eMedicine Specialties > Endocrinology > Thyroid

Hyperthyroidism: 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
Contributor Information and Disclosures

Updated: Jun 8, 2009

Differential Diagnoses

Euthyroid Hyperthyroxinemia
Struma Ovarii
Goiter
Thyrotoxicosis
Goiter, Diffuse Toxic
Graves Disease
Plummer-Vinson Syndrome

Other Problems to Be Considered

Subclinical hyperthyroidism
Toxic multinodular goiter
Toxic thyroid adenoma

Workup

Laboratory Studies

  • Laboratory evaluation of thyrotoxicosis: The most reliable screening measure of thyroid function is a TSH level. TSH levels usually are suppressed to immeasurable levels (<0.05 µIU/mL) in thyrotoxicosis. Third-generation TSH assays are recommended for screening purposes.
    • The degree of thyrotoxicosis cannot be estimated easily by the TSH level and must be measured using an assay of thyroid hormone levels in the plasma. Thyroid hormone circulates as T3 and T4 with 99% bound to protein. Only the free unbound thyroid hormone is biologically active. T3 is 20-100 times more biologically active than T4. Of patients with thyrotoxicosis, 5% have only elevated T3 levels. Therefore, measuring free T4 (and T3 if T4 levels are normal) is recommended in patients with suspected thyrotoxicosis when TSH is low.
    • Many laboratories do not measure free T4 directly and use a calculation to estimate the FT4 levels. The free thyroxine index (FTI) is equal to total T4 multiplied by the correction for thyroid hormone binding, such as thyroid hormone-binding ratio [THBR] or triiodothyronine resin uptake [T3 RU]). A similar calculation can be used with total T3.
    • Subclinical hyperthyroidism is defined as a suppressed TSH level (<0.5 μU/mL in many laboratories) in combination with serum concentrations of T3 and T4  that are within the reference range.
    • Thyroid autoantibodies - The most specific autoantibody for autoimmune thyroiditis is an enzyme-linked immunosorbent assay (ELISA) for anti-TPO antibody. The titers usually are significantly elevated in the most common type of hyperthyroidism, Graves thyrotoxicosis, and usually are low or absent in toxic multinodular goiter and toxic adenoma. A significant number of healthy people without active thyroid disease have mildly positive TPO antibodies; thus, the test should not be performed for screening purposes. TSI, if elevated, helps establish the diagnosis of Graves disease. A positive anti-TG antibody test does not predict the development of thyroid dysfunction and should not be measured.

Imaging Studies

  • Nuclear thyroid scintigraphy iodine 123 (123 I) uptake and scan - If the etiology of thyrotoxicosis is not clear after physical examination and other laboratory tests, it can be confirmed by an123 I uptake. (See images below and Images 1, 3, 5.) Values are elevated in patients with Graves disease and toxic multinodular goiters.123 I and technetium-99m (99m Tc) can be used for thyroid scanning, which provides anatomic information on the type of goiter (eg, diffuse vs nodular). Scans essentially are pictures of the thyroid and do not necessarily confirm or refute the presence of hyperthyroidism per se; only123 I uptake provides information in this area.
    • Graves disease is associated with diffuse enlargement of both thyroid lobes, with an elevated uptake (see Image 1).
    • A toxic multinodular goiter demonstrates an enlarged thyroid with multiple nodules and areas of increased and decreased isotope uptake (see Image 1).
    • Subacute thyroiditis usually demonstrates very low123 I isotope uptake.
    • A toxic adenoma demonstrates a solitary hot nodule with suppression of function in the surrounding normal thyroid tissue (see Image 1).
    • If a dominant nodule is found upon examination of a patient with thyrotoxicosis, obtain an123 I thyroid scan to assure that the dominant nodule is functioning. If the nodule is cold, perform a biopsy on the nodule by fine-needle aspiration to exclude concomitant malignancy.


Iodine 123 (<SUP><FONT size=-1>123</FONT></SUP>I)...

Iodine 123 (123I) nuclear scintigraphy: 123I scans of a normal thyroid gland (A) and common hyperthyroid conditions with elevated radioiodine uptake, including Graves disease (B), toxic multinodular goiter (C), and toxic adenoma (D).

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Iodine 123 (<SUP><FONT size=-1>123</FONT></SUP>I)...

Iodine 123 (123I) nuclear scintigraphy: 123I scans of a normal thyroid gland (A) and common hyperthyroid conditions with elevated radioiodine uptake, including Graves disease (B), toxic multinodular goiter (C), and toxic adenoma (D).



