Hyperthyroidism and Its Most Common Drug List

Hyperthyroidism is a disorder characterized by an overproduction of thyroid hormones by the thyroid gland. Thyroid gland, a 2-inches long butter-fly shaped gland in neck, releases two hormones, namely triiodothyronine (T3) and tetraiodothyronine (T4). Tetraiodothyronine is also known as thyroxine. These hormones on entering the cells of the body are responsible for regulating the cells metabolism i.e. the ability of the cells to utilize food to produce energy. Thus, both inadequate or excess of thyroid hormones is a harmful clinical scenario.

Hyperthyroidism can be well managed through medications. However, it is important to know that hyperthyroidism affects the cardiovascular health of an individual, hence if left untreated, it can be a life-threatening condition.

Symptoms

Increased metabolism caused by raised levels of circulating thyroid hormones, can manifest as various signs and symptoms, which are described below.

• Sudden weight loss, despite a normal appetite
• Rapid heartbeat, medically termed as tachycardia
• Irregular heartbeat, medically known as arrhythmia
• High blood pressure and palpitations (pounding heartbeat)
• Nervousness, irritability and anxiety
• Hand tremors
• Increased sweating
• Intolerance to heat
• Menstrual irregularities
• Frequent bowel movements
• A swelling of the thyroid gland, visible at the base of the neck- This condition is medically known as Goiter
• Thin skin and brittle hair
• Muscle weakness and fatigue
• Difficulty in sleeping

Treatment

The treatment of hyperthyroidism depends on the age of the patient, the underlying cause and the severity of the condition.

The goal of treatment is to provide symptomatic relief and to reduce the amount of circulating thyroid hormones. Medical therapy forms the mainstay of treatment of hyperthyroidism. Most of these medications are available on prescription. Anti-thyroid drugs and radioactive iodine ablation constitute the most targeted drug therapy in hyperthyroidism. Beta- blockers and iodides are used as treatment adjuncts.

Glucocorticoids are administered to manage the complications of hyperthyroidism, i.e. Graves’ Opthalmopathy and Dermopathy.

However, all cases of hyperthyroidism may not respond well to medications. In such persistent cases of hyperthyroidism, doctors may resort to surgical treatment. The part of thyroid gland releasing excess hormone is identified and removed. This may involve partial removal of thyroid gland (partial thyroidectomy) or complete removal of the gland (total thyroidectomy).

Most commonly used drugs in hyperthyroidism are described below.

1. Thioamides (Anti-thyroid drugs)

The formation and release of thyroid hormones occur in a sequential manner. The synthesis of thyroid hormones require iodine. Dietary iodide is absorbed by the thyroid follicles. This iodide is then oxidized to iodine by an enzyme, known as thyroid peroxidase. The iodine then combines with something called tyrosyl residues, to eventually form T3 and T4.

Anti-thyroid drugs bind to thyroid peroxidase enzyme and prevent the oxidation of iodide. Thus, this group of drug inhibits the synthesis of thyroid hormones and counteracts the hyperthyroid state.

Anti-thyroid drugs include thioamides, namely propylthiouracil, methimazole and carbimazole.

Available as: Oral preparations

I. Propylthiouracil

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: propylthiouracil
Brand name: Propylthiouracil tablet
Side-effects: Black tarry stools, chills, cough, chest pain, fever, shortness of breath, painful urination, sore throat
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

II. Methimazole

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: methimazole
Brand name: Methimazole tablet
Side-effects: Cough, fever, chills, chest pain, backache, black tarry stools, sore throat, shortness of breath
Indicated in pregnancy: Usually contraindicated as it crosses placenta and may cause cretinism (i.e. hypothyroidism present at birth) or goiter (swelling in the neck due to enlarged thyroid gland) in the fetus
Alcohol Content: Absent

III. Carbimazole

Carbimazole is a pro-drug, i.e. it does not act directly, rather converts to its active metabolite, methimazole, which reduces the thyroid hormone level.

