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Abstract
Drugs can affect thyroid functional status in numerous ways. They may influence thyroid homeostasis
at any level from their synthesis, secretion, transport or end-organ action resulting in hypothyroidism or
hyperthyroidism. Amiodarone is an important drug in this group. The effects of amiodarone on thyroid
function result from iodine release and intrinsic drug properties. Both amiodarone-induced thyrotoxicosis
(AIT) and amiodarone -induced hypothyroidism (AIH) may develop in apparently normal thyroid glands or
in glands with preexisting, clinically silent abnormalities. Treatment of AIH consists of thyroxine replacement
while continuing or discontinuing amiodarone therapy. In type I AIT the main medical treatment consists of
simultaneous administration of thionamides and potassium perchlorate, while in type II AIT, glucocorticoids
are the most useful therapeutic option. It is important to evaluate patients before and during amiodarone
therapy. The list of drugs affecting thyroid function is long with new drugs being added. Some of them are
clinically important while others just produce diagnostic dilemmas. The possible effect of drugs on the results
of thyroid-function tests should always be considered while making decisions regarding patient care. ©
Table 1 : Drugs that influence thyroid function : transfer protein and extra thyroidal metabolism
Mechanism of interference Drugs
Altering thyroid hormone Increase Thyroid Binding Globulin Estrogen, Tamoxifen
serum transfer proteins (TBG) concentration Heroin, Methadone
Clofibrate
5- Flurouracil, Mitotane
Perphenazine
Decrease TBG concentration Androgens
Anabolic steroids (eg. Danazol)
Glucocorticoids
Slow release nicotinic acid
Interfere with thyroid hormone binding Frusemide
to TBG and/ or transthyretin Fenoflenac
Mefanamic acid
Salicylates
Phenytoin
Diazepam
Sulphonylureas
Free fatty acids
Heparin
Agents that alter extra-thyroidal Inhibit conversion of T4 to T3 PTU
metabolism of thyroid hormone Glucocorticoids
Propranolol
Iodinated contrast agents
Amiodarone
Clomipramine
Increased hepatic metabolism Phenobarbital
Rifampicin
Phenytoin
Carbamazepine
Drugs that decrease T4 absorption Cholestyramine, Colestipol
or enhance excretion Aluminium hydroxide
Ferrous sulphate
Sucralfate Amiodarone
(Adapted and reproduced from Surks MI, Siewert R. Drugs and Thyroid Function. NEJM 1995;333:1688-94)
months) phases that follow amiodarone exposure6 Table 4 : Effects of amiodarone on thyroid hormone
(Table 4). Indeed, more than 50% of patients who receive profile in euthyroid subjects
long-term amiodarone therapy show abnormal results Parameters Duration of Treatment
on thyroid function test, though the majority remains < 3 months > 3 months
clinically euthyroid. Occasionally, amiodarone can also
T4 / Free T4 50% 20-40% above baseline
cause goiter without apparent thyroid dysfunction. T3 / Free T3 15-20% 15-20%
Although the majority of patients given amiodarone Reverse T3 200% Remains >150%
remain euthyroid, some develop thyroid dysfunction, TSH 20-50%, remain
<20 mU/L Normal
i.e., thyrotoxicosis and hypothyroidism. Amiodarone-
TBG Normal Normal
induced thyrotoxicosis (AIT) appears to occur more
frequently in geographical areas with low iodine intake, (Adapted and reproduced from Basaria S, Cooper DS. Amiodarone
and the thyroid. The American J Medicine 2005;118:706-14)
whereas Amiodarone induced hypothyroidism (AIH)
is more frequent in iodine-sufficient areas.7-9 In a study
carried out simultaneously in Italy (moderately low former and 2% in the latter, while the incidence of AIH
iodine intake) and United States (normal iodine intake), was 5% in Italy and 22% in the United States. In general,
it was found that the incidence of AIT was about 10% in the various published studies report an overall incidence
of AIT is unknown, but it may depend on the ambient After restoration of euthyroidism and normalization of urinary
iodine excretion, definitive treatment of the underlying thyroid
Table 5 : Classification of Amiodaroneinduced abnormalities by either radioiodine or thyroidectomy.
thyrotoxicosis If amiodarone cannot be withdrawn and medical therapy is
unsuccessful, consider total thyroidectomy.
