Prevention of Iodine Deficiency
John B. Stanbury, M.D.
International Council for the Control of
Iodine Deficiency Disorders
Requirements For Iodine
The thyroid hormones, thyroxin and triiodothyronine (T4 and T3), contain four and three atoms of iodine, respectively (For a comprehensive review of this section, see Hetzel, 1989b). Triiodothyronine, formed by monodeiodination of thyroxin, is the effective hormone. Iodine must be obtained from the environment. It has no recognized role in mammalian biology other than as a component of the thyroid hormones, although there is some suspicion that iodine deficiency may be involved in fibrocystic disease of the breast. Normal development requires the thyroid hormones. They are synthesized and secreted solely by the thyroid gland and are largely circulated in the blood bound to thyroxin-binding globulin and less firmly to other circulating plasma proteins (Braverman and Utiger, 1996).
The absolute requirement for iodine is quite small (DeLange, 1994). Adult needs can be met by 100 to 150 micrograms daily, with perhaps another 50 micrograms daily in the event of pregnancy. Infants and children require less overall, but somewhat more per kilogram of body weight. The capacity of the thyroid to store iodine, the relatively long half-life of thyroid hormone in the blood, and the capacity of the thyroid system to adjust to fluctuating supplies of iodine ensure a constant supply of thyroid hormone to the organs and tissues of the body, although daily iodine intake fluctuates widely. The thyroid system is intrinsically stable.
The normal thyroid contains between 2 and 20 mg of iodine. About 70 percent is in the form of the amino acids mono- and diiodotyrosine, the precursor molecules of the thyroid hormones. They are in peptide linkage in the large storage iodoprotein, thyroglobulin (MW about 660,000). The hormones
are released through proteolysis under the stimulus of thyrotropin from the anterior pituitary.
Iodine is absorbed with high efficiency after ingestion. Most iodine containing substances are deiodinated in the gut and the resulting iodine absorbed. It is captured by the thyroid from the blood at a rate dependent on the history of supply. Most appear in the urine in inorganic form in amounts that largely reflect recent rates of ingestion. The daily excretion is the amount absorbed and that derived from hormone degradation, but not taken up by the thyroid. Under normal circumstances, the thyroid takes about 20 percent of the available iodine.
There are limits: too little iodine over too long a time leads to serious consequences, as described below. When too much is ingested, the thyroid may shut down; under certain circumstances, it becomes overactive.
Consequences Of Iodine Deficiency And Its Correction
The anatomical response to chronic iodine deficiency is enlargement of the thyroid gland. Initially there is hypertrophy of the thyroid epithelial cells. With fluctuating iodine supply, involuntary changes occur; the epithelial cells flatten, follicles fuse to form nodules, degenerative changes occur, cysts form, and calcifications are seen. The changes may be highly irregular from one site to another within the gland. Iodine-deficiency goiter may appear in preadolescence and nodules may form when the deficiency is severe, but there is usually a modest enlargement in the young that progresses over the years to multinodular goiter (Kopp et al., 1994; Parma et al., 1994; Taylor, 1953). It is customarily more evident in the female; regression usually occurs in the postadolescent male. When deficiency is severe, goiter rates may approach 100 percent, even in the young.
Goiter is usually harmless, if unattractive. Nevertheless, nodules may cause tracheal obstruction or impair the function of the laryngeal nerves. When surgery is required or elected, the risks of surgery in the local setting must be considered, and these may not be negligible. Malignant degeneration is a much debated issue; there is probably a slightly increased risk in endemic goiter (Riccabona, 1972).
Mental and Neuromotor Retardation
Neuromotor and cognitive impairments are the most important consequences of iodine deficiency. The endemic cretin is the classic example.
This outcome is seen when iodine deficiency is severe and of long duration; it is also likely that the mother has been severely iodine-deprived. The damage begins during the second trimester of pregnancy and is reversible if iodine is supplied, but the damage sustained after the end of the second trimester is permanent (DeLong et al., 1989). The neurological features are characteristic and distinct (DeLong, 1989). In addition to severe cognitive impairment, they may include hearing and speech deficits; a distinctive proximal neuromotor rigidity with sparing of the distal extremities; and, in some instances, cerebellar signs. Cretins are usually tractable and can often perform simple tasks; autonomic function seems undisturbed. DeLong has pointed out that head circumference is often reduced. The hearing impairment may arise both from middle-ear and central damage (Halpern, 1994).
Less extreme levels of iodine deficiency are responsible for lesser degrees of impairment, but the number of individuals affected is much greater than the population subject to the effects of severe deprivation. These changes extend from modest but detectable neurological changes to impaired learning capacity and performance in school or reduced capacity to handle formal tests of psychomotor function (Stanbury, 1994). A crucial question, and one that is difficult to answer, is how these changes within the community affect socioeconomic development. The consequences of moderate degrees of iodine deficiency for cognitive and motor performance have been examined in great detail (Stanbury, 1994). One of the earliest formal observations arose from the case of a village in rural, Andean Ecuador. Many residents were without physical deformity or other signs suggestive of cretinism, but it seemed quite obvious that they were mentally retarded (Dodge et al., 1969a,b). A meta-analysis of 18 studies of cognitive and neuromotor function (Bleichrodt et al., 1989) that covered a total of 2,214 individual subjects provided mean scores that were 13.5 IQ points lower in the iodine-deficient group than among the controls.
Rates of reproduction may continue to be high in iodine-deficient populations, but there is evidence that the rates are lower than in otherwise similar communities that are not deficient (McMichael et al., 1980; Pharaoh et al., 1971; Thilly et al., 1980). There are many possible reasons for this disparity. Fetal and pre- and postnatal survival are reduced by iodine deficiency (Connolly et al., 1979), as is motor performance during childhood (Connolly et al., 1979). Correction in one group of Chinese communities resulted in a doubling of the survival rate of neonates (G. R. DeLong, Division of Pediatric Neurology, Duke University Medical Center, personal communication).
Impaired Agricultural Productivity
Information on this point is scanty, but the question is an important one. DeLong (1989) has reported from China that there has been a remarkable increase in sheep survival and growth following introduction of iodine into the drinking water in an iodine-deficient region. The value of introducing iodine in the sheep industry of Australia and the cattle industry of the American Northwest has been reported, and iodine supplementation of feeds has been implemented. There is little evidence that iodine has any influence on plant growth. (Pandav and Mannar, 1996).
While it seems intuitively obvious that iodine deficiency causes economic stagnation, it is difficult to produce unassailable supporting evidence. Socioeconomic conditions improved dramatically in a traditionally deprived and backward village in China, Jixian, after iodization of salt, but confounding variables leave doubts about the exclusive role of the fortification (Hetzel et al., 1987). Reduced energy, lowered learning capacity, and the burden of increased fetal and postnatal mortality must surely impede socioeconomic development (Dunn, 1994a; Hershman et al., 1986).
It has been difficult to prove a relationship between physical growth and iodine nutrition alone because of the confounding variables of the other deficiencies that are usually present in iodine-deficient regions (Greene, 1973). Nevertheless, hypothyroidism (a consequence of iodine deficiency) clearly retards growth and development, and iodine-deficient individuals frequently are shorter than their iodine-sufficient peers.
Consequences Of The Correction Of Iodine Deficiency
Correction of iodine deficiency pays huge dividends in improved quality of life, elimination of cretinism and other lesser degrees of neuromotor and cognitive function, improved survival, and so on, but correction programs are not without some undesirable consequences (see following section on Costs and Benefits). Whenever thyroid nodules develop in the iodine-deficient gland and iodine is introduced—especially if introduction is poorly controlled and monitored—a fraction of the population will develop thyrotoxicosis. Because autonomy of function occurs in the iodine-deficient thyroid as a consequence of
mutational events, it is probable that the changes are irreversible without medical intervention. The magnitude of this problem is not known. Epidemics of thyrotoxicosis were reported when iodine was introduced into the diet in the United States, Tasmania (Stewart and Vidor, 1976), and a number of other countries, but the consequences have not been measured in their prevalence and long-term damage. The problem is age-old: how much harm can one accept in order to reap the many obvious benefits?
Interaction With Other Micronutrients
Interactions of other micronutrients with iodine deficiency have not been defined with sufficient clarity, and further investigation is needed. Vitamin A deficiency may impair thyroid hormonogenesis by reducing retinol-binding protein, which is involved in glycosylation of the key protein thyroglobulin (Ingenbleek, 1983). It was observed that the presence of vitamin A deficiency appeared to worsen clinical features of iodine deficiency in Senegal (Ingenbleek, 1983). Selenium is a key component of a large number of enzymes, some of which, such as thyroxin deiodinase, are involved in thyroid function. Lack of selenium, a component of glutathione peroxidase, may contribute to the accumulation of peroxide in the gland, which is destructive and may contribute to the damaged gland observed in a study of the cretins of Zaire (Contempre et al., 1995). Uptake of iodine by the thyroid is an oxidative process, and energy is required for hormone synthesis and secretion. These processes require iron-containing catalysts, but the role of iron deficiency in thyroid function is not well defined. Iron is less well absorbed in the hypothyroid state, and subjects with hypothyroidism are frequently anemic (Ansell, 1991).