US-FDA Status: Unpproved for Hyperthyroidism
Generic name: carbimazole
Brand name: Neo-Mercazole tablet
Side-effects: Itching, skin rashes, headache, dizziness, pain in joints
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

2. Radioactive Iodine (131I)

131I is an isotope of iodine with medicinal importance. Oral dose of radioactive iodine is the most common definitive treatment method for hyperthyroidism in USA.
Thyroid gland is highly receptive to iodine. When radioactive iodine is administered, it is absorbed by the thyroid gland. This iodine being radioactive, emits radiation within the thyroid gland and destroys a part or all of the thyroid gland without affecting any other body part. Thus, it normalizes the thyroid hormone levels, shrinks the enlarged gland and alleviates the symptoms.

Available as: Oral preparations (solution only)

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: sodium iodide I131
Brand name: Sodium Iodide I131 solution
Side-effects: Joint pain, hives, swelling of lymph glands, headache
Indicated in pregnancy: Absolutely contraindicated
Alcohol Content: Absent

3. Ionic Inhibitors

The mechanism of action of this group of drug is based on the process of iodide absorption by thyroid gland. Thyroid gland has the ability to concentrate iodide taken through food and water.

Ionic inhibitors, such as thiocyanates and perchlorates, inhibit the iodide uptake and thus, terminate the synthesis of thyroid hormones.

However, this group of drug is infrequently used in hyperthyroidism due to its major side-effects.

Available as: Oral preparations

I. Potassium Perchlorate
US-FDA Status: Unapproved for Hyperthyroidism
Availability: Discontinued
Generic name: potassium perchlorate
Brand name: Perchloracap capsule
Side-effects: Vomiting, gastric irritation, nausea, skin rashes, fever
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

4. Iodides

Although iodide is essential for synthesis of thyroid hormones, a high concentration of iodide leads to inhibition of synthesis of thyroid hormones. Hence, an optimal level of iodide is necessary to regulate the synthesis of thyroid hormones.

In hyperthyroidism, iodide may be administered to increase the plasma concentration of iodide, thus blocking the synthesis of thyroid hormones.

Iodide administration also shrinks the enlarged thyroid gland (medically known as goiter), seen in hyperthyroidism. However, if iodide is consumed for a longer duration of time, the thyroid gland tends to escape the blocking action of iodide and hyperthyroidism may recur.

Therefore, iodide is not commonly used in routine therapy. It is primarily administered prior to surgery and in cases of thyroid storm. Thyroid storm is a life-threatening condition characterized by dangerously high temperature, heart rate and blood pressure. It is also indicated to protect the thyroid gland in radiation exposure emergency.

Available as: Oral preparations

I. Organic Contrast Radiographic Iodides

These are more commonly used than inorganic iodide in hyperthyroidism. These are also used as a contrast medium for radiographic examination of internal organs, such as gall bladder and biliary tract.

A. Iopanoic Acid
US-FDA Status: Unapproved for Hyperthyroidism
Availability: Discontinued
Generic name: iopanoic acid
Brand name: Telepaque tablet
Side-effects: Diarrhea, difficulty in urination, nausea
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

B. Ipodate Sodium
US-FDA Status: Unapproved for Hyperthyroidism
Availability: Discontinued
Generic name: ipodate sodium
Brand name: Oragrafin Sodium capsule
Side-effects: Few side-effects with renal failure occurring at high doses
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

II. Inorganic Iodide

A. Potassium iodide
US-FDA Status: Unapproved for Hyperthyroidism
Generic name: potassium iodide
Brand name: SSKI tablet
Side-effects: Nausea, vomiting, headache, fever
Indicated in pregnancy: Absolutely contraindicated
Alcohol Content: Absent

B. Sodium Iodide
US-FDA Status: Unapproved for Hyperthyroidism
Generic name: sodium iodide
Brand name: Iodopen
Side-effects: Joint pain, hives, swelling of lymph glands
Indicated in pregnancy: Absolutely contraindicated
Alcohol Content: Absent

5. β- blockers

This group of drug does not directly act on the thyroid gland and is used only to relieve symptoms of the patient. β- blockers block the beta-adrenergic receptors and rapidly control the symptoms of sympathetic over-stimulation (tachycardia and hypertension), thus causing a reduction in heart rate and blood pressure.

