eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Hyperthyroidism: Differential Diagnoses & Workup

Author: Robert J Ferry Jr, MD, Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Medical Center, University of Tennessee Health Science Center at Memphis, and St Jude Children's Research Hospital; Field Surgeon (Medical Corps), 162nd Area Support Medical Company, Army National Guard
Coauthor(s): Jonathan G Gold, MD, Assistant Professor, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University
Contributor Information and Disclosures

Updated: Jun 4, 2009

Differential Diagnoses

Crohn Disease
Eating Disorder: Anorexia
Mood Disorder: Bipolar Disorder
Mood Disorder: Depression
Mood Disorder: Dysthymic Disorder
Pheochromocytoma

Workup

Laboratory Studies

  • Hyperthyroidism can be confirmed simply and quickly with measurements of T4, T3, T3 resin uptake (T3RU), and thyroid-stimulating hormone (TSH). Patients with Graves disease have elevated levels of T4, T3, and T3RU and low or undetectable levels of TSH.
  • The T4 level measures the total concentration of T4 in serum (ie, free and bound). Patients who are clinically euthyroid but have elevated levels of T4 may have increased plasma proteins, primarily T4-binding globulin (TBG). Biochemically, these patients can be distinguished easily from truly hyperthyroid patients by measuring either free T4, which is normal, or T3RU, which is decreased.
  • Free T4 can be measured directly by means of immunoassay. Alternatively, T3RU can be obtained. T3RU correlates inversely with the available binding sites on thyroid-binding globulin (TBG). Conditions that cause elevated TBG levels (eg, pregnancy) increase the number TBG binding sites for T4 and T3 and decrease the T3RU level. In contrast, conditions causing hyperthyroidism decrease the number of free TBG binding sites and, therefore, increase T3RU. The number derived from multiplication of the total T4 and the T3RU, variably called the free T4 index, T7, or T12, has been used as a surrogate for measured free T4. T3RU is no longer commonly used and is being replaced by better and more sensitive thyroid hormone testing.
  • An elevated TSH level in a patient with thyrotoxicosis is extremely unusual and indicates altered regulation at the level of the pituitary gland. Patients may potentially have either a TSH-secreting pituitary adenoma or isolated pituitary resistance to thyroid hormone.
  • Measurement of TSH receptor–stimulating autoantibodies (ie, thyroid-stimulating immunoglobulins [TSI]) is rarely necessary for diagnosis of Graves disease. TSI titers are high in Graves disease. This test has 95% sensitivity and 96% specificity for Graves disease; however, the test is also labor intensive, expensive, and not widely available. TSI levels are suggested to correlate with remission of Graves disease; however, this has not been confirmed in clinical studies.
  • Markedly elevated antithyroglobulin and antithyroid peroxidase antibodies without TSI may help to distinguish the hyperthyroid phase of chronic lymphocytic thyroiditis (hashitoxicosis) from Graves disease. A more reliable method to distinguish the 2 is a thyroid iodine I 123 uptake and scan. In Graves disease, the uptake is elevated and diffuse, whereas in Hashimoto thyroiditis, the uptake is generally low and patchy in distribution.
  • Obtaining a CBC count before the initiation of antithyroid medications may be valuable for separating patients with underlying leukopenia or thrombocytopenia from patients who develop drug toxicity. Mild leukopenia can be observed in many patients with Graves disease, whereas agranulocytopenia is a rare side effect of antithyroid medications. Because the onset of agranulocytosis is unpredictable and idiosyncratic, routine blood counts during follow up do not aid in the treatment of patients with hyperthyroidism. However, if a patient on propylthiouracil (PTU) or methimazole develops fever or ulcerations in the mouth, a prompt CBC count is necessary.
  • A newer, rapid, fully automated electrochemiluminescence immunoassay reportedly provides the same or better results as existing commercial products and shortens the measuring time.3

Imaging Studies

  • Currently, diagnostic radioiodine I 131 uptake is rarely performed. Either technetium 99m or123 I scan may be useful if the gland does not have a uniform consistency. Functioning nodules trap radioactive iodine and technetium, yielding a hot area of increased uptake on the scintiscan.
  • If the patient is hyperthyroid from such a hot nodule, the remaining thyroid does not take up iodine because of the suppression of TSH and the absence of TSI.

