More than 12% of the United States population will develop a thyroid condition during their lifetime. Hyperthyroidism is one type of thyroid disease characterized by the excess production of thyroid hormones, leading to an overactive metabolism.
Understanding the causes of hyperthyroidism enhances diagnostic accuracy and treatment efficacy. While autoimmune conditions like Graves' disease are the most common culprits, other factors that you may not be aware of might be triggering excess hormone production.
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How the Thyroid Gland Functions
The thyroid gland is a small, butterfly-shaped organ located in the front of the neck. Its primary function is to regulate metabolism. The thyroid achieves this by producing hormones that influence various bodily functions, including heart rate, body temperature, and how efficiently the body uses energy.
A feedback loop known as the hypothalamic-pituitary-thyroid (HPT) axis controls thyroid hormone production. This axis involves three key components: the hypothalamus, the pituitary gland, and the thyroid gland.
- The hypothalamus (in the brain) secretes thyrotropin-releasing hormone (TRH).
- TRH stimulates the pituitary gland (also in the brain) to release thyroid-stimulating hormone (TSH).
- TSH signals the thyroid gland to produce and release thyroxine (T4) and triiodothyronine (T3).
Hypothyroidism can occur when the thyroid gland produces too little T3 and T4.
When the thyroid gland produces excessive amounts of T3 and T4, hyperthyroidism results.
Primary Causes of Hyperthyroidism
The most common reasons hyperthyroidism occurs are autoimmunity and hyperfunctioning thyroid nodules (28).
Graves' Disease
Graves' disease is an autoimmune thyroid disease and the leading cause of hyperthyroidism, attributed to nearly 80% of all cases.
In Graves' disease, the immune system mistakenly attacks the thyroid gland by producing abnormal antibodies known as thyroid-stimulating immunoglobulins (TSI) or thyrotropin receptor antibodies (TRAb). These antibodies bind to the surface of thyroid cells and mimic the action of TSH to stimulate those cells to overproduce and release thyroid hormones. This results in an overactive thyroid gland. (22)
The exact cause of Graves' disease is not fully understood, but, as with any autoimmune disease, it is believed to be influenced by genetic and environmental factors. Stress, infections, and smoking have been identified as potential triggers for the onset of the disease in genetically predisposed individuals. (56)
Toxic Multinodular Goiter
Toxic multinodular goiter (TMNG), or Plummer's disease, is a thyroid disorder characterized by multiple nodules in the thyroid gland and the second most common cause of hyperthyroidism (27).
These nodules become overactive ("toxic"), functioning independently of the normal regulatory control of TSH, and release too much T3 and T4 (27).
Compared to Graves' disease, TMNG is not driven by autoimmune processes and typically occurs later in life, particularly during the sixth and seventh decades (27).
Thyroid Nodule (Toxic Adenoma)
Thyroid adenomas are benign (non-cancerous), solitary thyroid nodules. A single nodule is called a toxic adenoma when it produces excess thyroid hormones independently of the body's regulatory signals. Thyroid adenomas are more likely to develop in regions of the world where iodine deficiency is prevalent. (34)
Less Common Causes and Triggers
Several other conditions can less frequently trigger the thyroid gland to release excessive thyroid hormones.
Thyroiditis
Thyroiditis is inflammation of the thyroid gland. There are many types of thyroiditis, many of which begin with the destruction of thyroid cells via an inflammatory immune mechanism, releasing excessive amounts of thyroid hormones into circulation.
Many forms of thyroiditis cause transient hyperthyroidism, often followed by a hypothyroid phase as hormone levels drop and eventually return to a euthyroid (normal thyroid function) state (48).
Thyroiditis can occur from:
- Autoimmune disease (Graves' disease, postpartum thyroiditis, silent thyroiditis)
- Infection (subacute thyroiditis)
- Exposure to radiation
- Medications (drug-induced thyroiditis): amiodarone, lithium, and chemotherapy agents
- Fibrosis (Riedel thyroiditis)
Excessive Iodine Intake
High iodine levels, whether from diet, supplements, or medications, can trigger hyperthyroidism, particularly in individuals with pre-existing thyroid conditions like nodular goiters or latent Graves' disease (42).
Iodine is a nutrient required for the thyroid hormone synthesis. While the thyroid typically adjusts its hormone output in response to iodine levels, an excessive intake can overwhelm this regulatory mechanism, resulting in the Jod-Basedow phenomenon (iodine-induced hyperthyroidism).
Sources of excess iodine include:
- Contrast dyes used in medical imaging
- Over-the-counter supplements, such as kelp/seaweed products and multivitamins
- Prescription medications, such as amiodarone
Pituitary Gland Dysfunction
Secondary hyperthyroidism is caused by anterior pituitary dysfunction, leading to excessive TSH production, thyroid gland overstimulation, and overproduction of thyroid hormones.
