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Endocrine Care |
Department of Diabetes and Endocrinology (K.G., S.B., K.B.), Westmead Hospital, New South Wales, Australia 2145; Royal Hobart Hospital (J.R.B., V.P.) and Menzies Centre for Population Health Research (K.H.), University of Tasmania, Hobart, Tasmania, Australia 7001
Address all correspondence and requests for reprints to: Dr. John R. Burgess, M.D., F.R.A.C.P., Consultant Endocrinologist, Department of Diabetes and Endocrinology, Royal Hobart Hospital, G.P.O. Box 1061L Hobart 7001, Tasmania, Australia. E-mail: . jburges{at}utas.edu.au
Abstract
Even mild iodine deficiency during early childhood and pregnancy has the potential to impair neurological development. Often considered a problem of developing nations, a number of industrialized countries are at risk of deficiency. Despite past success with intentional and unintentional iodine fortification, recurrence of deficiency is an ever-present risk. Tasmania, an island state of the Commonwealth of Australia, has a history of endemic iodine deficiency, which was successfully eliminated by iodine prophylaxis initiated in 1950. In this report we describe a formal assessment of iodine nutrition in the Tasmanian population, 50 yr after initiation of the prophylaxis program. The requirements and obstacles to achieving sustainable iodine prophylaxis in an otherwise affluent community are considered. A cross-sectional study was undertaken during the yr 2000. Urinary iodine excretion (UIE) and thyroid ultrasonography were assessed in a representative statewide sample of school-age children. Children (n = 225) aged 4 to 17 yr from throughout Tasmania were studied. The sample comprised 99 girls and 126 boys. The median UIE was 84 µg/liter (87 µg/liter for males and 81 µg/liter for females), with UIE 50 µg/liter or less in 20%. Based on age-specific World Health Organization/International Council for the Control of Iodine Deficiency Disorders normative data for thyroid volume, the prevalence of elevated thyroid volume was 5.3% for boys and 3.5% for girls. However, after correcting the World Health Organization/International Council for the Control of Iodine Deficiency Disorders reference data, the prevalence increased to 24.6% for boys and 20.7% for girls. No significant difference in the thyroid volumes was found between males and females in this study. These data confirm the recurrence of mild iodine deficiency in Tasmania. The failure of sustained iodine prophylaxis highlights the universal importance of persistent surveillance, use of sustainable measures, public awareness, and a specific legislative framework for managing ongoing iodine prophylaxis. Our findings also emphasize the importance of accurate reference data for assessment thyroid volume.
A DIET DEFICIENT in iodine is associated with a wide spectrum of consequences, collectively known as iodine deficiency disorders (IDDs) (1, 2, 3). Although endemic goiter is the most visible effect of iodine deficiency, it is the fetal and neonatal neurocognitive sequelae that are most deleterious (3, 4, 5). The neurological consequences of severe iodine deficiency are overtly manifest as endemic cretinism, in which cognitive and auditory impairment is accompanied by pyramidal and extrapyramidal signs (3, 4). However, even mild iodine deficiency has the potential to produce subtle attenuation of intellectual aptitude and auditory function (5, 6). Although these deficits may not be overtly evident in the individual, the socioeconomic consequences for a population are potentially serious (7, 8). Although the precise impact of mild iodine deficiency is uncertain, the average intelligence quotient of communities with more severe iodine deficiency could be reduced by as much as 13.5 intelligence quotient points (9).
Following the World Summit for Children in 1990, most nations pledged to eliminate iodine deficiency by the yr 2000 (7, 8). International agencies such as the International Council for the Control of Iodine Deficiency Disorders (ICCIDD), World Health Organization (WHO), and United Nations International Children’s Emergency Fund, in conjunction with support from industrialized nations such as Australia, achieved some success, particularly in developing countries (7, 8). However, although IDD is often considered a disease of less affluent nations, a number of industrialized nations including the United States, Australia, the United Kingdom, and many western European countries contain endemias of variably treated iodine deficiency (10, 11, 12, 13).
