eMedicine Specialties > Endocrinology > Thyroid

Iodine Deficiency: Differential Diagnoses & Workup

Author: Stephanie L Lee, MD, PhD, Fellow, Association of Clinical Endocrinology; Director of Thyroid Nodule and Cancer Center, Associate Chief, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center; Associate Professor, Department of Medicine, Boston University School of Medicine
Coauthor(s): Sonia Ananthakrishnan, MD, Attending Physician, Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine/Boston Medical Center; Elizabeth N Pearce, MD, MSc, Assistant Professor of Medicine, Boston Medical Center/Boston University Medical School
Contributor Information and Disclosures

Updated: Apr 22, 2009

Differential Diagnoses

Constipation
Hypothermia
De Quervain Thyroiditis
Hypothyroidism
Depression
Infertility
Dysmenorrhea
Lymphomas, Endocrine, Mesenchymal, and Other Rare Tumors of the Mediastinum
Erectile Dysfunction
Pericardial Effusion
Euthyroid Sick Syndrome
Thyroid Nodule
Goiter
Thyroid, Anaplastic Carcinoma
Goiter, Lithium-Induced
Thyroid, Follicular Carcinoma
Goiter, Nontoxic
Thyroid, Papillary Carcinoma
Goiter, Toxic Nodular
Thyroxine-Binding Globulin Deficiency
Hurthle Cell Carcinoma

Other Problems to Be Considered

Endemic goiter can be differentiated from sporadic, nontoxic, multinodular goiter only by a history of iodine deficiency. The nodules of a goiter associated with iodine deficiency disorder (IDD) cannot be distinguished from thyroid cancer based on the results from a physical examination. Any patient with a discrete nodule of at least 1-1.5 cm should be referred to an endocrinologist for evaluation with a fine-needle aspiration biopsy. Hypothyroidism secondary to IDD must be distinguished from Hashimoto disease or subacute thyroiditis.

Workup

Laboratory Studies

  • The kidneys excrete approximately 90% of ingested iodine. Therefore, the best diagnostic test to identify iodine deficiency disorder (IDD) in a population is a median 24-hour urine iodine collection. If a 24-hour urine collection is not practical, a random urine iodine-to-creatinine ratio can be used instead. In this case, a median of 50-100 mcg of iodine per liter is consistent with mild iodine deficiency, 20-49 mcg of iodine per liter is consistent with moderate deficiency, and less than 20 mcg of iodine per liter is consistent with severe deficiency. No test that can reliably diagnose iodine deficiency in individual patients is available.
  • Population studies have shown that newborns with IDD have elevated TSH levels at birth that normalize when evaluated again several weeks later. The extent of their transient hypothyroidism correlates with the severity of the iodine deficiency (see the table Iodine Deficiency Characteristics).
  • Measurement of a dried whole-blood spot level of thyroglobulin (Tg) can be a useful indicator of the thyroid function in children and may be a more sensitive early measure of iodine repletion than serum TSH or thyroxine (T4).11 Current limitations of the use of dried blood spot Tg measurements include assay complexity and the unknown utility of measuring antithyroglobulin antibody levels in children.

Imaging Studies

  • The 24-hour radioactive iodine uptake value is increased substantially in the presence of iodine deficiency disorder because of increased TSH stimulation and reduction in the nonisotopic iodine pool. Therefore, thyroid uptake values in iodine-sufficient areas, such as the United States, are significantly lower than in areas with iodine deficiency, as in many regions of Europe.
  • Thyroid size estimated on ultrasonograms has been shown to reflect the iodine sufficiency of a population. When goiter appears in more than 5% of a regional population, iodine deficiency should be considered (see the table Iodine Deficiency Characteristics).

Other Tests

  • Results from thyroid function studies are usually within the reference range in the presence of mild iodine insufficiency. However, in patients with euthyroidism and iodine deficiency, serum TSH levels may be normal to increased, T3 levels may be normal or slightly elevated, and T4 levels may be normal or decreased. Only in very extreme iodine deficiency does hypothyroidism develop, accompanied by an elevated serum TSH value and decreased T3 and T4 levels.

