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Iodine deficiency in ambulatory participants at a Sydney teaching hospital: is Australia truly iodine replete?

Jenny E Gunton, Graham Hams, Marcelle Fiegert and Aidan McElduff
Med J Aust 1999; 171 (9): 467-470.
Research

Iodine deficiency in ambulatory participants at a Sydney teaching hospital: is Australia truly iodine replete?

Jenny E Gunton, Graham Hams, Marcelle Fiegert and Aidan McElduff

MJA 1999; 171: 467-470
For editorial comment, see Eastman

Abstract - Introduction - Methods - Results - Discussion - References - Authors' details
- - More articles on Endocrinology


Abstract Objective: To assess iodine status in four separate groups -- pregnant women, postpartum women, patients with diabetes mellitus and volunteers.
Design and setting: Prospective cross-sectional study at a tertiary referral hospital in Sydney.
Participants: 81 pregnant women attending a "high risk" obstetric clinic; 26 of these same women who attended three months postpartum; 135 consecutive patients with diabetes mellitus attending the diabetes clinic for an annual complications screen; and 19 volunteers. There were no exclusion criteria.
Methods: Spot urine samples were obtained, and urinary iodine was measured by inductively coupled plasma mass spectrometer.
Outcome measures: Iodine status based on urinary iodine concentration categorised as normal (> 100 µg/L), mild deficiency (51-100 µg/L) and moderate to severe deficiency (< 50 µg/L).
Results: Moderate to severe iodine deficiency was found in 16 pregnant women (19.8%), five postpartum women (19.2%), 46 patients with diabetes (34.1%) and five volunteers (26.3%). Mild iodine deficiency was found in an additional 24 pregnant women (29.6%), nine postpartum women (34.6%), 51 patients with diabetes (37.8%) and 9 normal volunteers (47.4%). Median urinary iodine concentration was 104 µg/L in pregnant women, 79 µg/L in postpartum women, 65 µg/L in patients with diabetes mellitus and 64 µg/L in volunteers.
Conclusions: The high frequency of iodine deficiency found in our participants suggests that dietary sources of iodine in this country may no longer be sufficient. Further population studies are required.


Introduction It is currently believed that iodine deficiency does not exist in Australia.1,2 However, iodine status is seldom, if ever, measured in routine clinical care, and iodine deficiency may have significant adverse consequences, particularly during pregnancy (Box 1). Box 2 shows some of the reasons why iodine intake in Australia may be inadequate.

The recommended daily intake (RDI) of iodine is 100 µg daily for the general population and 150-200 µg daily for women who are pregnant or breastfeeding6-8,10 (iodine demand increases during pregnancy because of increased renal clearance and fetal iodine transfer).

Approximately 90% of iodine is excreted in the urine,1,11 and iodine status is usually assessed by measuring urinary iodine concentration.

The accepted minimum adequate level of urinary iodine is 100 µg/L, and levels above this are considered normal.1,6-9,12 Urinary iodine concentrations below 25 µg/L are classified as severe deficiency, and are associated with an increased risk of cretinism; 26-50 µg/L is classified as moderate deficiency, and 51-100 µg/L is regarded as mild iodine deficiency.1,6-9,12 The World Health Organization (WHO) recommends that the median urinary iodine concentration for populations as a whole should be more than 100 µg/L, that less than 20% of the population should have a urinary iodine concentration below 50 µg/L, and that no cretinism occurs.12

Having previously found low levels of free thyroxine in pregnant women,13 and in light of the adverse consequences of iodine deficiency during pregnancy, we initially set out to test the iodine status of a group of pregnant women. We subsequently included other groups to widen our investigation of iodine status.


Methods

Study participants
Our study was conducted at a tertiary referral hospital in Sydney. Participants in the study included women who attended a specialist "high risk" obstetric clinic, patients of both sexes with diabetes who attended the hospital's diabetes clinic, and healthy, non-pregnant volunteers recruited after a presentation about iodine.

Participants thus comprised 81 consecutive pregnant women who attended the obstetric clinic between 1 August 1998 and 1 April 1999, 26 of these same women who were reassessed at three months postpartum, 135 consecutive patients who attended the diabetes clinic for an annual complications screen between 1 November 1998 and 1 February 1999, and 19 volunteers recruited between 1 February and 1 July 1999. All participants provided a routine urine sample. There were no exclusion criteria.

