Hyperthyroidism – Causes, Symptoms, Diagnosis, Treatment

Hyperthyroidism
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Hyperthyroidism is a condition that occurs due to excessive production of thyroid hormone by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerancediarrhea, enlargement of the thyroid, and weight loss. Symptoms are typically less in the old and during pregnancy. An uncommon complication is a thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature and often results in death. The opposite is hypothyroidism when the thyroid gland does not make enough thyroid hormone

Causes of Hyperthyroidism

The major causes in humans are

  • Graves’ disease. An autoimmune disease (usually, the most common etiology with 50-80% worldwide, although this varies substantially with location- i.e., 47% in Switzerland (Horst et al., 1987) to 90% in the USA (Hamburger et al. 1981)). Thought to be due to varying levels of iodine in the diet. It is eight times more common in females than males and often occurs in young females, around 20 – 40 years of age.
  • Toxic thyroid adenoma (the most common etiology in Switzerland, 53%, thought to be atypical due to a low level of dietary iodine in this country)
  • Toxic multinodular goiter

High blood levels of thyroid hormones (most accurately termed hyperthyroxinemia) can occur for a number of other reasons

  • Inflammation of the thyroid is called thyroiditis. There are several different kinds of thyroiditis including Hashimoto’s thyroiditis (Hypothyroidism immune-mediated), and subacute thyroiditis (de Quervain’s). These may be initially associated with secretion of excess thyroid hormone but usually progress to gland dysfunction and, thus, to hormone deficiency and hypothyroidism.
  • Oral consumption of excess thyroid hormone tablets is possible (surreptitious use of thyroid hormone), as is the rare event of consumption of ground beef contaminated with thyroid tissue, and thus thyroid hormone (termed “hamburger hyperthyroidism”). Pharmacy compounding errors may also be a cause.
  • Amiodarone, an antiarrhythmic drug, is structurally similar to thyroxine and may cause either under-or overactivity of the thyroid.
  • Postpartum thyroiditis (PPT) occurs in about 7% of women during the year after they give birth. PPT typically has several phases, the first of which is hyperthyroidism. This form of hyperthyroidism usually corrects itself within weeks or months without the need for treatment.
  • A struma ovarii is a rare form of monodermal teratoma that contains mostly thyroid tissue, which leads to hyperthyroidism.
  • Excess iodine consumption notably from algae such as kelp.

Thyrotoxicosis can also occur after taking too much thyroid hormone in the form of supplements, such as levothyroxine (a phenomenon known as exogenous thyrotoxicosis, alimentary thyrotoxicosis, or occult factitial thyrotoxicosis).

Hypersecretion of thyroid-stimulating hormone (TSH), which in turn is almost always caused by a pituitary adenoma, accounts for much less than 1 percent of hyperthyroidism cases.

Symptoms of Hyperthyroidism

ConstitutionalWeight loss, heat intolerance, perspiration
CardiopulmonaryPalpitations, chest pain, dyspnea
NeuropsychiatricTremor, anxiety, double vision, muscle weakness
NeckFullness, dysphagia, dysphonia
MusculoskeletalExtremity swelling
ReproductiveIrregular menses, decreased libido, gynecomastia

Signs of Hyperthyroidism

Vital signsTachycardia, widened pulse pressure, fever
CardiovascularHyperdynamic precordium, CHF, atrial fibrillation, systolic flow murmur
OphthalmologicWidened palpebral fissure, periorbital edema, proptosis, diplopia, restricted superior gaze
NeurologicTremor, hyperreflexia, proximal muscle weakness
DermatologicPalmar erythema, hyperpigmented plaques, or non-pitting edema of the tibia
NeckEnlarged or nodular thyroid

Symptoms of Hyperthyroidism

Generalized hypermetabolism from hyperthyroidism causes increased Na+/K+-ATPase to promote thermogenesis. There is increased catecholamine secretion and, beta-adrenergic receptors are also upregulated in various tissues. As a result of the hyperadrenergic state, peripheral vascular resistance is decreased. In the heart, hyperthyroidism causes a decreased amount of phospholamban, a protein that normally decreases the affinity of calcium-ATPase for calcium in the sarcoplasmic reticulum. As a result of decreased phospholamban, there is increased Ca+ movement between the sarcoplasmic reticulum and cytosol, leading to increased contractility. Increased beta-receptors on the heart also lead to increased cardiac output.

