Hyperthyroidism is a set of disorders that involve excess synthesis and secretion of thyroid hormones by the thyroid gland, which leads to the hypermetabolic condition of thyrotoxicosis.  Hyperthyroidism can accelerate body’s metabolism, causing unintentional weight loss and a rapid or irregular heartbeat.

Several treatments are available for hyperthyroidism. Anti-thyroid medications and radioactive iodine may slow the production of thyroid hormones. Sometimes, hyperthyroidism treatment involves surgery to remove all or part of your thyroid gland.

The most common forms of hyperthyroidism include diffuse toxic goiter (Graves disease), toxic multinodular goiter (Plummer disease), and toxic adenoma.

Associated Anatomy

The thyroid gland is a bilobed structure located in the anterior aspect of the trachea between the cricoid cartilage and the suprasternal notch. Each lobe of the thyroid connects via a thyroid isthmus. It is supplied via the superior thyroid artery which stems from the external carotid artery and the inferior thyroid artery, which is a branch of the thyrocervical trunk.

Histologically, the thyroid gland is surrounded by a thin, connective-tissue covering that penetrates the gland and divides the thyroid gland into compartments. The thyroid gland is composed of spherical, polarized follicular cells that surround a gel-like, thyroglobulin-rich colloid. Thyroglobulin is the organic precursor for thyroid hormones and requires iodide to form thyroid hormone. Dietary iodine is transported into thyroid follicular cells via the sodium-iodide symporter after conversion to iodide via thyroid peroxidase enzyme. The process of iodide becoming incorporated into monoiodotyrosine (MIT) or diiodotyrosine (DIT) molecules is referred to as organification, and the process is relatively self-regulated. Low dietary iodide facilitated upregulation of the sodium-iodide symporter while high dietary iodide temporarily inhibits the organification process, a phenomenon known as the Wolff-Chaikoff effect. Iodide incorporation into the thyroid hormone precursors, MIT and DIT, is due to peroxidase enzyme. The organic coupling of one molecule of MIT with one molecule of DIT leads to the production of triiodothyronine (T3) while the coupling of 2 DIT molecules leads to thyroxine (T4).

The thyroid gland secretes thyroxine (T4) in response to thyroid-stimulating hormone (TSH) originating from the anterior pituitary gland. The secreted T4 is converted to a more potent and triiodothyronine (T3) via deiodinase enzymes. Most of the conversion of T4 to T3 takes places extrathyroidally, although the thyroid gland possesses the intrinsic ability for T3 production.

From a physiologic perspective, the hypothalamus releases thyrotropin-releasing hormone (TRH) in response to low circulating thyroid stimulating hormone (TSH), T3 or T4.  TRH promote anterior pituitary secretion of thyroid-stimulating hormone (TSH) which, in turn, promotes T4 secretion from the thyroid gland. T4 and T3 exert a negative feedback control on both the hypothalamus and the anterior pituitary.

The term “hyperthyroidism” defines a syndrome associated with excess thyroid hormone production. It is a common misconception that the terms thyrotoxicosis and hyperthyroidism are synonyms of one another. The term “thyrotoxicosis” refers to a state of excess thyroid hormone exposure to tissues.  Although hyperthyroidism can lead to thyrotoxicosis and can be used interchangeably, it is important to note the difference between the two.


In the United States and most western countries, Graves disease is the most common cause of hyperthyroidism. As Graves disease is autoimmune in etiology, this form of hyperthyroidism tends to manifest itself in younger populations. In the older demographic, toxic multinodular goiter is the most common cause of hyperthyroidism.

Although Graves disease and toxic multinodular goiter are the more common causes of hyperthyroidism, other causes of hyperthyroidism include iodine-induced hyperthyroidism (Jod-Basedow phenomenon), thyroid adenomas, deQuervain thyroiditis (subacute thyroiditis), postpartum thyroiditis, and factitious thyroiditis (thyrotoxicosis factitia).

Factitious thyroiditis is hyperthyroidism that is associated with inappropriate or excessive use of pharmaceutical thyroid hormone. Due to a well-received side effect of weight loss, thyroxine has the potential for abuse and any history of a hyperthyroid patient should include a medication list and an assessment of possible misuse (whether intentional or unintentional).