More on Hyperthyroidism

Overview: Hyperthyroidism
Differential Diagnoses & Workup: Hyperthyroidism
Treatment & Medication: Hyperthyroidism
Follow-up: Hyperthyroidism
Multimedia: Hyperthyroidism
References
[ CLOSE WINDOW ]

References

  1. Bartalena L, Baldeschi L, Dickinson AJ, et al. Consensus statement of the European group on Graves' orbitopathy (EUGOGO) on management of Graves' orbitopathy. Thyroid. 2008;18:333-46. [Medline].

  2. Bahn R. The EUGOGO consensus statement on the management of Graves' orbitopathy: equally applicable to North American clinicians and patients. Thyroid. 2008;18:281-2. [Medline].

  3. Yoshimura Noh J, Miyazaki N, et al. Evaluation of a new rapid and fully automated electrochemiluminescence immunoassay for thyrotropin receptor autoantibodies. Thyroid. 2008;18:1157-64. [Medline].

  4. US Preventative Services Task Force. Screening for thyroid disease: recommendation statement. Ann Intern Med. Jan 20 2004;140(2):125-7. [Medline].

  5. FDA MedWatch Safety Alerts for Human Medical Products. Propylthiouracil (PTU). US Food and Drug Administration. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm164162.htm. Accessed June 3, 2009.

  6. Allannic H, Fauchet R, Orgiazzi J, et al. Antithyroid drugs and Graves disease: a prospective randomized evaluation of the efficacy of treatment duration. J Clin Endocrinol Metab. 1990;70:675-679. [Medline].

  7. Bazakis AM, Kunzler C. Altered mental status due to metabolic or endocrine disorders. Emerg Med Clin North Am. Aug 2005;23(3):901-8, x-xi. [Medline].

  8. Buckingham BA, Costin G, Roe TF, et al. Hyperthyroidism in children. A reevaluation of treatment. Am J Dis Child. Feb 1981;135(2):112-7. [Medline].

  9. Collen RJ, Landaw EM, Kaplan SA, Lippe BM. Remission rates of children and adolescents with thyrotoxicosis treated with antithyroid drugs. Pediatrics. Mar 1980;65(3):550-6. [Medline].

  10. Cooper DS. Antithyroid drugs. N Engl J Med. Nov 22 1984;311(21):1353-62. [Medline].

  11. Dallas J, Foley T. Hyperthyroidism. In: Pediatric Endocrinology. 3rd ed. 1996:401-415.

  12. Daneman D, Howard NJ. Neonatal thyrotoxicosis: intellectual impairment and craniosynostosis in later years. J Pediatr. Aug 1980;97(2):257-9. [Medline].

  13. Gorton C, Sadeghi-Nejad A, Senior B. Remission in children with hyperthyroidism treated with propylthiouracil. Long-term results. Am J Dis Child. Oct 1987;141(10):1084-6. [Medline].

  14. Hayek A, Chapman EM, Crawford JD. Long-term results of treatment of thyrotoxicosis in children and adolescents with radioactive iodine. N Engl J Med. Oct 29 1970;283(18):949-53. [Medline].

  15. Hershman JM. Does thyroxine therapy prevent recurrence of Graves hyperthyroidism?. J Clin Endocrinol Metab. May 1995;80(5):1479-80. [Medline].

  16. Karpman BA, Rapoport B, Filetti S, Fisher DA. Treatment of neonatal hyperthyroidism due to Graves disease with sodium ipodate. J Clin Endocrinol Metab. 1987;64:119-123. [Medline].

  17. Kubo T, Shimizu J, Furujo M, et al. An infant case of Graves disease with ophthalmopathy. Endocr J. Oct 2005;52(5):647-50. [Medline].

  18. LaFranchi S, Mandel SH. Graves disease in the neonatal period and childhood. 1996;1000-1008.

  19. Lippe BM, Landaw EM, Kaplan SA. Hyperthyroidism in children treated with long-term medical therapy: twenty-five percent remission every two years. J Clin Endocrinol Metab. Jun 1987;64(6):1241-5. [Medline].

  20. Malabu UH, Alfadda A, Sulimani RA, et al. Graves' disease in Saudi Arabia: a ten-year hospital study. J Pak Med Assoc. 2008;58:302-304. [Medline].

  21. McIver B, Rae P, Beckett G, et al. Lack of effect of thyroxine in patients with Graves hyperthyroidism who are treated with an antithyroid drug. N Engl J Med. 1996;334:220-224. [Medline].

  22. Nabhan ZM, Kreher NC, Eugster EA. Hashitoxicosis in children: clinical features and natural history. J Pediatr. Apr 2005;146(4):533-6. [Medline].

  23. Pagliara AS, Caplan RH, Gundersen CB, et al. Peripheral resistance to thyroid hormone in a family: heterogeneity of clinical presentation. J Pediatr. Aug 1983;103(2):228-32. [Medline].

