . As t o overallgoiter prevalence in La Esperanza, the re-


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SI

TOTAL P OP ULATION # {1 4 9 }

814 WOMEN o--cME N

70

60 .

:11 #{149}________#{149}

..#{149}.#{149}.#{149}.#{149}#{149}{149}#{149}#{149}{149}

40

30

20

10

0

0

MONTHS

5 10 15 20 25

T I ME IN MONTHS

(;oiter in Ecuador and Peru 1601

=000I-LiiI.-00U -0Li0zLii00z

FIG. 1. Effect of adm inistration of iodized poppy seed oil (Ethiodol) on the incidence of goiter in avillage of rural E cuador. Insert show s the ratio of goiter in w om en and m en.

su its in dicated that tllere w as a significantincrease during the sam e period.

The f i nd i ngs i n t i l e t h r e e Pe r uv i a n v i l -l a ge s w ere sim ilar. Fifty percent of thepopulation w ere affected wi t h goiter dur-ing the first 5 years of life. This w as pri-niarily of the Ob de g r ee ; t he r ea f t er , mo r ethan 90% w ere go i t r ous . Si z e o f go i t e r a ndnodu l a r i t y i n c r e a s e d wi t h a ge . The p r e v -alence of endem ic cretinism and otherdefects varied from 1.0% to 3.6% in thethree villages.

Goi t e r pr e v a l en c e i n t he i od i z e d g r oupin Peru decreased steadily for 18 m onthsafter tile injection program (Fig. 2). As t r i k i ng f a l l f r om 5 8 t o 1 6% i n v i s i b l egoiter as w ell as from 86 to 52% in palpablegoiter occurred in tile iodized group, w hilet h e p l a c e bo g r oup c ha nge d on l y s l i g h t l yfrom 52 to 45% in t h e f o r me r a nd 8 1 t o78% in the latter. In both groups the de-crease w as m ore m arked in m ales than infem ales. In addition, the decline appeared

to be m ore pronounced in the 13- to 18-year- and unde r - 6- ye a r - ol d g r oups t ha n int he 6 - t o 1 2 - ye a r - o l d s ub j e c t s .

T hyro id Fu nc tion an d Iod ine M etabo lismIn tile Ecuadorian study, uptake of

I by t he t h y r o i d p r o v e d t o be de p r e s s e da t t he t i me of t he s u r v e y a t 6 m onths. Arestoration tow ard norm ality w as observedi n s uc c e s s i v e c ont r ol surveys ( Fi g. 3 ) . T heurinary excretion of iodine (U EI) (Fig. 4)follow ed an exponential pattern. Sincet h e s ub j e c t s on whom UEI de t e r mi na -t i on s we r e done we r e a du l t s who ha d r e -c e i v e d 2 m l of Ethiodol (950 mg) , e l i m n a -tion of those 9 5 0 mg woul d be v i r t u a l l yaccom plished at t h e 40th m onth after in-jectiom i. These results iniply that a doseequal to half of that used w ould reduce thet ot a l e f f ec t i v e t i me by only 5 m onths.

C hanges in thyroid function tests atdifferent stages of the Peruvian study areshow n in Fig. 5. The 24-hr t hy r oi d upt a k e


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(7

>

Ma l e

Placebo

dized O il

M onths

FIG . 2. D ecline in goiter in three Peruvian villages after the adm inistration of iodized poppy seed oil.A com parison is m ade w ith subjects injected w ith noniodized oil. In each case the ordinate isfrom 0 to100%.

3 24

90

8 0

70 -

60

50

40

30 -

20

10

3k

2 0 25

I 602

0

a-

Li.4Q- w

_j___l

S e x e s

TIM E IN M O N TH SM A R C H 1 9 6 6 - AP RI L 1 9 6 8

Fio. 3. E ffect of adm inistration of iodized oil on radioactive iodine uptake by the thyroid.


