Drug Management of Thyroid Disease

8/14/2019 Drug Management of Thyroid Disease

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Types

Hyperthyroidism Thyrotoxic crisis

Hypothyroidism Myxedemic coma


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Hyperthyroidism

Hyperthyroidism is caused by excess synthesisand secretion of thyroid hormone by the thyroidgland.

Mostly Graves Disease

Thyroid hormone levels can be extremelyelevated in this condition.


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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

Hyperthyroidism


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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-stimulatingimmunoglobulin (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 toactivate thyroid hormone synthesis and release and thyroid growth(hypertrophy).


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Laboratory findings

TSH levels usually are suppressed toimmeasurable levels (


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Therapeutic management

The treatment of hyperthyroidism includes:

symptom relief antithyroid medications, radioactive iodine 131 (I-131),

thyroidectomy.


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Symptom relief

Propranolol 40 mg od or bd

Should be tapered once T4 levels arenormal


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Antithyroid drugs

THIOAMIDES (Methimazole, CarbimazolePropylthiouracil) are routinely used for hyperthyroidismfor the last 5 decades

These drugs inhibit different steps in the synthesis of T4and T3. Propylthiouracil , but not methimazole, alsoinhibits peripheral conversion of T4 to T3.

This leads to a gradual reduction in thyroid hormonelevels over 2-8 weeks


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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 haveanother recurrence of hyperthyroidism within thefollowing year

They may be given another course of antithyroiddrug or throidectomy


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Choice of Drug The choice between propylthiouracil and methimazole

depends from patient to patient

Patient compliance is better with methimazole because itis taken once or twice daily, while propylthiouracil 3 or 4times daily.

Propylthiouracil often is the drug of choice in severehyperthyroidism because of the additional benefit of inhibition of T4 to T3 conversion.

Only propylthiouracil is use in pregnancy (crossplacental to LESS extent, because of more plasmaprotein binding)


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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 andhepatitis

Agranulocytosis occurs in 0.2-0.5% of patients, with anequal 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 maynot normalize for 10-14 days. Granulocyte colony-stimulating factor (G-CSF) is the

drug of choice in these patients


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Radioactive iodine therapy

Most commonly used in adults who do not respond toother 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 theradioactive iodine

So very few adverse effects are associated with thistherapy.


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Radioactive iodine therapy

The dose of I-131 is 75-200 Ci/g of estimated

thyroid tissue divided by the percent of I-123uptake 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 theinfant's thyroid and result in hypothyroidism or malformation

Radioactive iodine is contraindicated in patientswith severe disease and heart disease


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Other drugs:

Anion inhibitors Iodides

Not commonly used


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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 haveprecipitated it


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Hypothyroidism

It is a common endocrine disorder resulting from deficiency of thyroidhormone

Cretinism is congenital hypothyroidism


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SymptomsThe 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


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Laboratory data

Patients with hypothyroidism have

elevated TSH levels (normal referencerange for serum TSH is 0.40-4.2 mIU/L

decreased free hormone levels


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Therapeutic goals

Reversal of clinical progression and thecorrections of metabolic derangements asevidenced by normal blood levels of TSHand free T4.

Thyroid hormone is administered tosupplement or replace endogenousproduction.

In general, hypothyroidism can beadequately treated with a constant dailydose of levothyroxine (LT4).


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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 heartdisease, treatment should begin with one fourth to onehalf the expected dose, and the dose should be adjustedin small increments no sooner than 4-6 weeks.

The associated dyslipidemias usually do not require anydrug therapy and are corrected once hypothyroidism iscorrected


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Myxedimic coma

In untreated or poorly treatedhypothyroidism

Progressive weakness, stupor,hypothermia, hypoglycemia, stupor,hyponatremia

It is a medical emergency IV T4 ( 300-400g stat and 50 g od) Other supportive therapies

Drug Management of Thyroid Disease

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