Guarding our Nation’s Thyroid Health

John T. Dunn

Division of Endocrinology, Department of Medicine, University of Virginia, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Dr. J. T. Dunn, Box 800414, HSC/UVA, Charlottesville, Virginia 22908. E-mail: jtd{at}virginia.edu

Recent international events have forced the United States to critically examine its defenses, including those against diseases. This heightened awareness and the article by Hollowell et al. (1) in this issue of JCEM make it timely to consider our national thyroid health and how to secure it from its enemies.

Thyroid diseases are common, disruptive, expensive, and treatable. Many are also preventable. Numerous studies support these descriptions: 1) common—anywhere from 5–20% of the American population have some thyroid abnormality, depending on the indicator chosen; this fraction increases in certain subpopulations (e.g. autoimmune disease in older women); 2) disruptive—both hypothyroidism and hyperthyroidism impair physical and mental performance, produce morbidity, and pose special risks for pregnancy and the developing fetus and neonate (2, 3); 3) expensive—T4 is among the most commonly prescribed medications in the United States; testing of thyroid function is a routine laboratory procedure costing millions of dollars annually; the effects of iodine deficiency on the thyroid alone cost one country (Germany) an estimated annual $1 billion (4); 4) treatable—highly satisfactory therapies exist for all the common problems: hyperthyroidism, hypothyroidism, nodules, cancer, and iodine deficiency; and 5) preventable—the consequences of iodine deficiency are readily avoided by optimal iodine nutrition; appropriate diagnosis and treatment can keep at bay the effects of hypothyroidism on human development; avoidance of excess iodine can prevent many of its complications, including goiter, hypothyroidism, hyperthyroidism, and autoimmune disease.

Environmental factors are major determinants of thyroid disease, so modifying them may reduce morbidity. Iodine malnutrition, the world’s most prevalent thyroid disorder, is the most important of these. Iodine deficiency depresses fetal and child survival, physical and mental development, educability, economic productivity, and quality of life (5). Some examples are: correction of iodine deficiency in Western China lowered neonatal mortality by 65% (6); a meta-analysis concluded that iodine deficiency per se lowered IQ by approximately 13.5 points (7); introduction of iodized salt in northern China coincided with better school performance, and improvement in economic output and per capita income, each by about 10-fold (8); endemic goiter and cretinism have disappeared from most parts of the world where iodine sufficiency has been achieved (9). Farther afield, scattered reports suggest that iodine deficiency can impair the immune response (10) and may relate to fibrocystic breast disease (11).

Iodine excess also causes disease. In previously deficient areas, hyperthyroidism is common after iodine supplementation, particularly among older individuals with autonomous nodules (12). As iodine intakes increase in the population, so do the incidences of autoimmune thyroid disease and papillary thyroid cancer (13, 14). Induction of thyroiditis in experimental animals is directly proportional to the iodine content of the immunizing thyroglobulin. Typical autoimmune changes, including thyroid cytology and serum antibodies, appeared in humans exposed to increased dietary iodine, and these changes reversed on withdrawal of the iodine excess (15). Epidemiological studies show that increased dietary iodine in a population parallels increased autoimmune thyroid disease, both hyperthyroidism (Graves’ disease) and hypothyroidism (Hashimoto’s thyroiditis) (13, 14, 16). Iodine-containing drugs (e.g. Amiodarone) and radiocontrast dyes are important occasional contributors to thyroid morbidity. Follicular thyroid cancer has a higher incidence in iodine-deficient populations that decreases with its correction, whereas the incidence of papillary thyroid cancer increases with iodine intake.

Other environmental factors also contribute to thyroid disease. Childhood radiation exposure causes thyroid cancer, usually papillary. This effect has important public health implications. The fallout from nuclear explosions typically contains large amounts of radioactive iodine, and coexisting iodine deficiency worsens the damage in children. Thus, the Chernobyl disaster increased the incidence and aggressiveness of childhood papillary cancer in iodine-deficient Belarus and Ukraine, but not in Poland where immediate large-scale iodine prophylaxis was given (17). Fear of the aging nuclear reactors in surrounding countries led Austria to increase the iodine levels in its iodized salt to lessen this risk. An uphill battle by the American Thyroid Association and others over nearly 20 yr has finally led to agreement on the part of the United States government to provide potassium iodide in the event of a nuclear attack or accident, again to prevent thyroid cancer.