While not micronutrients in a restricted sense, other dietary components may contribute to the impact of iodine deficiency. One group, the thioglucosides, such as linamarin, found in cassava, yields thiocyanate on hydrolysis in the gut if improperly prepared, and the resulting thiocyanate competes with iodine for uptake of iodine by the thyroid. There are many other dietary and environmental substances that interfere with thyroid function that merit consideration (Gaitan, 1989).
Extent Of Iodine Deficiency
This traditional technique continues to be useful as a preliminary screen or when more precise methods of assessment are not available. It has the limitation
of observer variation, especially in classifying thyroids of smaller sizes by palpation. In recent years ultrasonography has permitted improved precision and definition of what is abnormal; it has also provided a graphic account of structure. The technique can be applied in field conditions with portable equipment, and subject turnover can be quite rapid and efficient.
A simplified classification for practical purposes is provided below in Box 5-1, adapted from a consensus statement by ICCIDD, WHO, and UNICEF (UNICEF, 1994).
Iodine deficiency may be strongly suspected if more than 5 percent of school-age children fall into grade 1 or 2.
Ultrasonography is rapidly becoming widely available for estimation of thyroid size and configuration. Several recent studies (e.g., DeLange et al., in press) have established mean and median values for normal thyroid volume in relation to age, gender, height, weight, and body surface for iodine-sufficient children. Thyroids greater than 2 standard deviations (SDs) from the mean for normals are classified as goiters. This method can be applied to as many as 200 children in a day. It has the advantage that it may disclose nodules that are missed in routine examination.
Advances in methodology now permit rapid and accurate measurements of the iodine in urine. When done in samplings of appropriate size, these measures provide an excellent measure of the recent iodine nutrition of a community (UNICEF, 1991). The results are customarily expressed in ug/L; values below 50 are considered unacceptably low, and those above 100 are taken to signal sufficiency. Values below 25 ug/L indicate an urgent need for preventive action. Measurement of urinary iodine (UI) in representative samples from a population is presently the most convenient and reliable method to assess iodine nutritional status (Dunn et al., 1993a,b). Many studies confirm that iodine excretion rates correlate inversely with goiter size, and that when values are very low, the prevalence of neuromotor and cognitive impairment is high.
Box 5.1 Classification of Goiter
Grade 0: No palpable or visible goiter
Grade 1: Not visible with the neck in normal position. The mass moves upward when the subject swallows. Nodular alterations can occur even when the thyroid is not visibly enlarged.
Grade 2: A swelling in the neck that is visible when the neck is in a normal position and is consistent with an enlarged thyroid by palpation.
Measurements of UI (urinary iodine) serve as an excellent monitoring technique. Failure in programs of salt iodization can be detected, as well as the addition of too much iodine to the salt supply. Continuing spot monitoring of UI should be part of every prophylactic program, and occasional samples should be confirmed by an independent laboratory.
Measurements of TSH
The technology of TSH measurements has advanced rapidly and is becoming available for the assessment of iodine deficiency. There are easier and less expensive methods to detect iodine deficiency, but universal neonatal screening can provide a good ongoing indicator of iodine deficiency, and it can also monitor the adequacy of a continuing prophylactic program, provided the neonatal screening is universal. The samples should be collected by heel stick and spotted on paper for later analysis.
This technique is not yet available in most countries experiencing a significant iodine deficiency. It is also not applicable as an initial survey method unless there are sufficient births for sampling within the time frame of the survey, which is rarely the case. At the same time, surveys with larger population groups may disclose evidence of iodine deficiency if representative samples are available. The upper limit of normal in current assay methods is 5 to 6 uU/ml, and a significant number of results above this level suggests the presence of iodine deficiency. Introduction of high-sensitivity TSH assays has made it possible to determine the prevalence of iodine-induced thyrotoxicosis after the introduction of replacement iodine. Surveys of this kind could answer questions about the persistence and incidence of thyrotoxicosis or clinically inapparent thyrotoxicosis in regions with limited medical care. Values below 0.2 uU/ml raise concern about the presence of iodine-induced thyrotoxicosis.
The current disadvantage of TSH measurements as a survey instrument is cost. UI is far less expensive and more readily applicable in the field.
The abnormal thyroid of iodine deficiency leaks thyroglobulin into the blood, and this can be measured routinely with commercially available kits. This may prove to be a more accurate and reliable method for the assessment of iodine deficiency than goiter surveys by palpation or TSH measurements (Benmiloud et al., 1994). The method is sensitive and can be performed on dried bloodspots (Missler et al., 1994). This measure is also nonspecific—other conditions raise serum Tg values just as they produce goiters, but such conditions are fairly uncommon in the general population. The available assays
vary in their normal range, and thus the technique and normative data must be specified when results are reported.
Persons with adequate intake of iodine have mean levels of serum thyroglobulin of 10 ng/ml, with an upper normal limit of 20 ng/ml. The method has the disadvantage of expense.
Iodine in Food and Water
Methods are available for field use to assess the presence or degree of iodine deficiency, but assays on food are difficult. Measurements of the iodine content of locally available water, while technically satisfactory, are at best a poor indicator of the level of iodine deficiency in the community because sources vary in less developed communities, there are seasonal fluctuations, and there is a poor correlation with the levels of iodine available from other sources.
Extent and Distribution of Iodine Deficiency
Iodine is sparsely distributed in the earth's surface. As a result, iodine deficiency disorders (IDDs) have been exceedingly common in most populations (Hetzel, 1989b; Hetzel and Pandav, 1996; Mannar, 1996). These disorders were highly prevalent in the United States prior to the introduction of iodine through iodized salt. In the past, IDDs were frequent in much of Western Europe, and a severe problem in most Latin American countries, throughout most of Africa, in the Middle East, in the Himalayan region and southward on the subcontinent, in China, and in Southeast Asia. Iodine deficiency is a current problem among the countries of the former Soviet Union. Fortunately, the efforts of the past decade have made signal advances in elimination of IDDs through universal salt iodization (USI).
WHO has estimated that over 1.5 billion persons worldwide reside in regions of environmental iodine deficiency (ID) and are at risk of IDDs. This may be a soft figure, but it suggests the importance of the problem for public health. Of those at risk, possibly half have clinically detectable thyroid abnormalities; of this group, probably one-fifth have health-significant impairments, and an unknown number have reduced intellectual function. Recognition of the baleful effects of iodine deficiency on the development of the nervous system has led to the recognition of ID (iodine deficiency) as the most common cause of preventable mental retardation in the world.
Economic Costs of Iodine Deficiency
Any attempt to assess the costs of iodine deficiency would be subject to tenuous assumptions and large-scale errors. Costs would be region-dependent:
for example, the costs of a case of cretinism in the rural highland Andes or Central Africa are not comparable to the costs in an industrial region. The costs of lost productivity, premature death, fetal losses, and reduced energy would require—at best—guesswork.
The costs of surgical procedures for goiter in Germany have been calculated, and they have been huge (Gutekunst, 1993). It has been said that only a few years ago, half the surgical procedures done in the major hospital in western Austria were performed to address goiter. Thyroidectomies were the mainstay of some of the busiest and most important clinics in the United States before the iodization of salt.
Calculating costs without comparing benefits would be a relatively pointless enterprise. When efforts have been made to do so, the ratio of benefits to costs has been enormous (Correa, 1980; Dunn, 1994a; Hershman et al., 1986). Prevention is thus a highly advantageous undertaking.
Indicators Of Iodine Deficiency And Impact Of Prevention
Identifying Target Populations
One may begin with the assumption that ID exists virtually everywhere, except where satisfactory prevention programs have been introduced or in the few regions of the world with ample iodine in the environment. What is a target population for an intervention program? Is it one with a borderline or moderately low mean daily intake of iodine, but no clinically evident IDDs, or only populations with positively identified IDDs? The former condition and grades of the latter will dictate the urgency of a program of fortification or supplementation.
Identification of a target group is partially dependent on formally designed surveys that employ one or more of the tools described above. The structure of surveys depends on local or regional conditions, geography, transport, and resources. Highly stylized epidemiological surveys run the risk of missing important pockets of IDDs; some exploration may be required to follow up dubious information or intuition.