Other sources of hyperthyroidism include ectopic foci of thyroxine-secreting tissue. The more prevalent (although rare) form of this etiology is struma ovarii, consisting of ectopic and functional thyroid tissue (often compromising greater than 50% of total mass) in the ovary.

Amiodarone or other iodine-containing medications can induce iodine-associated hyperthyroidism or thyrotoxicosis. This iodine-induced hyperthyroidism is referred to as the Jod-Basedow phenomena (Jod is the German word for iodine).

Differential Diagnosis

Hyperthyroidism presents with rather nonspecific signs and symptoms such as palpitations, increased frequency of bowel movements, weight loss, among others. Other pathologies should be ruled out as possible explanations of the patient’s symptomatology.

For etiologies of hyperthyroidism, differential diagnosis can be made based on the physical findings of the thyroid gland. Palpation of a normal thyroid gland in the context of hyperthyroidism can be due to Graves disease, painless thyroiditis, or factitious hyperthyroidism (thyrotoxicosis factitia). Graves disease can also present as a non-tender, enlarged thyroid.

Palpation of a tender, enlarged thyroid may be indicative of DeQuervain thyroiditis (subacute thyroiditis). Palpation of a single thyroid nodule is likely thyroid adenoma, and palpation of multiple thyroid nodules is strongly indicative of toxic multinodular goiter.

Other differential diagnoses include euthyroid hyperthyroxinemia (a condition in which serum total T4 and T3 are elevated, but the TSH level is within normal limits) and struma ovarii.


Methimazole (Northyx, Tapazole)

With few exceptions, methimazole should be used in every patient who needs antithyroid drug therapy for hyperthyroidism. The exceptions are women in the first trimester of pregnancy, patients in thyroid storm, and patients with methimazole allergy or intolerance. Methimazole is avoided in early pregnancy because of increased placental transfer and risk of a rare fetal condition (cutis aplasia). Compared with propylthiouracil, it has a higher transfer rate into the milk of lactating women.

Methimazole inhibits thyroid hormone by blocking oxidation of iodine in the thyroid gland. However, it is not known to inhibit peripheral conversion of thyroid hormone. The drug is available as 5-mg or 10-mg tablets. It is readily absorbed and has a serum half-life of 6-8 hours. Methimazole is less protein-bound than propylthiouracil is.

Methimazole’s duration of action is longer than its half-life, and the drug should be dosed every 12-24 hours. Studies have shown that rectal suppositories or retention enemas can be used at the same dose as orally administered methimazole for patients who cannot take oral medications. Usually, after thyroid function improves, the dose must be decreased or the patient will become hypothyroid.

Propylthiouracil (PropylThyracil, PTU)

Propylthiouracil is a derivative of thiourea that inhibits organification of iodine by the thyroid gland. It blocks oxidation of iodine in the thyroid gland, thereby inhibiting thyroid hormone synthesis; the drug inhibits T4-to-T3 conversion (and thus has an advantage over other agents).

Propylthiouracil remains the drug of choice in uncommon situations of life-threatening severe thyrotoxicosis. It may be preferable during and before the first trimester of pregnancy.

In 2010, the US Food and Drug Administration (FDA) added a boxed warning to the prescribing information for propylthiouracil, emphasizing the risk for severe liver injury and acute liver failure, some cases of which have been fatal.

Propylthiouracil is available as a 50-mg tablet. It is readily absorbed and has a serum half-life of 1-2 hours. It is highly protein-bound in the serum. The drug’s duration of action is longer than its half-life, and propylthiouracil generally should be dosed every 6-8 hours (though it can also be administered twice daily). If patient compliance is an issue, methimazole may be a better choice because it can be given as a single daily dose in many cases.

Thyroid hormone levels (thyroid-stimulating hormone [TSH], T4, free thyroxine index [FTI] or free T4, and T3) should be reassessed in 4-6 weeks after starting propylthiouracil. The dosage is increased if thyroid hormone levels have not significantly fallen or decreased if thyroid hormone levels have fallen by 50% or more (even if the patient is still thyrotoxic).