Deficiencies of selenium, vitamin A, and iron can all compound the effects of iodine deficiency on thyroid hormone production and metabolism. Other dietary factors, such as thiocyanate from cassava and goitrogenic compounds from millet, can also block thyroid hormone synthesis and make hypothyroidism and goiter worse; although these are probably not significant in the United States, they are major contributors to endemic goiter in the many developing countries where they are food staples.

These examples emphasizing the close relation of thyroid diseases to our environment bring me to the study by Hollowell et al. (1). It offers a welcome addition to current knowledge of thyroid status in the United States and complements a previous report on urinary iodine concentration in the same survey (18). Strengths of the National Health and Nutrition Examination Survey (NHANES) studies are the careful sampling design and the opportunity for comparison over decades. They also have limitations, which the authors carefully acknowledge. The data they report here were collected about 10 yr ago, clearly a long time when trying to define current trends. The absence of information on hormone binding compromises interpretation of serum total T4 values. The study provides no information on clinical features or on thyroid size of the individuals included. These data come from a larger study, and the limitations from policy decisions made over a decade ago cannot be blamed on Hollowell et al. (1), but they do suggest ways to improve future data gathering, to develop a more comprehensive picture of national thyroid status. The Centers for Disease Control has more recent data but has not released them yet. Their prompt review will help greatly in updating assessment of our current iodine status.

The study by Hollowell et al. (1) touches several issues that deserve comment. For one, the TSH is selected as the primary indicator of thyroid hormone effect. This is a generally accepted practice among thyroidologists, but we need to remember its limitations. Differences in serum TSH levels in the same individual or population over time may indicate changing thyroid function, but can be difficult to recognize because the overall values remain within the normal range. Even the concept of subclinical hypothyroidism (an elevated TSH with normal free T4) makes many thyroidologists uncomfortable because it puts total reliance on a single laboratory test. The problem is compounded by the wide range of symptoms and clinical features that often accompany nonoptimal thyroid function and by the fact that hypothyroidism is entirely reversible, so that failure to diagnose and treat it becomes a lost opportunity to improve health. Although most of us treat subclinical hypothyroidism with hormone replacement, the scientific basis for this decision is not rigorously established.

Other issues raised by the study of Hollowell et al. (1) are the relative importance of T3 as compared with T4 at the pituitary and at peripheral tissues, and the effects of aging on response to thyroid hormone and, therefore, on TSH production. Even the definitions of normal thyroid size and function remain inexact. Changes in binding proteins, ethnic diversity, genetic variations, gestational state, and iodine nutrition all may affect thyroid function. Ultimately, the physician needs to critically inspect the data on the individual patient, relate them to other clinical features, and make an informed decision about treatment. We should take a similar approach in advising the community about its collective thyroid health.

With the above limitations in mind, I offer recommendations on the following points:

Monitoring iodine nutrition

I have written often (some colleagues will say "incessantly") on the indispensable role of monitoring in maintaining optimal iodine nutrition. The previous paper by the present authors (18) showed a dramatic decrease in urinary iodine excretion between NHANES I and NHANES III. A decision to include iodine in future NHANES surveys was made only after considerable discussion and advocacy. The consequences of both deficiency and excess of iodine are well established and usually avoidable, but only if we know how much iodine we are getting, and this will come only with continued monitoring. Several less affluent countries (e.g. China) are doing a much better job on this front than is the United States.

Adult screening for thyroid disease

Others have clearly made the point that hypothyroidism is common among older women and that it is easily treatable. The economic benefits of screening by serum TSH measurement have been widely discussed, and we must not forget to add the intangible but highly important benefits of having patients feel and work better (19). This screening should also apply to those who are already being treated for hypothyroidism, in view of the large number whose therapy is not optimal (20).

Hypothyroxinemia during pregnancy

Low maternal serum T4 is associated with pregnancy complications including impaired offspring (3, 21, 22, 23). Interestingly, this effect relates more to the hypothyroxinemia per se than to changes in serum TSH or T3. Women with autoimmune disease are more vulnerable. A strong argument can be made for routine screening with serum free T4 during pregnancy, most conveniently around 12 wk when other testing is often done.

