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Hyperthyroidism Clinical Presentation

  • Author: Stephanie L Lee, MD, PhD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
 
Updated: Jul 13, 2016
 

History

The presentation of thyrotoxicosis is variable among patients. Thyrotoxicosis leads to an apparent increase in sympathetic nervous system symptoms. Younger patients tend to exhibit symptoms of sympathetic activation, such as anxiety, hyperactivity, and tremor, while older patients have more cardiovascular symptoms, including dyspnea and atrial fibrillation with unexplained weight loss.[1] The clinical manifestations of thyrotoxicosis do not always correlate with the extent of the biochemical abnormality.

Common symptoms of thyrotoxicosis include the following:

  • Nervousness
  • Anxiety
  • Increased perspiration
  • Heat intolerance
  • Hyperactivity
  • Palpitations

Generally, a constellation of information, including the extent and duration of symptoms, past medical history, and social and family history, in addition to the information derived from physical examination, help to guide the clinician to the appropriate diagnosis. For example, Graves disease is an autoimmune disease, and patients often have a family history or past medical history of autoimmune disease (eg, rheumatoid arthritis, vitiligo, pernicious anemia).

Patients with Graves disease often have more marked symptoms than patients with thyrotoxicosis from other causes, because thyroid hormone levels usually are the highest with this form of hyperthyroidism. The diagnosis of Graves disease should also be considered if any evidence of thyroid eye disease exists, including periorbital edema, diplopia, or proptosis.

Toxic multinodular goiters occur in patients who have had a known nontoxic goiter for many years or decades. Often, patients have emigrated from regions of the world with borderline- low iodine intake or have a strong family history of nontoxic goiter.

Subclinical hyperthyroidism, defined as a low thyroid-stimulating hormone (TSH) level with normal free thyroxine (FT4) and free triiodothyronine (FT3) levels, is associated with no or minimal clinical symptoms of thyrotoxicosis. However, certain conditions (eg, atrial fibrillation, osteoporosis, or hypercalcemia) may suggest the possibility of thyrotoxicosis. In fact, subclinical hyperthyroidism may be associated with a 3-fold increase in the risk of atrial fibrillation. The prevalence of subclinical hyperthyroidism may be as high as 2% in the general population.

The risk of atrial fibrillation may be elevated even in persons with high-normal thyroid function. In a report from the Netherlands on 1426 patients whose TSH levels were in the normal range (0.4-4.0 mIU/L), the hazard ratio for atrial fibrillation was 1.94 for the lowest versus the highest quartile of TSH, after a median follow-up of 8 years.[16]

Radiation exposure increases the risk of benign and malignant nodular thyroid diseases, especially with the higher radiation levels used in radiation therapy. External radiation therapy is associated with an increase in the incidence of autoimmune hyperthyroidism when the thyroid is in the radiation field.

The family history should include careful documentation of the following:

  • Autoimmune disease
  • Thyroid disease
  • Emigration from iodine-deficient parts of the world

Review a complete list of medications and dietary supplements. A number of compounds—including expectorants, amiodarone, iodinated contrast dyes, and health food supplements containing seaweed or thyroid gland extracts—contain large amounts of iodine that can induce thyrotoxicosis in a patient with thyroid autonomy. Rarely, iodine exposure can cause thyrotoxicosis in a patient with an apparently healthy thyroid.

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Physical Examination

The thyroid is located in the lower anterior neck. The isthmus of the butterfly-shaped gland generally is located just below the cricoid cartilage of the trachea, with the wings of the gland wrapping around the trachea. Physical examination often can help the clinician to determine the etiology of thyrotoxicosis.

Common signs of thyrotoxicosis include the following:

  • Tachycardia or atrial arrhythmia
  • Systolic hypertension with wide pulse pressure
  • Warm, moist, smooth skin
  • Lid lag
  • Stare
  • Hand tremor
  • Muscle weakness
  • Weight loss despite increased appetite (although a few patients may gain weight, if excessive intake outstrips weight loss)
  • Reduction in menstrual flow or oligomenorrhea

Thyroid examination

Thyrotoxicosis from Graves disease is associated with a diffusely enlarged and slightly firm thyroid gland. Sometimes, a thyroid bruit can be heard by using the bell of the stethoscope.

Toxic multinodular goiters generally occur when the thyroid gland is enlarged to at least 2 to 3 times the normal size. The gland often is soft, but individual nodules occasionally can be palpated. Because most thyroid nodules cannot be palpated, thyroid nodules should be documented by thyroid ultrasonography, but overactive thyroid nodules can be demonstrated only by nuclear thyroid imaging with radioiodine (I-123) or technetium (Tc99m) thyroid scan.

If the thyroid is enlarged and painful, subacute painful or granulomatous thyroiditis is the likely diagnosis. However, degeneration or hemorrhage into a nodule and suppurative thyroiditis should also be considered.