In the case of Australia, the United States, and the United Kingdom, iodine sufficiency was achieved by the efforts of a past generation, often through a combination of both active and serendipitous iodine fortification (10, 11, 12). Although public health strategies using iodized salt and bread have been important direct initiatives, the role of silent prophylaxis as a byproduct of commercial activity cannot be underestimated (10, 11, 12). Use of iodine-containing products in agriculture, either to improve livestock nutrition and boost farm productivity or as adventitious contaminants (such as in the case of the iodophor disinfectants widely used by the dairy industry), has been particularly important (12, 13, 14, 15).
Sustained elimination of iodine deficiency also requires accurate classification of population iodine intake (16, 17). Contemporary screening and monitoring programs frequently use measures of urine iodine excretion (UIE), thyroid volume by ultrasonography, and neonatal TSH derived from population-based newborn screening (16, 17, 18). The interpretation of thyroid volumetric data in relation to mild iodine deficiency is currently problematic (19, 20, 21, 22). It has been suggested the WHO/ICCIDD reference criteria for thyroid volume are too high, potentially resulting in underrecognition of elevated thyroid volume associated with mild iodine deficiency (22). In a recent report, Zimmermann et al. (22) proposed a factor for correcting systematic bias in the WHO/ICCIDD reference data.
Tasmania is a mountainous island state at the southeastern tip of the Australian mainland. Long recognized as an area of endemic goiter, a program of iodine supplementation was introduced in 1950 (23). Initially school-age children were provided potassium iodide tablets, and since 1966 potassium iodate was added to bread to achieve universal prophylaxis (23, 24). However, during the early 1960s, serendipitous iodine contamination of milk by newly introduced iodophor dairy disinfectants led to a dramatic increase in iodine intake (23, 24). Initially not appreciated as a source of dietary iodine, it was only following a marked rise in iodine-induced hyperthyroidism that milk iodine levels were evaluated (23, 25). A maximum milk iodine content was subsequently enforced (23, 24).
Milk proved so successful, that since 1974 iodization of bread was discontinued, and milk provided the primary method of repletion (23, 24). However, milk iodine content remained an adventitious consequence of commercial activity. Unlike maximum iodine concentration, there was no legislative framework to ensure a minimum level. Effective monitoring of human iodine nutrition and milk iodine content by the Tasmanian Health Department continued for over two decades (15). From the late 1960s, assessments of UIE demonstrated sustained iodine sufficiency with iodine/creatinine ratios greater than100 µ/g in more than 80% of individuals studied (23). Some decline in UIE was noted in studies from the mid-1980s, although the median iodine/creatinine ratio remained mostly greater than100 µ/g (23). In the absence of overtly recurrent deficiency and given satisfactory milk iodine levels, routine annual monitoring had lapsed by the late 1980s (23, 24).
The belief also existed that free and regular trade with mainland Australia in conjunction with the diverse dietary practices of a contemporary society would prevent recurrence of iodine deficiency. However, by the mid-1990s, anecdotal clinical evidence suggested a rise in the prevalence and severity of thyroid disease related to iodine deficiency (24, 26).
In 1996 a preliminary Health Department evaluation involving 93 8-yr-old children indicated moderate iodine deficiency with a UIE of 42 µg/liter (27). However, this small group was not representative of the Tasmanian population, deriving as it did from a cohort of children initially assembled to study risk factors for sudden infant death syndrome (28). This cohort was from southern Tasmania and exhibited a low socioeconomic status (SES) bias. A subsequent Health Department study in 1999 assessed 241 children aged between 4 and 14 yr and randomly selected from throughout Tasmania. This study indicated mild iodine deficiency with a median UIE of 75 µg/liter. Thyroid ultrasonography was not undertaken in these studies, and it remained unclear as to whether geographic and socioeconomic factors were important determinants of iodine nutrition in contemporary Tasmania.
In this report we describe a statewide assessment of contemporary iodine nutrition in Tasmania using assessments of UIE and thyroid ultrasonography. The assessment was undertaken in the yr 2000 to coincide with the 50th anniversary of the initiation of population-based iodine supplementation and monitoring.
