Introduction

Thyroid gland

The thyroid gland is an very important hormone secreting gland in endocrine systems, it is 2-inch-long, butterfly-shaped consists of two bulky lateral lobes connected by a relatively thin isthmus, usually located below and anterior to the larynx. It is one of the glands that make up the endocrine system. Thyroid follicular epithelial cells convert thyroglobulin into thyroxine (T₄) and lesser amounts oftriiodothyronine (T₃). T₄ and T₃ are released into the systemic circulation. The binding proteins serve to maintain the serum unbound ("free") T₃ and T₄ concentrations within narrow limits yet ensure that the hormones are readily available to the tissues.

According to Dorland's medical dictionary, Hyperthyroidism is defined as an excessive thyroid gland activity, marked by an increased metabolic rate, goiter, and disturbance in autonomic nervous system and in creatine metabolism. It is a hypermetabolic state caused by elevated circulating levels of free T₃ and T₄, most commonly by abnormal increased function of the thyroid gland. However, in certain conditions the oversupply is related to either excessive release of preformed thyroid hormone or to an extra-thyroidal source.

Thyroid hormones affect metabolism, brain development, breathing, heart and nervous system functions, body temperature, muscle strength, skin dryness, menstrual cycles, weight, and cholesterol levels.

Many common symptoms and signs of increased thyroid hormone (hyperthyroidism) are similar to those of adrenergic excess, such as nervousness, palpitations, hyperactivity, increased sweating, heat hypersensitivity, fatigue, increased appetite, weight loss, insomnia, weakness, and frequent bowel movements (occasionally diarrhea).

Hyperthyroidism has several causes, including:

 ·   Graves' disease (toxic diffuse goiter)

·   Inappropriate TSH secretion

·   Molar pregnancy, choriocarcinoma, and hyperemesis gravidarum

·   Nonautoimmune autosomal dominant hyperthyroidism

·   Toxic solitary or multinodular goiter (Plummer's disease)

·   Inflammatory thyroid disease (thyroiditis)

·   Drug-induced hyperthyroidism (amiodarone, interferon-α)

·   Thyrotoxicosis factitia

·   Excess iodine ingestion

·   Metastatic thyroid cancer

• Struma ovarii

Epidermiology

-Hyperthyroidism is present in approximately 0.5% of the population.

-About 1 percent of the U.S. population has hyperthyroidism. Women are five to 10 times more likely than men to develop hyperthyroidism. The American Thyroid Association recommends that adults, particularly women, have a blood test to detect thyroid problems every 5 years starting at age 35.

-An additional 0.8% of the population has mildly suppressed or undetectable serum thyroid stimulating hormone (TSH) levels but circulating thyroid hormone levels in the normal range. -Additionally, the rate of development of the various causes of hyperthyroidism varies according to geographic location and is believed to be related to the iodine intake of the population. For example, an epidemiologic survey comparing an area of normal iodine intake to one with insufficient iodine intake found that Graves disease accounted for 80% of cases of hyperthyroidism in the iodine sufficient population but toxic uninodular and multinodular goiter accounted for the majority of cases in the iodine deficient population.

Signs and Symptoms

Most symptoms and signs are the same regardless of the cause. Exceptions include infiltrative ophthalmopathy and dermopathy, which occur only in Graves' disease.

The clinical presentation may be dramatic or subtle. A goiter or nodule may be present. Many common symptoms and signs of hyperthyroidism are similar to those of adrenergic excess, such as nervousness, palpitations, hyperactivity, increased sweating, heat hypersensitivity, fatigue, increased appetite, weight loss, insomnia, weakness, and frequent bowel movements (occasionally diarrhea). Hypomenorrhea may be present. Signs may include warm, moist skin; tremor; tachycardia; widened pulse pressure; atrial fibrillation and palpitations.

Elderly patients, particularly those with toxic nodular goiter, may present atypically (apathetic or masked hyperthyroidism) with symptoms more akin to depression or dementia. Most do not have exophthalmos or tremor. Atrial fibrillation, syncope, altered sensorium, heart failure, and weakness are more likely. Symptoms and signs may involve only a single organ system.

Eye signs include stare, eyelid lag, eyelid retraction, and mild conjunctival injection and are largely due to excessive adrenergic stimulation. They usually remit with successful treatment. Infiltrative ophthalmopathy, a more serious development, is specific to Graves' disease and can occur years before or after hyperthyroidism. It is characterized by orbital pain, lacrimation, irritation, photophobia, increased retro-orbital tissue, exophthalmos, and lymphocytic infiltration of the extraocular muscles, producing ocular muscle weakness that frequently leads to double vision.

Infiltrative dermopathy, also called pretibial myxedema (a confusing term, because myxedema suggests hypothyroidism), is characterized by nonpitting infiltration by proteinaceous ground substance, usually in the pretibial area. It rarely occurs in the absence of Graves' ophthalmopathy. The lesion is often pruritic and erythematous in its early stages and subsequently becomes brawny. Infiltrative dermopathy may appear years before or after hyperthyroidism.