Usually, after thyroid function improves, the dosage should be gradually decreased to 50-150 mg/day in divided doses. Otherwise, the patient will become hypothyroid.

Potassium iodide (SSKI, ThyroSafe, ThyroShield, iOSAT)

Potassium iodide inhibits thyroid hormone secretion. Iodide therapy is primarily used for the treatment of thyroid storm or given preoperatively, 10-14 days before surgical procedures (including thyroidectomy).

Until high levels of iodine build up in the thyroid follicular cell, however, administration of iodine can increase thyroid hormone synthesis and lead to higher serum levels of thyroid hormone. Thus, it is usually recommended that iodine not be started until after antithyroid drug therapy has been initiated. In thyroid storm, iodine should be administered at least 1 hour after methimazole or propylthiouracil.

Potassium iodide and iodine (Lugol’s solution)

Lugol’s solution is primarily administered for 10 days before thyroidectomy or during thyrotoxic crisis because high levels of iodine in the follicular thyroid cell temporarily inhibit thyroid hormone synthesis and secretion. T4 and T3 concentrations can be reduced for several weeks.

Until high levels of iodine build up in the thyroid follicular cell, however, administration of iodine can increase thyroid hormone synthesis and lead to higher serum levels of thyroid hormone. Thus, it is usually recommended that iodine not be started until after antithyroid drug therapy has been initiated.

Sodium iodide 131I (Iodotope, Hicon)

Radioactive iodine is approved by the FDA for treatment of hyperthyroidism in adults. It can also be used with a radioactive uptake test to evaluate thyroid function. The agent is quickly absorbed and taken up by the thyroid. No other tissue or organ in the body is capable of retaining radioactive iodine; therefore, few adverse effects develop.

Propranolol (Inderal, Inderal LA, InnoPran XL)

Propranolol is the drug of choice for treating cardiac arrhythmias resulting from hyperthyroidism. It controls cardiac and psychomotor manifestations within minutes.

Atenolol (Tenormin)

Atenolol selectively blocks beta1 receptors, with little or no effect on beta2 types. It is a longer-acting drug that can be more useful than propranolol for intraoperative and postoperative control.


The prevalence of hyperthyroidism is different according to the ethnic group while in Europe the frequency is affected by dietary intake of Iodine and some cases are due to autoimmune disease. Subclinical hyperthyroidism occurs more in women older than 65 than in men while overt hyperthyroidism rates are 0.4 per 1000 women and 0.1 per 1000 men and vary with age.

Any analysis of the global epidemiology of hyperthyroidism will delineate along the lines of iodine-sufficient regions and iodine-deficient regions. While iodine excess can lead to hyperthyroidism, iodine deficiency can lead to both hypothyroidism and hyperthyroidism.

Graves disease is typically seen in younger patients and is the most common cause of hyperthyroidism in that demographic. Toxic multifocal goiter is typically seen in older individuals and is the most common cause of hyperthyroidism in this respective demographic. Both Graves disease and toxic multifocal goiter have a female predilection and are typically seen in patients with pertinent family and personal medical histories.

The 1977 Whickham Survey was an evaluation of the spectrum of thyroid disorders in County Durham in northeastern England. Although the demographics of the Whickham Survey consisted of primary inhabitants of a community of northeastern England (and hence, poor extrapolation potential), the survey did show interesting results of hyperthyroidism. The Whickham Survey demonstrated a prevalence of hyperthyroidism in women approximately 10-times more than that of men (2.7% versus 0.23%).

Natural Progression

Untreated or unmanaged hyperthyroidism can lead to an extreme case of hyperthyroidism referred to as thyroid storm. Reflecting the hypermetabolic state of hyperthyroidism, the patient experiencing thyroid storm will present with tachycardia, increased GI motility, diaphoresis, anxiety, and fever. Thyroid storm is a potentially life-threatening complication of hyperthyroidism, thus requiring immediate attention.