Subjects and Methods
Study population
Tasmania is an island state of the Commonwealth of Australia with a population of relatively stable size and structure. There are three major population centers located in the south, north, and northwest of Tasmania where three quarters of the population reside. The remainder of the population lives in a semirural setting.
Study subjects
The parents or guardians of children who had participated in the two prior public health studies (undertaken in 1996 and 1999) were contacted with an invitation to participate in the current study. Group 1: In 1996, 93 children 8 yr old were randomly selected from participants in a study of risk factors for sudden infant death syndrome (28). Assessment of UIE at this time demonstrated a median of 42 µg/liter. This group was from southern Tasmania and exhibited a low SES bias. Group 2: In 1999 a group of 241 schoolchildren aged between 4 and 14 yr was selected randomly from throughout Tasmania. These children derived from 30 Tasmanian primary schools (including government primary and district schools, nongovernment private schools, and special schools) with a probability proportional to the number of eligible students. Individual children were selected at random from school enrollment lists. This study showed mild iodine deficiency with a median UIE of 75 µg/liter.
For the purposes of the current study, children from groups 1 and 2 were defined as index children and were sought for follow-up in the yr 2000. Of the original 334 index children, 10 subjects (five from each group) were no longer residing in Tasmania and deemed ineligible for participation. Of the 88 eligible index children from group 1 and 236 eligible index children in group 2, 21 (24%) and 88 (37%), respectively, agreed to participate in an assessment of UIE and thyroid volume (Table 1
). In addition, the siblings (aged 4–17 yr) of each index child were also invited to undergo assessment of UIE and thyroid ultrasound. An additional 116 siblings relating to 85 of the index children were assessed, resulting in a total of 225 participants.
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UIE
Morning urine samples were collected for assessment of UIE. Urine iodine analysis was performed using a modified acid digestion method (method E) based on the reaction between cerium Iv and arsenic III (Sandell Kolthoff reaction) using a Technicon autoanalyzer II (Pulse Instrumentation, Saskatoon, Canada). Samples were analyzed by the Institute of Clinical Pathology and Medical Research at Westmead Hospital in Australia. The method used by the institute is validated against the manual acid digestion method (29, 30). The results were expressed as microgram of iodine per liter of urine.
Thyroid ultrasound
Ultrasonographic assessment was undertaken by experienced sonographers using a number of ultrasound machines. In each case ultrasound was performed in the supine position with the neck hyperextended and using a 7.5-MHz transducer. Volume (milliliter) of each lobe was calculated according to the formula: width (centimeter) x length (centimeter) x thickness (centimeter) x 0.479 and the lobe volumes were added. The volume of the isthmus was not included. Thyroid glands were classified as normal or enlarged using both the WHO/ICCIDD reference data [thyroid volume for age and thyroid volume for body surface area (BSA)] and the corrected WHO/ICCIDD reference data [multiplying the current WHO/ICCIDD values by 0.71 as described by Zimmerman et al. (22)]. Thyroid volume greater than the 97th percentile were considered elevated. The denominators for calculating the prevalence of elevated thyroid volume are based on those children with either age or BSA within the ranges relevant to the respective WHO/ICCDD data sets. Thus, only those children aged 6–15 yr (114 boys and 87 girls) or those children with BSA 0.8–1.7m2 (118 boys and 87 girls) were used in the relevant prevalence calculations.
Anthropometry
Weights and standing heights were collected. The BSA (square meters) was calculated by using the formula: BSA = weight (kg) (0.425) x height (cm) (0.725) x 71.84 x 10-4.
Statistical methods
Data were analyzed using the statistical software package (version 10.0, SPSS, Inc., Chicago, IL). Analysis of covariance was used to test for statistical significance. The thyroid volumes were log transformed before analysis to ensure approximate normality. Univariate general linear models were fitted to the log-transformed thyroid volumes. The effects of age BSA and gender were corrected for within-family dependencies by fitting family identity as a random factor in all analyses. The 94% prediction intervals for individual log (thyroid volume) scores by age or BSA were exponentiated to give the predicted 3rd and 97th percentiles for thyroid by age or BSA.
