Thyroid Dysfunction Induced by Amiodarone Therapy Workup

Updated: Oct 06, 2022
  • Author: Mini Gopalan, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Laboratory Studies

Lab findings for AIH are similar to those for spontaneous hypothyroidism and include decreased levels of serum free T4 and increased levels of serum TSH. Serum thyroglobulin levels are often increased, probably because of TSH-enhanced thyroid stimulation.

Lab findings for AIT are elevated levels of serum total and serum free T4 and T3, and undetectable levels of TSH. Low TSH levels and elevated free T4 levels are also commonly seen in the early phases of amiodarone therapy and in patients with severe nonthyroidal illness who have euthyroidism and are treated with amiodarone. Therefore, the measurement of free T3 levels may be helpful in differentiating conditions, because free T3 levels are increased in hyperthyroidism, while they are decreased in early phases of treatment with amiodarone. Serum rT3 levels are also markedly increased. However, serum rT3 levels are not part of a routine workup.

Because amiodarone has no effect on the serum concentration of thyroid hormone-binding globulin, changes in the levels of free T4 and free T3 mirror those for total T4 and total T3.

In the absence of hypothyroid symptoms, moderately elevated serum TSH levels with high normal or raised serum free T4 levels may reflect subclinical hypothyroidism. Close monitoring and repeat testing after 6 weeks is recommended.

Serum sex hormone–binding globulin concentration is increased in patients with AIT but not in patients with hyperthyroxinemia and euthyroidism who are treated with amiodarone therapy. This assay is of limited importance, however, because of the numerous factors that affect the serum levels.

Serum thyroglobulin levels are not diagnostic because they are usually higher in type 2 AIT but can be elevated in both types of AIT. Thyroglobulin levels can be increased in patients with goiters independent of the association with destructive thyroiditis.

In some studies, serum interleukin 6 levels were lower in type 1 AIT and markedly elevated in type 2 AIT. The fact that interleukin 6 is also increased in patients with severe nonthyroidal illnesses limits the specificity of interleukin 6 determination.

Thyroid autoantibodies are generally absent in type 2 AIT. The presence of autoantibodies supports the diagnosis of type 1 AIT. However, a test negative for autoantibodies does not rule out type 1 AIT.

Urinary iodine excretion is not helpful in the initial assessment but may be useful long after the withdrawal of amiodarone to assess whether excess iodine levels are present.


Imaging Studies

Although the above lab studies can confirm a diagnosis of thyrotoxicosis, further studies are necessary to recognize the correct type of AIT. [6] This distinction is important when choosing treatment modalities.

  • An ultrasonogram of the thyroid that shows abnormalities such as hypoechoic or nodular patterns or increased gland size is more indicative of type 1.

  • Radioactive iodine uptake studies are not helpful in the United States. Normal or elevated values found in radioactive iodine uptake studies suggest type 1 AIT, but this is rarely seen in the United States. The high levels of iodine result in serum levels that compete with the tracer used to perform the uptake test; thus, test results of type 1 and type 2 usually have uptakes of less than 1%. Detectable 24-hour radioactive iodine uptake is seen in tests of most patients with AIH. This may be caused by excess stimulation of the thyroid by TSH.

Color flow Doppler ultrasonography visualizes the amount of blood flow within the thyroid. However, the accuracy of this tool is limited by the proficiency of the sonographer.

  • Pattern 0 (absent vascularity, gland destruction) is associated with type 2 AIT.

  • Patterns 1-3 (with vascularity) are associated with type 1 AIT.

Most patients with AIH have been reported to have positive results on the perchlorate discharge test, indicating defects in intrathyroidal iodide organification. People with AIT have negative test results. These tests are rarely indicated or performed outside an academic setting.

A study found technetium-99m – sestamibi (99m Tc-MIBI) thyroid scintigraphy to be effective in the differential diagnosis of AIT. [6, 13] According to the report, which utilized patients with either type 1 or type 2 AIT, or with an indefinite form of the condition, this modality proved superior to a variety of diagnostic tools, including color flow Doppler ultrasonography and radioactive iodine, in differentiating one form of AIT from another.


Histologic Findings

A biopsy of the thyroid gland is unnecessary in most patients. The histological changes that occur with amiodarone administration have been studied in a research setting and include the following:

  • Marked follicular disruption by diffuse fibrosis

  • Epithelial atrophy

  • Apoptosis

  • Necrosis

  • Markedly dilated endoplasmic reticulum

  • Intraluminal aggregates of vacuolated cells

  • Foci of nonspecific lymphocyte infiltration

Patients with euthyroidism treated with amiodarone therapy showed minimal or no evidence of thyroid follicular damage.