One of the 81 pregnant women had thyrotoxicosis as a result of Graves' disease -- she particpated before commencing therapy. Twenty-two of the patients attending the diabetes clinic (16.1%) had type 1 diabetes, 103 (76.3%) had type 2 diabetes and 10 (7.5%) had impaired glucose tolerance.

One of the patients with diabetes had recently received iodine-containing intravenous contrast medium during a coronary angiogram, and one was taking amiodarone. No other participant was known to have received contrast medium, or to be taking amiodarone or iodine supplements.

Urinary iodine measurement
Urinary iodine concentrations were determined by means of a Varian UltraMass inductively coupled plasma mass spectrometer with SPS-5 autosampler (Varian Inc., Palo Alto, California, USA). The measurement was calibrated over a range of 0-1000 µg iodine per litre. The lower limit of detection for the assay was 2 µg/L. The reproducibility of the assay as represented by the 100 µg/L calibrator assessed over three months was ± 6 µg/L (± 2 SD). Comparison with the colorimetric/Sandell-Koltkoff reaction method showed a highly significant correlation (P < 0.001; see Box 3). Other authors have also compared the methods and found high correlation.14 In particular, no systematic biases were found at low iodine concentrations.

Some investigators use the urinary iodine/creatinine ratio to determine iodine status.1,14 We thus measured urinary creatinine by the Creatinine Jaffa method (Boehringer Mannheim Systems, Mannheim, Germany) and calculated iodine/creatinine ratios (µg iodine/g creatinine) for each participant. The correlation between urinary iodine and iodine/creatinine ratio was high for non-pregnant participants (r = 0.969; P < 0.001) and lower for the pregnant group (r = 0.419; P < 0.001).

Twenty-four-hour urinary iodine measurement may be used to assess iodine status,6 but this method can be unreliable because of incorrect or incomplete collection,15 and is less practical than spot samples for population surveys.9,12 To compare this method with our spot sampling, we selected six pregnant women (on the basis of their spot urine concentrations to cover a range of values) who collected 24-hour urine samples for iodine content measurement. The correlation was highly significant (r2 = 0.82), thus confirming that spot urine samples were a reliable way of measuring iodine status.

As part of routine care, 70 of the 81 pregnant women and 121 of the 135 patients with diabetes had thyroid function tests. Free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels were measured by means of an automated chemiluminescence system (Chiron Diagnostics, Scoresby, Vic.).

We did not seek ethical approval for this study as it involved no deviation from usual care, except in the case of the 19 volunteers who agreed to provide a urine sample.

Statistical analysis
We used SPSS for statistical analysis.16 Means are expressed with ± 2 standard deviations, and medians with 95% confidence intervals (CI) are shown where data were not normally distributed. The results of non-parametric variables (including iodine results) were compared by means of the Mann-Whitney Wilcoxon rank sum test.


Results
Box 4 shows the mean and median ages and the results of spot urinary iodine concentration for the four groups. The three non-pregnant groups had similar urinary iodine concentration results, with a slightly higher median in the postpartum group compared with the group with diabetes. As expected,17-19 the pregnant women had higher urinary iodine concentrations than the other groups as a whole (P = 0.004). The iodine/creatinine ratios also show a high proportion of abnormal results (Box 4).

The median iodine concentration in the 26 postpartum women (79 µg/L) who provided repeat urine samples for iodine measurement three months after delivery was considerably lower than that in the 81 pregnant women (104 µg/L). However, this difference was not statistically significant (P = 0.249).

The patient with diabetes who had received iodine-containing intravenous contrast medium during a coronary angiogram in the month before the urinary spot test had a urinary iodine concentration of 2170 µg/L.

Box 5 shows TSH levels and FT4 levels versus iodine status in pregnant and non-pregnant participants. There was no significant relationship between iodine status and FT4 or TSH levels in either the pregnant group or non-pregnant group. Separate analysis of patients with diabetes and postpartum women did not significantly alter these results. However, there was a weak correlation between FT4 and urinary iodine levels when examined as a continuous variable (Pearson correlation coefficient, 0.26; P = 0.016).