Monitoring Intervention Programs and Their Impact
The key to success in prevention of IDD is longitudinal monitoring of both the supply of iodine and the impact of the prevention program on the targeted population. Too many programs have lapsed because of failed monitoring, with the subsequent reappearance of IDDs. Monitoring should be institutionalized on a continuing and stable basis. The iodine content of salt should be measured
from the factory or import portal, to the retailer, and on to the household. Swings in concentration should be investigated and corrected. Quite simple and reliable methods are now generally available to measure the iodine content of salt to assure that it is within satisfactory limits (Sullivan et al., 1994). Results should be confirmed by external control laboratories.
The impact of programs should be monitored by periodic assessment of the status of IDDs. Success is signaled by a decline in IDDs as indicated by one or more of the assessment techniques described above. Care is needed in interpreting the information gained through monitoring, For example, if the surveyed population is comprised of older subjects with long-standing goiter and the technique of assessment is goiter rate, little change may be observed.
The time frame for monitoring depends on what is being monitored. The iodine content of salt should be monitored on a daily basis at the factory or at the point of import and it should be frequently checked again at the store or point of sale, whereas little would be gained by measuring thyroid size more frequently than once each year. A national neonatal TSH screening program—if universally employed—would provide continuous monitoring of the frequency of IDDs.
The ideal framework for monitoring would include most or all of the following components. Monitoring must include appropriate and effective responses if deficiencies are detected:
- After an initial goiter survey by ultrasonography, zones of suspicion would be monitored annually.
- A neonatal TSH screening program that is universally applied is needed.
- The iodine content of salt is monitored daily at the site of production or point of import.
- Spot monitoring of table salt is done at the retailer and at the consumer's table.
- Measurements are taken of UI. Initial measurements are made in statistically valid samples; measurements are done occasionally after the program of iodine distribution has begun.
- Measurements are made of plasma thyroglobulin in statistically valid samples of serum.
Prevention And Correction
Fortification of salt has a unique advantage among the micronutrient supplements—it requires no change in dietary habits, because everyone uses salt
(Mannar, 1996). The one disadvantage it shares with any other program of micronutrient fortification is that the improved product costs slightly more than the original. This must be countered, either through subsidy by donor organizations or by intensive social marketing that makes the iodized salt more desirable and worth the additional cost. The experience is that cost has rarely been a major stumbling block. Importation of noniodized salt across borders has occasionally been a problem, especially when the product has been labeled as iodized but actually contains no iodine. Small traders or local producers of salt near salt deposits have been a problem in rural Bolivia, Ecuador, and Argentina, for example. Demand for the iodized product has been created by professional social marketing techniques, as in Ecuador. Mass media campaigns that employed posters, press, pamphlet distribution, and radio were used in all regions.
The goal in the prevention of IDDs is universal salt iodization (USI). Programs must take into account possible losses between point of manufacture or import and the consumer's table. Losses may vary among the forms of iodine used (iodide vs. iodate), heat, purity, humidity, packaging, shelf time, and losses in cooking. Programs should also be designed around salt consumption patterns in order to make the maximum effort to ensure an intake of iodine within the desired range. A mean consumption of 15 grams or more daily has been observed in some communities; in others as little as 2 grams have been consumed. Salt may be iodized in several ways, including dry mixing, drip, or spray techniques. Generally the iodine is sprayed or drip-fed on the salt as it flows down a mixing-screw conveyer; if the salt is finely ground, the iodine may be added dry (Dunn, 1995; Holman and McCartney, 1960). The long-term costs of producing iodized salt to supply the needs of an individual amounts to only three or four cents yearly. Unfortunately, in some instances a high, unwarranted premium is added to the cost of the salt to the consumer. Iodine is available principally from Chile and Japan.
Difficulties arise in implementing programs when the salt industry is widely dispersed among a large number of small producers. Ensuring distribution of iodate to all parties for local production is difficult, and compliance is a problem. In Thailand, small, electrically powered rotating drums for mixing iodate into the salt are manufactured and are being widely distributed to remote areas to address this problem.
The increasing use of plastic bagging has reduced iodine losses between manufacture and consumer, as has the sale of smaller packaging to effect more rapid turnover of the product.
A customary level of fortification is in the range of 25–50 mg of iodine per kg of salt. This level will require variation to accommodate local conditions. The cost—considering all factors of plant operation, cost of the iodate, and control—should add little to the cost to the consumer and is a trivial increment, considering the low cost of bulk salt. When the salt is imported it must be reprocessed
at the portal of entry, or the supplier must be convinced to cooperate and ship only a properly iodated product.
A final determination of cost must include expenses of the iodine, processing costs (including labor and supervision), packing (including polyethylene lining of the containers), shipping, administration (including monitoring), and plant amortization. One estimate has placed the total cost, in addition to that of the basic salt, at US$0.02 to US$0.06 per person yearly. This represents somewhere between 2 and 20 percent of the retail price of the product.
Experience has shown that most manufacturers or suppliers of salt are quite willing to cooperate in iodinating their salt, once the importance of salt fortification has been explained. In some instances international agencies, particularly UNICEF, have been instrumental in introducing USI (universal salt iodization) and have assisted producers by supplying the machinery required for the iodization process.
An outstanding need in the salt iodization process is maintenance of the level of added iodine within safe and effective limits. This means, at the very least, that the concentration of the commercial product must be measured at frequent intervals. Fortunately, the technique required for this measurement is reasonably accurate.
Three programs—in the Netherlands, Russia, and Tasmania—have used bread as a vehicle for the distribution of iodine. Both the Dutch and the Australian programs were dropped for logistical reasons, because of an attendant rise in iodine-induced thyrotoxicosis, or because iodine became available from other sources. The Russian program is too recent to judge, but it appears promising in communities where bread is centrally prepared and iodized salt is unavailable.
Water has been successfully used as a vehicle for the prevention of IDDs. A silastic cylinder containing iodine has been used in bore holes in several African countries to achieve some success in raising community iodine intake, but the many associated difficulties have prevented its widespread use (Fisch et al., 1993). In selected rural regions of Thailand and Indonesia, iodine is added intermittently to cisterns that store water for drinking and cooking (Suwanik et al., 1989). The current program of USI in Thailand will doubtless eliminate use of this method in the near future. Iodine has been introduced into city water supplies in Sicily with a bypass through an iodine-containing canister. Reduction in IDDs was reported, but the method fell into disuse because of mechanical, legal, and monitoring problems.
An ambitious program to introduce iodine into irrigation water in the desert areas of western China (by DeLong and colleagues) has been hugely successful in increasing yields in sheep farming and in reducing infant death rates (G. R. DeLong, Division of Pediatric Neurology, Duke University Medical Center, 1997, personal communication).
Drops and Tablets of Iodine
The original study that proved iodine prevents goiter used sodium iodide, which was given to schoolchildren twice yearly (Marine and Kimball, 1921). Drops of Lugol's solution have also been used in schoolrooms. Tablets of salts of iodine, sometimes disguised with chocolate, have been dispensed intermittently. Recently there has been renewed interest in intermittent dosage in classrooms using tablets or drops containing iodine.
Iodinated poppy seed oil has been widely and successfully used in the prevention of IDDs since its introduction in the late 1950s in New Guinea (Fierro-Benitez et al., 1969; Hetzel et al., 1980). Other unsaturated oils have also been used. Needs may be met for a year or more by a single dose, depending on its size and route of administration. These mixtures have been used both intramuscularly and orally in doses varying from .2 ml to several ml. Most programs have used either 1 or 2 ml in older children and adults, but success has been achieved with smaller doses (Benmiloud et al., 1994). Side effects have been virtually nonexistent, except for occasional instances of induced thyrotoxicosis. The technique is more expensive than USI. Depending on the logistical and administrative costs added to the cost of the iodinated oil, the cost totals approximately US$0.10 to $0.50 per person annually. A major expense will be determined by the costs of the team, which is often posted to remote regions. Iodinated oil has been accepted well by target groups. It is currently reserved for communities where it is unlikely that USI will be introduced within the foreseeable future (and such areas are disappearing) and areas where the need is urgent and USI is unlikely to reach the target population immediately.
Irrigation water has been successfully iodinated in western China (Cao et al., 1994). The water is derived from glacial streams, and never reaches the sea. All farms and households in the region subsisted on this water. Potassium iodide in 5 percent solution was slowly dripped into the water from tanks at a rate that provided approximately 10 to 80 µG iodide per liter for several weeks each season. There followed a sharp rise in iodine excretions among the population and
a sustained rise in iodide in the soil. Improvements were noted in survival and weight gain among domestic animals, and growth of children also improved.
