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.