Hyperthyroidism

Signs and symptoms

In excess, thyroid hormone both overstimulates metabolism and exacerbates the effect of the sympathetic nervous system, causing a "speeding up" of various body systems and symptoms resembling an overdose of epinephrine (adrenaline). For some people, mild (subclinical) hyperthyroidism may be asymptomatic, requiring blood tests to detect any anomalies in TSH levels. In others, excess thyroid hormone can potentially cause significant symptoms, although these symptoms will vary between people.

Due to thyroid hormone’s effect on the sympathetic nervous system, common symptoms may include:

• tachycardia 
• palpitations
• nervous system tremors (e.g., of the hands)
• irritability
• anxiety
• muscle weakness
• sleeping issues
• digestive system hypermotility
• unintended weight loss
• poor heat tolerance
• excessive sweating
• delirium
• thyroid enlargement
• thinning of the skin 
• fine brittle hair
• polyuria
• polydipsia
• pretibial myxedema
• Graves’ disease
• lower serum cholesterol level 

During pregnancy and in the elderly, some of these symptoms may be less severe since these are atypical patients. Pregnancy is a temporary state that changes blood volumes, heart rate, hormone and lipid levels. Pregnant patients have increased demand for nutrition and are often hot and irritable, which may mask symptoms caused by hyperthyroidism.

In overt primary hyperthyroidism, TSH levels are low while T4 and T3 levels are high. Subclinical hyperthyroidism is a milder form of hyperthyroidism characterized by low or undetectable serum TSH level, but with a normal serum free thyroxine level.

Following treatment or proper management of the hyperthyroid state, patients will usually experience complete remission of symptoms 1 to 2 months after an euthyroid (normal thyroid function) state is obtained, with a marked reduction in anxiety, sense of exhaustion, irritability, and depression. Though some individuals may have an increased rate of anxiety or persistence of affective and cognitive symptoms for several months after an euthyroid state is established.

An uncommon, but serious complication of hyperthyroidism is the thyroid storm, which is a severe form of thyrotoxicosis (hyperthyroidism). It presents with a high fever (often above 40 degrees), rapid and often irregular heart rate, vomiting, diarrhea, and worsening symptoms such as confusion and mental agitation. In severe cases, heart failure and myocardial infarction can occur, resulting in death. Thyroid storm can occur in a severe untreated hyperthyroidism, or in any condition that leads to fast destruction of thyroid gland cells in patients with pre-existing hyperthyroidism, such as an infection. Both cases result with releasing of great amounts of thyroid hormones into the bloodstream which cause the thyroid storm symptomatology. This condition is a medical emergency and requires immediately hospital care to control the symptoms as rapidly as possible.

Pathogenesis

There are a number of circumstances that can cause a hyperactive thyroid gland, including:

• autoimmune disorders
• inflammation
• excess iodine
• certain medications
• toxic nodular or multinodular goiters
• X-rays

Any cause of excessive thyroid hormone can result in thyrotoxicosis, which is a condition that includes hyperthyroidism.

The most common cause of hyperthyroidism is Graves’ disease, an autoimmune disorder whereby thyroid-stimulating immunoglobulin (TSI) antibody is produced in excess, resulting in overproduction of thyroid hormone by the thyroid gland. In addition to the common hyperthyroid symptoms, patients with Graves’ disease may uniquely experience eye disease (Graves’ ophthalmopathy), neck swelling (goiter), and a skin condition known as pretibial myxoedema (Graves’ dermopathy). This addition symptoms are caused by autoimmune infiltration. Classically in Graves’ disease, ophthalmopathy may cause the eyes to look enlarged and swollen since the eye muscles swell and push the eye forward, such that they appear to be bulging from the sockets. This condition is uniquely referred to as exophthalmos in Graves’ disease, and is caused by immune-mediated inflammation in the retro-orbital (eye socket) fat. In some cases, patients display swelling of the front of the neck from an enlarged thyroid gland (a goiter). More minor ocular signs include eyelid retraction (staring), extra-ocular muscle weakness, and lid-lag (von Graefe’s sign). These signs should rescind with treatment of the underlying cause, hyperthyroidism.

Toxic nodular and multinodular goiters are lumps or nodules in the thyroid gland, can also cause the thyroid to produce excessive amounts of thyroid hormones. On examination via palpation the nodule nature of the thyroid will feel different to the generalized enlargement of Graves’ disease. Additionally, thyroiditis (inflammation of the thyroid gland due to an immune response, such as to a viral infection) can also cause temporarily elevated levels of thyroid hormone and therefore hyperthyroidism. Uniquely amongst the causes of hyperthyroidism, thyroiditis can cause a tender or painful thyroid. Exogenous conditions can include excess iodine consumptions from food (e.g., kelp-- a type of algae) or supplements, or iodine-containing medications (e.g., amiodarone-- structurally similar to thyroxine, which causes hypo- or hyper-thyroid symptoms). Finally, women can develop hyperthyroidism during pregnancy or in the first year after giving birth. In some, hyperthyroidism can eventually lead to osteoporosis and risk of bone fractures.

Diagnosis

Hyperthyroidism is diagnosed based on symptoms, physical exam, and blood tests. The initial test for suspected hyperthyroidism is a blood test for TSH levels, where a diagnosis of hyperthyroidism is confirmed by a decreased TSH level (indicating feedback inhibition of the thyroid gland from increased levels of T4 and/or T3 in the blood) and elevated T4 and T3 levels. In addition to testing the TSH levels, panels may also be run for T3, free T3, T4, and/or free T4 for more detailed results. To then identify the specific cause of hyperthyroidism, additional tests can be performed. Such as, if Graves’ disease is suspected a blood test for anti-TSH-receptor antibodies can be performed to confirm.

A radioactive iodine uptake test and thyroid scan together can identify the cause of hyperthyroidism. The uptake test uses radioactive iodine injected or taken orally on an empty stomach to measure the amount of iodine absorbed by the thyroid gland. Patients with hyperthyroidism will absorb much more iodine than healthy individuals, including the radioactive iodine which is easily measured. A thyroid scan typically follows an uptake test to allow visual examination of the over-functioning thyroid gland. Therefore, an ultrasound or nuclear medicine scan of the thyroid can identify nodules, or determine whether the thyroid is inflamed or overactive. Of note, excess radioiodine that does not get absorbed into the thyroid gland will be eliminated by the body in urine. Some patients may experience a slight allergic reaction to the diagnostic radioiodine and may be given an antihistamine, but this procedure is not otherwise harmful to the patient.