Could amiodarone still affect a patient's TSH if it was stopped 5 months ago?

Could amiodarone still affect a patient's TSH if it was stopped 5 months ago?

Comment by InpharmD Researcher

Due to high lipid solubility, amiodarone has a prolonged elimination half-life lasting as long as 142 days with a single dose. Consequently, the use of amiodarone may result in lingering thyroid effects for several months after discontinuation of the drug, particularly after chronic use. One study found amiodarone-induced thyrotoxicosis can occur up to 18 months after medication discontinuation. Routine monitoring of free thyroxine and TSH may be recommended for at least one year after amiodarone discontinuation.

Background

The American Thyroid Association’s guidance documents on hypothyroidism and thyrotoxicosis state amiodarone use has been associated with a need for increased levothyroxine dose. They also identify the iodine content within amiodarone could worsen hypothyroidism or potentially cause amiodarone-induced thyrotoxicosis However, they discuss no recommended monitoring timeline. [1], [2]

Due to its lipid affinity, amiodarone is highly concentrated in tissues and can result in hypothyroidism (amiodarone-induced hypothyroidism) and hyperthyroidism (amiodarone-induced thyrotoxicosis). Several reviews mention the long-term effects which may result from the use of amiodarone, even after discontinuation. These effects have been reported to potentially continue up to several months after discontinuation, thus, routine monitoring of free thyroxine and thyroid-stimulating hormone (TSH) levels is recommended for at least one year after discontinuation of amiodarone. Patients with underlying thyroid gland abnormalities may be more prone to prolonged persistent thyrotoxicosis. [3], [4], [5]

Relevant Prescribing Information

Amiodarone hydrochloride inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause increased thyroxine levels, decreased T 3 levels, and increased levels of inactive reverse T 3 (rT3) in clinically euthyroid patients. Amiodarone hydrochloride can cause either hypothyroidism (reported in up to 10% of patients) or hyperthyroidism (occurring in about 2% of patients). Monitor thyroid function prior to treatment and periodically thereafter, particularly in elderly patients, and in any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction. [6]
Following single dose administration in 12 healthy subjects, amiodarone exhibited multi- compartmental pharmacokinetics with a mean apparent plasma terminal elimination half-life of 58 days (range 15 to 142 days) for amiodarone and 36 days (range 14 to 75 days) for the active metabolite. Because of amiodarone's long half-life, expect drug interactions to persist for weeks to months after discontinuation of amiodarone. [6]

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Could amiodarone still affect a patient's TSH if it was stopped 5 months ago?

Please see Table 1 for your response.

The Onset Time of Amiodarone-Induced Thyrotoxicosis (AIT) Depends on AIT Type
Design	Retrospective, single-center, observational study N= 200
Objective	Two main forms of amiodarone-induced thyrotoxicosis (AIT) may occur: type 1 is a form of iodine-induced hyperthyroidism occurring in patients with underlying thyroid abnormalities, and type 2 is a destructive thyroiditis mainly due to direct cytotoxic effects of amiodarone on thyroid follicular cells of a normal thyroid gland To evaluate whether AIT type 1 (AIT1) and AIT type 2 (AIT2) may have different onset times in a large series of patients
Study Groups	AIT type 1 (n= 42) AIT type 2 (n= 158)
Inclusion Criteria	Diagnosis of AIT based on clinical and laboratory findings Diagnosis of AIT2 was based on the following criteria: normal or slightly increased TV without nodules (≥1 cm) at conventional ultrasonography, absent hypervascularity at color-flow Doppler sonography, absence of circulating thyroid-directed autoantibody (anti-thyroglobulin [TgAb], anti-thyroid peroxidase [TPOAb], anti-TSH receptor [TRAb]), and low/undetectable thyroid radioiodine uptake (RAIU) values (<5% at 24 h)
Exclusion Criteria	None specified
Methods	This was a retrospective study of patients with AIT referred to an endocrinology department of an academic center in Italy. While there were clear criteria for diagnosing type 2 AIT, the remaining subjects (e.g., patients with Graves’ disease, toxic adenoma, and multinodular goiter) who did not meet the criteria were classified as type 1 AIT.
Duration	January 1987 to December 2012
Outcome Measures	Onset of AIT: the period elapsed from initiation of amiodarone therapy and first diagnosis of thyrotoxicosis Onset time after amiodarone withdrawal: the period elapsed from the withdrawal of amiodarone therapy and first diagnosis of thyrotoxicosis in patients who developed thyrotoxicosis after amiodarone discontinuation
Baseline Characteristics		AIT type 1 (n= 42)	AIT type 2 (n= 158)
	Age, years	65.3 ± 10.6	61.4 ± 10.6
	Male	31 (73.8%)	123 (77.8%)
	BMI, kg/m²	26.1 ± 4.6	25.4 ± 3.9
	Duration of amiodarone treatment, months Amiodarone dose, mg	9.9 ± 11.8 193 ± 38	28.7 ± 16.1 192 ± 54
	Thyroid levels Free T4, pg/mL Free T3, pg/mL FT4/FT3 TSH, mIU/L	28.2 ± 15.3 7.2 ± 4.7 4.2 ± 2.2 <0.01	41.7 ± 16.4 10.2 ± 5.2 4.4 ± 1.3 <0.01
	AIT after amiodarone discontinuation	2/40 (5%)	36/122 (30%)
Results		AIT type 1 (n= 42)	AIT type 2 (n= 158)
	Median time to AIT onset, months (range)	3.5 (1-61)	30 (1-95)
	Median time to AIT onset after discontinuation, months (range)	6.5 (1-12)	5.5 (1-18)
	Patients who developed type 2 AIT after discontinuation were significantly younger on average (56.8 ± 11.9 vs 62.8 ± 13 years, respectively; P=0.014).
Adverse Events	N/A
Study Author Conclusions	Patients with preexisting thyroid abnormalities (candidate to develop AIT1) may require a stricter follow-up during amiodarone therapy than those usually recommended. In AIT1, the onset of thyrotoxicosis after amiodarone withdrawal is rare, while AIT2 patients may require periodic tests for thyroid function longer after withdrawing amiodarone.
InpharmD Researcher Critique	While this was a retrospective study from a single-center study in Italy, the results suggest thyroid function should be monitored for at least 2 years after amiodarone withdrawal, particularly in patients without apparent thyroid abnormalities. While the authors attempted to identify risk factors for AIT development after medication withdrawal, the low incidence (particularly in type 1 AIT patients) makes it difficult to characterize risk stratification. Additionally, this study included older data before AIT was classified into two different types, meaning some of the data may be misleading.

References:

Tomisti L, Rossi G, Bartalena L, Martino E, Bogazzi F. The onset time of amiodarone-induced thyrotoxicosis (AIT) depends on AIT type. Eur J Endocrinol. 2014;171(3):363-368. doi:10.1530/EJE-14-0267