Summary Statement on Fortification and Supplementation
No one questions the priority of USI in the world program for the elimination of iodine deficiency and its disorders. The use of iodinated oil, iodinated water, iodinated bread, and tablets and drops are all reserved for special circumstances until IDDs are eliminated as a health problem. Of the alternative methods, iodinated oil has proved to be the most successful, but it requires a skilled team, availability of disposable syringes and needles, and carries an attendant risk of infection. Nevertheless, iodinated oil has a well-defined role in the international campaign against IDDs. Other modalities are limited to special circumstances. With support as needed from the international health agencies, USI should continue to move rapidly forward, with only occasional and limited requirements for other methods of prevention.
National Programs: Some Examples Of Success And Failure
There is evidence of the presence of endemic goiter in Andean Ecuador reaching back to pre-Columbian times. Goiter was occasionally mentioned over the years, and in 1957–1958, a national survey disclosed a remarkably high prevalence of goiter and cretinism. At about this time, Professor Rodrigo Fierro-Benitez began an intensive study of the prevalence and pathophysiology of goiter in several remote villages north of Quito, and in 1966 he began a controlled trial of the administration of iodinated oil. Although there was legislation prescribing iodization of salt, compliance was spotty and intermittent, depending on the interest of the government and the Ministry of Public Health.
In 1984 a joint enterprise between the government and the foreign assistance program of the government of Belgium was inaugurated, and experts from Ecuador have worked closely with their Belgian counterparts since that time. A central office under the guidance of an Ecuadorian expert was established, and a strategy was developed that proved to be efficient in the control of the deficiency. Small and well-trained teams were placed in every affected province to intensify education and communication activities and to begin a surveillance system that is still in place. A system for data collation was established. General education, using both Spanish and Quechua, regarding salt iodization was promoted through individual schools, radio spot commercials, slide shows, lectures,
and the press, and the cooperation of the salt industry was secured. Meanwhile, research activities under Dr. Fierro's direction continued to provide information on the effectiveness of the iodinated oil program. He was also a key figure in the continuing encouragement of the Ministry of Public Health to assist in the program. Both UNICEF and WHO, together with the Belgian contingent, have been important forces in sustaining interest and activity in the program.
Once a country with an extraordinary high prevalence rate of IDDs, Ecuador has now achieved virtual elimination of these disorders. The program with iodinated oil was initially extended to many villages in the highlands, with excellent results. Iodized salt has now replaced iodinated oil, and it reaches virtually all consumers. There has been only an occasional intrusion of contraband uniodized salt, from the north. Surveillance continues and appears to be established as a permanent operation, with the central government assuming increasing responsibility. A recent survey by ultrasonography in a previously severely affected area disclosed the absence of goiter in all persons who had received prophylactic iodine, except for older individuals, some of whom retained firm nodules that were established before the programs began.
This successful program illustrates the importance of persistent efforts by dedicated medical scientists, working in concert with the national health sector and bilateral and multilateral agencies. This long-term cooperative venture lends optimism to the prospect of continuing eradication of IDDs from the country.
Nigeria has not been identified as a site of severe IDDs except in a few isolated regions, but a modest prevalence in at least eight states has long been recognized, and approximately 25 million people live in iodine-deficient regions. Iodization of salt has been recommended for at least 15 years, but has rarely been implemented. In the late 1980s an expert committee recommended formation of a national committee to review the problem, and mandatory iodization of salt has been recommended. A key to the strategy was a shift from dependence on the government to active involvement of the private sector. All of Nigeria's salt is imported, and there are only three major salt companies. Of these, the largest, Union Dicon Salt, processes 500,000 metric tons of the 630,000 metric tons utilized annually in the country. The company carefully monitors the iodine content of the salt produced. By 1995, 97 percent of the salt produced for human use was iodized (Asquo, 1995; Dunn, 1996b). The company has also been active in the promotion of iodized salt through local advertising efforts. In the
1980s a team from Japan made a series of surveys and investigations in the center of the country and forwarded a set of recommendations to the government, but these have not yet been implemented.
It is too early to judge the effectiveness of the national committee or its longevity. Political turbulence has hindered progress toward a well-established national program, and imported salt from neighboring countries has also made control difficult. It thus appears that while there are committed and active individuals and organizations in Nigeria, they find significant impediments to a needed national program. Not the least of these is a failure to recognize IDDs as a significant problem. Nevertheless, the experience of Union Dicon Salt illustrates the contribution that a socially responsible industry can make in the fight against IDDs. Cultivation of such companies can be important.
Landlocked, largely mountainous Bolivia has been known for goiter since colonial times. In 1981, a survey disclosed a goiter prevalence rate of 68.1 percent. A national program against goiter began with the formation of PRONALCOBO, a government agency, in the early 1980s. A crash program was initiated in 1988, and a large campaign using iodized oil reached about 1.4 million persons and continued until USI became institutionalized. A few highly isolated communities remain where iodinated oil is still necessary. The project was initiated with the help of funds provided by the Italian government. Implementation has relied on the country's well-developed regional health care system, and the project has been administered through each of the nine sanitary units. Nonprofessional community health workers throughout the country had the responsibility for the actual delivery of the oil, and they were aided by community organizations such as schools, political groups, and religious organizations. In each instance, records of individual subjects were kept.
Goiter prevalence fell from 65.3 percent in 1983 to 23.6 percent in 1989, and it has continued to fall. Median urinary iodine levels are well above 100 mg/L. Salt, which is available from abundant sources in the country, is iodized, packaged, and marked within the country (Dunn, 1996a; Havron, 1988). The major challenge now is sustaining the achievement. Past experience in Latin
America and elsewhere predicts that iodine deficiency will reemerge unless a sound monitoring system is in place. This success story points to the value of the combined, persistent efforts of a hardworking organization; international agencies and experts; and, most notably, national experts devoted to elimination of IDDs, such as Dr. Antonio Pardo. Together, these forces have created a program that gives every indication of continuing to succeed in a country where one would have every reason to believe that IDDs would return without prophylaxis.
Following the establishment of the Institute of Nutrition of Central America and Panama (INCAP) in 1949, several surveys were completed by the new institute that pointed out the high prevalence of goiter, although the technique used recognized only highly evident thyroid enlargement. The mean was 38 percent for the country and 55–59 percent in four departments (Dunn, 1991). By the early 1950s, INCAP had established the availability of iodine from potassium iodate, which proved to be stable in the crude, moist salt sold in the country, even in the tropical lowlands. INCAP persuaded the government to require the iodization of all salt for human consumption, and this began in 1956 at a level of 10 to 20 mg/kg. Compliance was monitored by the Department of Health. Guatemala went through a particularly turbulent political period in the 1980s, and the leadership of INCAP was decimated by the terrorist kidnapping of the director and administrator and by threats that caused most expatriate professionals to leave. In the early 1990s goiter had reappeared, and the salt was no longer being iodized. In 1995 the government restored salt iodization, but no new national survey has been available.
The failure of the program in Guatemala points to the disastrous results that follow failure of government support and when no established agency has taken the responsibility to be continuously mindful of the latent risks of iodine deficiency. In this instance, the powerful INCAP organization was weakened. The federal agencies needed constant reminders of the potential threat of IDDs, even when the problem seemed to have disappeared. Political instability compounded the difficulties.
After the demonstration by Marine and Kimball in the American Midwest that iodine prevents goiter, there was a huge wave of enthusiasm for resolution of this widespread and serious problem (Marine, 1923; Markel, 1987). This enthusiasm was expressed through many articles in medical journals and the lay press, voluminous advertising, and the cooperation of the salt industry. At about the same time there was testimony to the effect that salt iodization could be dangerous to subjects with nodular goiter, and a number of articles appeared that condemned the use of iodized salt. Salt iodization never became an issue for the federal government, and there was no legislation in the area, but the beneficial effects of iodization were quickly appreciated. In more recent times iodine has been widely used in a variety of ways, including its inclusion as a water purifying agent, in many medications, and in the dairy industry. The result has been that the mean daily intake of iodine has risen well above minimum daily needs, and there is a consensus that the United States has no further need for iodization of salt.
IDDs have vanished from the United States. Although iodized salt can be obtained in markets throughout the country, noniodized salt can be purchased as well, and there is no further pressure to use the iodized product. Thyroidectomy, once performed many times daily in the major medical clinics of the country, is necessary only when nodular goiter arises from a cause other than iodine deficiency. There are other indications of the absence of IDDs as well. The lesson to be learned from the experience of the United States is that in an advanced economy with a homogeneous food supply, especially if iodine is widely used in the dairy industry, there is a strong probability that iodine needs will be largely met without fortification. Nevertheless, iodine deficiency of mild degrees continues in some advanced countries of Europe, and occasional surveillance is still necessary.