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G oiter in Ecuador and Peru 1603

Li

Liz0 w-z zIL -.4z

OB S ER VED RES ULTS (2 m l o f E T H I 0 0 0 L )EXP ECTED RES ULTS (1 m l o f E TH I0 0 0 L)

E X C R E T IO N FA C T O R = UEI t = UE I . e # { 1 7 6 } 2 6

\ \ \ \\

\ \\\

\

20 0

100908070-

60

50 -

40 -

30 -

20

106 #{149}2 8 2 4 3 0 3 6 4 2

T IM E IN MO N T H Sof iodide follow ing adm inistration of iodized

1000900800700

600

500

40 0

300

F I G . 4. Ur i na r y e x c r et i onexponentially.

\

\

\

f e l l f r om a c ont r o l l ev e l o f 7 5 . 1 0.9% to1 5. 8 1.4% at 9 mon t hs bu t increasedslightly to 19.5 0.3% and 21.9 1.1%at 13 and 19 m onths, respectively. Thisc ha nge c or r e s ponde d t o a r i se a bov e nor-ma l l e v e l s o f bo t h s e r um i od i de a nd PBI .T he s e r e a c he d ma x i mum l e v e l s by t i l e 9 t hmont h and t h e n fell to norm al by the 1 9thm onth. Serum thyroxine rem ained w ithinnorm al l i mi t s . T i l e v a l ue s f or u r i na r y ex-cretion of iodide (U EI) in relation to tile(lose of Ethiodol at tw o different age levelsa p p ea r in Table III. The 6- to 12-yearg r o u p , w hich r e c e i v e d a bout doub l e t h edos e of i od i n e pe r k i l og r am o f body we i g h t

oil. T he iodide is excreted

(41.5 m g), ilad a higher U EI at 6 m onthst ha n t h e 1 3 - y e a r - a nd - o v e r gr oups , wh i c hhad an average dos e of 2 3 . 0 mg . Howe v e r ,values in bot h g r oups c on t i nu e d t o f a l l t oe qu i v a l e n t l e v e l s t h r oughout t he l a t e rperio(Is. The U EI for the latter group fellexponentially after 6 m onths. The slopes,and therefore t i le T1 1 2 , we r e s i mi l a r f o rboth 2.0 ml a n( 1 0 . 2 m l dos e s i n t h i s g r ou p( Fi g . 5 ) .Effects in In fan ts a nd C hild ren

A total of 92 deliveries w as recordedam ong the w om en of child-bearing agein the three Peruvian villages. O f these, 58


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0 6 9 13 9Months

1604 Kevany et al.

Values are in m icrograms.

2

too- lOU -

80- 8- Eo 00D 60 2

40 4.

2O 2-

Fic . 5 . Effect of iodized o il on radioactive iodineuptake , plasma thyro x ine iodine (I-T4 ), pro te in-bound iodine (PB !), and total serum iodine (SI) .

were in the iodized group. The plasmathyroxine levels in the pregnant noniodizedgroup had a mean value of 5 .2 0 .4 /Lg/100 ml during the last 5 months o f preg-nancy , and thus failed to rise , as no rmallyo ccurs. The mean value in the iodized sub-jec ts w as 7 .9 0 .7 g / 100 ml. The contento f iodine in milk from 9 women injec tedwith 2 ml of iodized o il w as 9 .7 1. 2g /100 m l, w hereas it w as 1 .9 0.7 /100 ml in women injected w ith 0 .2 mliodized o il, and 0 .0 to 0 .5 zg /100 ml infour g iven the placebo o il.

N ine ty children w ere bo rn in Tocachifrom March 1966 to A pril 1968 (to iodizedmo thers ); 16 (1 7%) died and 2 (2%) w ent

aw ay . One hundred seventy -seven childrenw ere born in La Esperanza (to untreatedmothers) during the same period; 17(9 .6%) died and 5 (2 .7%) w ent aw ay .The children of bo th Ecuadorian villagessubs ist in a generally poor env ironment;there is high infant morbidity and mor-tality . Children o f Tocachi presented ahigher deg ree of morbidity and also show eda higher deg ree o f undernutrition.