General

  • Rapid pulse
  • Elevated blood pressure
  • Protruding eyes
  • Enlarged thyroid gland
  • Heat intolerance
  • Weight loss
  • Increased appetite
  • Increased sweating from cutaneous blood flow increase
  • Weakness
  • Fatigue
  • Onycholysis (separation of nails from nail beds)
  • Pretibial myxedema

Eyes

  • Lid lag (when looking down, sclera visible above cornea)
  • Lid retraction (when looking straight, sclera visible above the cornea)
  • Graves ophthalmopathy

Goiter

  • Diffuse, smooth, non-tender goiter
  • The audible bruit can be heard at the superior poles

Cardiovascular

  • Tachycardia (can be masked by patients taking beta-blockers)
  • Palpitations
  • An irregular pulse from atrial fibrillation
  • Hypertension
  • Widened pulse pressure because systolic pressure increases and diastolic pressure decreases
  • Heart failure (elderly patients)
  • Chest pain
  • Abnormal heart rhythms

Musculoskeletal

  • Fine tremors of the outstretched fingers. Face, tongue, and head can also be involved. Tremors respond well to treatment with beta-blockers.
  • Myopathy affecting proximal muscles. Serum creatine kinase levels can be normal
  • Osteoporosis caused by the direct effects of T3. Elderly patients can present with fractures.

Neuropsychiatric system

  • Restlessness
  • Anxiety
  • Depression
  • Emotional instability
  • Insomnia
  • Tremoulousness
  • Hyperreflexia

Conditions associated with hypothyroidism

  • Iodine deficiency
  • Cretinism
  • Wolff-Chaikoff effect
  • Subacute thyroiditis
  • Postpartum thyroiditis
  • Riedel thyroiditis
  • Hashimoto thyroiditis
  • Drug-induced 

Conditions associated with hyperthyroidism

  • Graves disease
  • Iodine excess
  • Struma ovarii
  • Thyrotropic pituitary adenoma
  • Jod-Basedow phenomenon
  • Drug-induced: amiodarone, lithium
  • Thyrotoxicosis and thyroid storm
  • Toxic multinodular goiter 
  • Thyroid adenoma 

Scoring (Burch, Wartofsky)

FEVER
99-1005
100-10110
101-10215
102-10320
103-10425
>10430
TACHYCARDIA
90-1105
110-12010
120-13015
130-14020
>14025
MENTAL STATUS
Normal
Mild agitation10
Extreme lethargy20
Coma, seizure30
CHF
Absent
Mild (edema)5
Moderate (rales, atrial fibrillation)10
Pulmonary edema15
GI
None
Nausea/vomiting, abdominal pain10
Jaundice20
PRECIPITATING EVENT
None
Present10
  • >45: thyroid storm
  • 25-44: impending thyroid storm
  • <25: unlikely thyroid storm
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Other tests may be performed to further evaluate your diagnosis. These include:

  • Cholesterol test – Your doctor may need to check your cholesterol levelsLow cholesterol can be a sign of an elevated metabolic rate, in which your body is burning through cholesterol quickly.
  • T4, free T4, T3 – These tests measure how much thyroid hormone (T4 and T3) is in your blood.
  • Thyroid-stimulating hormone level test – Thyroid-stimulating hormone (TSH) is a pituitary gland hormone that stimulates the thyroid gland to produce hormones. When thyroid hormone levels are normal or high, your TSH should be lower. An abnormally low TSH can be the first sign of hyperthyroidism.
  • Triglyceride test – Your triglyceride level may also be tested. Similar to low cholesterol, low triglycerides can be a sign of an elevated metabolic rate.
  • Thyroid scan and uptake – This allows your doctor to see if your thyroid is overactive. In particular, it can reveal whether the entire thyroid or just a single area of the gland is causing the overactivity.
  • Ultrasound – Ultrasounds can measure the size of the entire thyroid gland, as well as any masses within it. Doctors can also use ultrasounds to determine if a mass is solid or cystic.
  • CT or MRI scans – A CT or MRI can show if a pituitary tumor is present that’s causing the condition.