The pathophysiology of hyperthyroidism depends on the particular variant of hyperthyroidism. In the case of Graves disease, the underlying cause is autoimmune, particularly the production of thyroid-stimulating immunoglobulins that bind to the TSH receptor and mimic the effects of TSH. Graves disease presents with 2 extra-thyroidal signs that are not typically seen in other forms of hyperthyroidism. The ophthalmopathy of Graves disease is characterized by the edema of retro-orbital tissues, thus causing anterior protrusion of the ocular globes. Pretibial myxedema is a plaque-like thickening of the skin anterior to the tibia due to infiltration of glycosaminoglycans in the dermis.

Toxic multinodular goiter presents with palpable thyroid nodules. It is the leading cause of hyperthyroidism, particularly in older populations. Toxic multinodular goiter leads to the production of excess thyroid hormone from autonomous ectopic tissue, thus leading to clinical thyrotoxicosis.

As opposed to toxic multinodular goiter which can present with multiple nodules, thyroid adenoma typically presents with a solitary papillary nodule that has the potential of causing hyperthyroidism. Hyperfunctioning thyroid adenomas can be distinguished from thyroid carcinomas by their clinical presentation. Thyroid hormone production by thyroid carcinomas is insufficient and cannot achieve thyroid hormone levels sufficient to cause overt hyperthyroidism. As a result, thyroid adenomas are generally benign.

Hyperthyroidism secondary to thyroiditis results in the transient increase in circulating thyroid hormone resulting from mechanical disruption of thyroid follicles. Subacute thyroiditis (DeQuervain thyroiditis) typically follows an acute infection, for example, upper respiratory infection. It is a granulomatous inflammatory process, resulting in an exquisitely tender thyroid gland. Painless thyroiditis is a form of hyperthyroidism, usually seen in postpartum stages. It is lymphocytic thyroiditis, and it can be distinguished from its subacute counterpart by the clinical history and palpation of the thyroid gland (which is non-tender in painless thyroiditis but painful in subacute thyroiditis).

Iodine-induced hyperthyroidism (Jod-Basedow phenomenon) is typically iatrogenic, resulting from administration of iodine-containing medications such as contrast media or amiodarone. As mentioned previously, the organification of iodide residues into precursor thyroid hormone molecules is relatively self-regulating. Excessive circulating iodide inhibits organification, a process known as the Wolff-Chaikoff effect. However, professionals believe that in patients with iodine-induced hyperthyroidism, areas of autonomous function permit excessive secretion of thyroid hormone in the presence of high iodide levels. Discontinuation of the offending agent typically results in resolution of the hyperthyroidism. Amiodarone-induced thyrotoxicosis has two types: type 1 and type 2. The distinction between the 2 subtypes is apparent from history, diagnostic findings, and treatment. Amiodarone-induced thyrotoxicosis, type 1 patients typically have pre-existing thyroid pathology, low RAI uptake, and increased thyroid parenchymal blood flow. The treatment is typically anti-thyroid medication. In contrast, amiodarone-induced thyrotoxicosis, type 2 patients may not have a history of previous thyroid disease. Diagnostics may show a relatively lower RAI uptake and decreased thyroid parenchymal blood flow. Treatment for the type 2 variant is typically steroids. While excess iodine exposure from amiodarone administration can result in hyperthyroidism, amiodarone itself can be directly cytotoxic, contributing to thyroid injury.

Excessively high levels of chorionic gonadotropin as seen in cases of trophoblastic tumors can cause hyperthyroidism via weak activation of the TSH receptors. This etiology of hyperthyroidism, however, is considerably rare compared to the previously mentioned causes of hyperthyroidism.

Possible Complications

Hyperthyroidism can lead to a number of complications:

  • Heart problems. Some of the most serious complications of hyperthyroidism involve the heart. These include a rapid heart rate, a heart rhythm disorder called atrial fibrillation that increases your risk of stroke, and congestive heart failure — a condition in which your heart can’t circulate enough blood to meet your body’s needs.
  • Brittle bones. Untreated hyperthyroidism can also lead to weak, brittle bones (osteoporosis). The strength of your bones depends, in part, on the amount of calcium and other minerals they contain. Too much thyroid hormone interferes with your body’s ability to incorporate calcium into your bones.
  • Eye problems. People with Graves’ ophthalmopathy develop eye problems, including bulging, red or swollen eyes, sensitivity to light, and blurring or double vision. Untreated, severe eye problems can lead to vision loss.
  • Red, swollen skin. In rare cases, people with Graves’ disease develop Graves’ dermopathy. This affects the skin, causing redness and swelling, often on the shins and feet.
  • Thyrotoxic crisis. Hyperthyroidism also places you at risk of thyrotoxic crisis — a sudden intensification of your symptoms, leading to a fever, a rapid pulse and even delirium. If this occurs, patients should seek immediate medical care.

