Thyrotoxicosis Imaging

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Overview

The term thyrotoxicosis refers to the hypermetabolic clinical syndrome resulting from serum elevations in thyroid hormone levels, specifically free thyroxine (T4) and/or triiodothyronine (T3). Thyroid hormone homeostasis is illustrated in the image below.


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Illustration of the negative feedback loop causing homeostasis of thyroid hormone levels. A decrease in blood thyroid hormone triiodothyronine (T3)/th....

Neoplasms leading to thyrotoxicosis include autonomously functioning toxic nodules and toxic, multinodular goiters (TMNGs).

Infections that can produce thyrotoxicosis include subacute thyroiditis (SAT) and, very rarely, acute suppurative thyroiditis.

Hyperthyroidism is a type of thyrotoxicosis in which accelerated thyroid hormone biosynthesis and secretion by the thyroid gland produce thyrotoxicosis. However, hyperthyroidism and thyrotoxicosis are not synonymous.[1] This is because, although many patients have thyrotoxicosis caused by hyperthyroidism, other patients may have thyrotoxicosis resulting from inflammation of the thyroid gland, which causes the release of stored thyroid hormone but not accelerated synthesis, or they may have thyrotoxicosis, which is caused by ingestion of exogenous thyroid hormone.

Differentiating between thyrotoxicosis caused by hyperthyroidism and thyrotoxicosis not caused by hyperthyroidism is important, because disease management and therapy differ for each form. Thyroid imaging and radiotracer thyroid uptake measurements, combined with serologic data, enable specific diagnosis and appropriate patient treatment.[2, 3, 4, 5]

The common causes of thyrotoxicosis have different pathophysiologic features and include autoimmune diseases, functioning thyroid adenomas, and infections.

Autoimmune diseases resulting in thyrotoxicosis include the following:

Neoplasms that cause thyrotoxicosis include autonomously functioning toxic nodules and TMNGs (see the images below); infections that lead to the condition include subacute thyroiditis (SAT) and, very rarely, acute suppurative thyroiditis.


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Iodine-123 scan in a patient with a palpable nodule in the right neck, a low serum level for thyrotropin, and a slightly elevated serum level of free ....


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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....

Recent studies

The assessment of thyroid blood flow by color-flow Doppler ultrasonography is valuable in the differentiation of destructive thyrotoxicosis from Graves disease, according to a study by Kumar et al. The study was carried out in 65 patients, between June 2007 and March 2008. Destructive thyrotoxicosis was present in 31 patients; the remaining patients had Graves disease.

Technetium-99m (99m Tc) pertechnetate scanning was performed when the diagnosis was not clear on the basis of clinical findings. Thyroid blood flow, as assessed by peak systolic velocity of the inferior thyroid artery, was significantly higher in patients with Graves disease. All patients with destructive thyrotoxicosis had low peak systolic velocity of the inferior thyroid artery, and 32 of 34 patients with Graves disease had high peak systolic velocity. Color-flow Doppler ultrasonography parameters correlated significantly with pertechnetate scan results, demonstrating a comparable sensitivity of 96% and a specificity of 95%.[6]

Phillips and Hennessey noted that, although radioactive iodine is often useful in the diagnosis and treatment of thyrotoxicosis, such tests cannot be performed in many patients because of recent use of iodinated contrast for other diagnostic studies, such as computed tomography (CT) scanning. In their study, the investigators found that 45% of patients with newly diagnosed thyrotoxicosis had received iodinated contrast within 2 weeks before endocrinology evaluation; 43 had received iodine for CT and the other 2 for angiography. Only 1 patient required emergent treatment of a condition diagnosed by CT before further diagnostic studies could have been performed.[7]

Donkol et al concluded that color Doppler flow of the inferior thyroid artery was useful in the differential diagnosis of thyrotoxicosis, particularly when a patient has a contraindication of thyroid scintigraphy by radioactive material.[8]

Preferred examination

The diagnosis of thyrotoxicosis is predominately based on laboratory results, including an elevated free T3/T4 level and suppressed thyrotropin level; however, the clinical examination may reveal the etiology. If the thyroid gland is normal or diffusely enlarged on physical examination, the most likely diagnosis is Graves disease.

If 1 or more thyroid nodules are palpated, the patient probably has an autonomously functioning thyroid nodule (AFTN) or a TMNG. If the thyroid gland is markedly tender, subacute thyroiditis is likely. However, silent thyroiditis is almost always in the differential diagnosis with Graves disease. In addition, some patients with silent thyroiditis may have a tender thyroid gland, and some patients with subacute thyroiditis have only mild thyroid tenderness.