Results
A total of 225 children aged 4–17 yr from throughout Tasmania were studied. The sample comprised 99 girls and 126 boys (Table 1
). The overall median UIE and interquartile range was 84 µg/liter (57–110) [87 µg/liter (59–111) for males and 81 µg/liter (54–111) for females], with the UIE 50 µg/liter or less in 20% children (Fig. 1). The only independent predictor of UIE was region. Specifically, the northeast region of Tasmania had significantly higher levels than other parts of Tasmania (102 µg/liter vs. 81 µg/liter) using the least significant difference method of multiple comparisons (P = 0.004). Socioeconomic status did not significantly influence iodine nutrition with median UIE of 82 µg/liter (57–108) and 88 µg/liter (54–138) in average and low SES subgroups, respectively (Table 1).
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). However, after correcting WHO/ICCIDD normative data as described by Zimmermann et al. (22), the prevalence was 24.6% CI (16.7, 32.5) based on age and 22.0% CI (14.6, 29.5) based on BSA (Fig. 2B).
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). However, the prevalence using the corrected WHO/ICCIDD data were 20.7% CI (12.0, 29.4) based on age and 20.7% CI (12.0, 29.4) based on BSA (Fig. 3B).
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Discussion
Iodine deficiency has recurred in Tasmania. This is despite the well-documented nature of the endemia, a previously successful fortification program, and the current affluence of the community. The results of the current study are consistent with the findings of prior public health studies undertaken in 1996 and 1999. The recurrence of iodine deficiency in Tasmania highlights the importance of persistent surveillance, use of sustainable repletion measures, public awareness, and a specific legislative framework for managing ongoing iodine prophylaxis in regions of endemic deficiency.
The possibility of iodine deficiency being more pronounced in families with lower SES was not confirmed in the current study. With the exception of a higher UIE in Tasmania’s northeast, compared with other parts of Tasmania, there was no significant relationship between iodine excretion and thyroid volume with SES or geographic region. The reason for differential in UIE between Tasmania’s sparsely populated northeast and other regions is unclear and warrants confirmation and further evaluation in subsequent studies. A potential limitation of this study relates to the selection of more than one child per household. Although this introduces dependence between individual observations because children within the same household are likely to share similar dietary and other determinates for iodine nutrition and thyroid volume, statistical correction for this was undertaken.
The relatively low level of participation in this study (34% of total invitees) may reflect that this was a follow-up project using two existing cohorts. This was the second request for parents to permit their child’s participation in iodine nutritional research, and unlike their initial involvement in which only UIE was assessed, participation in the current study required both a greater degree of investigation (necessity to attend for ultrasonography) and more extensive familial involvement (assessment of siblings). Although lower rates of participation increase the likelihood of bias, it is noteworthy that the current finding of iodine deficiency in Tasmania is supported by the original 1996 and 1998 studies of UIE in the source cohorts.
Iodine prophylaxis must be monitored by regular and appropriate population assessment. Regular measures of dietary iodine intake as well as biological outcome variables such as thyroid volume and neonatal TSH are essential. The optimal screening program for any given population will vary depending on geography, resources, and the population structure. However, in all cases, appropriate assessment methodologies and reference ranges are required before appropriate conclusions can be drawn. In addition to UIE, biologically relevant end points should be assessed. Assessments of neonatal TSH and thyroid volume in children are perhaps the most relevant and easily measured (16, 17, 18).
A number of recent publications have highlighted the need for revision of WHO/ICCIDD reference data for thyroid volume (17, 19, 20, 21, 22). Our results demonstrate the potential insensitivity of these reference criteria for identifying mild iodine deficiency. Although the Tasmanian population satisfies UIE criteria for mild iodine deficiency, the current WHO/ICCIDD normative data for both age and BSA indicate the Tasmanian population is not goitrous. However, Zimmermann et al. (22) have proposed a correction factor to overcome a recently quantified systematic bias in these normative data. Multiplication of the current WHO/ICCIDD values by a correction factor of 0.71 was suggested. Our data demonstrate the relevance of using this correction (Figs. 1 and 2). Using the corrected reference ranges, the prevalence of elevated thyroid volume based on BSA increased from 6.1% to 22.6% for boys and 3.5% to 16.1% for girls.
