Drug Management of Thyroid

Disease
Dr. SK Maulik
 Types
• Hyperthyroidism
– Thyrotoxic crisis

• Hypothyroidism
– Myxedemic coma
 Hyperthyroidism
• Hyperthyroidism is caused by excess synthesis
and secretion of thyroid hormone by the thyroid
gland.

• Mostly Graves’ Disease

• Thyroid hormone levels can be extremely

elevated in this condition.
 Hyperthyroidism
Clinical symptoms are:

• Nervousness, Anxiety
• Increased perspiration, Heat intolerance
• Tremor, Hyperactivity
• Palpitations
• Weight loss despite increased appetite
• Reduction in menstrual flow or oligomenorrhea (in women)
Common signs of thyrotoxicosis are:

• Tachycardia or atrial arrhythmia

• Systolic hypertension
• Warm, moist, and smooth skin
• Lid lag, Stare
• Tremor
• Muscle weakness
 Pathophysiology
• The commonest cause of hyperthyroidism is Graves disease (50-
60%).

• Graves’ disease is an thyroid-specific autoimmune disorder

• It is characterized by various circulating antibodies, like

antithyroperoxidase (anti-TPO), and antithyroglobulin (anti-TG)
antibodies.

• The most important autoantibody is thyroid-stimulating

immunoglobulin (TSI).

• TSI is directed toward TSH receptor and acts as a TSH-receptor

agonist.

• TSI binds to the TSH receptor on the thyroid follicular cells to

activate thyroid hormone synthesis and release and thyroid growth
(hypertrophy).
 Laboratory findings

• TSH levels usually are suppressed to

immeasurable levels (<0.05 µIU/mL)

• Elevated T4 level (T3 elevated in some patients)

• The titers of anti-TPO antibody

(thyroperoxidase). usually are significantly
elevated in the most common type of
hyperthyroidism
• Iodine 123 (I-123) uptake and scan: elevated
 Therapeutic management
The treatment of hyperthyroidism includes:

• symptom relief
• antithyroid medications,
• radioactive iodine 131 (I-131),
• thyroidectomy.
 Symptom relief
• Propranolol
• 40 mg od or bd
• Should be tapered once T4 levels are
normal
 Antithyroid drugs

• THIOAMIDES (Methimazole, Carbimazole

Propylthiouracil) are routinely used for hyperthyroidism
for the last 5 decades

• These drugs inhibit different steps in the synthesis of T4

and T3. Propylthiouracil , but not methimazole, also
inhibits peripheral conversion of T4 to T3.

• This leads to a gradual reduction in thyroid hormone

levels over 2-8 weeks
 Antithyroid drugs
• Patients go into a remission after treatment for
12-18 months

• Then the drug can be discontinued.

• Half the patients who go into remission have

another recurrence of hyperthyroidism within the
following year

• They may be given another course of antithyroid

drug or throidectomy
 Choice of Drug
• The choice between propylthiouracil and methimazole
depends from patient to patient

• Patient compliance is better with methimazole because it

is taken once or twice daily, while propylthiouracil 3 or 4
times daily.

• Propylthiouracil often is the drug of choice in severe

hyperthyroidism because of the additional benefit of
inhibition of T4 to T3 conversion.
• Only propylthiouracil is use in pregnancy (cross
placental to LESS extent, because of more plasma
protein binding)
 Adverse effects of antithyroid drugs
• The most common AEs are allergic reactions of fever,
rash, urticaria, and arthralgia, (1-5% of patients)
• Occurs usually within the first few weeks of treatment.
• Serious adverse effects (SAEs) are agranulocytosis,
aplastic anemia, polyarthritis, a lupus- like vasculitis and
hepatitis
• Agranulocytosis occurs in 0.2-0.5% of patients, with an
equal frequency for both drugs.
• Patients with agranulocytosis usually present with fever
and sore throat.
• The drug should be stopped immediately, granulocyte
counts usually start to rise within several days but may
not normalize for 10-14 days.
• Granulocyte colony-stimulating factor (G-CSF) is the
drug of choice in these patients
 Radioactive iodine therapy
• Most commonly used in adults who do not respond to
other drugs or in recurrence.

• Its effect is less rapid than antithyroid medication or

thyroidectomy,

• It is effective, safe, and does not require hospitalization.

• It is administered orally as a single dose

• No other tissue or organ in the body retains the

radioactive iodine
• So very few adverse effects are associated with this
therapy.
 Radioactive iodine therapy
• The dose of I-131 is 75-200 µCi/g of estimated
thyroid tissue divided by the percent of I-123
uptake in 24 hours.
• The dose should render the patient hypothyroid
• Radioactive iodine is contraindicated in pregnant
or lactating women and chidren
• Radioactive iodine can cross the placenta and
be excreted into milk, which can ablate the
infant's thyroid and result in hypothyroidism or
malformation
• Radioactive iodine is contraindicated in patients
with severe disease and heart disease
 Other drugs:
• Anion inhibitors
• Iodides
Not commonly used
 Thyrotoxic crisis
• Acute exacerbation of all symptoms
• Vigorous management is needed
• PROPRANOLOL1(-2 mg IV)
• Potassium iodide ( 10 drops po daily) to
prevent release of T4 from the gland
• Proppylthiouracil
• Supportive therapy tocontrol fever, CHF,
anyother disease which might have
precipitated it
 Hypothyroidism
• It is a common endocrine disorder
resulting from deficiency of thyroid
hormone

• Cretinism is congenital hypothyroidism

 Symptoms
The following are symptoms of hypothyroidism:
• Fatigue, loss of energy, lethargy ,Weight gain,
Decreased appetite
• Cold intolerance
• Dry skin, Hair loss
• Sleepiness
• Muscle pain, joint pain, weakness in the extremities
• Depression, Emotional lability, mental impairment
• Forgetfulness, impaired memory, inability to concentrate
• Constipation
• Menstrual disturbances, impaired fertility
• Paresthesia and nerve entrapment syndromes
• Blurred vision, Decreased hearing
• Fullness in the throat, hoarseness
 Laboratory data

Patients with hypothyroidism have

• elevated TSH levels (normal reference

range for serum TSH is 0.40-4.2 mIU/L

• decreased free hormone levels

 Therapeutic goals
• Reversal of clinical progression and the
corrections of metabolic derangements as
evidenced by normal blood levels of TSH
and free T4.
• Thyroid hormone is administered to
supplement or replace endogenous
production.
• In general, hypothyroidism can be
adequately treated with a constant daily
dose of levothyroxine (LT4).
 Drugs
• Clinical benefits begin in 3-5 days of start of
levothyroxine ( 2 microgram /kg / day)
• In infants the dose is higher (10 -15 microgram /kg / day)

• The effect is maximum in 4-6 weeks.

• In elderly patients or those with known ischemic heart

disease, treatment should begin with one fourth to one
half the expected dose, and the dose should be adjusted
in small increments no sooner than 4-6 weeks.

• The associated dyslipidemias usually do not require any

drug therapy and are corrected once hypothyroidism is
corrected
 Myxedimic coma

• In untreated or poorly treated

hypothyroidism
• Progressive weakness, stupor,
hypothermia, hypoglycemia, stupor,
hyponatremia
• It is a medical emergency
• IV T4 ( 300-400µg stat and 50 µg od)
• Other supportive therapies