Thyroid gland
Endocrine abnormalities
Amiodarone induced hyperthyroidism

Author: Julie Guilmette, M.D. and Anthony Chi, M.D. (see Authors page)

Revised: 27 July 2016, last major update July 2016

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Amiodarone-induced hyperthyroidism[title]
Cite this page: Amiodarone induced hyperthyroidism. PathologyOutlines.com website. http://pathologyoutlines.com/topic/thyroidamiodarone.html. Accessed December 8th, 2016.
Definition / General
  • Amiodarone is an antiarrhythmic medication for atrial and ventricular tachyarrhythmias, and less commonly for ischemic heart disease and congestive heart failure; also used for fetal tachycardia (Arch Cardiovasc Dis 2008;101:619, eMedicine)
  • Contains 37% iodine by weight, and structurally resembles thyroxine, which interferes with thyroid hormone metabolic pathways, causing hypo- or hyperthyroidism
  • The relative frequency of amiodarone induced hypothyroidism (AIH) and amiodarone induced thyrotoxicosis (AIT) depends on the iodine status of the population
    • In populations with iodine deficiency, amiodarone induced thyrotoxicosis is more common
    • Conversely, in the United States, amiodarone induced hypothyroidism is more common (Proc (Bayl Univ Med Cent) 2008;21:382)
  • AIT is classified in two subtypes, type 1 AIT and type 2 AIT
  • Distinguishing between the two subtypes is important as both arise in different settings and have different treatments (Case Rep Med. 2014;2014:231651)
Essential Features
  • Amiodarone induced thyrotoxicosis (AIT) is classified in two subtypes (Case Rep Med. 2014;2014:231651)
  • Type 1 AIT arises in thyroid glands with pre-existing disease (Jod-Basedow phenomenon)
  • Type 2 AIT develops in a previously normal thyroid gland due to a destructive amiodarone induced inflammatory process
  • Presents with worsening cardiac arrhythmia, recurrent atrial fibrillation and palpitations (NCBI-Amiodarone Induced Thyrotoxicosis)
  • Diagnosis requires correlation of clinical, imaging and laboratory findings
  • Histologically, type 1 AIT has features of pre-existing disease; type 2 AIT shows involuted follicles filled with desquamated vacuolated epithelial cells, scattered inflammatory infiltrate composed of foamy macrophages and lymphocytes, and fibrosis (Proc (Bayl Univ Med Cent) 2008;21:382, Pathol Int 2008;58:55)
Epidemiology
  • More frequent in males than in females (3:1)
  • Occurs in 3% of patients treated with amiodarone in North America, increasing to 10% in countries with low iodine dietary intake (NCBI-Amiodarone Induced Thyrotoxicosis)
Sites
Pathophysiology
  • Thyrotoxicosis is due to amiodarone’s iodine content and structural resemblance to thyroxine
  • Amiodarone has pharmacological properties enabling its toxicity (Can J Cardiol 2009;25:421), including:
    • Lipophilia, promoting accumulation in adipose tissue, cardiac and skeletal muscle, and thyroid
    • Inhibition of thyroidal T4 and T3 production and release within the first two weeks of treatment (Wolff-Chaikoff effect)
    • Direct toxicity to cultured thyroid cells exposed to media with concentrations above those normally found in patients
Clinical Features
  • Associated with worsening cardiac arrhythmia with recurrence of atrial fibrillation and palpitations (NCBI)
  • May occur suddenly in patients treated with amiodarone for several years, likely due to its long half life, lipid solubility and accumulation in almost all tissue
  • Type 1 amiodarone induced thyrotoxicosis:
    • Occurs with pre-existing thyroid disease, due to iodine-induced excess thyroid hormone synthesis
    • Microscopic changes are due primarily to pre-existing disease
  • Type 2 amiodarone induced thyrotoxicosis:
  • Amiodarone is probably the cause of thyroid cell damage in some patients, and follicular disruption (with consequent release of iodothyronines into the circulation) is likely to be an important contributor to associated thyrotoxicosis (Am J Surg Pathol 1987;11:197)
Diagnosis
  • Based on clinical, laboratory and imaging correlations
Laboratory
  • To confirm the diagnosis of amiodarone induced thyrotoxicosis, it is necessary to demonstrate a suppressed serum TSH associated with an increase in serum free T3 and free T4 levels in a patient treated with amiodarone (NCBI)
  • In type 1: increased T4/T3 due to destructive thyroiditis, in addition to increased levels of antibodies to thyroglobulin and TPO
  • In type 2: elevated levels of IL6; 8% also have increased levels of antibodies to thyroglobulin and TPO
Radiology Description
  • Color flow Doppler ultrasonography is useful to differentiate between type 1 and type 2 (NCBI, World J Surg 2006;30:1957)
  • Type 1:
    • Increased intra-thyroidal vascular flow
    • Normal or raised radioactive iodine update
    • Tc sestamibi thyroid scan shows a diffusely increased uptake and retention in an enlarged thyroid gland (Clin Nucl Med 2016;41:566)
  • Type 2:
    • Reduced or absent vascular flow
    • Low or absent radioactive iodine update
Case Reports
Treatment
  • Differs for type 1 and 2 amiodarone induced thyrotoxicosis (Minerva Endocrinol 2008;33:213)
  • Up to 20% of mild cases spontaneously resolve (NCBI)
  • Type 1: treat with high doses of thioamides to block synthesis of thyroid hormones
    • Potassium perchlorate can also be combined to increased sensitivity to thioamides
    • Once the thyroid function is normalized, hyperthyroidism can be treated by either radioactive iodine or thyroidectomy depending on its severity
  • Type 2: treat with prednisone; thionamides are generally not useful
  • Clinically, “mixed” AIT is common, in which patients seems to be respond only to therapy with both thioamides and glucocorticoids (Proc (Bayl Univ Med Cent) 2008;21:382)
  • Dronedarone is an alternative but less effective anti-arrhythmic agent without the adverse thyroid effects (Clin Endocrinol (Oxf) 2009;70:2)
Gross Description
Micro Description
  • Associated with type 1 amiodarone induced thyrotoxicosis: changes are those of pre-existing disease, usually multinodular goiter
  • Associated with type 2 amiodarone induced thyrotoxicosis: often with no history of thyroid disorder
    • Randomly distributed disrupted follicles filled with desquamated vacuolated epithelial cells, foamy macrophages and scattered lymphocytes, involutional changes, fibrosis
    • Associated with hypothyroidism: involuted follicles with flattened follicular cells, dilated lumina with dense colloid; also small numbers of damaged follicles infiltrated by macrophages (Pathol Int 2008;58:55)
Micro Images

Images hosted on Pathout server:

Amiodarone thyroiditis
Contributed by Dr. Mark R. Wick



Images hosted on other servers:
Missing Image

Amiodarone-induced
thyrotoxicosis

Missing Image

Fig A / B: type 2 thyrotoxicosis

Missing Image

Type 2: H&E, CD68, keratin

Electron Microscopy Description