Treatment

The long-term outlook for hyperthyroidism depends on its cause. Some causes can go away without treatment.

Supportive measures

  • Volume resuscitation and cooling
  • Benzodiazepines for agitation

Beta-blockade

  • Propranolol 60-80mg PO q4h
  • Propranolol 0.5-1.0mg IV, repeat q15min then 1-2mg q3h
  • Esmolol continuous infusion

Antithyroid drugs 

Antithyroid drugs that work in the thyroid gland

  • Perchlorate – inhibits Na+/I- symporter – blocks iodide uptake
  • Thionamides – inhibits TPO – block thyroid hormone synthesis
  • Iodide > 5mg – inhibits Na+/I- symporter and TPO – blocks iodide uptake and thyroid hormone synthesis
  • Lithium – inhibits thyroid hormone release (off-label use for thyroid storm)

Antithyroid drugs that work in peripheral tissue – all these drugs inhibit the deiodinase enzymes. Deiodinase enzymes normally convert T4 into the active form T3. These drugs inhibit the conversion of T4 to T3 and reduce its activity.

  • Propylthiouracil (ethionamide)
  • Dexamethasone
  • Amiodarone
  • Propranolol
  • Thermostatic (antithyroid drugs) are drugs that inhibit the production of thyroid hormones, such as carbimazole (used in the UK) and methimazole (used in the US, Germany, and Russia), and propylthiouracil. Thyrostatics are believed to work by inhibiting the iodination of thyroglobulin by thyroperoxidase and, thus, the formation of tetraiodothyronine (T4).
  • Propylthiouracil also works outside the thyroid gland, preventing the conversion of (mostly inactive) T4 to the active form T3. Because thyroid tissue usually contains a substantial reserve of thyroid hormone, hydrostatics can take weeks to become effective and the dose often needs to be carefully titrated over a period of months, with regular doctor visits and blood tests to monitor results.
  • Antithyroid medications, such as methimazole (Tapazole), stop the thyroid from making hormones. They are a common treatment.
  • Radioactive iodine is given to over 70 percent of U.S. adults with hyperthyroidism, according to the American Thyroid Association. It effectively destroys the cells that produce hormones.

Hyperthyroidism can also cause your bones to become weak and thin, which can lead to osteoporosis. Taking vitamin D and calcium supplements during and after treatment can help strengthen your bones. Your doctor can tell you how much vitamin D and calcium to take each day.

Your doctor may refer you to an endocrinologist, who specializes in treating bodily hormone systems. Stress or infections can cause thyroid storms. A thyroid storm happens when a large amount of thyroid hormone is released and it results in a sudden worsening of symptoms. Treatment is important to prevent thyroid storms, thyrotoxicosis, and other complications.

Beta-blockers

Many of the common symptoms of hyperthyroidism such as palpitations, trembling, and anxiety is mediated by increases in beta-adrenergic receptors on cell surfaces. Beta-blockers, typically used to treat high blood pressure, are a class of drugs that offset this effect, reducing rapid pulse associated with the sensation of palpitations, and decreasing tremor and anxiety.

Some minimal effect on thyroid hormone production however also comes with Propranolol – which has two roles in the treatment of hyperthyroidism, determined by the different isomers of propranolol. L-propranolol causes beta-blockade, thus treating the symptoms associated with hyperthyroidism such as tremors, palpitations, anxiety, and heat intolerance. D-propranolol inhibits thyroxine deiodinase, thereby blocking the conversion of T4 to T3, providing some though minimal therapeutic effect. Other beta-blockers are used to treat only the symptoms associated with hyperthyroidism. Propranolol in the UK, and Metoprolol in the US, are most frequently used to augment treatment for hyperthyroid patients.