This country belongs to the Himalayan chain that has always been known for a high prevalence of IDDs. It fiercely maintained its independence and isolation until recently. Surveys in the late 1980s disclosed an overall goiter prevalence of about 60 percent, with rates as high as 85 percent in some regions
(Dunn, 1994b). Cretinism has been common. In the western region, UI was less than 25 ug/gm creatinine in over 50 percent of those surveyed, and some villages harbored a 10 percent cretin population, with no estimate of the number of ''subcretins." All salt is imported through the town of Phuntsholing on the Indian border. The import and distribution of salt is managed by the Food Corporation of Bhutan, a government operation. A plant for salt iodization was established at the portal of entry in 1985, and it has slowly begun to iodize all salt at a level of 60 mg I/kg. Administration of iodinated oil was initiated, and more than 50,000 injections were given along the border with India, where there was some infiltration of noniodized salt, but this program is giving way as tighter control of salt iodization is realized.
Tight control of iodization of all salt in the kingdom appears to have been achieved. This has resulted in the finding of adequate amounts of iodine in samples of urine collected in the course of surveys, and the salt seems to be adequately, but not excessively, iodized. The median urinary iodine levels were approximately 250 mg/L in the follow-up in 1992. The salt iodization system occasionally breaks down, which creates the need for better control at the entry point. Because of distance, salt may not be purchased frequently by the householder, and monitoring at that level needs attention. There is also a need for increased education of the general public and the field workers. A serious risk is that as foreign assistance for the operation is phased out, the government may not support the continued operation of the several facets of the county's control program. The lesson to be drawn from the Bhutan program is that careful initial planning, which must include planning for the long term, is needed. It is also evident that planning must involve several sectors of the government, including those responsible for health, economic affairs, and education. Planning must also include provision for monitoring both the salt supply and the population; ideally, a system for universal neonatal screening would be in place as well.
Landlocked Zimbabwe has been known to have endemic goiter for at least 35 years, with goiter rates in some regions as high as 73 percent. With independence in 1980, a Department of National Nutrition was formed within the Ministry of Health and was charged with oversight in the area of micronutrients. In one region, the Chinamora District, levels of iodine in the urine were between 25 and 50 ug/gm creatinine. Planning to address this deficiency included a program to administer iodinated oil in the severely IDD-endemic areas and to institute
USI by the year 1990. An impediment to progress is the need to import all salt, from South Africa for the most part. The import of iodized salt slowly began to build up in about 1992. In late 1994, the mean concentration of iodine in salt collected nationwide was 29 mg/kg, and 81 percent of samples had at least 10 mg/kg.
By late 1994 or early 1995, physicians began to report an increased rate of thyrotoxicosis, and in 1995 a survey of attendance at the teaching hospital in Harare disclosed a near-tripling of such patients (Todd et al., 1995). These cases were primarily, but not exclusively, among the elderly with nodular goiters. Fourteen deaths were recorded. These occurrences led to considerable international concern, and much tighter controls were imposed on the level of iodization of salt coming into the country. The lesson of the Zimbabwe experience is that whenever iodine supplementation or fortification is introduced into an iodine-deficient region, there will almost surely be a small number of subjects, especially those with nodular goiter of long standing, who develop thyrotoxicosis, and this occurrence must be anticipated. It is also evident that tight monitoring of the iodine content of salt—from producer to consumer—is needed, and the possible occurrence of iodine-induced thyrotoxicosis requires vigilance.
Structure Of Preventive Programs
The guidelines that follow are generally those recommended by the International Council for the Control of Iodine Deficiency Disorders (ICCIDD; Dunn and van der Haar, 1990). The prevention of ID is being rapidly subsumed by governments through their health ministries as USI is adopted. Initial programs were often begun by private voluntary organizations such as the ICCIDD, in close collaboration with USAID and WHO, or by the Belgian, Canadian, or Swedish foreign assistance organizations. Research into the pathophysiology or extent of IDDs sometimes served as the stimulus needed to take action. With the selection of IDDs as a priority concern by UNICEF and other international development assistance organizations, elimination of IDDs has become a priority goal of many developing countries, and the number is growing. Political disorganization, as currently seen in Central Africa, has not helped efforts toward this goal.
What is required for long-term success is the creation of a reasonably well-supported and stable commission or equivalent organization that is charged with advising the authorities to ensure continuing supervision of the program and adequate monitoring of the state of iodine nutrition in each individual country. Such commissions require support and continuity. They need to work closely
with the international agencies such as UNICEF, ICCIDD, and WHO. The commission or its advisees must run, or have ready access to, a laboratory equipped to perform the needed assays.
It should be the responsibility of the IDD commission or its equivalent to carry out the periodic assessments described above, including regular monitoring of iodized salt and its effects. In addition, there should be periodic assessments of IDD status by an external, independent team working with the local commission. Results of these external reviews should be communicated to the respective governments for action.
The salt industry should be involved in ID control from the beginning. In general, the leaders of the industry have been cooperative. Difficulties arise when the industry is badly fragmented into multiple, small producers. When salt is overly or inadequately iodized, this must be detected and corrected. The international assistance agencies have supplied manufacturers with the equipment to fortify salt in many instances.
Education concerning ID is needed at several levels. Programs must be designed to inform the responsible governmental officials, including those in the health ministries; health care providers; the salt manufacturers and distributors; and the general population. A number of video productions have featured IDDs and have been distributed to appropriate audiences in many countries. Similarly, slide shows, flip charts, and radio spots have illustrated IDDs and the need for iodine. Country and regional conferences throughout the world have involved significant persons from countries where IDDs have been a problem in the past decade. An international IDD day, promoted by UNICEF and ICCIDD, has been an educational instrument.
Several countries, especially in Latin America, have enacted legislation requiring iodization of salt. In a few instances this has been useful, but in others the law has been ignored. It is clearly helpful to have this legislation on the
books. Care is needed in drafting legislation to ensure that requirements are not too rigid and can be adapted to local or regional conditions.
Why has legislation failed to be effective or been ignored? To the casual observer, IDDs do not appear to be a pressing problem in need of priority attention. Legislation has failed because the responsible health officials have not advocated enforcement of the legislation enacted, because funds have not been appropriated, or because other health problems have been more pressing. There have been occasions when the salt industry has not been cooperative or the execution of legislation has not seemed practicable because of the dispersed nature of the salt industry and the difficulty of assuring compliance. There have also been instances when misinformation has led the medical profession to oppose salt iodization.
The enthusiasm for IDD control that followed the 1990 UNICEF Summit Declaration has fostered a rash of legislation around the world. One fears that in some instances this will not be followed by sustained action. The solution will often be found in continuing attention to the problem of IDDs by individuals or small groups, especially when motivated by scientific or humanitarian groups outside the mainstream of government.
Having a law on the books that mandates iodization of salt is only a first step. The law must make provision for enforcement, which means the creation of machinery to inspect, monitor, and report. These functions all require a line item in the country's budget, and such expenditures may meet with resistance. The only solution appears to be the continuation of pressure and advocacy by interested persons until salt iodization is thoroughly imbedded in the economic culture of the country.
Impediments To IDD Control
Problems occur in policy, program structure, technology, and financial support for IDD control. Some of these are discussed below. Many publications and country reviews provide more details (for example, Dunn, 1996a,b,c; Dunn and van der Haar, 1990; Hetzel, 1989a; Pandav, 1994) of the difficulties encountered.
In the Domain of Policy
Inadequate Political and Popular Support
Hammering away at advocacy through a range of techniques should help create the needed support. For an IDD control project to work, it must be accepted by the government, including the health sector, and by the population at large. When salt iodization began in the United States, there was intense backing
by the popular press, organized medicine, and the salt industry. The federal government was not involved. Iodization took place largely through the advocacy of individuals who recognized the problem, wrote papers, gave talks, and educated the salt industry. This remarkable success story has been told only infrequently (Marine, 1923; Markel, 1987) and needs more extensive review.
Inadequate Involvement of the Salt Industry in Achieving Local or Universal Iodization of Salt
As noted elsewhere, salt manufacturers have generally proved to be cooperative in iodizing their product. The salt producers must be approached, informed, and encouraged. Means have to be secured to see that they are properly compensated for the additional cost of iodizing the salt. With the approaching universal iodization of all salt, it becomes necessary for the manufacturers involved in the international salt trade to join in the campaign.
The importance of IDDs and their correction should be made clear at all levels, including the government, the medical establishment, schools, and prenatal clinics and should be publicized through all available media.