Australia, like the United States and the United Kingdom, has been considered iodine sufficient. Although each has a history of endemic deficiency, past interventions have normalized iodine nutrition. However, reliance on past success is not sufficient to ensure ongoing elimination of IDD. In places such as Tasmania in which iodine repletion is the indirect result of commercial activity, special caution and ongoing monitoring is required. It is perhaps relevant to other parts of Australia and internationally that iodophor usage is in decline because of changes in industry practice (8, 11, 13, 14, 30). Although milk is still a potential source of some iodine, levels are likely to continue to decline. Similarly, iodized salt is infrequently used in households both because of its minor market share and declining salt usage in general because of health campaigns against salt consumption.
This is well illustrated by the current situation in Tasmania. Iodine repletion has relied on the indirect consequence of a commercial activity (use of iodophors in the dairy industry), a strategy that ultimately has proved a failure. Similarly, it was argued in the late 1980s that liberal interstate trade between Tasmania and continental Australia would prevent the recurrence of iodine deficiency. This is particularly interesting because current studies from mainland Australia suggest that, but for past iodophor usage, key regions of continental Australia are also inherently iodine deficient (14, 30). The Tasmanian experience is similar to that reported in Europe, in which extensive trade in farm produce has not resolved regional endemic iodine deficiency (13).
It is clear that complex commercial and social forces have the potential to undo past successes in combating IDD. Overreliance on adventitious sources of iodine is hazardous. Commercial activities are driven by market forces and cost considerations, the imperatives of which lead to ever-changing practices. If the source, quantity, and efficacy of iodine repletion is not clearly identified, continuously monitored, and appropriately regulated by legislation, relapse of iodine deficiency is almost assured.
It is noteworthy that in the United States iodine intake has been steadily declining over recent decades (12). Although recognized recently in an evaluation of National Health and Nutrition Examination Surveys I and III, it is not clear that the cause and significance of this ongoing decline has been appreciated by either the government or broad community. Complacency in conjunction with one or all of Dunn’s (7, 8) seven deadly sins would appear as relevant to affluent industrialized countries as to the third world.
Conclusions
These data confirm the recurrence of iodine deficiency in Tasmania. The failure of sustained iodine prophylaxis highlight the universal importance of persistent surveillance, use of sustainable repletion measures, public awareness, and a specific legislative framework for managing ongoing iodine prophylaxis. Similarly, economic transition to affluence is not alone sufficient to overcome the underlying geologic determinants of iodine nutrition in an endemia. In all cases, constant vigilance is required to control this readily preventable yet potentially devastating nutritional disorder.
Our findings also emphasize the importance of accurate reference data for thyroid volumetric determination of iodine sufficiency. For interpretation and correct assessment of thyroid volume measurements, it seems appropriate to use ethnically appropriate reference values (if available) and thyroid size should be corrected for BSA.
Acknowledgments
Footnotes
This work was supported by a Dick Buttfield Research Fellowship.
Abbreviations: BSA, Body surface area; CI, confidence interval; ICCIDD, International Council for the Control of Iodine Deficiency Disorders; IDD, iodine deficiency disorder; SES, socioeconomic status; UIE, urine iodine excretion; WHO, World Health Organization.
Received October 2, 2001.
Accepted February 25, 2002.
References
This article has been cited by other articles:
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  G. Stilwell, P. J. Reynolds, V. Parameswaran, L. Blizzard, T. M. Greenaway, and J. R. Burgess The Influence of Gestational Stage on Urinary Iodine Excretion in Pregnancy J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1737 - 1742. [Abstract] [Full Text] [PDF]
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A. McElduff, P. McElduff, V. Wiley, and B. Wilcken Neonatal Thyrotropin as Measured in a Congenital Hypothyroidism Screening Program: Influence of the Mode of Delivery J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6361 - 6363. [Abstract] [Full Text] [PDF]
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