Discussion
By WHO criteria,12 the median iodine levels in our pregnant participants were only just adequate, while those in postpartum women, patients with diabetes and normal volunteers were inadequate. The slightly higher median iodine level in the postpartum group compared with that in the group with diabetes may have been the result of this concentration not having returned to baseline after pregnancy, although further study is required to document the rate of change post partum. We believe the low values in patients with diabetes was not a problem specific to diabetes, but merely a reflection of low urinary iodine levels in the general population. The similarity between the patients with diabetes and our small group of volunteers supports this view. Our data are consistent with generally low iodine intake.

Our findings mirror recent reports from other countries.9,11,20 A United States study showed that the median urinary iodine concentration in 1988-1994 had decreased by more than 50% from that in 1971-1974.9,11 The 1988-1994 results showed 11.7% of the US population to be iodine deficient (a 4.5-fold increase since 1971-1974). The mean urinary iodine concentration in that population was 265 µg/L, and people from higher socioeconomic groups were more likely to be iodine deficient. Our data may also reflect this effect, as, although our patients were attending a public clinic, the hospital catchment area is a relatively high socioeconomic group. Our data suggest that Australia may be experiencing a similar trend to that seen in the US.

Iodine deficiency during pregnancy can affect the thyroid glands of both the mother and baby,10,17-19 and may have many adverse health consequences (Box 1). Some, but not all, researchers have found an increase in urinary iodine levels during pregnancy.10,17-19 Smyth et al studied urinary iodine concentration in a group of pregnant women in an area of Ireland with known borderline iodine deficiency.10 In the third trimester, they found a mean urinary iodine concentration of 132 µg/L (standard error of the mean, 6.8), and found that urinary iodine concentration increased during pregnancy. In a more iodine-deficient area, Glinoer et al found that urinary iodine concentration did not increase during pregnancy (median iodine concentration 45 µg/L after 20 weeks' gestation, no mean given).19 So, it is not clear whether the apparently higher levels in our pregnant women were pregnancy related or, in fact, masked iodine deficiency in pregnancy.

We found that a considerable percentage of pregnant women (4.9%) were severely iodine deficient, with spot urine results of < 25 µg/L. While this is the threshold below which cretinism may occur, other factors, such as selenium deficiency and the presence of dietary goitrogens, also play a part in determining cretinism,21 and these two factors are not usually seen in Sydney. Therefore, we would not expect to see an increased incidence of cretinism in Sydney on the basis of these results alone. However, more subtle adverse fetal outcomes may occur.

Our findings suggest that we should no longer automatically consider Australia an iodine-replete country. We found that iodine deficiency was common among 235 people attending a Sydney teaching hospital and speculate that these data are applicable to the general population, although this will require independent confirmation. The frequency of iodine deficiency in our pregnant population (18.8%) approaches the maximum acceptable level recommended by WHO (20%); this recommendation was exceeded in our group with diabetes (34.1%) and the normal volunteers (26.3%). The postpartum women had a median iodine concentration of 79 µg/L, which is lower than the WHO recommendation of 100 µg/L. This has important public health implications.

The weaknesses of this study include the small group of normal volunteers, and perhaps the use of a sample from a teaching hospital rather than the community. The normal volunteers had results which are equivalent to those seen in postpartum women and non-pregnant patients with diabetes. Our subjects were all ambulatory, not inpatients at the time of testing, and generally well. Although 24-hour urinary iodine excretion studies may be the ideal method of assessing iodine status, these are not generally performed in large numbers for a variety of technical and practical reasons.

A weak correlation between urinary iodine and free thyroxine was observed for all non-pregnant participants in total, and for the participants with diabetes mellitus. Because of the large number of other factors which influence thyroid function (including pregnancy),13 the relatively loose correlations are an expected finding.

Further studies are needed, and these include (i) population surveys in Sydney and elsewhere in Australia; (ii) assessment of thyroid size (eg, by ultrasound) in relation to iodine status; and (iii) detailed assessment of neonates, including thyroid size, neonatal TSH levels, and detailed neurological outcomes.