As a result of the clinical overlap, knowledge of thyroid iodine uptake is necessary for specific diagnosis and appropriate therapy in most patients. Also, thyroid radionuclide scintigraphy can help to distinguish Graves disease from a toxic nodule and a TMNG.

Limitations of techniques

Thyroid uptake testing, thyroid scintigraphy, and thyroid ultrasonography are not the primary testing modalities for the diagnosis of thyrotoxicosis, but their findings can be critical in the differential diagnosis of the disease and in selecting treatment once thyrotoxicosis is established with serologic test results.[9, 10]

FDA Alert

On June 4, 2009, the US Food and Drug Administration (FDA) issued an alert for propylthiouracil regarding the risk of serious liver injury, including liver failure and death, in adults and children being treated for hyperthyroidism caused by Graves disease. In general, propylthiouracil is considered second-line drug therapy, after methimazole, except in patients who are allergic to or intolerant of methimazole. Physicians should therefore carefully consider which drug to use in recently diagnosed cases of Graves disease. Patients should especially be closely monitored during the first 6 month of therapy.

At the time of the alert, the FDA had identified 32 cases (22 adult and 10 pediatric) of serious liver injury associated with propylthiouracil. Of the adult cases, 12 deaths and 5 liver transplants had occurred; among pediatric patients, 1 case had resulted in death and 6 in liver transplants. Methimazole was also known at that time to have caused 5 cases of serious liver injury, with all 5 cases having occurred in adult patients and 3 of those having resulted in death.[11]

Ultrasonography

Thyroid ultrasonography is not necessary for the differential diagnosis of thyrotoxicosis, although certain findings are important.

In Graves disease, the thyroid appears normal or moderately enlarged. Color-flow imaging demonstrates a general mild to marked increase in blood flow through the parenchyma, as seen in the image below. With AFTN and TMNG, sonograms demonstrate 1 or more nodules, but they do not indicate the functional status of any nodule.[12, 13]


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Color-flow ultrasonogram in a patient with Graves disease. Generalized hypervascularity is visible throughout the gland, which often can be heard as a....

In silent thyroiditis and PPT, the gland may be normal, or it may be generally large or plump. The pyramidal lobe may be prominent. The parenchyma may be heterogeneously hyperechoic. With SAT, the gland is edematous; the edema is reflected as hypoechogenicity. This finding can be regional, because the gland may not be affected uniformly.

Nuclear Imaging

Nuclear medicine examinations are used to differentiate the causes of thyrotoxicosis after the diagnosis is made clinically and confirmed by using appropriate laboratory tests. At that point, measurements of thyroid radiotracer uptake with iodine-123 (123 I) or iodine-131 (131 I) and findings on a thyroid scan obtained with123 I or99m Tc confirm the diagnosis, and treatment can be initiated. Iodine uptake is demonstrated in the images below.[14, 15]


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Iodine-123 thyroid scan in a patient with Graves disease: Tracer uptake is uniform throughout the gland. The 5-hour iodine uptake was high at 53%.


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Iodine-123 thyroid scan in a patient with Graves disease. The 5-hour iodine uptake was elevated at 29%. Note the high level of iodine concentration ne....


View Image

Iodine-123 scan in a patient with a palpable nodule in the right neck, a low serum level for thyrotropin, and a slightly elevated serum level of free ....


View Image

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....

Establishing the cause of thyrotoxicosis

In the thyroid radioiodine tracer uptake test, a measured dose of radiotracer, usually123 I or131 I, is administered to the patient.[7]

After 4-24 hours, activity in the thyroid (ie, neck activity corrected for background levels) is imaged, and the percentage of the administered dose within the thyroid is calculated. Each laboratory should establish their normal values, but generally, normal values are in the range of 5-25%. Thyrotoxicosis (ie, Graves disease, AFTN, TMNG) caused by hyperfunctional thyroid tissue is associated with normal to markedly increased uptake.

Thyrotoxicosis (ie, SAT, silent thyroiditis) caused by inflammation of the thyroid gland has low to absent uptake. Thyroid scintigraphy after the oral administration of123 I or intravenous administration of99m Tc is helpful in demonstrating diffuse tracer uptake (Graves disease) versus nodular tracer concentration (AFTN, TMNG). The image can also be used distinguish low thyroid uptake from a high thyroid uptake, but the findings are not as quantitative as those of the thyroid uptake test.

Degree of confidence

With concordant clinical, laboratory, and imaging findings, confidence in a specific diagnosis is high.