Possible Treatment

Treatment of hyperthyroidism depends on the underlying etiology and can be divided into 2 categories: symptomatic therapy and definitive therapy. The symptoms of hyperthyroidism such as palpitations, anxiety, and tremor can be controlled with a beta-adrenergic antagonist such as atenolol. Calcium channel blocker, such as verapamil, can be used as second-line therapy for patients who are beta blocker intolerant or have contraindications to beta-blocker therapy.

Transient forms of hyperthyroidism such as subacute thyroiditis or postpartum thyroiditis should be managed with symptomatic therapy alone as the hyperthyroidism in these clinical situations tends to be self-limiting.

There are 3 definitive treatments of hyperthyroidism, all of which predispose the patient to potential long-term hypothyroidism: radioactive iodine therapy (RAI), thionamide therapy, and subtotal thyroidectomy. Clinical assessment and monitoring of free T4 are imperative for patients who undergo any of these treatments. TSH-monitoring status after definitive therapy is of poor utility since TSH remains suppressed until the patient becomes euthyroid. Thus, TSH monitoring for thyroid status is not recommended immediately following definitive therapy.

The choice of which definitive treatment modality depends on the etiology. RAI therapy is considered the treatment of choice in almost all patients with Graves disease due to a high efficacy. Despite the relative safety and high efficacy, RAI is contraindicated in patients who are pregnant or patients who are breastfeeding.

In RAI therapy, radioactive iodine-131 is administered with subsequent destruction of thyroid tissue. A single dose is sufficient enough to control hyperthyroidism in a significant portion of patients, and the effects of other parts of the human body are essentially negligible due to the high thyroid uptake of the radioactive iodine-131. In a female patient of reproductive potential, it is highly recommended to obtain a beta-hCG to rule out pregnancy prior to initiation of RAI therapy. Any patient on a thionamide (methimazole or propylthiouracil) should be instructed to discontinue this therapy approximately 1 week prior to RAI therapy since thionamide administration can interfere with the therapeutic benefit of RAI therapy. Several months are typically needed status post-RAI therapy to achieve euthyroid status. Typically, patients are evaluated in 4- to 6-week intervals with increased time intervals for stable, plasma-free, T4 levels. Failure to achieve euthyroidism after RAI therapy may indicate either for repeat RAI therapy (for symptomatic hyperthyroidism) or the initiation of thyroxine therapy (for hypothyroidism).

RAI therapy involves the release of stored thyroid hormone, leading to transient hyperthyroidism. This is generally well tolerated, although this transient hyperthyroidism is of concern in patients with significant cardiac disease. For patients with cardiac disease, pretreatment with a thionamide to deplete the stored hormone is recommended to avoid potential exacerbation of cardiac disease.

Thionamide therapy is used as a definitive treatment for hyperthyroidism inpatient unwilling to undergo RAI therapy or have contraindications to RAI therapy, for example, allergy or pregnancy. Methimazole and propylthiouracil both inhibit thyroid hormone synthesis by thyroid peroxidase. Thyroid peroxidase is the enzyme responsible for the conversion of dietary iodine into iodide. Propylthiouracil (PTU) also lowers peripheral tissue exposure to active thyroid hormone by blocking the extrathyroidal conversion of T4 to T3. Thionamide therapy has no permanent effect on thyroid function and remission of hyperthyroidism is common in patients who discontinue thionamide therapy.

Establishment of a euthyroid status typically requires several months after initiation of thionamide therapy. Although methimazole and PTU are equally effective, methimazole is preferred due to a relatively better safety profile. An exception to this recommendation is in pregnant patients, in which PTU is preferred. Methimazole is associated with an increased risk of congenital defects, and thus PTU is preferred in the management of gestational hyperthyroidism.

