PERM STATE MEDICAL

UNIVERSITY
DRUG INDUCED THYROID
PROBLEMS
- -JOISY ALOOR
- 6TH YEAR
 INTRODUCTION

• Drug-induced thyroid dysfunction should be considered when thyroid

function test results are inconsistent with the clinical scenario or when a
patient is taking a medication known to commonly disrupt thyroid
function.
• Pseudo-abnormalities in thyroid function tests should be differentiated
from true thyroid dysfunction.
• Certain drugs or agents can cause either or both of these abnormalities
and understanding their potential thyroidal effects will help the clinician
to appropriately manage the patient.
• The use of certain drugs or agents have the potential to interfere with various steps of
thyroid hormone metabolism which results in hypothyroidism or hyperthyroidism:
a) Thyroid hormone absorption (in patients already taking levothyroxine [LT4]
therapy).
b) Hypothalamic and pituitary regulation of thyroid hormone production.
c) Thyroid hormone synthesis and production.
d) Binding of T4 and T3 (Triiodothyronine) to serum carrier proteins, mainly thyroxine
binding globulin (TBG).
e) Thyroid hormone pharmacokinetics.
f) Thyroid hormone pharmacodynamics (e.g. interference with the conversion of T4 to
T3 in peripheral target organs).
• Thyroid dysfunction can be transient or permanent, depending on the
specific drug or agent, status of iodine nutrition, and presence of absence
of any pre-existing autonomous thyroid nodules, subclinical thyroid
dysfunction, and thyroid autoantibodies.
• Because primary hypothyroidism (e.g. Hashimoto’s disease) or
hyperthyroidism (e.g. Graves’ disease, toxic multinodular goiter, silent
thyroiditis) are common, the distinction between drug-induced and
primary thyroid dysfunction cannot always be easily made. Clinical
judgment should dictate whether the suspected drug should be
withdrawn and how the thyroid dysfunction should be further
investigated and treated.
• Various drugs may cause thyroid dysfunction. The drugs which may cause
thyrotoxicosis include interferon, molecular-targeted agents, amiodarone, thyroid
hormone itself and so on. Those which cause hypothyroidism include anti-thyroid
drugs, lithium and iodine etc. which inhibit thyroid hormone synthesis and secretion,
and dopamine etc. which block TSH secretion.
• Those drugs which alter the thyroid hormone metabolism or the binding to TBG or
those inhibit thyroid hormone absorption may cause hypothyroidism or deteriorate it
in patients with hypothyroidism treated with thyroid hormone or those with
diminished reserved capacity. When thyroid dysfunction occurred, it is better to
discontinue the causative drug, but in many cases, the patients are forced to be
treated with the drug being continued.
 DEFINITION
• Induced thyroid disorders (ITD) are conditions that occur when
certain medicines or treatments change the amount of hormone
the thyroid produces.
• Thyroid hormones regulate body temperature, heart rate, and
weight gain or loss.
 SOME CAUSES
• Amiodarone is used to treat arrhythmia. Its high iodine content is primarily responsible for
producing a hyperthyroid state, though the medication may itself induce autoimmune
thyroid disease.
• Interferon is used to treat tumors and other diseases, such as hepatitis C. This medicine
directly attacks thyrocytes. This may lead to high or low amounts of thyroid hormones in the
blood.
• Lithium treats mental disorders. It can increase the production of antibodies against thyroid
cells and cause hypothyroidism.
• Radiotherapy uses radiation as treatment for head and neck tumors. Radiation may cause
damage to the thyroid cells and may decrease the production of thyroid hormones.
• Iodine-induced - Occurs after administration of either supplemental
iodine to those with prior iodine deficiency or pharmacologic doses of
iodine (contrast media, medications) in those with underlying nodular
goiter
• Antineoplastic agents - Agents may cause thyroid dysfunction in 20-50%
of patients. Symptoms of thyrotoxicosis may be mistaken for sepsis or an
adverse drug effect, so monitoring of thyroid function must be
considered.
• Lithium therapy causes overt hypothyroidism in 5 to 15% of patients, and goitre in
up to 37%.
• Thyroid function tests should be performed prior to initiating lithium therapy, and
at 6-monthly intervals thereafter. Iodine and iodine-containing drugs (e.g
radiographic contrast media, iodinated glycerol and amiodarone) can have
profound and variable effects on thyroid function.
• Glucocorticoids also lead to thyroid dysfunction.
 DRUG INDUCED
HYPO/HYPERTHYROIDISM
• Drug-induced hypothyroidism is an under active thyroid gland caused by certain
medications. The medications that can cause hypothyroidism may be drugs
normally used to treat hyperthyroidism or that are related to thyroid function
and a group of non-thyroid related drugs.
• The drugs used to treat hyperthyroidism or are related to thyroid function that
can result in drug-induced hypothyroidism are propylthiouracil, radioactive
iodine, potassium iodide, and methimazole. Iodides, in general, alter thyroid
function. Total T3 and total T4 are 3 and 4 iodinated tyrosines. Even iodide
containing solutions used for sterilization or iodides used in dyes and contrast
media can cause hypothyroidism. Iodide can also causes hyperthyroidism.
• Drug-induced hypothyroidism presents with the same signs and symptoms as are
seen with other hypothyroid conditions (i.e., fatigue, cold intolerance, weight
gain, depression, and dry skin).
• The same is with hyperthyroidism.
• Drugs and iodine can cause hyperthyroidism. Drugs include amiodarone,
interferon-alpha, programmed death receptor-1 (PD-1) inhibitors (such as
nivolumab and pembrolizumab), alemtuzumab, and, rarely, lithium. Excess
iodine, as may occur in people taking certain expectorants, or in those given
iodine-containing contrast agents for x-ray studies, may cause hyperthyroidism.
Taking too much thyroid hormone orally can also cause hyperthyroidism.
 DRUG-INDUCED THYROIDITIS

