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Hyperthyroidism

Contents

Overview

Hyperthyroidism is a condition in which the thyroid gland is overactive  and produces excessive amounts of thyroid hormone. It is therefore also known as overactive thyroid, and hyperthyreosis. The thyroid is responsible for controlling various processes in the body, including: protein synthesis, energy metabolism, sensitivity and release of hormones, breathing rate, heart rate, and body temperature. Therefore, when the thyroid gland is hyperactive (hyperthyroidism), the processes in the body speeds up and can result in nervousness, anxiety, fatigue, muscle weakness, tachycardia, hand tremor, excessive sweating, dry skin, and weight loss.

Anatomy

The thyroid gland is an endocrine organ consisting of two connected lobes that are found situated on the trachea, just inferior to the thyroid cartilage (Adam’s apple). The principle thyroid hormones that regulate functions in the body are thyroxine (T4) and triiodothyronine (T3). T4 is mainly inactive, and is converted peripherally in the body to make the more active T3. T3 and T4 are synthesized from iodine and tyrosine.

Thyroid gland - ventral view

Thyroid gland - ventral view

Hormonal output from the thyroid is regulated by negative feedback. Beginning from the hypothalamus, thyrotropin-releasing hormone (TRH) is released, which results in the production of thyroid-stimulating hormone (TSH) by the anterior pituitary that in turn stimulates production of T3 and T4. Excess amounts of T3 and T4 provides negative feedback at both the level of the anterior pituitary and hypothalamus. Calcitonin is also produced by the thyroid, and plays a role in calcium homeostasis.

Clinical

Signs & 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.

Thyroid gland - cross-sectional view

Thyroid gland - cross-sectional view

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 occurs when a patient with pre-existing hyperthyroidism develops a concurrent infection. 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.

Goiter

Goiter is a swelling of the front of the neck from an enlarged thyroid gland.

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.

Treatment

Treatment and management will depend on the cause and severity of disease. There are three main treatment options: radioiodine therapy, medications, and thyroid surgery.

  • For management medications, such as beta blockers, they can control certain symptoms (e.g., tachycardia and tremors) and temporarily help while waiting for other treatments to have their intended effect. Anti-thyroid medications such as methimazole (US), carbimazole (UK), and propylthiouracil (only in first trimester of pregnancy) are used to block the binding of iodine which reduces the level of thyroid hormone produced. The most serious side effect of these medicines are agranulocytosis, which is characterised by a low white cell count. This suppression of the immune system leads to an increased risk of serious infection roughly in 1/250 patients.

  • Radioiodine therapy (RAI, I-131) involves taking oral iodine-131, which becomes concentrated in the thyroid and will destroy the thyroid over the next few weeks to months. This will result in a hypothyroidism (under-active thyroid). Patients will require long-term hormone replacement therapy with synthetic thyroid hormone.

  • Thyroid surgery to remove the thyroid is another option. This option will be selected for patients with very large thyroids, when cancer is a concern, or when patients have too many side effects or fail to respond to the other treatments.

  • Thyroid eye disease (TED), with or without Graves' disease, can be treated with eye drops for dry eye, steroids to reduce inflammation, and surgery for: releasing tension, correcting vision, or re-positioning eye.

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Show references

References:

  • Saladin, K.S., Sullivan, S.J., & Gan, C.A. (2015). Anatomy & Physiology: The Unity of Form and Function. New York, NY: McGraw-Hill Education.
  • Gilroy, A.M., MacPherson, B.R., Ross, L.M., Schuenke, M. (2016). Atlas of Anatomy.  New York, NY: Thieme Medical Publishers.
  • E.J. (2013). Rapid Review Pathology. Philadelphia: Saunders.
  • Hyperthyroidism. (n.d.). Retrieved January 05, 2017
  • Hyperthyroidism. (n.d.). Retrieved January 05, 2017

Article, Review and Layout:

  • Alice Ferng
  • Franchesca Druggan
  • Adrian Rad

Illustrators:

© Unless stated otherwise, all content, including illustrations are exclusive property of Kenhub GmbH, and are protected by German and international copyright laws. All rights reserved.

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