Side effects of thionamide therapy include agranulocytosis, hepatitis, vasculitis, and drug-induced lupus. Although these are rare side effects, patients should be warned about the potential for these side effects. Patients should also be advised to discontinue to the thionamide immediately and notify their physician if symptoms suggestive of agranulocytosis occur (fever, chills, rapidly progressive infection, sore throat, among others). Routine monitoring of leukocyte counts is not recommended when starting a patient on a thionamide due to the rapid onset of agranulocytosis. A baseline comprehensive metobolic panel (CMP) to assess hepatic status would not be unreasonable due to the potential for hepatitis.

Subtotal thyroidectomy is utilized for long-term control of hyperthyroidism. Preparation of the patient for a subtotal thyroidectomy includes pretreatment with methimazole to achieve a nearly euthyroid status. Supersaturated potassium iodide is then added on a daily basis approximately 2 weeks before surgery and discontinued postoperatively. Alternatively, atenolol can be started 1 to 2 weeks before surgery to reduce resting heart rate. Supersaturated potassium iodide is also dosed and discontinued postoperatively. The rationale behind these management plans is to reduce complications associated with perioperative exacerbation of hyperthyroidism.

Complications of subtotal thyroidectomy include hypothyroidism due to the decreased secretory potential of T4. Hypothyroidism remains the most common complication associated with subtotal thyroidectomy. The proximity of the parathyroid glands to the thyroid gland can result in removal of parathyroid glands along with thyroid tissue, resulting in hypoparathyroidism. Due to the risk of iatrogenic injury to the recurrent laryngeal nerve, vocal cord paralysis is also a complication of subtotal thyroidectomy. All of these complications should be discussed with the patient, and the discussion should be documented.

Primary Prevention

Smoking cessation, control of alcohol consumption, and thyroid autoimmunity (positive antibody alone) are listed among measures of primary prevention of thyroid disorders.

Risk factors

Risk factors for hyperthyroidism, include:

  • A family history, particularly of Graves’ disease
  • Female sex
  • A personal history of certain chronic illnesses, such as type 1 diabetes, pernicious anemia and primary adrenal insufficiency

Secondary Prevention

Patients should be educated on the importance of compliance with therapy and educated on the signs and symptoms of extreme hyperthyroidism (thyroid storm).

Signs or Symptoms

Hyperthyroidism can mimic other health problems, which can make it difficult for your doctor to diagnose. It can also cause a wide variety of signs and symptoms, including:

  • Unintentional weight loss, even when your appetite and food intake stay the same or increase
  • Rapid heartbeat (tachycardia) — commonly more than 100 beats a minute
  • Irregular heartbeat (arrhythmia)
  • Pounding of your heart (palpitations)
  • Increased appetite
  • Nervousness, anxiety and irritability
  • Tremor — usually a fine trembling in your hands and fingers
  • Sweating
  • Changes in menstrual patterns
  • Increased sensitivity to heat
  • Changes in bowel patterns, especially more frequent bowel movements
  • An enlarged thyroid gland (goiter), which may appear as a swelling at the base of your neck
  • Fatigue, muscle weakness
  • Difficulty sleeping
  • Skin thinning
  • Fine, brittle hair

Older adults are more likely to have either no signs or symptoms or subtle ones, such as an increased heart rate, heat intolerance and a tendency to become tired during ordinary activities.

Graves’ ophthalmopathy

Sometimes an uncommon problem called Graves’ ophthalmopathy may affect your eyes, especially if you smoke. This disorder makes your eyeballs protrude beyond their normal protective orbits when the tissues and muscles behind your eyes swell. Eye problems often improve without treatment.

Signs and symptoms of Graves’ ophthalmopathy include:

  • Dry eyes
  • Red or swollen eyes
  • Excessive tearing or discomfort in one or both eyes
  • Light sensitivity, blurry or double vision, inflammation, or reduced eye movement
  • Protruding eyeballs


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Hyperthyroidism is classified according to the origin of the lesion into primary, secondary, and tertiary hyperthyroidism. Grave’s disease, toxic thyroid nodule, thyroid adenoma and multinodular goiter cause primary hyperthyroidism. Secondary hyperthyroidism is caused by pituitary adenoma or by intracranial tumors pressing pituitary gland, while the tertiary hyperthyroidism is caused by intracranial tumors or masses involving hypothalamus.