References
  1. Hetzel BS. Iodine deficiency disorders. In: Garrow JS, James WPT, editors. Human nutrition and dietetics. Edinburgh: Churchill Livingstone, 1993: 534-555.
  2. Mortimer RH. Thyroid disease and pregnancy. Aust N Z J Med 1998; 28: 647-653.
  3. Tasmanian Thyroid Advisory Committee. Study in disease surveillance. 1950-1979. Med J Aust 1981; 2: 234-238.
  4. Clements FW. Goitre studies. 1. The incidence of endemic goitre in three areas in Australia. Med J Aust 1948; 21: 637-639.
  5. Hales I. Studies in diseases of the thyroid gland [MD thesis] Sydney: University of Sydney, 1971.
  6. Boyages S. Iodine deficiency disorders. J Clin Endocrinol Metab 1993; 77: 587-591.
  7. Clugston GA, Hetzel BS. Iodine. In: Shils ME, Olson JA, Shike M, editors. Modern nutrition in health and disease. 8th ed. Vol. 1. Philadelphia: Lea and Febiger, 1994; 252-263.
  8. Delange F. The disorders induced by iodine deficiency. Thyroid 1994; 4: 107-128.
  9. Hollowell JG, Staehling NW, Hannon WH, et al. Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from the National Health and Nutrition Examination Surveys I and III (1971-1974 and 1988-1994). J Clin Endocrinol Metab 1998; 83: 3401-3408.
  10. Smyth PPA, Hetherton AMT, Smith DF, et al. Maternal iodine status and thyroid volume during pregnancy: correlation with neonatal iodine intake. J Clin Endocrinol Metab 1997; 82: 2840-2843.
  11. Dunn JT. What's happening to our iodine? [editorial]. J Clin Endocrinol Metab 1998; 83: 3398-3400.
  12. World Health Organization Nutrition Unit. Indicators for assessing iodine deficiency disorders and their control through salt iodization. Document No. WHO/NUT 94.6. Geneva: WHO, 1994: 36.
  13. McElduff A. Measurement of free thyroxine levels (fT4) in pregnancy. Aust N Z J Obstet Gynaecol 1999; 39: 158-161.
  14. May SL, May WA, Bourdoux PP, et al. Validation of a simple, manual urinary iodine method for estimating the prevalence of iodine-deficiency disorders, and interlaboratory comparison with other methods. Am J Clin Nutr 1997; 65: 1441-1445.
  15. McElduff A, Shuter B, Cooper R, et al. Measuring renal function in patients with diabetes mellitus. J Diabetes Complications 1997; 11: 225-229.
  16. SPSS [computer program], version 6.0. Chicago, Ill: SPSS Inc, 1996.
  17. Silva JE, Silva S. Interrelationships among serum thyroxine, triiodothyronine, reverse triiodothyronine, and thyroid-stimulating hormone in iodine-deficient pregnant women and their offspring: effects of iodine supplementation. J Clin Endocrinol Metab 1981; 52: 671-677.
  18. Glinoer D, De Nayer P, Bourdoux et al. Regulation of maternal thyroid during pregnancy. J Clin Endocrinol Metab 1990; 71: 276-287.
  19. Glinoer D, Delange F, Laboureur I, et al. Maternal and neonatal thyroid function at birth in an area of marginally low iodine intake. J Clin Endocrinol Metab 1992; 75: 800-805.
  20. Valiex P, Zarabska M, Preziosi P, et al. Iodine deficiency in France [letter]. Lancet 1999; 353: 1766-1767.
  21. Moreno-Reyes R, Suetens C, Mathieu F, et al. Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status. N Engl J Med 1998; 339: 1112-1120.

Received 13 Apr, accepted 21 Aug, 1999


Authors' details Royal North Shore Hospital, St Leonards, NSW.
Jenny E Gunton, MB BS, Endocrine Fellow, Department of Endocrinology.
Graham Hams, MAppSc, Senior Staff Scientist, Pacific Laboratory Medicine Services.
Marcelle Fiegert, BEd, MNutri Diet, Dietitian, Department of Nutrition.
Aidan McElduff, FRACP, PhD, Senior Staff Specialist in Endocrinology, Department of Endocrinology.

Reprints: Dr J E Gunton, C/- Clinic 1, Royal North Shore Hospital, St Leonards, NSW 2065.
jennyegAThotmail.com.