This major issue is discussed in the sections on Consequences of the Correction of Iodine Deficiency, and Monitoring Intervention Programs and Their Impacts. Proper and continuing monitoring is basic to achieving elimination of IDDs.
Satisfaction with the status quo, forgetfulness, political instability, diversion of scarce financial resources, and intra- and interagency and governmental rivalries and feuding can all lead to sidetracking of IDD control programs and have done so in the past. IDD control must be embedded in the political structure, where it cannot be ignored.
In the Domain of Programs
The following impediments can damage efforts toward IDD control:
- Unreliable or inadequate field data, including assessment
- Insufficient monitoring
- Insufficient training of field workers
- Inadequate laboratory support
- Insufficient moral and financial support of organizations attacking the problems.
In the Domain of Research
The following is a partial list of the issues of importance to the implementation and success of programs for IDD control that require further research and clarification.
- Frequency, time course, and patterns of autonomy accompanying chronic iodine deficiency; reversibility; clinical impact over time, particularly after iodine replacement; dose effects. The problem of development of autonomy in the iodine-deficient thyroid is central to understanding the origin of IDDs. This issue is currently under active investigation and is closely allied to nodule formation and thyroid cancer. The question is yielding to the approaches of molecular biology.
- The effects and value of postnatal iodine replacement on growth and performance attributable to direct tissue effects (brain and somatic development irreversible) in comparison with effects mediated through reduced thyroid function (reversible). Some of the damage observed in the iodine-deprived individual is derived from irreversible disorders in the evolving nervous system, while other deficits are reversible and derive from postnatally limited hormone. There may not be a sharp dividing line between these two sources.
- Effects of prophylactic programs on social and economic development and performance and on agronomy. These effects are difficult to quantify and attribute because of the complexity of the factors that affect development. Nevertheless, there is emerging evidence of beneficial effects on the economy, such as sheep survival in China, where iodine has been added to the drinking water.
- Development of better and more easily and accurately applied monitoring tools, such as urine iodine measurements and Tg and TSH assays. An expensive, accurate, and easily applied TSH method for field application would be enormously useful and is possible with emerging technology.
- Mutations in the evolution of hyperplasia in the thyroid into nodules.
- Field research using kinase-interacting phosphatase (KAP) surveys to enhance implementation of prophylactic programs or determine why they are less than successful.
- Long-term outcome of the children of mothers with multinodular iodine-deficient goiters who received iodinated oil during pregnancy.
- Cost/benefit analyses are needed under a variety of economic and social conditions. These could have practical value in advocacy, but such research has rarely been attempted.
In the Domain of Financial Support
If ID and IDDs are to be minimized, it is the obligation of the international agencies (WHO, UNICEF, Swedish International Development Authority-SIDA [Sweden], Canadian International Development Authority-CIDA [Canada], USAID, the World Bank, UNDP, and foreign assistance programs of other developed countries) and the committed private voluntary organizations (PVOs) to assure that the requisite funding is secured and distributed responsibly. It is the belief of this author that realistic support must be provided for program and project execution, as well as for the required administrative costs. The individual countries also bear responsibility for support insofar as their economies and priorities permit.
Costs and Benefits
Only limited analyses have been made on the costs and benefits of IDD preventive programs, and much more attention is needed. Those that have been made are strongly in favor of prophylaxis. Further research is needed in this area.
Assessment. The costs of assessment will depend on the magnitude of the enterprise, the tools chosen, the terrain, the personnel, and the detail employed and desired. If one limits assessment to goiter size, the expense may be minimal, but the information obtained will also be limited. If one chooses a full-scale country evaluation of all aspects of IDD using sophisticated indicators, the costs will be substantial, but again, their magnitude will depend largely on local conditions, both political and practical.
The benefits of assessment that leads to interventions that eliminate IDDs are enormous, and far below the costs of IDDs or any control program. This estimate is largely intuitive. Any formal cost/benefit analysis should take into account that the benefits must be measured against the cost of IDDs, as well as the costs of a prevention program.
Programs. These costs depend on many factors, including size, intervention chosen (iodinated oil or iodized salt), level of monitoring, and the infrastructure available and its commitment and reliability. While the benefits to human (and animal) health are scarcely calculable, any cost/benefit analysis must take into account the costs of IDDs. The costs of a modest, or even severe,
mental deficiency in an agriculturally primitive society would be quite different from the costs of the same abnormality in the industrial world, and the ratio might be adjusted downward accordingly.
Value of Benefits. Several attempts have been made to quantify the benefits of IDD prophylaxis. These are subject to many assumptions, but the benefits clearly outweigh the costs by a substantial value. In India, Pandav (Pandav, 1994) found a benefit—cost ratio of 3. Correa (Correa, 1980) has estimated the value of improvements in the intelligence quotient brought about by iodization and elimination of cretinism with the gain in income, and found that iodization was more valuable than a number of other interventions, such as education, infant nutrition, and physical capital. Elimination of cretinism, improvement in general intelligence and neuromotor function, and an enhanced energy level are the dividends of the elimination of iodine deficiency.
Action Plans For The International Agencies
Evaluation of the current status of ID, IDDs, and the structure of country programs has been made in a few countries by independent external teams. For permission, credibility, and future corrections, these evaluations must be requested by the respective governments. If no ID commission is operational, creation of such a body can be strongly recommended by the external team. External evaluation also assures objectivity. The external team must have access to suspect regions and must be permitted to obtain independent data. Its report should go to the responsible government agency. ICCIDD (International Council for the Control of Iodine Deficiency Disorders) has proposed guidelines for assessing progress toward the sustainable elimination of ID (see Appendix).
Independent evaluation will necessarily take time. Meanwhile, monitoring is essential and urgent. This will continue to be a high priority for agencies involved in ID and IDD control, such as ICCIDD. Efforts are being made to improve methods for measuring iodine in salt and in urine. Failure to monitor the iodine content of salt could undermine the whole structure of IDD preventive programs by allowing wide variations in iodine content to continue uncorrected (Pandav, 1994).
Strengthening the Role of Regional and Country Program Directors
The commitment and participation of groups that have a network of regional coordinators and country members involved in micronutrient nutrition, such as ICCIDD, need to be enhanced. This requires enthusiastic and dedicated leadership in addition to fiscal resources.
Enhancing Cooperative Efforts among Agencies
There are instances where interagency rivalries have paralyzed progress toward elimination of IDDs. But there are also examples of agencies that have begun to work together because of their common objective of eliminating ID. There is plenty for everyone to do.
Pursuing Relevant Research
Needed research includes basic inquiries into the nature of IDDs, the impact of prophylactic programs on the health of differing segments of a targeted society, and applied research directed toward the improvement of programs. Research costs money, and the international agencies must recognize their obligation to support acquisition of new knowledge. (Examples appear elsewhere in these paragraphs.)
Extension of a Micronutrient Database
A database in iodine nutrition has been established by ICCIDD with USAID support. It can be readily accessed on ICCIDD's homepage (http:avery.med.virginia.edu/˜jtd/iccidd/home.html), and contains country-based information on ID and IDDs and information regarding current and recent publications. Hundreds of papers appear each year that cover problems related to iodine deficiency, and many appear in journals that are not immediately available to all those in the field. Also, many of the publications derive from regional meetings or appear in agency publications that do not find their way into libraries. These elusive articles can be accessed with increasing ease through an extended database. Comparable information about iron and vitamin A could be added to this base.
Extending and Expanding Communications
E-mail is widely available to members of the ID and IDD community and is extensively used. ICCIDD has a page on the Worldwide Web, and it is linking with other databases, including those of Micronutrient Initiatives (which already
has a database on iron and vitamin A), the Salt Institute, and the Latin American Thyroid Association. Others are being developed.
Advocacy must be expanded by exposing government officials, health professionals, and the general public to the IDD message through formal and informal pathways. Regional representatives should develop and exploit contacts with the appropriate persons in government and industry to promote advocacy.
Closing Gaps in Knowledge of the Extent of ID and IDDs
The ID map of the world needs to be completed. With the current rapid progress in the campaigns against IDDs, the IDD and the USI maps require frequent updating through information supplied by ICCIDD regional representatives and the other international agencies, such as WHO and UNICEF.
Conferences and Workshops at the Country, Regional, and International Levels
Conferences and workshops have proved invaluable in sustaining enthusiasm, consolidating knowledge, and identifying needs and opportunities. They require organizational effort and financial support. The former has come from ICCIDD or its regional representatives, but the financial support has come, and will continue to come, from the international agencies; private foundations, such as the Thrasher Research Foundation and Kiwanis; and industry, such as Merck Darmstadt and segments of the salt industry.