False positives/negatives

Normal results on 4- to 24-hour thyroid uptake scans do not preclude a diagnosis of hyperthyroidism. Many multivitamins and other food supplements contain large amounts of iodine, and the extra iodine competes with radioiodine for thyroid clearance. Other sources of iodine ingestion also may be present.

Author

John L Floyd, MD, FACR, FRCR, Director of Nuclear Medicine Services, Department of Nuclear Radiology, St Luke's Methodist Hospital and Mercy Medical Center; Consulting Staff, Radiology Consultants of Iowa

Disclosure: Nothing to disclose.

Specialty Editors

Hussein M Abdel-Dayem, MD, Professor of Radiology, New York Medical College

Disclosure: Nothing to disclose.

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand

Disclosure: Nothing to disclose.

C Douglas Phillips, MD, FACR, Director of Head and Neck Imaging, Division of Neuroradiology, New York-Presbyterian Hospital; Professor of Radiology, Weill Cornell Medical College

Disclosure: Nothing to disclose.

Robert M Krasny, MD, Resolution Imaging Medical Corporation

Disclosure: Nothing to disclose.

Chief Editor

Eugene C Lin, MD, Attending Radiologist, Teaching Coordinator for Cardiac Imaging, Radiology Residency Program, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine

Disclosure: Nothing to disclose.

References

  1. Kittisupamongkol W. Hyperthyroidism or thyrotoxicosis? (NOVEMBER 2008). Cleve Clin J Med. Mar 2009;76(3):152. [View Abstract]
  2. De Waele S, Van den Bruel A, Selleslag D, Van Den Berghe I, Decallonne B. Acute thyrotoxicosis after SCT. Bone Marrow Transplant. Nov 17 2008;[View Abstract]
  3. Kasagi K, Hattori H. A case of destructive thyrotoxicosis induced by neck trauma. Thyroid. Dec 2008;18(12):1333-5. [View Abstract]
  4. Motohashi K, Sakai R, Hagihara M, Enaka M, Kanamori H, Maruta A, et al. Thyrotoxicosis after cord blood transplantation for acute myelogenous leukemia. Rinsho Ketsueki. Dec 2008;49(12):1631-3. [View Abstract]
  5. Romero-Rodríguez N, Cabeza Letrán ML, Villa Gil Ortega M, Ballesteros Pradas S. Thyrotoxicosis-induced vasospastic angina. Rev Esp Cardiol. Dec 2008;61(12):1355-6. [View Abstract]
  6. Hari Kumar KV, Pasupuleti V, Jayaraman M, Abhyuday V, Rayudu B R, Modi KD. Role of thyroid Doppler in differential diagnosis of thyrotoxicosis. Endocr Pract. Jan-Feb 2009;15(1):6-9. [View Abstract]
  7. Phillips BD, Hennessey JV. Iodinated contrast prior to evaluation for thyrotoxicosis. J Hosp Med. Mar 4 2009;[View Abstract]
  8. Donkol RH, Nada AM, Boughattas S. Role of color Doppler in differentiation of Graves' disease and thyroiditis in thyrotoxicosis. World J Radiol. Apr 28 2013;5(4):178-83. [View Abstract]
  9. Zhao X, Chen L, Li L, Wang Y, Wang Y, Zhou L, et al. Peak systolic velocity of superior thyroid artery for the differential diagnosis of thyrotoxicosis. PLoS One. 2012;7(11):e50051. [View Abstract]
  10. Alzahrani AS, Ceresini G, Aldasouqi SA. Role of ultrasonography in the differential diagnosis of thyrotoxicosis: a noninvasive, cost-effective, and widely available but underutilized diagnostic tool. Endocr Pract. Jul-Aug 2012;18(4):567-78. [View Abstract]
  11. FDA MedWatch Safety Alerts for Human Medical Products. Propylthiouracil (PTU). US Food and Drug Administration. US Food and Drug Administration. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm164162.htm. Accessed June 3, 2009.
  12. Miles J, Charles P, Riches P. A review of methods available for the identification of both organ- specific and non-organ-specific autoantibodies. Ann Clin Biochem. Jan 1998;35 ( Pt 1):19-47. [View Abstract]
  13. Loy M, Perra E, Melis A, Cianchetti ME, Piga M, Serra A, et al. Color-flow Doppler sonography in the differential diagnosis and management of amiodarone-induced thyrotoxicosis. Acta Radiol. Jul 2007;48(6):628-34. [View Abstract]
  14. Floyd JL, Rosen PR, Borchert RD, et al. Thyroid uptake and imaging with iodine-123 at 4-5 hours: replacement of the 24-hour iodine-131 standard. J Nucl Med. Aug 1985;26(8):884-7. [View Abstract]
  15. Piga M, Cocco MC, Serra A, Boi F, Loy M, Mariotti S. The usefulness of 99mTc-sestaMIBI thyroid scan in the differential diagnosis and management of amiodarone-induced thyrotoxicosis. Eur J Endocrinol. Oct 2008;159(4):423-9. [View Abstract]

