Amiodarone-Induced Thyroid Dysfunction


Hypothyroidism

  • commonest in iodine-replete areas
  • also increased risk if anti-TPO antibodies are elevated
  • nearly always occurs in first 12 months of therapy
  • treat in usual way with thyroid replacement, but expect (and tolerate) slightly higher TSH levels due to inhibition of pituitary D2

Hyperthyroidism

Amiodarone-induced thyrotoxicosis (AIT) type I

  • commonest in iodine-deplete areas
  • also increased risk if pre-existing multinodular goitre
  • also increased risk if latent Graves' disease or other thyroid abnormalities
  • nearly always occurs in first 12 months of therapy
  • treat with thionamides initially
  • consider lithium or potassium iodide/perchlorate if refractory
  • radioiodine or surgery are likely to be required for definitive therapy

Amiodarone-induced thyrotoxicosis (AIT) type II

  • direct toxic effect of amiodarone
  • abrupt onset months to years (average 12 months) after starting treatment
  • thyroid non-tender, may be slightly enlarged
  • USS shows reduced vascularity in AIT II
  • glucocorticoids are effective (use with caution in heart failure due to fluid retention)
Algorithm for treatment of amiodarone-induced hyperthyroidism

Amiodarone

  • 37% iodine by mass
  • 200mg tablet contains 75mg iodine
  • 10% of this is liberated as free iodine
  • effective half-life is around 50 days

Deiodinases

Type 1

  • converts T4 to T3
  • mainly liver, kidney, thyroid
  • Other inhibitors of type 1 deiodinase:
    • glucocorticoids
    • propranolol (and apparently nadolol)
    • propylthiouracil (hence common pattern of high T4, low T3 on PTU)

Type 2

  • converts T4 to T3
  • mainly muscle, but contribution to circulating T3 is unclear
  • also brain and pituitary
  • inhibition of D2 means pituitary sees less thyroid hormone so TSH rises

Type 3

  • deactivating enzyme
  • converts T4 to inactive rT3
  • converts T3 to inactive T2
  • mainly liver, kidney, thyroid
  • inhibited by propyltiouracil

Physiological effects

Direct effects of drug

  • inhibition of peripheral type 1 deiodinase (60% reduction in T3, 10% increase in T4, 150% increase in rT3)
  • inhibition of pituitary type 2 deiodinase (modest increase in TSH - NB type 2 deiodinase is ex)
  • 200mg tablet contains 75mg iodine
  • 10% of this is liberated as free iodine
  • effective half-life is around 50 days

Iodine load effects

  • amiodarone maintenance contains about 250-fold more iodine than normal diet
  • increases thyroid iodide content and reduces uptake of radioiodine
  • Wolff-Chaikoff effect normally protects against hyperthyroidism in the presence of large iodine load by transiently inhibiting iodide uptake
  • with underlying autoimmune disease, there may be failure to escape Wolff-Chaikoff effect, hence hypothyroidism in Hashimoto's or amelioration of Graves' disease
  • in goitre with autonomous function (usually multinodular), loss of autoregulation results in hyperthyroidism