Special emphasis has been placed on thee ffec ts o f iodized o il on grow th and de-I-Up takev elopment of infants and children. Thesestudies have been materially enhanced bythe availability of a full-time physic ian anda midw ife for the prog ram in Ecuador.Particular attention has been g iven to theperinatal period. Somatic grow th has gen-erally been sim ilar in children from To -cachi and La Esperanza. It has been low erin both v illages than in a low income in-fant group from Quito , and relative ly low erstill when compared w ith American stand-ards.

There w as a fallo ff in dev elopmentalaverag es of children around 6 months o ld.Gains in w eight and he ight lagged moremarkedly after this age . The percentag eincrease in height 12 months after deliverywas 37% in Tocachi and 40 .5% in LaEsperanza. Thus, in Tocachi there is thesame kind of handicap in height as isfound in adults. The expected normal in-crement for height is , at this age , 5 0%.The w eight and height deceleration areobvious signs o f undernutrition, possibly

TABLE IIIUrinary excretion of iodine pe r 24-hr period afte r administration of Ethiodol

A ge in yearsDose M onths after inj ection

Ethiodol,ml Iodine,mg/kg 6 9 1 3 15 19

6-1213 o r over13 o r over

2.02.00.2

41.5 1 .123.0 0.72.0

1 ,079 101859 64230 45

497 49621 47

346 29345 2976 16

274 24253 2562 6

169 15168 1648 4


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G oiter in Ecuador and Peru 1605

including iodine undernutrition, and thehigh incidence of disease.

The increase in head circum ference inboth villages and for each group w as low erthan the A m erican standard. H ow ever, itwa s i nt e r e s t i n g to note that averages inTocachi w ere slightly better than thosei n La Es p e r a n z a i n a l l a g e g r o u p s .

A l a r g e n u mb e r o f i n f a n t s a n d y o u n gc h i l d r e n we r e f o u n d i n La Es p e r a n z a w ithO b t h y r o i d s a n d 4 % h a d gr a de I d i f f u s eg o i t e r . No c a s e o f t h y r o i d e n l a r g e me n tw as found in Tocachi in the com parableage group.

Le v e l s of neurologic m aturation (G esellss t a n d a r d s ) we r e r e a c h e d i n b o t h v i l l a g e s a to l d e r ages t ha n i s c o n s i de r e d n o r ma l . Th e r ewa s p r o g r e s s i v e b e h a v i o r a l r e t a r d a t i o n i nb o t h v i l l a g e s as t e s t e d b y ma n i p u l a t i ve ,perceptual, linguistic, and gross m otort a s k s . Av e r a g e developm ental quotienti n To c a c h i wa s 9 2 . 7 7 % ( n o r ma l ) . I t wa s89% in La Esperanza (low norm al).

P ossib le Toxic E ffec tsIn the s u r v e y c o n d u c t e d 6 mo n t h s a f t e r

adm inistration of Ethiodol, there w ereabout 15 subjects in Tocachi w ho presenteda clinical picture suggesting hyperthyroid-i s m. Th e y we r e t a k e n t o Qu i t o f o r h o s -p i t a l i z a t i o n a n d exam ination. The dis-ease w as confirm ed in three w om en, allelderly and w ith large nodular goiter. Thelaboratory tests useful for their diagnosisw ere the basal m etabolic rate and the buta-n o l - e x t r a c t ab l e i o d i ne s e r um, s i nc e t h e o t he rtests w ere exactly the sam e as for otheriodized subjects w ho w ere not suspectedof having hyperthyroidism . A ll three re-sponded satisfactorily to therapy.

N either iodine thyroiditis, iodism ,n o r l o c a l r e a c t i o n s we r e o b s e r v e d . Mo s t o fthe new born w ere seen w ithin a few dayso r we e k s a f t e r delivery, and none w asfound to have goiter. Treatm ent w ith thy-roid w as begun at once w hen a diagnosisof cretinism w as m ade.