Compared to primary hyperthyroidism (in which the thyroid gland itself is responsible for the overproduction of thyroid hormones), secondary hyperthyroidism is much less common, accounting for less than 1% of all hyperthyroid cases.
Risk Factors for Developing Hyperthyroidism
These factors may make it more likely for an individual to develop hyperthyroidism:
Family History and Genetics
Individuals with a family history of thyroid disorders, particularly autoimmune thyroid diseases, are more likely to develop hyperthyroidism. Genetic predisposition accounts for up to 80% of the risk for Graves' disease.
This suggests that certain genetic variations increase susceptibility to these conditions. For instance, genes involved in immune system regulation, such as those associated with human leukocyte antigens (HLA), are often linked to autoimmune thyroid disorders.
Age and Gender
Women are up to ten times more likely to develop hyperthyroidism than men.
Age also influences the risk of hyperthyroidism. The incidence of Graves' disease is highest between ages 30 and 50 (32). Conversely, the risk of TMNG increases with age, with its incidence peaking after 60 years (52).
Smoking
Research indicates that smokers are at a higher risk of developing Graves' disease. This risk increases with the amount and duration of smoking. Specifically:
- Individuals who smoke 25 or more cigarettes per day
- Individuals with a higher number of pack-years ("pack-years" quantifies a person's smoking history by multiplying the number of packs smoked per day by the number of years they have smoked)
Smoking can also cause Graves' disease to progress faster, worsen symptoms, and lead to poorer treatment response. Smokers with Graves' disease are also more likely to develop thyroid eye disease.
Autoimmune Triggers
The immune dysfunction observed in autoimmune disease is believed to result from the interplay between environmental exposures and genetic predisposition, leading to the loss of self-tolerance and upregulation of exaggerated immune responses. Some of these environmental triggers include:
Symptoms to Watch For
Symptoms of hyperthyroidism include:
- Anxiety, irritability, and nervousness
- Rapid heart rate (tachycardia)
- Heart palpitations
- Unintentional weight loss
- Increased hunger
- Hair loss
- Increased sweating and body temperature
- Insomnia
- Irregular menstrual cycles (light and infrequent periods)
- Tremors and shaking
- Diarrhea
- Muscle weakness
Hyperthyroid symptoms can vary depending on the underlying cause of the disease. For example:
- Some individuals with Graves' disease develop Graves' ophthalmopathy, which causes the eyes to bulge (exophthalmos) due to inflammation and swelling behind the eyes.
- The primary symptom of subacute thyroiditis is pain in the front of the neck that can radiate to the jaw or ears.
- Nodules and thyroid inflammation can cause thyroid enlargement (goiter). If a goiter becomes very large, it can compress surrounding structures in the neck, resulting in symptoms like difficulty swallowing, hoarse voice, and fullness/tightness in the neck.
How Hyperthyroidism Is Diagnosed
Clinical suspicion of hyperthyroidism should prompt laboratory testing to confirm the diagnosis. The diagnostic process begins with the doctor taking a comprehensive medical history and performing a physical examination. During the exam, look for common signs of hyperthyroidism, such as weight loss, rapid heart rate, increased sweating, tremors, and thyroid goiter or nodules.
Blood Tests
Initial testing in patients presenting with signs and symptoms suggestive of hyperthyroidism is thyroid function testing. This includes (43):
- TSH has the highest sensitivity and specificity of any single blood test and should be used as an initial screening test for hyperthyroidism.
- When hyperthyroidism is strongly suspected, TSH should be ordered with free T4 and total T3 to improve diagnostic accuracy.
Lab findings that confirm hyperthyroidism include (43):
- Overt Hyperthyroidism: TSH is low (usually < 0.01 mU/L), and free T4 and total T3 are elevated
- Subclinical Hyperthyroidism: TSH is low, and free T4 and total T3 are normal
- Secondary Hyperthyroidism: TSH, free T4, and total T3 are elevated
Measuring the serum level of thyroid antibodies can help distinguish Graves' disease from other causes of hyperthyroidism. Over 90% of patients with Graves' disease will have elevated TRAb.
About 70% and 60% of patients will also have raised thyroid peroxidase (TPO) and thyroglobulin (TG) antibodies, respectively, although these are more commonly associated with Hashimoto's hypothyroidism.
Imaging Studies
Imaging studies can provide detailed information about the thyroid's structure and function, assisting in identifying the underlying cause of hyperthyroidism if it is unclear from the patient's clinical presentation and initial laboratory evaluation.