Typical Test

Physical examination

Hyperthyroidism may manifest as weight loss despite an increased appetite, palpitation, nervousness, tremors, dyspnea, fatigability, diarrhea or increased GI motility, muscle weakness, heat intolerance, and diaphoresis. The signs and symptoms of thyroid hormone exposure to peripheral tissues reflect a hypermetabolic state. A patient with hyperthyroidism classically presents with signs and symptoms that reflect this state of increased metabolic activity. Common symptoms that a patient may report include unintentional weight loss despite unchanged oral intake, palpitations, diarrhea or increased frequency of bowel movements, heat intolerance, diaphoresis, and/or menstrual irregularities.

Physical examination of the thyroid may or may not reveal an enlarged thyroid (referred to as goiter). The thyroid may be diffusely enlarged, or one or more nodules may be palpated. The thyroid may be painless to palpation or extremely tender to even light palpation.

Laboratory workup and imaging

Thyroid stimulating hormone (TSH) is the initial diagnostic test of choice and is considered the best screening test for assessing pathology of the thyroid and for the monitoring of thyroid replacement therapy. Due to the negative feedback that T3 and T4 exert on the pituitary gland, elevated T3 and/or elevated T4 will cause decreased TSH production from the anterior pituitary gland. Abnormal TSH is often followed up with a measurement of free T4 and/or free T3. Concerns for an autoimmune process such as Graves’ disease will warrant further evaluation by assessing serum levels of TSH-receptor antibodies.

TSH levels in the context of acute illness should be interpreted with more discretion as TSH levels are considerably more susceptible to the effects of illness.

Hyperthyroidism is a common etiology for atrial fibrillation, thus further workup with an ECG may be warranted, especially in a patient complaining of palpitations. Obtaining troponin levels is not routine unless the clinical presentation warrants further cardiac ischemic workup, for example, active chest pain, among others.

Radiological diagnostics such as chest x-rays serve little diagnostic utility in the management of hyperthyroidism. Diagnostics such as ultrasound are not useful in diagnosing hyperthyroidism, but the ultrasound findings of nodules could potentially determine an etiology.

Since a majority of cases of hyperthyroidism are due to Graves disease or toxic multinodular goiter, confirmation of the diagnosis can be made based on history, clinical findings, and palpating of the thyroid. In cases of diffuse goiter or no thyroid enlargement, a 24-hour radioactive iodine uptake (RAIU) is needed to distinguish between Graves disease and other hyperthyroidism etiologies. Radioactive iodine uptake is the percentage of iodine-131 retained by the thyroid after 24 hours. For the typical western diet, the normal range of RAIU is typically 10% to 30%.

Graves’ disease, toxic multinodular goiter, and thyroid adenoma are etiologies of hyperthyroidism with increased RAIU, reflecting an increased synthesis of thyroid hormone. Subacute thyroiditis, painless thyroiditis, iodine-induced hyperthyroidism, and factitious hyperthyroidism have decreased RAIU. Thyroiditis represents a disruption of the thyroid follicles with subsequent release of thyroid hormone. Since there is no increased synthesis of thyroid hormone, RAIU will be low in thyroiditis.

If RAIU is not available or is contraindicated, then measurement of thyroid receptor antibodies can be used as an alternative test for diagnosis of Graves disease.

A radioisotope thyroid scan is a diagnostic tool which utilizes technetium-99m pertechnetate as a radioactive tracer. The technetium-99m pertechnetate is taken up by the thyroid gland by the sodium-iodide symporter. The scan itself assesses the functional activity of thyroid nodules, classifying as either “cold” (hypofunctioning), “warm” (isofunctioning), or “hot” (hyperfunctioning). “Cold” nodules raise concern for potential malignancy due to ineffective uptake of iodide and synthesis of thyroid hormone typically seen in thyroid carcinomas.





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