Absence of iodine 123 (<SUP><FONT size=-1>123</FO...

Absence of iodine 123 (123I) radioactive iodine uptake in a patient with thyrotoxicosis and subacute painless or lymphocytic thyroiditis. Laboratory studies at the time of the scan demonstrated the following: thyroid-stimulating hormone (TSH), less than 0.06 mIU/mL; total thyroxine (T4), 21.2 mcg/dL (reference range, 4.5-11); total triiodothyronine (T3), 213 ng/dL (reference range, 90-180); T3-to-T4 ratio, 10; and erythrocyte sedimentation rate (ESR), 10 mm/h. The absence of thyroid uptake, the low T3-to-T4 ratio, and the low ESR confirm the diagnosis of subacute painless thyroiditis.

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Absence of iodine 123 (<SUP><FONT size=-1>123</FO...

Absence of iodine 123 (123I) radioactive iodine uptake in a patient with thyrotoxicosis and subacute painless or lymphocytic thyroiditis. Laboratory studies at the time of the scan demonstrated the following: thyroid-stimulating hormone (TSH), less than 0.06 mIU/mL; total thyroxine (T4), 21.2 mcg/dL (reference range, 4.5-11); total triiodothyronine (T3), 213 ng/dL (reference range, 90-180); T3-to-T4 ratio, 10; and erythrocyte sedimentation rate (ESR), 10 mm/h. The absence of thyroid uptake, the low T3-to-T4 ratio, and the low ESR confirm the diagnosis of subacute painless thyroiditis.



Scan in a patient with a toxic multinodular goite...

Scan in a patient with a toxic multinodular goiter. The 5-hour iodine uptake was elevated at 28%. Note the multiple foci of variably increased tracer uptake.

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Scan in a patient with a toxic multinodular goite...

Scan in a patient with a toxic multinodular goiter. The 5-hour iodine uptake was elevated at 28%. Note the multiple foci of variably increased tracer uptake.




Other Tests

  • Hyperthyroidism in older patients often presents with atrial arrhythmias or CHF. ECG is recommended if an irregular heart rate or CHF is noted upon examination.

More on Hyperthyroidism

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

  1. Dahl P, Danzi S, Klein I. Thyrotoxic cardiac disease. Curr Heart Fail Rep. Sep 2008;5(3):170-6. [Medline].

  2. [Best Evidence] Heeringa J, Hoogendoorn EH, van der Deure WM, et al. High-normal thyroid function and risk of atrial fibrillation: the Rotterdam study. Arch Intern Med. Nov 10 2008;168(20):2219-24. [Medline].

  3. 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.

  4. Stalberg P, Svensson A, Hessman O, et al. Surgical treatment of Graves' disease: evidence-based approach. World J Surg. Jul 2008;32(7):1269-77. [Medline].

  5. Shindo M. Surgery for hyperthyroidism. ORL J Otorhinolaryngol Relat Spec. 2008;70(5):298-304. [Medline].

  6. [Best Evidence] Worni M, Schudel HH, Seifert E, et al. Randomized controlled trial on single dose steroid before thyroidectomy for benign disease to improve postoperative nausea, pain, and vocal function. Ann Surg. Dec 2008;248(6):1060-6. [Medline].

  7. Porterfield JR Jr, Thompson GB, Farley DR, et al. Evidence-based management of toxic multinodular goiter (Plummer's Disease). World J Surg. Jul 2008;32(7):1278-84. [Medline].

  8. Allahabadia A, Daykin J, Holder RL. Age and gender predict the outcome of treatment for Graves' hyperthyroidism. J Clin Endocrinol Metab. Mar 2000;85(3):1038-42. [Medline]. [Full Text].

  9. Auer J, Scheibner P, Mische T, et al. Subclinical hyperthyroidism as a risk factor for atrial fibrillation. Am Heart J. Nov 2001;142(5):838-42. [Medline].

  10. Bahn RS, Heufelder AE. Pathogenesis of Graves' ophthalmopathy. N Engl J Med. Nov 11 1993;329(20):1468-75. [Medline].

  11. Bal CS, Kumar A, Pandey RM. A randomized controlled trial to evaluate the adjuvant effect of lithium on radioiodine treatment of hyperthyroidism. Thyroid. May 2002;12(5):399-405. [Medline].

  12. Bartalena L, Marcocci C, Bogazzi F, et al. Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy. N Engl J Med. Jan 8 1998;338(2):73-8. [Medline].