Diet

People with autoimmune hyperthyroidism should not eat foods high in iodine, such as edible seaweed and kelps. From a public health perspective, the general introduction of iodized salt in the United States in 1924 resulted in lower disease, goiters, as well as improving the lives of children whose mothers would not have eaten enough iodine during pregnancy which would have lowered the IQs of their children.

Surgery

Surgery (thyroidectomy to remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method, and because there is a risk of also removing the parathyroid glands, and of cutting the recurrent laryngeal nerve, making swallowing difficult, and even simply generalized staphylococcal infection as with any major surgery. Some people with Graves’ may opt for surgical intervention. This includes those that cannot tolerate medicines for one reason or another, people that are allergic to iodine, or people that refuse radioiodine.

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If people have toxic nodules treatments typically include either removal or injection of the nodule with alcohol.

Radioiodine

In iodine-131 (radioiodine) radioisotope therapy, which was first pioneered by Dr. Saul Hertz, radioactive iodine-131 is given orally (either by pill or liquid) on a one-time basis, to severely restrict, or altogether destroy the function of a hyperactive thyroid gland. This isotope of radioactive iodine used for ablative treatment is more potent than diagnostic radioiodine (usually iodine-123 or a very low amount of iodine-131), which has a biological half-life from 8–13 hours. Iodine-131, which also emits beta particles that are far more damaging to tissues at short range, has a half-life of approximately 8 days. Patients not responding sufficiently to the first dose are sometimes given an additional radioiodine treatment, at a larger dose. Iodine-131 in this treatment is picked up by the active cells in the thyroid and destroys them, rendering the thyroid gland mostly or completely inactive.

Common Questions Frequently Asked By Patients

How is the test used?

The thyroid-stimulating hormone (TSH) test is often the test of choice for initially evaluating thyroid function and/or symptoms of a thyroid disorder, including overactive or underactive thyroid (hyperthyroidism or hypothyroidism).

A TSH test is frequently ordered along with or prior to a free T4 test. Other thyroid tests that may be ordered include total or free T3 tests and thyroid antibodies (if autoimmune-related thyroid disease is suspected). TSH, free T4 and sometimes free T3 may be ordered together as a thyroid panel. Total T3 and free T3 should not both be ordered.

TSH testing may be used with free T4 and sometimes total or free T3 tests to:

  • Help diagnose a thyroid disorder in a person with signs and symptoms
  • Monitor thyroid replacement therapy in people with hypothyroidism
  • Monitor anti-thyroid treatment in people with hyperthyroidism
  • Help evaluate the function of the pituitary gland (occasionally)

At present, screening the general population for thyroid disorders is not recommended. However, expert opinions vary on this. In 2015, the U.S. Preventive Services Task Force found insufficient evidence to recommend for or against routine screening for thyroid disease in asymptomatic adults.

On the other hand, guidelines released in 2012 by the American Thyroid Association and the American Association of Clinical Endocrinologists summarize recommendations endorsed by several societies. They say that screening for hypothyroidism should be considered in people over the age of 60. Because the signs and symptoms of both hypothyroidism and hyperthyroidism are so similar to those seen in many common disorders, healthcare practitioners often need to rule out thyroid disease even though the patient has another problem.

When is it ordered?

A healthcare practitioner may order a TSH test when someone has signs and symptoms of hyperthyroidism or hypothyroidism and/or when a person has an enlarged thyroid gland (goiter) or thyroid nodule.

Signs and symptoms of hyperthyroidism may include:

  • Increased heart rate
  • Anxiety
  • Weight loss
  • Difficulty sleeping
  • Tremors in the hands
  • Weakness
  • Diarrhea (sometimes)
  • Light sensitivity, visual disturbances
  • There may be puffiness around the eyes with dryness, irritation, and, in some cases, bulging of the eyes.
  • Menstrual irregularity in women

Signs and symptoms of hypothyroidism may include:

  • Weight gain
  • Dry skin
  • Constipation
  • Cold intolerance
  • Puffy skin
  • Hair loss
  • Fatigue
  • Menstrual irregularity in women and/or fertility problems in women

TSH may be ordered at regular intervals when an individual is being treated for a known thyroid disorder. When a person’s dose of thyroid medication is adjusted, the American Thyroid Association recommends waiting 6-8 weeks before testing the level of TSH again.