Iodine supplementation

We want people to get the right amount of iodine. Too little is worse than too much, but both deficiency and excess are avoidable. Because pregnancy is the most vulnerable period, I favor additional iodine, usually 150 µg per day, throughout pregnancy and lactation. Many antenatal vitamin/mineral preparations already include this supplement, and it should ensure adequate iodine for the fetus. The woman who is already receiving enough iodine should have no ill effects from this small addition, and the total intake will normally be well below the tolerable upper limit of 1100 µg per day as set by the Food and Nutrition Board, Institute of Medicine (24).

Should Americans use iodized salt? About 70% do; it sits next to the noniodized product on grocery store shelves, and most people are not aware of the difference. In contrast, Canada requires that all table salt be iodized. The iodization level in both countries is 100 ppm (100 µg potassium iodide or 77 µg iodine per gram of NaCl), a much higher figure than is generally recommended for the rest of the world. Most other countries use 20–40 ppm as iodine, and the United States and Canada should consider lowering the level of fortification to this range. In contrast to the situation in developing countries, most dietary salt in the West comes from prepared food rather than addition at the table. In North America and most of Europe (Switzerland is an exception), only the table salt is iodized. In the United States, table salt provides about 15% of dietary sodium intake; about 70% comes from processed foods, and the remaining 15% from natural occurrence in foods (R. Hanneman, personal communication). Thus, for a daily NaCl intake of 5 g, iodized table salt provides about 50 µg iodine. The NHANES III study shows that most Americans are getting adequate iodine and in the past were probably getting too much (18). We have little knowledge of or control over the many other sources of iodine we receive. People consuming moderate amounts of seafood, dairy products, and meat, or regularly taking iodine-containing vitamin/mineral preparations, are unlikely to become deficient in the United States. Other factors, such as losses of iodine during cooking and bioavailability of ingested iodine, complicate the estimation of iodine intake from food composition data. The decision to use iodized salt needs to be made individually in relation to dietary and other sources of iodine, but an additional 50–100 µg iodine per day are unlikely to be harmful, so if there is doubt about adequate iodine intake, I recommend using iodized table salt.

Role of the endocrinologist

Health professionals are usually the first to see the manifestations of thyroid disease and abnormal iodine nutrition. Typical presenting features are goiter and either hyper- or hypothyroidism, and these prompt evaluation by an endocrinologist. Thus, endocrinologists and other health professionals should be attuned to these manifestations and their likely causes. Suspicious findings should provoke investigation and remedial action as necessary. Societies such as the American Thyroid Association and The Endocrine Society should take the responsibility of regularly gathering intelligence about iodine nutrition and thyroid disease, and reporting it to the public and to health authorities for action.

More basic information

We need to expand our knowledge about thyroid function and iodine nutrition, to recognize and treat thyroid disease more effectively. Textbooks and review articles confirm that we already have a great deal of information about thyroid function and disease, and we are fortunate to have effective treatments for most disorders. At the same time, we are far from having all the answers and need further research to guide us toward more effective prevention and treatment. Examples are the pathogenesis of autoimmune thyroid disease and thyroid cancer, the influence of genetic changes, the cellular effects of thyroid hormones, the further intricacies of iodine metabolism, the definitions of optimal thyroid function and iodine nutrition, the relation of the immune system to thyroid function—the list could go on interminably.

To conclude, thyroid disease is preventable and treatable. Constant vigilance is our most effective strategy and needs reinforcement now. Endocrinologists owe it to their country to be an active part of this effort.

Footnotes

Abbreviation: NHANES, National Health and Nutrition Examination Survey.

Received December 18, 2001.

Accepted December 19, 2001.