  24. Read CH, Tansey MJ, Menda Y. A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves' patients. J Clin Endocrinol Metab. Sep 2004;89(9):4229-33. [Medline]. [Full Text].

  25. Rojdmark S, Calissendorff J, Danielsson O, Brismar K. Hunger-satiety signals in patients with Graves thyrotoxicosis before, during, and after long-term pharmacological treatment. Endocrine. Jun 2005;27(1):55-61. [Medline].

  26. Ruiz M, Rajatanavin R, Young RA, et al. Familial dysalbuminemic hyperthyroxinemia: a syndrome that can be confused with thyrotoxicosis. N Engl J Med. Mar 18 1982;306(11):635-9. [Medline].

  27. Safa AM, Schumacher OP, Rodriguez-Antunez A. Long-term follow-up results in children and adolescents treated with radioactive iodine (131I) for hyperthyroidism. N Engl J Med. Jan 23 1975;292(4):167-71. [Medline].

  28. Shiroozu A, Okamura K, Ikenoue H, et al. Treatment of hyperthyroidism with a small single daily dose of methimazole. J Clin Endocrinol Metab. Jul 1986;63(1):125-8. [Medline].

  29. Sills IN. Hyperthyroidism. Pediatr Rev. Nov 1994;15(11):417-21. [Medline].

  30. Slyper AH, Wyatt D, Boudreau C. Effective methimazole dose for childhood Graves disease and use of free triiodothyronine combined with concurrent thyroid-stimulating hormone level to identify mild hyperthyroidism and delayed pituitary recovery. J Pediatr Endocrinol Metab. 2005;18:597-602. [Medline].

  31. Tamai H, Hayaki I, Kawai K, et al. Lack of effect of thyroxine administration on elevated thyroid stimulating hormone receptor antibody levels in treated Graves disease patients. J Clin Endocrinol Metab. 1995;80:1481-1484. [Medline].

  32. Vaidya VA, Bongiovanni AM, Parks JS, et al. Twenty-two years experience in the medical management of juvenile thyrotoxicosis. Pediatrics. Nov 1974;54(5):565-70. [Medline].

  33. Zimmerman D, Gan-Gaisano M. Hyperthyroidism in children and adolescents. Pediatr Clin North Am. Dec 1990;37(6):1273-95. [Medline].

  34. Zimmermann MB, Ito Y, Hess SY, et al. High thyroid volume in children with excess dietary iodine intakes. Am J Clin Nutr. Apr 2005;81(4):840-4. [Medline]. [Full Text].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

hyperthyroidism, thyrotoxicosis, Graves disease, Graves' disease, thyroid disease, thyroid gland, thyroid hormone, thyroid-stimulating hormone, TSH, thyrotropin-releasing hormone, TRH, triiodothyronine, T3, thyroxine, T4, diabetes mellitus, Addison disease, systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis, vitiligo, immune thrombocytopenic purpura, pernicious anemia, treatment, diagnosis, craniosynostosis, developmental delay, hypercalcemia, McCune-Albright syndrome, precocious puberty, attention deficit hyperactivity, disorder, insomnia, heat intolerance, diarrhea, menstrual irregularities, goiter, tachycardia, exophthalmos, toxic adenoma, toxic nodular goiter, subacute thyroiditis, chronic lymphocytic thyroiditis, pituitary adenoma, exogenous thyroid hormone, polyostotic fibrous dysplasia, café-au-lait spots, Jod-Basedow phenomenon

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Robert J Ferry Jr, MD, Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Medical Center, University of Tennessee Health Science Center at Memphis, and St Jude Children's Research Hospital; Field Surgeon (Medical Corps), 162nd Area Support Medical Company, Army National Guard
Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society
Disclosure: Nutropin Speakers Bureau Honoraria Speaking and teaching; Genotropin Speakers Bureau Honoraria Speaking and teaching; Eli Lilly & Co. Grant/research funds Independent contractor; MacroGenics, Inc. Grant/research funds Independent contractor; Ipsen, S.A. (formerly Tercica, Inc.) Grant/research funds Independent contractor

Coauthor(s)

Jonathan G Gold, MD, Assistant Professor, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University
Jonathan G Gold, MD is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Thomas A Wilson, MD, Professor of Clinical Pediatrics, Department of Pediatrics; Director of Pediatric Endocrinology, Division of Pediatric Endocrinology, Department of Pediatrics, State University of New York at Stony Brook
Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London), Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece
George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.