Thyroid storm: Thyroid storm is an acute form of hyperthyroidism that results from untreated or inadequately treated severe hyperthyroidism. It is rare, occurring in patients with Graves' disease or toxic multinodular goiter (a solitary toxic nodule is less common and generally less severe). It may be precipitated by infection, trauma, surgery, embolism, diabetic ketoacidosis, or preeclampsia. Thyroid storm produces abrupt florid symptoms of hyperthyroidism with one or more of the following: fever, marked weakness and muscle wasting, extreme restlessness with wide emotional swings, confusion, psychosis, coma, nausea, vomiting, diarrhea, and hepatomegaly with mild jaundice. The patient may present with cardiovascular collapse and shock. Thyroid storm is a life-threatening emergency requiring prompt treatment.

Infiltrative Ophthalmopathy (Picture taken from Merk Manual)

Pretibial Myxedema in a Patient With Graves' Disease(Picture taken from Merk Manual)

Pathophysiology

Any process that causes an increase in the peripheral circulation of unbound thyroid hormone can cause signs and symptoms of hyperthyroidism. Disturbances of the normal homeostatic mechanism can occur at the level of the hypothalamus, the pituitary gland and the thyroid gland, as illustrated in diagram above.

Defect of hypothalamus and pituitary gland can be hyper-secreting of hormone which can induce excessive secretion of thyroid hormone causing hyperthyroidism. But this is rare. Hyper-secretion may be due to certain tumor or any other defects. On investigation, this defect can increase level of tri-iodothyronine (T3) and level of thyroxine (T4) in plasma. Level of Thyroid Releasing Hormone (TRH) and/or level of Thyroid Stimulating Hormone (TSH) also may be increased. Goiter that is enlargement of thyroid gland may be present.

Defect also can be originated from the thyroid gland itself. Hyper-secreting of thyroid hormone may be one of the causes with absent of goitre. Other than that, is Graves’s Disease which is the common cause of hyperthyroidism. Graves’s Disease is an autoimmune disease in which the body abnormally produces thyroid-stimulating immunoglobulin (TSI), an antibody whose targeting the TSH receptor on the thyroid cells. TSI will stimulates both secretion and growth of the thyroid in a manner similar to TSH. 

Unlike TSH, TSI is not subjected for negative feedback inhibition by thyroid hormone, so thyroid secretion and growth continued unchecked. On investigation, level of T3 and T4 may be high while level of TSH remains normal or low. Goiter may be present. Last causes of hyperthyroidism are Apathetic Hyperthyroidism which refers to thyrotoxicosis occurring in elderly, in whom old age and various co-morbidities may blunt typical features of thyroid hormone excess seen in younger patients. The diagnoses of throtoxicosis in these individual are often made during laboratory work-up for unexplained weight loss or worsening cardiovascular disease.

Clinical manifestations of hyperthyroidism are induces by abnormal increased in thyroid hormone. Thyroid hormone can cause three major effects that is hyper metabolic state, over stimulation of sympathetic nervous system and cardiac effect as compensatory mechanism of certain condition caused by increased thyroid hormone. 

Thyroid hormone can lead to hyper metabolic state by increasing general metabolic rate. Normally, thyroid hormone participated in inducing synthesis and degradation of carbohydrate, fat and protein. However, overall metabolic effects of thyroid hormone at normal physiologic level are to favor the consumption rather than storage of body fuel. So, when thyroid hormone becomes abnormally high, it will increase the overall basal metabolic rate by increasing rate of degradation. Skin of patient may be soft, warm and flushed. Heat intolerance and excessive sweating also can be noted.

Thyroid hormones has sympathomimetic action which the actions are similar to one produced by sympathetic nervous system. Normally, thyroid hormone stimulates proliferation of specific cathecholamines target cell receptors which can induce sympathomimetic effect. Increased in thyroid hormone can induce overstimulation of sympathetic effects which can lead to condition known as ‘Thyroid Storm’ which is an abrupt onset of acute hyperthyroidism. Thyroid Storm is a medical emergency situation which significant number of untreated patients led to cardiac arrhythmias.

Overstimulation of gut will induce hypermotility which led to diarrhea and eventually malabsoption. Overstimulation of levator palpebrae superioris of the eye will result in ocular manifestation of wide, gaze, starring and lid lag of the eyes. Overstimulation of neuromuscular will lead to nervousness, irritability and tremor. Nearly 50% develop proximal muscle weakness called thyroid myopathy.

Increasing thyroid hormone also can lead to thyroid effects. Heart rate and contractility of heart muscle will be increase due to increase in heart’s responsiveness towards circulating cathecolamines. In addition, in response to heat load generated by cholinergic effect of thyroid hormone as discussed above, peripheral vasodilatation occurs to carry extra heat to body surface for elimination to the environment. Palpitation that is conscious of increasing heart beat and tachycardia that is abnormally rapid heartbeat is commonly seen in patient with hyperthroidosis.