Anti-thyroid drugs and radioactive iodine therapy do not produce rapid results. Thus, while the response is awaited, beta-blockers are prescribed to provide symptomatic relief to the patients.

β- blockers are particularly useful during thyroid storm. However, beta blocker therapy is stopped once the normal level of thyroid hormones is restored.

Available as: Oral preparations and Injectable preparations

I. Non-Selective beta-blockers

These beta-blockers act on both beta 1 and beta 2 receptors, present in various parts of body, such as heart, bronchi, blood vessels, uterus, etc. However, their inhibitory action on receptors of heart and blood vessels render them useful in hyperthyroidism.

A. Propranolol

It is the most preferred beta-blocker in hyperthyroidism. It has an inhibitory action on peripheral conversion of T4 to T3 hormone, which is the active form of thyroid hormone. But this inhibitory effect is mild and requires administration of high doses of propranolol.

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: propranolol hydrochloride
Brand name: Inderal LA capsule
Side-effects: Chest tightness, cough, black tarry stools, abdominal pain
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

II. Cardioselective beta-blockers

Our heart has beta-1 blockers only. Cardioselective beta-blockers act specifically on beta-1 receptors of the heart and produce symptomatic relief in hyperthyroid patients. These are as effective as propranolol in hyperthyroidism.

A. Atenolol
US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: atenolol
Brand name: Tenormin tablet
Side-effects: Confusion, blurred vision, cold hands or feet, difficulty in breathing, sweating, chest tightness
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

B. Metoprolol
US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: metoprolol
Brand name: Lopressor HCT tablet
Side-effects: Chest pain, blurred vision, confusion, shortness of breath, sweating
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

C. Esmolol
It is an ultrashort-acting cardioselective beta-blocker. It is usually administered as an infusion in cases of thyroid storm.

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: esmolol hydrochloride
Brand name: Brevibloc injection
Side-effects: Confusion, blurred vision, drowsiness, increased sweating
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

Beta blockers are chief medications in hypertension and arrhythmias.

6. Calcium-Channel Blockers

It is usually indicated in hyperthyroid patients who are intolerant to beta blockers.
This group of drug inhibits the entry of calcium ions in the cells of the heart and dilates the blood vessels, thus reducing the heart rate and blood pressure. Similar to beta blockers, this group of drug also forms a part of symptomatic treatment of the patient as it does not affect the thyroid gland.

However, this drug therapy is stopped once the circulating thyroid hormones are within the normal range.

Calcium channel blockers are widely used in cardiac conditions such as arrhythmia and angina.

Available as: Oral preparations

I. Diltiazem
US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: diltiazem hydrochloride
Brand name: Cardizem tablet
Side-effects: Cough, congestion, body pain, fever, sore throat, runny nose
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

II. Verapamil

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: verapamil hydrochloride
Brand name: Calan tablet
Side-effects: Blurred vision, chest pain, confusion, dizziness
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

Drugs for Graves’ Dermopathy

Graves disease is the most common form of hyperthyroidism. It is an autoimmune disease process resulting in an overactive thyroid gland.

Patients of graves’ disease may present with a condition known as Dermopathy. It is characterized by a non-pitting swelling and redness of skin, in particular, skin of the shin (medically known as pretibial area). Hence, graves’ dermopathy is also known as pretibial myxedema. This occurs due to infiltration of dermis by inflammatory cells and glycosaminoglycans. Dermopathy is usually seen accompanying ophthalmopathy.

In most cases, dermopathy resolves on its own. However, in severe cases, topical steroids may be applied under an occlusive dressing to effectively counteract the inflammatory condition and provide relief.

1. Topical Glucocorticoids

Glucocorticoids are synthetic derivatives of steroid hormone, known as cortisol which is normally released by the adrenal glands. These are potent anti-inflammatory agents and can effectively combat skin inflammation seen in graves’ dermopathy.