Type 1 Type 2 Type II AIT
Glucocorticoids for 23 months (starting dose, prednisone 40
Underlying thyroid Yes No
mg/day or equivalent).
abnormality
Discontinue amiodarone if possible.
Thyroid autoantibodies Often present Usually absent
In mixed forms add thionamides and potassium perchlorate.
Goitre Often present Usually absent
After restoration of euthyroidism, follow-up for possible
Thyroidal radioactive Low, rarely normal
spontaneous progression to hypothyroidism.
iodine uptake or increased Low
If amiodarone cannot be withdrawn and medical therapy is
Serum IL-6 Slightly Markedly
unsuccessful, consider total thyroidectomy.
concentrations increased increased
Amiodarone-induced hypothyroidism
Cytologic findings ?
Underlying Thyroid Abnormalities (Usually HashimotoÊs
Abundant colloid, histiocytes
Thyroiditis) Amiodarone therapy can be continued. L-T4
Pathogenic mechanism Excessive Thyroid Destructive
replacement therapy is added.
hormone synthesis Thyroiditis
Apparently Normal Thyroid Gland
Colour flow Normal/increased Decreased
Doppler pattern blood flow blood flow If amiodarone cannot be discontinued, L-T4 replacement
therapy is initiated. If amiodarone is withdrawn, strict
Response to thionamides Yes (Poor) No
follow-up is required for possible spontaneous restoration
Response to perchlorate Yes No
of euthyroidism. A short course of potassium perchlorate (1
Response to g/day for 1030 days) can be given to accelerate return to
Glucocorticoids Probably No Yes euthyroidism.
Subsequent
Hypothyroidism Unlikely Possible (Adapted and reproduced from Martino. E, Bartalena L, Bogazzi
F, Braverman LE. The Effects of Amiodarone on the Thyroid.
(Adapted and reproduced from Bartalena L, Grasso L, Bragioni S, Endocrine Reviews 2001;22:24054)
et al. Serum interleukin-6 in Amiodarone induced thyrotoxicosis. J
Clin Endocrinol Metab 1994;78:42327)
Announcement
4th Infectious Disease Certificate Course - IDCC -2007
PD Hinduja National Hospital and Medical Research Centre, Mumbai, India
In collaboration with Henry Ford Health System, Detroit, MI, USA
26th Aug (Sunday) to 2nd September (Sunday) 2007
8.30 am to 5.00 pm
Objective: Diagnosis, Management and Prevention of Infectious Diseases.
Focus: Acute febrile illnesses (including Dengue, Enteric, Malaria), Tuberculosis, HIV, Infections in
ICU/ Pediatrics/ Immunocompromised, Organ Specific Infections
Format: Ward Rounds, Archived Cases, Interactive Lectures, Work Mats, Microbiology Discussions, Visit
to Infectious Disease Hospital
Credit hours: 55 hours of Category 1 credit towards the American Medical Association PhysicianÊs
Recognition Award.
Eligibility: Post graduates in Medicine/ Pediatrics and Microbiology (Final year postgraduates may also
be considered)
Registration procedure: Candidates to send short bio data with Demand Draft/ Cheque of Rs 3,000/- or
100 USD in favor of PD Hinduja National Hospital and Medical Research Centre payable at Mumbai.
(Outstation cheques will not be accepted)
Candidates to make their own arrangement for accommodation
Last date for registration: 30th June 2007
Course Information/ Detailed Programme: www.hindujahospital.com/IDCC2007
Inquiries: 022-24447704 or marketing@hindujahospital.com
Course Coordinators:
Dr FD Dastur /Dr Rajeev Soman/ Dr Camilla Rodrigues/ Dr Tanu Singhal