What does the test result mean?

TSH results may be evaluated with other thyroid testing results (i.e., free T4 and sometimes total or free T3).

A high TSH result may mean that:

  • The person tested has an underactive thyroid gland that is not responding adequately to the stimulation of TSH due to some type of acute or chronic thyroid dysfunction; Hashimoto thyroiditis is the most common cause of hypothyroidism.
  • A person with hypothyroidism or who has had their thyroid gland removed is receiving too little thyroid hormone replacement medication and the dose may need to be adjusted
  • A person with hyperthyroidism is receiving too much anti-thyroid medication and the dose needs adjusting
  • There is a problem with the pituitary gland, such as a tumor producing unregulated levels of TSH
  • A rare inherited disorder is present in which the body and/or pituitary do not respond normally to thyroid hormones, resulting in high TSH despite clinically normal thyroid function

A low TSH result may indicate:

  • An overactive thyroid gland (hyperthyroidism); Graves disease is the most common cause of hyperthyroidism.
  • Excessive amounts of thyroid hormone medication taken by those who are being treated for an underactive (or removed) thyroid gland
  • Insufficient anti-thyroid medication in a person being treated for hyperthyroidism; however, it may take a while for TSH production to resume after successful anti-thyroid treatment. This is why the American Thyroid Association recommends monitoring this treatment with tests for thyroid hormones (free T4 and total and free T3) as well as TSH levels.
  • Damage to the pituitary gland that prevents it from producing adequate amounts of TSH
  • People with thyroid cancer may be treated with medications intended to suppress thyroid hormones, so they may have a low TSH.

Whether high or low, an abnormal TSH indicates an excess or deficiency in the amount of thyroid hormone available to the body, but it does not indicate the reason why. An abnormal TSH test result is usually followed by additional testing to investigate the cause of the increase or decrease.

The following table summarizes some examples of typical test results and their potential meaning.

NOTE: LABORATORY RESULTS MUST ALWAYS BE CORRELATED WITH THE CLINICAL FINDINGS OF THE PATIENT.
TSHFREE T4TOTAL OR FREE T3MOST LIKELY DIAGNOSIS
NormalNormalNormalNormal thyroid function (e.g., “euthyroid”)
Normal or decreasedNormal or decreasedDecreasedNormal adjustment in thyroid function due to illness (nonthyroidal illness or sick euthyroid syndrome)
IncreasedNormalNormalSubclinical hypothyroidism1; in a person with hypothyroidism on treatment, not enough thyroid hormone is being given
IncreasedDecreasedNormal of decreasedHypothyroidism resulting from a problem with the thyroid gland itself (primary hypothyroidism)
Normal or increasedIncreasedIncreasedHyperthyroidism resulting from a problem with the pituitary gland signals (central hyperthyroidism) or from a problem with the thyroid hormone receptor (thyroid hormone resistance)
DecreasedNormalNormalSubclinical hyperthyroidism2; in a person with hypothyroidism, too much thyroid hormone is being given
DecreasedNormalIncreasedHyperthyroidism resulting from the thyroid gland making too much active thyroid hormone T3 (uncommon, also known as T3 toxicosis)
DecreasedIncreasedIncreasedHyperthyroidism resulting from the gland making too much thyroid hormones (primary hyperthyroidism)
DecreasedDecreasedDecreasedHypothyroidism resulting from a problem with the hypothalamus or pituitary signals that govern the thyroid gland (central hypothyroidism)
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In affected adults, the diagnosis of subclinical hypothyroidism is applied when the TSH level is elevated and the free T4 level is normal on repeat testing over a number of weeks or months. Adults with subclinical hypothyroidism may have few or no overt symptoms of hypothyroidism. However, subclinical hypothyroidism places affected adults at somewhat increased risk for an elevated LDL cholesterol level, increased risk for cardiovascular disease, and reduced mental acuity.