Ophthalmologic and dermatologic examination

Approximately 50% of patients with Graves thyrotoxicosis have mild thyroid ophthalmopathy. Often, this is manifested only by periorbital edema, but it also can include conjunctival edema (chemosis), injection, poor lid closure, extraocular muscle dysfunction (diplopia), and Proptosis (see the image below). Evidence of thyroid eye disease and high thyroid hormone levels confirms the diagnosis of autoimmune Grave disease.

Severe proptosis, periorbital edema, and eyelid re Severe proptosis, periorbital edema, and eyelid retraction from thyroid-related orbitopathy. This patient also had optic nerve dysfunction and chemosis (conjunctival edema) from thyroid-related orbitopathy.

In rare instances, Graves disease affects the skin through deposition of glycosaminoglycans in the dermis of the lower leg. This causes nonpitting edema, which is usually associated with erythema and thickening of the skin, without pain or pruritus (see the image below).

Bilateral erythematous infiltrative plaques on low Bilateral erythematous infiltrative plaques on lower extremities in 42-year-old man with Graves disease are consistent with pretibial myxedema. Myxedematous changes of skin usually occur in pretibial areas and resemble orange peel in color and texture.
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Contributor Information and Disclosures
Author

Stephanie L Lee, MD, PhD Associate Professor, Department of Medicine, Boston University School of Medicine; Director of Thyroid Health Center, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center; Fellow, Association of Clinical Endocrinology

Stephanie L Lee, MD, PhD is a member of the following medical societies: American College of Endocrinology, American Thyroid Association, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Sonia Ananthakrishnan, MD Assistant Professor of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center, Boston University School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Frederick H Ziel, MD Associate Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; 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, andInternational Society for Clinical Densitometry

Disclosure: Nothing to disclose.

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

  2. [Guideline] Bahn Chair RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011 Jun. 21(6):593-646. [Medline].

  3. Lumbroso S, Paris F, Sultan C. Activating Gsalpha mutations: analysis of 113 patients with signs of McCune-Albright syndrome--a European Collaborative Study. J Clin Endocrinol Metab. 2004 May. 89(5):2107-13. [Medline].

  4. Betterle C, Dal Pra C, Mantero F, Zanchetta R. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev. 2002 Jun. 23(3):327-64. [Medline].

  5. Plagnol V, Howson JM, Smyth DJ, Walker N, Hafler JP, Wallace C, et al. Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. PLoS Genet. 2011 Aug. 7(8):e1002216. [Medline]. [Full Text].

  6. Chu X, Pan CM, Zhao SX, Liang J, Gao GQ, Zhang XM, et al. A genome-wide association study identifies two new risk loci for Graves' disease. Nat Genet. 2011 Aug 14. 43(9):897-901. [Medline].

  7. Simmonds MJ, Brand OJ, Barrett JC, Newby PR, Franklyn JA, Gough SC. Association of Fc receptor-like 5 (FCRL5) with Graves' disease is secondary to the effect of FCRL3. Clin Endocrinol (Oxf). 2010 Nov. 73(5):654-60. [Medline]. [Full Text].

  8. Newby PR, Pickles OJ, Mazumdar S, Brand OJ, Carr-Smith JD, Pearce SH, et al. Follow-up of potential novel Graves' disease susceptibility loci, identified in the UK WTCCC genome-wide nonsynonymous SNP study. Eur J Hum Genet. 2010 Sep. 18(9):1021-6. [Medline]. [Full Text].

  9. Nakabayashi K, Shirasawa S. Recent advances in the association studies of autoimmune thyroid disease and the functional characterization of AITD-related transcription factor ZFAT. Nihon Rinsho Meneki Gakkai Kaishi. 2010. 33(2):66-72. [Medline].

  10. Chu X, Dong Y, Shen M, Sun L, Dong C, Wang Y, et al. Polymorphisms in the ADRB2 gene and Graves disease: a case-control study and a meta-analysis of available evidence. BMC Med Genet. 2009 Mar 13. 10:26. [Medline]. [Full Text].

  11. Gabriel EM, Bergert ER, Grant CS, van Heerden JA, Thompson GB, Morris JC. Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter. J Clin Endocrinol Metab. 1999 Sep. 84(9):3328-35. [Medline].

  12. Mittra ES, Niederkohr RD, Rodriguez C, El-Maghraby T, McDougall IR. Uncommon causes of thyrotoxicosis. J Nucl Med. 2008 Feb. 49(2):265-78. [Medline].

  13. Davies TF, Larsen PR. Thyrotoxicosis. Larsen PR et al, eds. Williams Textbook of Endocrinology. 10th ed. Philadelphia: Saunders; 2003. 374-421.

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

  15. Zhyzhneuskaya S, Addison C, Tsatlidis V, Weaver JU, Razvi S. The Natural History of Subclinical Hyperthyroidism in Graves' Disease: The Rule of Thirds. Thyroid. 2016 Jun. 26(6):765-9. [Medline].

  16. 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. 2008 Nov 10. 168(20):2219-24. [Medline].

  17. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, 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. 2002 Feb. 87(2):489-99. [Medline]. [Full Text].

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

  19. [Guideline] De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012 Aug. 97(8):2543-65. [Medline].