C O M M E N T S

Endem ic goiter and its accom panyingdefects are found today in their virgin formin som e of the rural com m unities of A n-dean Ecuador and Peru. Iodization ofcom m on salt has not been im plem ented inthe highland regions of these countries.The socioeconom ic conditions of the A n-dean people, basically com posed of A m er-indian and m ixed European stock, havevaried little since Spanish colonial tim es.Everything points to an endem ic of ancientdate, the prim ary causative factor of w hichh a s b e e n a d e f i c i e n c y o f iodine.

B ecause of econom ic strictures andgeographical isolation there is little ex-pectation that national program s for m an-ufacture and distribution of iodized saltw ill reach som e of these rural populationsin the near future. A ccordingly, it has beennecessary to consider alternative form s forsupplying iodine. O ne of t h e s e is by par-enteral adm inistration of iodized oil, sincet h e s e p r e p a r a t i o n s r e l e a s e t h e i r i od i d e a t as l o w rate and m ay fulfill iodide needs form any m onths after a s i ng l e i n j e c t i o n .

The results that have been obtainedconform to the reports of sim ilar fieldtrials in N ew G uinea and recently in A frica(9) and indicate that this m ethod of dis-tributing iodine is technically sim ple, freeof serious risk, and effective to a consider-able degree. Sequential surveys in the io-dized population in both the Ecuadorianand the Peruvian studies have discloseda gratifying reduction in goiter size and,com pared to control groups, a failure ofgoiter to appear. In the Peruvian groupa decline has been m ore evident in visiblegoiter than in palpable goiter at all inter-vals (72% and 40% , respectively, by the18th m onth) as a result of progressiveshrinkage of goiters of large size. M any ofthese have not com pletely disappearedand rem ain as palpable goiters of Ob de-gree. W hether they w ill com pletely dis-appear in tim e rem ains to be seen. Sim ilar


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1606 K evany et al.

results have been obtained in Ecuador,but a sm all rise w as seen in the occur-rence of goiter betw een the 19th and the25th m onth. The effectiveness of the io-dized oil treatm ent as a preventive m ethodis dem onstrated by the fact that only1.5% of new cases w ere recorded in iodizedchildren versus 7.2% in the controls.

A finding of possible significance isthat in pregnant w om en the physiologicrise of PB I during norm al pregnancyfailed to occur in the group that did notreceive prophylactic iodine. M any of thesevalues w ere in the hypothyroid range, andcorresponding plasm a thyroxine valuesw ere even low er. A lthough a geneticallyim paired t hy r o x i ne - b i nd i ng p r o t e i n sys-tem m ay have been the cause of this phe-nom enon, this possibility seem s to be ruledout by norm ally rising values in iodizedpregnant w om en. The fetal thyroid un-doubtedly shares w ith the m others glandthe low iodine supply from the diet. Thissharing results in a low er am ount of io-dine being available for the m othersgland, w hich in turn is unable to m ain-tain the required horm one levels. In anycase, it m ay be expected that the horm onecontribution of the m other to the fetusm ust be sm all, because free T4 in all sub-jects is decreased during pregnancy.W hether the fetus is capable of synthe-sizing its ow n T4 is unknow n.

It is too early to know the effectivenessof the iodization program in term s of lineargrow th, honey developm ent, psychologi-cal and neurological grow th, and learningability. D ata presently available are con-sistent w ith, and suggestive of, a dram aticeffect on the prevention of cretinism , butthe num bers involved are presently sm all.The data on honey developm ent, denti-tion, and linear grow th show little im -provem ent resulting from the single facto r change, i.e., injection of iodine. M entalperform ance seem ed im proved in onelarge, but adm ittedly prelim inary, survey

am ong young schoolchildren. It w ill re-quire at least 2 additional years of observa-tion before the im pact of the program onm any aspects of health can be appraised.M eanw hile, there seem s to be every reasonto advise an extension of the program toother com m unities w here endem ic goiteris severe and w here there is no presentpossibility of an effective program of saltiodization.