Funding for ID, IDD action plans, and the organizations involved is currently grossly inadequate for the task of sustained correction. The bilateral and multilateral international agencies and nongovernmental organizations (NGOs) must constantly be reminded of their commitment and obligations to the correction of iodine deficiency.
Dedicated Team Approach
A useful approach to IDD elimination is offered by a team comprised of persons of diverse professional and geographical backgrounds that is organized
to work as a unit in correcting micronutrient deficiencies. The ICCIDD has been one such group since its formation in 1985. It has been a resource for the development and guidance of programs; advocacy through conferences, publications, and personal contacts; aggregating a large constituency; and research regarding the varied aspects of IDDs. Such a group can only be successful if it is comprised of professionals who are dedicated to the mission. Examples of such individuals, and their years of involvement in IDD elimination, would include Fierro-Benitez in Ecuador (35 years), Pretell in Peru (30 years), Pandav in India (20 years), Lantum in Cameroon (15 years), Kavishe in Tanzania (10 years), and others.
In summary, the following points are cited.
- The thyroid hormones are essential for normal development. Iodine, an integral component of the thyroid hormones, has no other function, although a role has been suggested, but not proven, in fibrocystic disease of the breast and stomach cancer. Iodine is scarce in most countries, and when insufficient, results in the iodine deficiency disorders (IDD). Prominent among these is retarded neuromotor and cognitive development of varying degrees of severity, depending upon the degree of the iodine deficiency.
- Although much progress has been made in the past decade in the control of iodine deficiency in many countries around the world, the problem of the disorders deriving from iodine deficiency continues to exist.
- Iodine deficiency and IDDs have largely but not entirely disappeared from North America and Western Europe, but some areas of Germany, Italy, Denmark, and Belgium continue to have suboptimal levels of iodine that require correction. ID is still present in much of the African continent, the Middle East, and large parts of Asia. It is also found in the countries of the former Soviet Union, but less is known about its extent and severity.
- The techniques available to assess ID and IDDs include palpation of the thyroid, ultrasonographic mapping of thyroid size and structure, measurements of iodine in the urine, and assays for thyroid hormone, TSH, and thyroglobulin. Of these methods, the one currently providing the most information for epidemiological purposes and the most practicable is measurement of urinary iodine.
- Universal iodization of salt is the most effective method for preventing IDDs. When the degree of IDDs demands a prophylactic program and iodized salt is not immediately available, iodinated oil may be given intramuscularly or orally as a long-term, interim preventative.
- The single most important activity in programs of IDD prevention after a program has been initiated is careful monitoring. This includes measurement of
- iodine in the salt from point of manufacture or entry to the consumer's table. Biological monitoring is also essential, and urinary iodine concentration is usually the preferred indicator. When facilities, skills, and resources are available, other biological monitoring is useful, such as measurements of TSH, T4, plasma thyroglobulin, and clinical status. Other important activities include general education regarding the role of iodine in health and continuing research on iodine deficiency and its prevention at the basic and applied levels.
- Many problems impede progress toward elimination of IDDs. Political or popular support may be lacking for a variety of reasons. The salt industry may also present difficulties. Complacency and fiscal constraints may impose barriers to success or the continuation of prophylaxis.
- By virtually any measure, the benefits to a community or country far outweigh the costs of programs.
- Action plans directed toward minimizing IDDs include internal monitoring of national programs, periodic monitoring by an independent commission, strengthening the role of regional and country program directors, enhancing cooperation among involved international agencies, expanding communications among those involved, and securing the resources needed to put the effort on a sound financial base.
Appendix: ICCIDD Guidelines For Assessment Of Progress Toward IDD Elimination
- A country with universal neonatal screening, using a sufficiently sensitive TSH assay, may be declared free of iodine deficiency if fewer than 3 percent of the newborns have TSH levels of more than 5 mU/l whole blood.
- For countries where there is no universal newborn screening, at least two of the following three criteria should be met:
- All salt for human and animal consumption in the regions where IDD is known or suspected is iodized at a recommended level at the factory. This will ensure that representative samples obtained regularly from retail outlets, or preferably from homes, have an iodine content sufficient to ensure a daily intake of 150 mg of iodine per person daily. [The actual requirement for the level of iodine in salt at the household level will vary, depending on the quality of salt, the prevailing climate conditions (warm-moist, warm-dry, or cool-moist, cool-dry), pack-aging (bulk sack with polyethylene lining or retail pack), storing, and the daily consumption of salt.]
- More than 50 percent of urine samples obtained on a regular basis in a statistically valid mode have an iodine content of 100 mg/l or
- greater, and more than 80 percent of urine samples have an iodine content of 50 mg/l or greater.
- In regions where IDD has been known or suspected, the prevalence of total goiter in representative surveys of children of school-age (6–12 years old) is less than 5 percent as ascertained by competent observers, and preferably confirmed by ultrasonography, if available.
- In addition to meeting two of the above three criteria, sustainability should be established according to the following guidelines, as applicable:
- A national IDD program has been set up; it is responsible for continuous monitoring of the status of iodine deficiency and of iodine content of salt, according to established criteria. The responsibility also includes mandatory public reporting of IDD status at regular specified intervals (e.g., every 3 to 5 years), by designated units (e.g., the program, the Ministry of Health) that are technically competent and adequately financed.
- The government, the private sector, and consumers have a high awareness of iodine deficiency and are committed to its sustained elimination.
- The salt industry has the commitment, technical resources, and responsibility (frequently mandated by legislation) to sustain effective iodization of salt, including its production, distribution, and monitoring.
- The supply of iodine for salt iodization is ensured, either through private purchase by the salt manufacturers or through the government.
- The availability and perceived health benefits of iodized salt, despite its marginally higher cost, compel consumers to buy iodized salt rather than the noniodized product.
- The IDD program has ready access to local and regional facilities to measure iodine levels in salt and to a central laboratory, competent to measure iodine in urine or neonatal blood TSH, or both, at affordable rates.
There is a voluminous literature relating to iodine deficiency. The references given below can serve only as point of entry into that literature.
Ansell, J. E. 1991. The blood in hypothyroidism. In The Thyroid, L. E. Braverman and R. D. Utiger, eds., p. 1022. Philadelphia: J. B. Lippincott.
Asuquo, M. H. 1995. How salt companies can take the lead in iodization: an example from Nigeria. ICCIDD Newsl. 11:31.
Benmiloud, M., M. L. Chaouki, R. Gutekunst, et al. 1994. Oral iodized oil for correcting iodine deficiency: optimal dosing and outcome indicator selection. J. Clin. Endocrinol. Metab. 79:20.
Bleichrodt, N., R. Escobar del Rey, G. Moreale de Escobar, I. Garcia, and C. Rubio. 1989. Iodine deficiency. Implications for mental and psychomotor development in children. In Iodine and the Brain, G. R. DeLong, J. Robbins, and P. G. Condliffe, eds. New York: Plenum.
Braverman, L. E., and R. D. Utiger, eds. 1996. The Thyroid, 7th ed. Philadelphia: J. B. Lippincott.
Cao, X-Y, X-M Jiang, A. Kareem, et al. 1994. Iodination of irrigation water as a method of supplying iodine to a severely iodine-deficient population. Lancet 344:107.
Connolly, K. J., P. O. D. Pharoah, and B. S. Hetzel. 1979. Fetal iodine deficiency and motor performance during childhood. Lancet ii:1149.
Contempre, B., J. E. Dumont, J-F Denef, and M-C Many. 1995. Effects of selenium deficiency on thyroid necropsis, fibrosis and proliferation: a possible role in myxedematous cretinism. Eur. J. Endocrinol. 133:99–109.
Correa, H. 1980. A cost–benefit study of iodine supplementation programs for the prevention of endemic goiter and cretinism. In Endemic Goiter and Endemic Cretinism, J. B. Stanbury, ed., pp. 566–588. New York: John Wiley & Sons.
DeLange, F. 1994. The disorders induced by iodine deficiency. Thyroid 4: 107–128.
DeLange, F., G. Benker, P. Caron, O. Eber, W. Ott, F. Peter, et al. In press. Thyroid volume and urinary iodine in European schoolchildren. Standardization of values for assessment of iodine deficiency. Eur. J. Endocrinol.
DeLong, G. R. 1989. Observations on the Neurology of Endemic Cretinism in Iodine and the Brain, G. R. DeLong, J. Robbins, and P. G. Condliffe, eds. New York: Plenum.
DeLong, G. R., J. Robbins, and P. G. Condliffe, eds. 1989. Iodine and the Brain. New York: Plenum.
Dodge, P. R., I. Ramirez, and R. Fierro-Benitez. 1969a. Neurological Aspects of Endemic Cretinism. In Endemic Goiter, J. B. Stanbury, ed. Pan American Health Organization Scientific Publication No. 193, Washington, D.C.