• Drug-induced thyroiditis can be the result of several mechanisms,

the most common being an inflammatory/ destructive process
induced by drugs.
• The mechanisms of drug-induced thyroiditis may be summarized as
follows:
Cytotoxic
Immune dysregulation
Ischemic, by blocking the vascular endothelial growth factor
receptor
• Patients with positive thyroperoxidase antibodies (TPOAbs) are at an increased risk of
developing drug-induced hypothyroidism with several of the non-thyroid related drugs.
Patients with positive TPOAbs are at particular risk when a preexisting Hashimoto’s
thyroiditis is present or when taking amiodarone. Amiodarone is an iodine containing
antiarrhythmic.
• The National Academy of Clinical Biochemistry has specific guidelines for patients taking
amiodarone. These guidelines recommend:
• if TSH is abnormal, a complete physical examination with baseline TSH, TPOAb, free T4, and
free T3 should be undertaken prior to amiodarone therapy initiation
• thyroid status should be monitored every 6 months via TSH after amiodarone initiation.
• TPOAb is a risk factor for developing drug-induced hypothyroidism at any time during
amiodarone therapy
• Amiodarone induced hyperthyroidism (AIH) can also occur.
• Symptoms of hypothyroidism may include brittle fingernails, coarsening and thinning of hair,
puffy eyes, weakness, and constipation. Symptoms expressing themselves later in the course
of the disease are hoarseness; menstrual disorders; puffy hands, face, and feet; thickening of
the skin; thinning of eyebrows; increased cholesterol levels; muscle and/or joint aches and
stiffness; slowed speech; and decreased hearing.
 The predisposing factors for ITD are:

• Autoimmune thyroiditis
• Post-treatment of hyperthyroidism
• Previous hemithyroidectomy for the treatment of nodular goiter
• A history of postpartum thyroiditis, subacute thyroiditis, drug-induced thyroiditis
• Thalassemia major (thyroid hemosiderosis)
• Chronic renal disease
• The National Academy of Clinical Biochemistry guidelines for testing of hospitalized patients
with non-thyroid illness recommendations indicate:
• Acute or chronic non-thyroid illness has complex effects on thyroid function testing. Whenever
possible, diagnostic testing should be deferred until the illness has resolved, except in cases in
which there is a suggestion of presence of thyroid dysfunction.
• Physicians should be aware that some thyroid tests are inherently not interpretable in severely ill
patients or patients receiving multiple medications.
• TSH in the absence of dopamine or glucocorticoid therapy is the more reliable test.
• TSH testing in the hospitalized patient should have a functional sensitivity of less than 0.02
mIU/L; otherwise, sick, hyperthyroid patients with profoundly low TSH cannot be differentiated
from patients with mild transient TSH suppression caused by non-thyroid illness.
• An abnormal free T4 in the presence of serious somatic disease is unreliable. In hospitalized
patients, abnormal free T4 testing should reflex to total T4. If both free T4 and total T4 are abnormal
in the same direction, a thyroid condition may exist. Discordant free T4 and total T4 abnormalities
are more likely the result of illness, medication, or a testing artifact.
• Total T4 abnormalities should be considered in conjunction with the severity of the patient illness. A
low T4 in patients not in intensive care is suspicious of hypothyroidism, since low total T4 levels in
non-thyroid illness in hospitalized patients are most often seen in sepsis. If a low total T4 is not
associated with an elevated TSH and the patient is not profoundly sick, hypothyroidism secondary
to pituitary or hypothalamic deficiency should be considered.
• Reverse T3 formed by the loss of an iodine group from T4 where the position of the iodine atoms on
the aromatic ring is reversed is rarely helpful in the hospital setting, because paradoxically normal or
low values can result from impaired renal function and low binding protein concentrations.
 HOW IS ITD DIAGNOSED?

• Thyroid function tests.

• An ultrasound.
• A thyroid scan.
• Fine needle biopsy.
Exposure to iodine-based compounds is also reflected in alterations
of laboratory tests:
• TSH increase
• Decrease in thyroid hormones levels
• Increase in the amount of urinary iodine excretion over 24 hours
 TREATMENT
• Pregnancy: Prenatal vitamins contain iron and calcium that can impair the absorption
of thyroid hormone from the gastrointestinal tract. Consequently, levothyroxine and
prenatal vitamins should not be taken at the same time and should be separated by at
least 4 hours.
• Beta-blockers such as propranolol or metoprolol help control many of the symptoms
of hyperthyroidism. These drugs can slow a fast heart rate, reduce tremors, and
control anxiety.
• Doctors therefore find beta-blockers particularly useful to control symptoms of
hyperthyroidism until the person responds to other treatments. However, beta-
blockers do not reduce excess thyroid hormone production. Therefore, other
treatments are added to bring hormone production to normal levels.
• Methimazole and propylthiouracil are the drugs most commonly
used to treat hyperthyroidism. They work by decreasing the
gland’s production of thyroid hormones. Each drug is taken by
mouth, beginning with high doses that are later adjusted
according to blood test results.
• These drugs can usually control thyroid function within 6 to 12
weeks. Larger doses of these drugs may work more quickly but
increase the risk of side effects.