SU M M A R YEn d e mi c g o i t e r c o n t i n u e s t o b e a s i g -

nificant health problem in m any areas ofthe w orld. In som e areas the disease is sosevere that cretinism and other associateddefects are found. In m any areas, geo-graphic, econom ic, and other factors pre-vent the use of iodized salt as a preven-tive m easure.

A pilot program using iodized poppyseed oil has been instituted in tw o ruralcom m unities in Ecuador and three in Peru.R esults after approxim ately 2 years indi-cate the feasibility and effectiveness of theprogram s. There has been a sharp reduc-tion in the incidence of goiter. C retinismhas not yet appeared am ong the progenyof the population i n j e c t e d wi t h i o d i z e doil, but several instances have appeared incontrol groups. The use of iodized oil asa public health procedure for the preven-tion of endem ic goiter and its associateddefects is an acceptable m easure in regionsw here salt-iodization program s cannot bepresently undertaken.

R E F E R E N C E S1. W orld H ealth O rganization. E ndem ic G oitre.

W orld H ealth O rgan. M onograph Ser., no. 44,G eneva: W orld H ealth O rgan., 1960.

2 . S T A N B U R Y , J. B . E ndem ic G oiter. Sym p. 3rdM eeting Scientific G roup on R esearch in Endem icG oiter of PA H O , June 27-29, 1968, Puebla,M exico. W orld H ealth O rgan. In p r e s s .

3. HENNES S Y , W . B . G oitre prophylaxis in N ewG uinea w ith intram uscular injections of iodizedo i l . M ed . J. A u stra lia 1: 505, 1964.

4. BU i - FF IELD , I. H ., M . L . BLA CK , M . J. HO F FM A N N ,E. K . M A SO N A N D B. S. H E TZ EL . C orrection of


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iodine deficiency in N ew G uinea natives byio dised o il in jectio n. Lancet 2: 767, 1965.

5. B u i - r F i E LD, I. H ., A N D B . S. H ETZEL. Endem icgoitre in eastern N ew G uinea. Bull. Wor ld H ea l thO r g an . 36: 243, 1967.

6. FIER RO -BEN ITEz, K ., I. R A M IR E Z , E. E S T R E L L A , C .JA R A M IL L O , C . DIAz A N D J. U R R E S T A . Iodized oil inthe prevention of endem ic goiter and associateddefects in the A ndean region of E cuador. I. Pro-gram design, effects on goiter prevalence, thy-roid function and iodine excretion. Symp . 3r dMeetin g Sc ien tific G r ou p on Re sea r ch in E ndemicG o i ter o f PAHO, June 27-29, 1968, Puebla,M exico. W orld H ealth O rgan. In press.

7. PflR E Z, C ., N . S. SC R IM SH A W A N D J. A . M uz.Technique of endem ic goitre surveys. In: En -dem ic G oitr e . W orld H ealth O rgan. M onograph

Ser., no. 44, G eneva: W orld H ealth O rgan. 1960,p. 369.

8. P R E T E L L , E . A ., F. M O N C LO A , R . SALINA S, R .G U E R R A -G A R C IA , A . K A W A N O , L. G U T I ER R E Z , M .W A N A N D J. PR E T E L L . E ndem ic goiter in ruralPeru: E ffect of iodized oil on prevalence and sizeof goiter and on thyroid iodine m etabolism inknow n goitrous populations. Symp. 3r d MeetingScien tific G r oup on Resea r ch in Endemic Go iterof PAHO, June 27-29, 1968, Puebla, M exico.W orld H ealth O rgan. In press.

9. D E L A N G E , F., C . T H I L L Y , P. P0U R B A IX A N D A . M .E R M A N S. T reatm ent of Idjw i Island endem icgoiter by iodized oil. Symp. 3 r d Meeting Scien tificG roup on Resea r ch in Endemic Goite r o f P AHO ,June 27-29, 1968, Puebla, M exico. W orld H ealthO rgan. In press.

profilaxis y tratamiento de bocio ,peru-ecuador

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