  13. Franklyn JA. The management of hyperthyroidism. N Engl J Med. Jun 16 1994;330(24):1731-8. [Medline].

  14. Frost L, Vestergaard P, Mosekilde L. Hyperthyroidism and risk of atrial fibrillation or flutter: a population-based study. Arch Intern Med. Aug 9-23 2004;164(15):1675-8. [Medline].

  15. Gittoes NJ, Franklyn JA. Hyperthyroidism. Current treatment guidelines. Drugs. Apr 1998;55(4):543-53. [Medline].

  16. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. Feb 2002;87(2):489-99. [Medline].

  17. Leslie WD, Ward L, Salamon EA, et al. A randomized comparison of radioiodine doses in Graves' hyperthyroidism. J Clin Endocrinol Metab. Mar 2003;88(3):978-83. [Medline].

  18. Loh KC. Amiodarone-induced thyroid disorders: a clinical review. Postgrad Med J. Mar 2000;76(893):133-40. [Medline].

  19. Mittra ES, Niederkohr RD, Rodriguez C, et al. Uncommon causes of thyrotoxicosis. J Nucl Med. Feb 2008;49(2):265-78. [Medline].

  20. Prummel MF, Wiersinga WM. Smoking and risk of Graves' disease. JAMA. Jan 27 1993;269(4):479-82. [Medline].

  21. Ringel MD. Management of hypothyroidism and hyperthyroidism in the intensive care unit. Crit Care Clin. Jan 2001;17(1):59-74. [Medline].

  22. Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med. Nov 10 1994;331(19):1249-52. [Medline].

  23. Siegel RD, Lee SL. Toxic nodular goiter. Toxic adenoma and toxic multinodular goiter. Endocrinol Metab Clin North Am. Mar 1998;27(1):151-68. [Medline].

  24. Weetman AP. Graves' disease. N Engl J Med. Oct 26 2000;343(17):1236-48. [Medline].

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Keywords

hyperthyroidism, thyroid, TSH, Graves disease, hyperthyroid, thyroiditis, thyroid hormone, thyroid nodule, thyroid function, thyroid treatment, thyroid goiter, thyroid medication, thyroid medicine, thyroid problem, thyroidectomy, enlarged thyroid, thyroid-stimulating hormone, thyroid problems symptoms, thyrotoxicosis, diffuse toxic goiter, Graves' disease, Hashimoto thyroiditis, toxic multinodular goiter, toxic multi-nodular goiter, Plummer disease, Plummer's disease, subacute thyroiditis, toxic adenoma, iodide-induced thyrotoxicosis, thyrotoxicosis factitia, thyroid-stimulating hormone, thyroid carcinoma, struma ovarii with thyrotoxicosis, antithyroid medication, anti-thyroid medication, radioactive iodine therapy, iodine radiotherapy, elevated levels of free thyroxine, elevated levels of free triiodothyronine, molar hydatidiform pregnancy, choriocarcinoma, pituitary tumors, metastatic thyroid carcinoma, heat intolerance, oligomenorrhea, unexplained weight loss, lid lag, sinus tachycardia, atrial fibrillation, high output failure, fine tremor, muscle weakness, anxiety, thyroid ophthalmopathy, pernicious anemia, periorbital edema, chemosis, conjunctival edema, conjunctival injection, proptosis, myasthenia gravis, vitiligo, adrenal insufficiency, type I diabetes mellitus, apathetic hyperthyroidism, follicular thyroid adenoma, toxic thyroid adenoma, Jod-Basedow syndrome, dermoid tumors, ovarian teratomas, congestive heart failure, CHF, left ventricular thickening, dermopathy, extraocular muscle dysfunction, diplopia, swelling of the pretibial area, tachycardia, atrial arrhythmia, systolic hypertension, rheumatoid arthritis, nontoxic goiter, thyroid autonomy, granulomatous thyroiditis, HLA-DRw3, HLA-B89, Hashimoto hypothyroidism

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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.

Medical Editor

Frederick H Ziel, MD, Associate Professor of Medicine, David Geffen School of Medicine at UCLA; Physician-In-Charge, Endocrinology/Diabetes Center, Director of Medical Education, Kaiser Permanente Woodland Hills; Chair of Endocrinology, Co-Chair of Diabetes Complete Care Program, Southern California Permanente Medical Group
Frederick H Ziel, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society for Bone and Mineral Research, California Medical Association, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

Pharmacy Editor

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

Managing Editor

Yoram Shenker, MD, Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison
Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical Research, and Endocrine Society
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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