Investigation

Although hyperthyroidism is clinically obvious, biochemical confirmation should be done before any treatment.

The measurement of serum TSH concentration is done because TSH levels are suppressed in hyperthyroidism. Diagnosis is confirmed with a raised free T₄ or T_3.  Then, measurement of radioactive iodine is done to determine the etiology of hyperthyroidism.

Treatment

Treatment depends on the cause and the severity of symptoms. Hyperthyroidism is usually treated with one or more of the following:

• Antithyroid medications

Carbimazole (10-20mg 8-hourly) blocks thyroid hormones synthesis and also poccesses immunosuppressive effects that will affect Graves’ disease process. After 2-3months at full dose, carbamazole is gradually reduced over the next 12-18 months to 5 mg daily. The most severe adverse effect of carbamazole is agranulocytosis, a disorder in which there is a severe acute deficiency of certain blood cells (neutrophil). All patients starting treatment must be warned to terminate the carbimazole and seek an urgent blood count if they delevop a sore throat or unexplained fever.

• Radioactive iodine (which destroys the thyroid and stops the excess production of hormones)

It is administered orally as sodium¹³¹ I.  It is contraindicated in pregnancy and while breast-feeding. It accumulates in the gland and results in local irritation and tissue damage with return to normal thyroid function over 4-12 weeks.

• Surgery to remove the thyroid

Suntotal thyroidectomy should only applied on patients who hadve been rendered euthyroid. Antithyroid drugs must be stopped 10-14days before the operation and replaced with oral potassium iodine, that inhibits release of thyroid hormone and reduce the vascularity of the gland. The complications include bleeding, hypothyroidism, hypoparathyroidism, hypocalcaemia, recurrent laryngeal nerve palsy and recurrent hypertension.

If the thyroid must be removed with surgery or destroyed with radiation, you must take thyroid hormone replacement pills for the rest of your life.

Beta-blockers such as propranolol are used to treat some of the symptoms, including tachycardia, sweating, and anxiety until the hyperthyroidism is controlled.

Counselling

It is essential to cure this disorder immediately or else it will hamper the normal functioning of other body organs. Some of the most effective home remedies for hyperthyroidism are as follows:

-Eat nutritious and balanced diet.

-Some vegetables and beans might have a potential to fight against this illness.  They are broccoli, c--cabbage, sprouts, cauliflower, soybeans, turnips and mustard green.

-Do not consume excessive dairy products for at least 3-4 months until the disease is cured.

-Do not take foods high in iodine because iodine will increase the activity of thyroid gland.

-Consume more vitamin B 12, vitamin C and vitamin E in diets is essential as they have antioxidant properties that are beneficial in deactivating the harmful effects of free radicals causing hyperthyroidism.

-Avoid taking nicotine, caffeine, alcohols, carbonated liquids and processed foods.

Cope with the condition and support the body during the healing process: 
-Do regular exercise. It is essential in order to improve muscle tone and cardiovascular system. Heavy exercise also plays an important role in order to maintain bone density. Besides that, it also can reduce apetite and increase your energy level.

- Learn relaxation techniques is also one of the important way to manage this illness. It can actually help you to maintain a positive outlook, especially when coping with illness. It is kown that hyperthyroidism is a stress related, so learning to relax and achieve balance in your life can help maintain physical and well-being.

Relief of discomfort: 

A comfortable environment should be provided for the patient. Cool bath and cool fluids are vital In order to help relief discomfort due to intolerance to heat. Bed linen should be changed frequently because of excess sweating. Light bed clothes should also be used for the patient.

Self esteem: 
If patient's condition is very bad, mirrors should not be into his or her room so as not to constantly keep them aware of their bad state. Patient should be reassured that the symptoms he is experiencing which include changes in appearance, weight and appetite will gradually go away as his treatment is maintained. So patient is not constantly over burden him or herself with their own disturbing image.

Prevention

-there was no prevention for this problem.

-since this problem cause by either tumor or inherited,thus knowledge of family history and close attention towards signs and symptoms are very important.

Prognosis

Hyperthyroidism is generally treatable with no long-term adverse effects and only rarely is life threatening. In most cases, the problem causing hyperthyroidism can be cured, or the symptoms can be eliminated or greatly reduced.

Side effects of medications used to treat hyperthyroidism may be more problematic in older people. Surgical removal of a portion of the thyroid (subtotal thyroidectomy) is generally effective but can result in inadequate production of thyroid hormone in the body. Older people are also at high risk for complications such as cardiac failure. If left untreated, however, hyperthyroidism places undue stress on the heart and many other organs.

 Hyperthyroidism caused by Graves disease (autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones) usually gets worse over time. It has many complications, some of which are severe and affect quality of life. If they were treated with anti-thyroid drugs, prolonged remissions of the illness may occur. Radioactive iodine also is an effective treatment for Graves' disease. It is almost always used in patients with overproducing thyroid nodules. However, this treatment may come with hypothyroidism as its complication. Fortunately, this condition can be easily treated with daily thyroid replacement medication.