Illustration of the negative feedback loop causing homeostasis of thyroid hormone levels. A decrease in blood thyroid hormone triiodothyronine (T3)/thyroxine (T4) levels results in the inhibition of thyrotropin-releasing hormone and thyrotropin production. The released thyrotropin stimulates synthesis and release of T3/T4 by the thyroid, which in turn tends to inhibit further thyrotropin release. THS is thyrotropin. TRH is thyrotropin-releasing hormone.

Iodine-123 thyroid scan in a patient with Graves disease: Tracer uptake is uniform throughout the gland. The 5-hour iodine uptake was high at 53%.

Iodine-123 thyroid scan in a patient with Graves disease. The 5-hour iodine uptake was elevated at 29%. Note the high level of iodine concentration near the thyroid. Also note the pyramidal lobe, which often is visualized in a hyperstimulated gland. The cold nodule in the right lobe must be addressed in the same way that a solitary cold nodule in a patient without Graves disease is evaluated. Fine-needle aspiration of the nodule prior to iodine-131 treatment did not reveal a carcinoma.

Iodine-123 scan in a patient with a palpable nodule in the right neck, a low serum level for thyrotropin, and a slightly elevated serum level of free triiodothyronine. The autonomously functioning nodule only partially suppresses uptake in the remainder of the gland. The 5-hour iodine uptake was mildly elevated at 22%.

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.

Color-flow ultrasonogram in a patient with Graves disease. Generalized hypervascularity is visible throughout the gland, which often can be heard as a hum or bruit with a stethoscope.

Iodine-123 thyroid scan in a patient with Graves disease: Tracer uptake is uniform throughout the gland. The 5-hour iodine uptake was high at 53%.

Iodine-123 thyroid scan in a patient with Graves disease. The 5-hour iodine uptake was elevated at 29%. Note the high level of iodine concentration near the thyroid. Also note the pyramidal lobe, which often is visualized in a hyperstimulated gland. The cold nodule in the right lobe must be addressed in the same way that a solitary cold nodule in a patient without Graves disease is evaluated. Fine-needle aspiration of the nodule prior to iodine-131 treatment did not reveal a carcinoma.

Iodine-123 scan in a patient with a palpable nodule in the right neck, a low serum level for thyrotropin, and a slightly elevated serum level of free triiodothyronine. The autonomously functioning nodule only partially suppresses uptake in the remainder of the gland. The 5-hour iodine uptake was mildly elevated at 22%.

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.

Illustration of the negative feedback loop causing homeostasis of thyroid hormone levels. A decrease in blood thyroid hormone triiodothyronine (T3)/thyroxine (T4) levels results in the inhibition of thyrotropin-releasing hormone and thyrotropin production. The released thyrotropin stimulates synthesis and release of T3/T4 by the thyroid, which in turn tends to inhibit further thyrotropin release. THS is thyrotropin. TRH is thyrotropin-releasing hormone.

Iodine-123 thyroid scan in a patient with Graves disease: Tracer uptake is uniform throughout the gland. The 5-hour iodine uptake was high at 53%.

Iodine-123 thyroid scan in a patient with Graves disease. The 5-hour iodine uptake was elevated at 29%. Note the high level of iodine concentration near the thyroid. Also note the pyramidal lobe, which often is visualized in a hyperstimulated gland. The cold nodule in the right lobe must be addressed in the same way that a solitary cold nodule in a patient without Graves disease is evaluated. Fine-needle aspiration of the nodule prior to iodine-131 treatment did not reveal a carcinoma.

Ultrasonogram of the right lobe of the thyroid in the same patient as in the previous image. Fine-needle aspiration of the nodule prior to iodine-131 treatment did not reveal a carcinoma.

Iodine-123 scan in a patient with a palpable nodule in the right neck, a low serum level for thyrotropin, and a slightly elevated serum level of free triiodothyronine. The autonomously functioning nodule only partially suppresses uptake in the remainder of the gland. The 5-hour iodine uptake was mildly elevated at 22%.

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.

Color-flow ultrasonogram in a patient with Graves disease. Generalized hypervascularity is visible throughout the gland, which often can be heard as a hum or bruit with a stethoscope.