Available as: Topical application only

I. Triamcinolone

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: triamcinolone acetonide
Brand name: Triderm cream
Side-effects: Irritation, itching, blistering, crusting of skin, thinning of skin with easy bruising
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Contains traces of alcohol

II. Betamethasone

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: betamethasone dipropionate
Brand name: Diprolene ointment
Side-effects: Burning, stinging or itching at the application site
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

III. Clobetasol

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: clobetasol propionate
Brand name: Clobex spray
Side-effects: Burning or stinging at the application site, dry skin, skin rash
Indicated in pregnancy: Usually contraindicated
Alcohol Content: Absent

IV. Mometasone

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: mometasone furoate
Brand name: Elocon lotion
Side-effects: Burning, itching, irritation, dryness, thinning of skin with easy bruising
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Contains traces of alcohol

V. Flucinolone

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: flucinolone acetonide
Brand name: Synalar cream
Side-effects: Congestion, cough, body ache, fever, headache, sore throat
Indicated in pregnancy: Usually contraindicated
Alcohol Content: Absent

Drugs for Graves’ Ophthalmopathy (GO)

3 to 5% of Graves’ disease patients may develop Graves’ Ophthalmopathy. It is an autoimmune inflammatory condition affecting the orbit and periorbital tissues. This may be mild, moderate or severe. Severe GO is characterized by visual impairment such as diplopia (double vision) or blurred vision. This is caused by swelling of muscles and tissues of the eye. When this swelling increases to a larger extent, it can compress the optic nerve, thus creating a medical emergency. In such cases, conventional approach may not be efficient and medical therapy is required.

According to a research paper published in The Medical Clinics of North America Journal, immunomodulators including glucocorticoids and non-steroidal immunomodulators can produce positive results in graves’ ophthalmopathy.^[1]

1. Oral and Systemic Glucocorticoids

Glucocorticoids have anti-inflammatory and immunosuppressant properties which can relieve the orbital inflammation and provide symptomatic relief.

Available as: Oral preparations and Injections (intravenous infusion)

I. Prednisolone

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: prednisolone
Brand name: Prelone syrup
Side-effects: Agitation, blurred vision, anxiety, aggression, dizziness
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Contains 5% alcohol

II. Methylprednisolone

US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: methylprednisolone sodium succinate
Brand name: Sol-U-Medrol
Side-effects: Agitation, blurred vision, anxiety, aggression, dizziness
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Contains 5% alcohol

2. Non-steroidal Immunomodulators

This group of drug includes drugs which inhibit the immune cells of the body, i.e. T-cells and B-cells, thus coutneracting the autoimmune process of graves’ ophthalmopathy.

Available as: Oral preparations and Injections (intravenous infusion)

I. Specific T-cell Inhibitor

A. Cyclosporine
US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: cyclosporine
Brand name: Gengraf capsule
Side-effects: Tremors, increased hair growth on face and body, abdominal pain, headache
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

II. Anti-B-Cell Agents

A. Rituximab
US-FDA Status: Approved for Hyperthyroidism
Availability: Prescription only
Generic name: rituximab
Brand name: Rituxan injection
Side-effects: Black tarry stools, bleeding gums, abdominal pain, blurred vision
Indicated in pregnancy: Only if benefit outweighs fetal risk
Alcohol Content: Absent

The non-steroidal immunomodulators are cytotoxic drugs and are primarily indicated in the treatment of cancer.

OTC

Because of the potential side-effects of the drugs used in hyperthyroidism, most of these drugs are available on prescription.

However, triamcinolone acetonide (topical preparation) is available as an over the counter drug for management of graves’ dermopathy in several countries, such as Australia, Canada, China, Germany, Greece, Italy, Japan, Mexico, Singapore, South Korea, Switzerland, Spain, UK and USA.

It must be remembered that a medical consultation is necessary to effectively manage the disease and self-medication is not recommended.