Dodge, P. R., H. Palkes, R. Fierro-Benitez, and I. Ramirez. 1969b. Effect on intelligence of iodine in oil administered to young Andean children—a preliminary report. In Endemic Goiter, J. B. Stanbury, ed. Pan American Health Organization Scientific Publication No. 193, pp. 378–380, Washington, D.C.
Dunn, J. T. 1991. IDD control in Latin America: Guatemala. IDD Newsl. 7:(2)12.
Dunn, J. T. 1994a. Societal implications of iodine deficiency and the value of its prevention. In The Damaged Brain of Iodine Deficiency, J. B. Stanbury, ed., pp. 309–314. New York: Cognizant Communications.
Dunn, J. T. 1994b. Bhutan makes dramatic progress toward IDD elimination. IDD Newsl. 10:23.
Dunn, J. T. 1995. Technical aspects of salt iodization: an update. IDD Newsl. 11:26–30.
Dunn, J. T. 1996a. Bolivia conquers iodine deficiency. IDD Newsl. 12:33–34.
Dunn, J. T. 1996b. Nigeria advances towards IDD elimination. IDD Newsl. 12:27–28.
Dunn, J. T. 1996c. Seven deadly sins in confronting endemic iodine deficiency, and how to avoid them. J. Clin. Endocrinol. Metabl. 81:1332–1335.
Dunn, J. T., and F. van der Harr. 1990. A Practical Guide to the Correction of Iodine Deficiency. Brussels: ICCIDD.
Dunn, J. T., H. E. Crutchfield, R. Gutekunst, and A. D. Dunn. 1993a. Methods for Measuring Iodine in Urine. ICCIDD/UNICEF/WHO. The Netherlands.
Dunn, J. T., et al. 1993b. Two simple methods for measuring iodine in urine. Thyroid 3:119–128.
Fernandez, R. L. 1990. A Simple Matter of Salt. Berkeley: University of California Press.
Fierro-Benitez, R., I., Ramirez, E. Estrella, et al. 1969. Iodized oil in the prevention of endemic goiter and associated defects in the Andean region of Ecuador. In Endemic Goiter, J. B. Stanbury, ed., pp. 306–340 (see also pp. 341–365). Washington, D.C.: PAHO.
Fisch, A., E. Pichard, T. Prazuk, et al. 1993. A new approach to combating iodine deficiency in developing countries: the controlled release of iodine in water by a silicone elastomer. Am. J. Publ. Health 83:540–545.
Gaitan, E., ed. 1989. Environmental Goitrogenesis. Boca Raton, Fla.: CRC.
Greene, L. S. 1973. Physical growth and development, neurological maturation and behavioral functioning in two Andean Ecuadorian communities in which goiter is endemic. Am. J. Phys. Anthropol. 38:119–134.
Gutekunst, R. 1993. Iodine deficiency costs Germany over one billion dollars per year. IDD Newsletter 9:29-31.
Halpern, J. P. 1994. The motor deficit in endemic cretinism and its implications for the pathogenesis of the disorder. In The Damaged Brain of Iodine Deficiency, J. B. Stanbury, ed. New York: Cognizant Communications.
Havron, M. D. 1988. Bolivia fights iodine deficiency. IDD Newsl. 4:1–3.
Hershman, J. M., G. A. Melnick, and R. Fastner. 1986. Economic consequences of endemic goiter. In Towards the Eradication of Endemic Goiter, Cretinism, and Iodine Deficiency, J. T. Dunn, E. A. Pretell, C. H. Daza, and F. E. Viteri, eds. Washington, D.C.: PAHO.
Hetzel, B. S. 1989a. National IDD control programs. In The Story of Iodine Deficiency, pp. 123–144. New York: Oxford Medical Publications.
Hetzel, B. S., ed. 1989b. The Story of Iodine Deficiency. New York: Oxford Medical Publications.
Hetzel, B.S., and C. S. Pandav. 1996. S.O.S. for a Billion, 2d ed. New York: Oxford University Press.
Hetzel, B. S., C. H. Thilly, R. Fierro-Benitez, et al. 1980. Iodized oil in the prevention of endemic goiter and cretinism. In Endemic Goiter and Endemic Cretinism, J. B. Stanbury and B. S. Hetzel, eds., pp. 513–532. New York: John Wiley & Sons.
Hetzel, B. S., J. T. Dunn, and J. B. Stanbury. 1987. The Prevention and Control of Iodine Deficiency Disorders. New York: Elsevier.
Holman, J. C. M., and W. McCartney. 1960. Iodized salt. In Endemic Goiter, pp. 411–441. Geneva: WHO.
Ingenbleek, Y. 1983. Vitamin A deficiency impairs the normal mannosylation, conformation and iodination of thyroglobulin: a new etiological approach to endemic goiter. Experientia 38(Suppl. 44):264.
Kopp, P., E. T. Kimura, S. Aeschmann, et al. 1994. Polyclonal and monoclonal thyroid nodules coexist within human multinodular goiters. J. Clin. Endocrinol. Metab. 89:134.
Mannar, V. G. 1996. The iodization of salt for the elimination of iodine deficiency disorders . In S.O.S. for a Billion, B. S. Hetzel and C. S. Pandav, eds., pp. 99–118. New York: Oxford University Press.
Marine, D. 1923. Prevention and treatment of simple goiter. Atlantic Med. J. 26:437–443.
Marine, D., and O. P. Kimball. 1921. The prevention of simple goiter in man. J. Am. Med. Assoc. 77:1068.
Markel, H. 1987. ''When it rains it pours": endemic goiter, iodized salt, and David Murray Cowie, M.D. Am. J. Public Health 77:219–229.
McMichael, A. J., J. D. Potter, and B. S. Hetzel. 1980. Iodine deficiency, thyroid function and reproductive failure. In Endemic Goiter and Endemic Cretinism, Iodine Nutrition in Health and Disease, J. B. Stanbury and B. S. Hetzel, eds., p. 445. New York: John Wiley & Sons.
Missler U., R. Gutekunst, and W. G. Wood. 1994. Thyroglobulin is a more sensitive indicator of iodine deficiency than thyrotropin: development and evaluation of dry blood spot assays for thyrotropin and thyroglobulin in iodine-deficient geographical areas. Eur. J. Clin. Chem. Clin. Biochem. 32:137–143.
Pandav, C. S. 1994. The economic benefits of the elimination of IDD. In S.O.S. for a Billion, B. S. Hetzel and C. S. Pandav, eds., pp. 128–145. New York: Oxford University Press.
Pandav, C. S. and Mannar, M. G. V. 1996. IDD in livestock—ecology and economics. In S.O.S. for a Billion, B. S. Hetzel and C. S. Pandav, eds., p. 375. New York: Oxford University Press.
Parma, L., J. Duprez, J. Van Sande, et al. 1994. Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning adenomas. Nature 335:649.
Pharoah, P. O. D., I. H. Buttfield, and B. S. Hetzel. 1971. Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy. Lancet i: 308.
Riccabona, G. 1972. Die Endemische Struma. Vienna: Urban & Schwarzenberg.
Stanbury, J. B., ed. 1994. The Damaged Brain of Iodine Deficiency. New York: Cognizant Communications.
Stewart, J. C., and G. I. Vidor. 1976. Iodine-induced thyrotoxicosis: a common unrecognized condition? Brit. Med. J. i:372.
Sullivan, K.M., Houston, R., Gorstein, J. and Cervinskas, J., eds. 1994. Monitoring Universal Salt Iodization Programmes. WHO, UNICEF, PAMM, and ICIDD. Obtainable from WHO, Geneva or UNICEF, New York.
Suwanik, R., R. Pleehachinda, C. Pattanachak, et al. 1989. Simple technology provides effective IDD control at the village level in Thailand. IDD Newsl. 5:1–6.
Taylor, S. 1953. The evolution of nodular goiter. J. Clin. Endocrinol. 12:1232.
Thilly, C., R. Lagasse, G. Roger, et al. 1980. Impaired fetal and postnatal development and high perinatal death-rate in a severe iodine deficient area. In Thyroid Research VIII, J. R. Stockigt and S. Nagataki, eds., p. 20. Canberra: Australian Academy of Sciences.
Todd, C. H., T. Allain, Z. A. R. Gomo, J. A. Hasler, M. Ndiweni, and E. Oken. 1995. Increase in thyrotoxicosis associated with iodine supplementation in Zimbabwe. Lancet 346:1563–1564.
UNICEF (United Nations Children's Fund). 1991. Training Course in Ultrasonography for Endemic Goiter. New York: Medizinische Universitat zu Lubeck. Also refer to
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