Histologic Findings

In young patients, the usual finding is diffuse hyperplasia of the thyroid gland. Histologically, extreme hyperplasia can be seen with little or no colloid (see image below and Image 4).

With aging, the diffuse goiter of iodine deficiency becomes more nodular. Histologically, the nodular goiter is caused by areas of hyperplasia separated by areas of degeneration and fibrosis. In older patients, the thyroid gland tends to be extremely heterogenous, containing colloid-containing vesicles, hyperplastic areas, degenerating areas, and fibrosis.

Histologic sections from a normal thyroid and fro...

Histologic sections from a normal thyroid and from an endemic goiter that was removed because of compressive symptoms. The normal thyroid (A) contains thyroid cells arranged in a monolayered sheet around a storage form of thyroid hormone, colloid, while the endemic goiter (B) shows intense hyperplasia with no colloid. Image courtesy of F. DeLange.

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Histologic sections from a normal thyroid and fro...

Histologic sections from a normal thyroid and from an endemic goiter that was removed because of compressive symptoms. The normal thyroid (A) contains thyroid cells arranged in a monolayered sheet around a storage form of thyroid hormone, colloid, while the endemic goiter (B) shows intense hyperplasia with no colloid. Image courtesy of F. DeLange.


More on Iodine Deficiency

Overview: Iodine Deficiency
Differential Diagnoses & Workup: Iodine Deficiency
Treatment & Medication: Iodine Deficiency
Follow-up: Iodine Deficiency
Multimedia: Iodine Deficiency
References
Further Reading
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References

  1. Zimmermann MB, Jooste PL, Pandav CS. Iodine-deficiency disorders. Lancet. Oct 4 2008;372(9645):1251-62. [Medline].

  2. de Benoist B, McLean E, Andersson M, Rogers L. Iodine deficiency in 2007: global progress since 2003. Food Nutr Bull. Sep 2008;29(3):195-202. [Medline].

  3. Zimmermann MB. Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: a review. Am J Clin Nutr. Feb 2009;89(2):668S-72S. [Medline].

  4. WHO Secretariat, Andersson M, de Benoist B, Delange F, Zupan J. Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2-years-old: conclusions and recommendations of the Technical Consultation. Public Health Nutr. Dec 2007;10(12A):1606-11. [Medline].

  5. Delange F. Optimal iodine nutrition during pregnancy, lactation and neonatal period. Int J Endocrinol Metab. 2004;89:3851.

  6. Azizi F, Smyth P. Breastfeeding and maternal and infant iodine nutrition. Clin Endocrinol (Oxf). May 2009;70(5):803-9. [Medline].

  7. Hollowell JG, Staehling NW, Hannon WH, et al. 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. Oct 1998;83(10):3401-8. [Medline]. [Full Text].

  8. Caldwell KL, Jones R, Hollowell JG. Urinary iodine concentration: United States National Health And Nutrition Examination Survey 2001-2002. Thyroid. Jul 2005;15(7):692-9. [Medline].

  9. Caldwell KL, Miller GA, Wang RY, Jain RB, Jones RL. Iodine status of the U.S. population, National Health and Nutrition Examination Survey 2003-2004. Thyroid. Nov 2008;18(11):1207-14. [Medline].

  10. Williams GR. Neurodevelopmental and neurophysiological actions of thyroid hormone. J Neuroendocrinol. Jun 2008;20(6):784-94. [Medline].

  11. Zimmermann MB, Moretti D, Chaouki N, et al. Development of a dried whole-blood spot thyroglobulin assay and its evaluation as an indicator of thyroid status in goitrous children receiving iodized salt. Am J Clin Nutr. Jun 2003;77(6):1453-8. [Medline]. [Full Text].

  12. Zimmermann MB. Iodine requirements and the risks and benefits of correcting iodine deficiency in populations. J Trace Elem Med Biol. 2008;22(2):81-92. [Medline].