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

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

  22. Wang J, Qin L. Radioiodine therapy versus antithyroid drugs in Graves' disease: a meta-analysis of randomized controlled trials. Br J Radiol. 2016 Jun 27. [Medline].

  23. Sisson JC, Freitas J, McDougall IR, Dauer LT, Hurley JR, Brierley JD, et al. Radiation safety in the treatment of patients with thyroid diseases by radioiodine ¹³¹i: practice recommendations of the american thyroid association. Thyroid. 2011 Apr. 21(4):335-46. [Medline].

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

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

  26. FDA Drug Safety Communication: New Boxed Warning on severe liver injury with propylthiouracil. US Food and Drug Administration, April 21, 2010. Available at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm209023.htm. Accessed: March 6, 2012.

  27. Yalamanchi S, Cooper DS. Thyroid disorders in pregnancy. Curr Opin Obstet Gynecol. 2015 Oct 19. [Medline].

  28. Burches-Feliciano MJ, Argente-Pla M, Garcia-Malpartida K, Rubio-Almanza M, Merino-Torres JF. Hyperthyroidism induced by topical iodine. Endocrinol Nutr. 2015 Aug 12. [Medline].

  29. Brandt F. The long-term consequences of previous hyperthyroidism. A register-based study of singletons and twins. Dan Med J. 2015 Jun. 62 (6):[Medline].

  30. Srinivasan S, Misra M. Hyperthyroidism in children. Pediatr Rev. 2015 Jun. 36 (6):239-48. [Medline].

 
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Severe proptosis, periorbital edema, and eyelid retraction from thyroid-related orbitopathy. This patient also had optic nerve dysfunction and chemosis (conjunctival edema) from thyroid-related orbitopathy.
Color flow ultrasonogram in patient with Graves disease. Generalized hypervascularity is visible throughout gland (note red areas), which often can be heard as hum or bruit with stethoscope.
Absence of iodine 123 (123I) radioactive iodine uptake in patient with thyrotoxicosis and subacute painless or lymphocytic thyroiditis. Laboratory studies at time of scan demonstrated the following: thyroid-stimulating hormone (TSH), less than 0.06 mIU/mL; total thyroxine (T4), 21.2 µg/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/hr. Absence of thyroid uptake, low T3-to-T4 ratio, and low ESR confirm diagnosis of subacute painless thyroiditis.
Three multinuclear giant cell granulomas observed in fine-needle aspiration biopsy of thyroid from patient with thyrotoxicosis from subacute painful or granulomatous thyroiditis.
Scan in patient with toxic multinodular goiter. 5-Hour 123I-iodine uptake was elevated at 28% (normal 5-15%). Note multiple foci of variably increased tracer uptake.
Iodine 123 (123I) nuclear scintigraphy: 123I scans of normal thyroid gland (A) and common hyperthyroid conditions with elevated radioiodine uptake, including Graves disease (B), toxic multinodular goiter (C), and toxic adenoma (D).
Gross photo of subtotal thyroidectomy for diffuse toxic goiter (Graves Disease) showing homogenous enlargement without nodules.
Low-power photomicrograph showing diffuse papillary hyperplasia (hallmark histologic feature of Graves disease).
High-power photomicrograph showing papillary hyperplasia of follicular cells with increased nuclear size and small nucleoli.
Bilateral erythematous infiltrative plaques on lower extremities in 42-year-old man with Graves disease are consistent with pretibial myxedema. Myxedematous changes of skin usually occur in pretibial areas and resemble orange peel in color and texture.
Hypothalamic-pituitary-thyroid axis feedback. Schematic representation of negative feedback system that regulates thyroid hormone levels. TRH = thyrotropin-releasing hormone; TSH = thyroid-stimulating hormone.
Table 1. Thyrotoxicosis and Hyperthyroidism
Common Forms (85-90% of Cases) 24-Hour RAIU Over Neck*
Diffuse toxic goiter (Graves disease) Increased (moderate to high: 40-100%)
Toxic multinodular goiter (Plummer disease) Increased (mild to moderate: 25-60%)
Thyrotoxic phase of subacute thyroiditis Decreased (very low: < 2%)
Toxic adenoma Increased (mild to moderate: 25-60%)
Less Common Forms
Iodide-induced thyrotoxicosis Variable but usually low (< 25%)
Thyrotoxicosis factitia Decreased (very low: < 2%)
Uncommon Forms
Pituitary tumors producing TSH Increased (mild to moderate: 25-60%)
Excess human chorionic gonadotropin (molar pregnancy/choriocarcinoma) Increased (variable: 25-100%)
Pituitary resistance to thyroid hormone Increased (mild to moderate: 25-60%)
Metastatic thyroid carcinoma Decreased
Struma ovarii with thyrotoxicosis Decreased
RAIU = radioactive iodine uptake; TSH = thyroid-stimulating hormone.



* A normal 6-hour RAIU is approximately 2-16%; a 24-hour RAIU is about 8-25% but is modified according to the iodine content of the patient’s diet. RAIU or scanning should not be performed in a woman who is pregnant (with the exception of a molar pregnancy) or breastfeeding.



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