References

  1. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE 2002 Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 87:489–499[Abstract/Free Full Text]
  2. Dunn JT, Delange F 2001 Damaged reproduction: the most important consequence of iodine deficiency. J Clin Endocrinol Metab 86:2360–2363[Free Full Text]
  3. Glinoer D, Delange F 2000 The potential repercussions of maternal, fetal and neonatal hypothyroxinemia on the progeny. Thyroid 10:871–887[Medline]
  4. Pfannenstiel P 1998 The cost of continuing iodine deficiency in Germany and the potential cost benefit of iodine prophylaxis. IDD Newsletter 14:11–12
  5. Delange F 2000 Iodine deficiency. In: Braverman LE, Utiger RD, eds. The thyroid. A fundamental and clinical text. Philadelphia: Lippincott; 295–316
  6. DeLong GR, Leslie PW, Wang SH, Jiang XM, Zhang ML, Rakeman M, Jiang JY, Ma T, Cao XY 1997 Effect on infant mortality of iodination of irrigation water in a severely iodine-deficient area of China. Lancet 350:771–773[CrossRef][Medline]
  7. Bleichrodt N, Born MP 1994 A metaanalysis of research on iodine and its relationship to cognitive development. In: Stanbury JB, ed. The damaged brain of iodine deficiency. New York: Cognizant Communication; 195–200
  8. Li J, Wang X 1987 Jixian: a success story in IDD control. IDD Newsletter 3:4
  9. Delange F, de Benoist B, Pretell E, Dunn JT 2001 Iodine deficiency in the world: where do we stand at the turn of the century? Thyroid 11:437–447[CrossRef][Medline]
  10. Marani L, Venturi S, Masala R 1985 Role of iodine in delayed immune response. Isr J Med Sci 21:864[Medline]
  11. Ghent WR, Eskin BA, Low DA, Hill LP 1993 Iodine replacement in fibrocystic disease of the breast. Can J Surg 36:453–460[Medline]
  12. Stanbury JB, Ermans AM, Bourdoux P, Todd C, Oken E, Tonglet R, Vidor G, Braverman LE, Medeiros-Neto G 1998 Iodine-induced hyperthyroidism: occurrence and epidemiology. Thyroid 8:83–100[Medline]
  13. Harach HR, Escalante DA, Onativa A, Outes JL, Day ES, Williams ED 1985 Thyroid carcinoma and thyroiditis in an endemic goitre region before and after iodine prophylaxis. Acta Endocrinol 108:55–60[Medline]
  14. Braverman LE 1994 Iodine and the thyroid: 33 years of study. Thyroid 4:351–356[Medline]
  15. Kahaly G, Dienes HP, Beyer J, Hommel G 1997 Randomized, double-blind, placebo-controlled trial of low dose iodide in endemic goiter. J Clin Endocrinol Metab 82:4049–4053[Abstract/Free Full Text]
  16. Laurberg P, Pederson KM, Hreidarsson A, Sigfusson N, Versen EI, Knudsen PR 1998 Iodine intake and the pattern of thyroid disorders: a comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland, Denmark. J Clin Endocrinol Metab 83:765–769[Abstract/Free Full Text]
  17. Robbins J, Schneider AB 2000 Thyroid cancer following exposure to radioactive iodine. Rev Endocr Metab Disord 1:197–203[CrossRef][Medline]
  18. Hollowell JG, Staehling NW, Hannon WH, Flanders DW, Gunter EW, Maberly GF, Braverman LE, Pino S, Miller DT, Garbe PL, DeLozier DM, Jackson RJ 1998 Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from National Health and Nutrition Examination Surveys I and III (1971–1974 and 1988–1994). J Clin Endocrinol Metab 83:3401–3408[Abstract/Free Full Text]
  19. Danese MD, Powe NR, Sawin CT, Ladenson PW 1996 Screening for mild thyroid failure at the periodic health examination: a decision and cost-effectiveness analysis. JAMA 276:285–292[Abstract]
  20. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC 2000 The Colorado thyroid disease prevalence study. Arch Intern Med 160:526–534[Abstract/Free Full Text]
  21. Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, O’Heir CE, Mitchell ML, Hermos RJ, Waisbren SE, Faix JD, Klein RZ 1999 Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 341:549–555[Abstract/Free Full Text]
  22. Pop VJ, Kuijpens JL, Baar ALV, Verkerk G, Van Son MM, de Vijlder JJ, Vulsma T, Wiersinga WM, Drexhage HA, Vader HL 1999 Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol 50:149–155[CrossRef][Medline]
  23. Morreale de Escobar G, Obregon MJ, Escobar del Rey F 2000 Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia. J Clin Endocrinol Metab 85:3975–3987[Abstract/Free Full Text]
  24. Panel on Micronutrients, Food and Nutrition Board, Institute of Medicine 2001 Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press