  13. Cerqueira C, Knudsen N, Ovesen L, et al. Association of iodine fortification with incident use of anti-thyroid medication - A Danish nationwide study. J Clin Endocrinol Metab. Apr 14 2009;[Medline].

  14. DeLange FM. Iodine deficiency. In: Braverman L, Utiger RD, eds. Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000:295-316.

  15. Dunn JT. IDD Newsletter. International Council for Control of Iodine Deficiency Disorders. 2001.

  16. Dunn JT, Van der Har F. A practical guide to the correction of iodine deficiency. The Netherlands: International Council for Control of Iodine Deficiency Disorders. 1990.

  17. Hetzel BS. The Story of Iodine Deficiency: An International Challenge in Nutrition. New York, NY: Oxford University Press; 1989.

  18. Hetzel BS, DeLange F. The iodine deficiency disorders. Thyroid Disease Manager [serial online]. 2001. Available from: Worchester, Mass: Endocrine Education. Available at http://www.thyroidmanager.org/Chapter20/20-frame.htm.

  19. Lee K, Bradley R, Dwyer J, Lee SL. Too much versus too little: the implications of current iodine intake in the United States. Nutr Rev. Jun 1999;57(6):177-81. [Medline].

  20. Santiago-Fernandez P, Torres-Barahona R, Muela-Martínez JA, et al. Intelligence quotient and iodine intake: a cross-sectional study in children. J Clin Endocrinol Metab. Aug 2004;89(8):3851-7. [Medline]. [Full Text].

  21. Zimmermann MB, Aeberli I, Torresani T, et al. Increasing the iodine concentration in the Swiss iodized salt program markedly improved iodine status in pregnant women and children: a 5-y prospective national study. Am J Clin Nutr. Aug 2005;82(2):388-92. [Medline]. [Full Text].

  22. Zimmermann MB, Wegmuller R, Zeder C, et al. Rapid relapse of thyroid dysfunction and goiter in school-age children after discontinuation of salt iodization. Am J Clin Nutr. Apr 2004;79(4):642-5. [Medline]. [Full Text].

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Keywords

iodine deficiency, thyroid, iodine, hypothyroidism, thyroid disease, hyperthyroidism, hypothyroid, thyroid symptoms, thyroiditis, hyperthyroid, thyroid hormone, goiter symptoms of thyroid, iodine supplements, symptoms of thyroid problems, thyroid disorder, thyroxine, thyroid disorders, thyroid tests, thyroid hormones, T3 thyroid, T4 thyroid, thyrotoxicosis, iodine foods, iodine diet, iodine supplement, iodine deficiency disorders, endemic goiter, cretinism, mental retardation

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Contributor Information and Disclosures

Author

Stephanie L Lee, MD, PhD, Fellow, Association of Clinical Endocrinology; Director of Thyroid Nodule and Cancer Center, Associate Chief, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center; Associate Professor, Department of Medicine, Boston University School of Medicine
Stephanie L Lee, MD, PhD is a member of the following medical societies: American College of Endocrinology, American Thyroid Association, and Endocrine Society
Disclosure: Nothing to disclose.

Coauthor(s)

Sonia Ananthakrishnan, MD, Attending Physician, Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine/Boston Medical Center
Disclosure: Nothing to disclose.

Elizabeth N Pearce, MD, MSc, Assistant Professor of Medicine, Boston Medical Center/Boston University Medical School
Elizabeth N Pearce, MD, MSc is a member of the following medical societies: American Association of Clinical Endocrinologists, American Thyroid Association, Endocrine Society, and Massachusetts Medical Society
Disclosure: Abbott Laboratories Consulting fee Consulting

Medical Editor

Harris C Taylor, MD, Clinical Professor of Medicine, Division of Clinical and Molecular Endocrinology, Case Western Reserve University School of Medicine
Harris C Taylor, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Thyroid Association, and Endocrine Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS, Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC
Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, American Society of Law Medicine and Ethics, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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