1: Iodine deficiency disorders

Maternal
  • Goitre
  • Hypothyroidism
  • Decreased fertility
  • Miscarriage

Fetal

  • Stillbirth

Neonatal
  • Cretinism
  • Increased mortality
  • Goitre
  • Hypothyroidism
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2: The iodine situation in Australia

  • In the past, an increased incidence of goitre and iodine deficiency was documented in certain parts of Australia.3-5

  • Prevention of iodine deficiency in industrialised countries most commonly relies on iodised salt, iodine in milk, or iodine-supplemented bread.1,6-8

  • The upper limit of the recommended daily intake of salt (NaCl) is 100 mmol, or 6 g (a heaped teaspoon); 100 mmol of iodised salt per day would provide 175-240 µg of iodine. However, most salt is incorporated into foods before purchase, and the three major Australian manufacturers of processed food we contacted all reported using non-iodised salt only.

  • Non-iodised table salt is readily available, and may be used more frequently than in the past as campaigns to use iodised salt are forgotten. (We reviewed supermarket shelves in our local area, and found that the space allocated for display suggests that more non-iodised than iodised salt is purchased.)

  • In the United States, only 50%-60% of salt currently consumed is iodised.9

  • Milk products, which used to contain significant concentrations of iodine (up to 300 µg/100 mL) by virtue of iodine-containing solutions used to clean the milk vats, now contain low levels of iodine because volatile cleaning solutions are used (Dairy Farmers Association, Nutrition Panel for Milks, personal communication).

  • While the incidence of iodine deficiency and goitre was decreased by legislation requiring iodine supplementation of bread in 1966,3 this is no longer a requirement (because of concerns about an increased incidence of thyrotoxicosis).

  • Marine fish, shellfish, seaweed and kelp contain high amounts of iodine,1,7 and such ocean seafood, as well as added iodised salt, provide most of the iodine in the Australian diet. However, many people may consume these products rarely, if at all.
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Box 3
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4: Iodine status results

GroupPregnant womenPostpartum womenPatients with diabetesVolunteers

Number of participants8126135 19
Age (years)
Mean (± 2 SD)32.9 ± 9.835.3 ± 11.350.1 ± 35.3*49.5 ± 17.4*
Median (95% CI)34 (24-42)35 (25-42)50 (25.7-83.0)49 (45.3-53.8)
Spot iodine concentration (µg/L)
Median10479‡65† 64
(95% CI)(89-129)(44-229)(58-89)(54-75)
No. of participants (%) with
Severe to moderate deficiency < 50 µg/L16 (19.8%)5 (19.2%)46 (34.1%)5 (26.3%)
Mild deficiency 51-100 µg/L24 (29.6%)9 (34.6%)51 (37.8%)9 (47.4%)
Normal iodine status > 100 µg/L41 (50.6%)12 (46.1%)38 (28.1%)5 (26.3%)
Iodine/creatinine ratio (µg iodine/g creatinine)
Median159131114 108
(95% CI)(169-232)(106-218)(93-505)(84-209)
No. of participants (%) with
Severe to moderate deficiency
< 50 µg iodine/g creatinine6 (7.4%)2 (7.7%)7 (5.2%)1 (5.3%)
Mild deficiency 51-100 µg iodine/g creatinine 22 (27.2%)9 (34.6%) 50 (37.0%)5 (26.3%)
Normal iodine status > 100 µg iodine/g creatinine53 (65.4%)15 (57.7%)78 (57.8%)13 (68.4%)

* P < 0.001 for comparison with pregnant women. †P < 0.01 for comparison with pregnant women. ‡P < 0.05 for comparison with patients with diabetes.
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5: Levels of thyroid-stimulating hormone and free thyroxine compared with iodine status in pregnant women and patients with diabetes

Thyroid-stimulating hormone (µIU/mL)Free thyroxine (pmol/L)
GroupNo.Mean (± 2 SD)Mean (± 2 SD)

Pregnant women70
Normal iodine status*411.56 ± 0.8012.9 ± 3.70
Mild deficiency†231.67 ± 0.9012.5 ± 3.00
Severe to moderate deficiency‡16 1.56 ± 0.7712.1 ± 2.25
Patients with diabetes121
Normal iodine status*342.1 ± 3.1015.0 ± 2.60
Mild deficiency†451.9 ± 1.2015.0 ± 2.60
Severe to moderate deficiency‡42 2.6 ± 2.4014.5 ± 2.90

* > 100µg/L. † 51-100 µg/L. ‡ < 50 µg/L.
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Jenny E Gunton
Graham Hams
Marcelle Fiegert
Aidan McElduff