Thyroid ultrasound is a non-invasive imaging technique that uses sound waves to create images of the thyroid gland. It is beneficial for evaluating the thyroid's size, shape, and texture. Possible findings on ultrasound may include (7):
- Thyroid nodules
- Goiter
- Signs of inflammation
A radioactive iodine uptake (RAIU) scan assesses the thyroid's function and activity through its ability to absorb iodine. After administering a small dose of radioactive iodine, the uptake is measured. Findings may include (28):
- Homogeneous increased uptake indicates Graves' disease
- Localized increased uptake indicates TMNG or toxic adenoma
- Low uptake indicates thyroiditis
Treatment Options Based on the Underlying Cause
Hyperthyroidism can be treated with antithyroid medications, radioactive iodine (RAI) therapy, or surgery, depending on the underlying cause, severity of the disease, and the patient's medical history and preferences.
Medications
Antithyroid medications, including methimazole and propylthiouracil (PTU), are a treatment option for managing hyperthyroidism in conditions like Graves' disease and TMNG. These medications work by inhibiting the thyroid gland's ability to produce hormones, thereby reducing levels of T3 and T4 in the bloodstream. (1)
Antithyroid medications can lead to significant symptom relief and normalization of thyroid hormone levels, allowing many patients to return to a euthyroid state. However, they may take several weeks to months to achieve full effect. (1)
Common side effects of antithyroid medications can include rash, joint pain, and gastrointestinal upset. Rare but serious side effects include agranulocytosis (severe low white blood cell count) and liver injury. (1)
Regardless of the cause of hyperthyroidism, beta-blockers (either atenolol or propranolol) can be prescribed to control adrenergic symptoms, such as nervousness, anxiety, restlessness, sweating, heat intolerance, tremors, palpitations, and tachycardia. Propranolol has the additional benefit of inhibiting the conversion of T4 to T3. (28)
Radioactive Iodine Therapy
RAI ablation of the thyroid is the most common treatment of hyperthyroidism in the United States. It is contraindicated during pregnancy but otherwise can be used to treat Graves' disease, TMNG, and toxic adenoma. (28)
RAI therapy treats hyperthyroidism by using radioactive iodine-131 (I-131) to selectively destroy overactive thyroid cells. I-131 is administered and accumulates in the thyroid gland. The radiation emitted by I-131 destroys the thyroid cells that are producing excessive hormones.
Many patients will develop permanent hypothyroidism between two and six months after RAI therapy and will require permanent thyroid hormone replacement therapy (28).
Surgery (Thyroidectomy)
Thyroidectomy is the surgical removal of part or all of the thyroid gland. It is the preferred treatment option in patients with goiter-induced compressive symptoms, suspicious thyroid nodules, or contraindications to other treatments. Risks associated with thyroidectomy include those related to general anesthesia, bleeding, and injury to the parathyroid glands and recurrent laryngeal nerve. (28)
Managing Temporary Hyperthyroidism
Many cases of hyperthyroidism related to thyroiditis are transient and self-resolve within weeks to months. In these cases, the goal of treatment is simply symptom management. (28)
For example, during the thyrotoxic phase of subacute thyroiditis, hyperthyroid symptoms can be managed with a beta-blocker, while pain can be treated with a nonsteroidal anti-inflammatory drug (NSAID) or corticosteroid (62).
When to Seek Medical Attention
Patients should see a doctor for concerns of hyperthyroidism if they experience new symptoms such as unexplained weight loss, rapid heartbeat, tremors, anxiety, or heat intolerance.
After receiving a diagnosis of hyperthyroidism, most people need to maintain routine follow-up visits with their healthcare provider to monitor the condition and screen for possible associated complications, such as:
- Irregular heartbeat (arrhythmia) that can lead to blood clots, stroke, and heart failure
- Graves' ophthalmopathy
- Osteoporosis
- Fertility issues
If hyperthyroid symptoms worsen or fail to improve with treatment, follow up with your doctor for additional thyroid evaluation and adjustment of the management plan.
Routine thyroid screening is important for individuals at high risk for thyroid disease, such as those with a family history of thyroid disorders, or those planning to become pregnant.
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Key Takeaways
- Hyperthyroidism can arise from a variety of causes, with the most common being Graves' disease, toxic multinodular goiter, and toxic adenoma.
- Other factors, such as genetics, high iodine intake, taking certain medications, and smoking, can also increase your risk for hyperthyroidism.
- Understanding the underlying cause of hyperthyroidism is important for choosing the most appropriate treatment, whether it be antithyroid medications, radioactive iodine therapy, surgery, or watchful waiting.
- If you experience symptoms suggestive of thyroid dysfunction, be proactive in seeking medical advice. Early diagnosis and an effective treatment plan can restore thyroid hormones to normal, preventing unwanted and potentially serious health complications.
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