In affected adults, the diagnosis of subclinical hyperthyroidism is applied when the TSH level is decreased and the free T4 level and T3 levels are normal on repeat testing over a number of weeks or months. Adults with subclinical hyperthyroidism may have few or no overt symptoms of hyperthyroidism. However, subclinical hyperthyroidism places affected persons at somewhat increased risk for atrial fibrillation and osteoporosis.

Is there anything else I should know?

It is important to note that TSH, free T4, and free T3 tests are a “snapshot” of what is occurring within a dynamic system. An individual person’s thyroid testing results may vary and may be affected by:

  • Increases, decreases, and changes (inherited or acquired) in the proteins that bind thyroid hormone (This is important for tests that measure total T3 but it is not likely important for free T4 and free T3 tests, which measure the thyroid hormones that are not bound to protein.)
  • Pregnancy
  • Liver disease
  • Systemic illness
  • Rarely, resistance to thyroid hormones

Illnesses not directly related to the thyroid, “nonthyroidal illnesses,” can affect thyroid hormone levels. In particular, the level of T3 can be low in nonthyroidal illness (NTI). Typically, the thyroid hormone levels return to normal after a person recovers from the nonthyroidal illness. Historically, this condition was referred to as “euthyroid sick syndrome” but that term is controversial because there is some question as to whether those affected have a thyroid gland that is functioning normally (euthyroid). Nevertheless, there is little data to support the treatment of NTI with thyroid hormone.

What medications can affect a TSH test?

  • Many multivitamins, supplements (especially hair and nail), and over-the-counter and prescription medications may affect thyroid test results and their use should be discussed with your healthcare practitioner prior to testing. For example, biotin (vitamin B7) can interfere with some lab tests, so your healthcare practitioner may advise you to refrain from taking biotin or supplements that contain biotin for a few days before having blood drawn for a TSH test. If you have a procedure done in which fluorescein dyes are injected into your blood (e.g., angiography), you may need to wait a few days before having a TSH test done.

Do healthcare practitioners test TSH during pregnancy?

  • Pregnancy causes normal changes in the function of many endocrine glands, including the thyroid gland. Healthcare practitioners do not generally test asymptomatic women, but those with symptoms and/or a known thyroid disorder will usually be tested at intervals to detect and monitor hyperthyroidism or hypothyroidism during pregnancy and after delivery of the baby.
  • Some experts have advocated screening pregnant women for elevated TSH during the first trimester (or preconception) even if they do not have a history of thyroid disease. However, most guidelines do not support this course of action.

For more information, see the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) webpage: Thyroid Disease and Pregnancy.

My newborn had a TSH test done. Why?

  • A TSH test may be used to screen for congenital hypothyroidism. Screening for this condition is routinely performed in the United States on newborns soon after birth as part of each state’s newborn screening program. Congenital hypothyroidism occurs when a baby is born with an underactive thyroid gland or a thyroid gland that is not located where it should be or is missing completely. For more details, see the information at the Hormone Health Network’s webpage on Congenital Hypothyroidism.

Are there things that I can do to raise or lower my TSH level?

  • In general, TSH does not respond to lifestyle changes. What is important is that the pituitary and thyroid glands are healthy and working together to produce appropriate amounts of thyroid hormone.

What is a 3rd generation TSH and an ultrasensitive TSH?

  • Almost all laboratories currently use “third-generation” or “ultrasensitive” TSH assays today.
  • The original tests (immunoassays) for TSH were not sensitive enough to differentiate the very low levels seen in patients with hyperthyroidism from levels seen in normal euthyroid individuals. In the 1980s, more sensitive assays (“second generation”) were developed and these were able to identify patients with TSH levels that were suppressed due to the excess amounts of free T4 present in hyperthyroidism. In the 1990s, TSH assays were made even more sensitive and, although these were able to measure even lower levels, they were widely adopted because they performed much better than the second-generation assays in the range that was important for differentiating normal from hyperthyroid.

References

Hyperthyroidism

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