Hyperthyroidism

Reviewed on 9/29/2022

What Is Hyperthyroidism?

The thyroid gland produces, stores, and releases hormones that control the body's metabolism. Hyperthyroidism occurs when there is excess thyroid hormone in the blood.
Picture of the thyroid gland produces, stores, and releases hormones that control the body's metabolism. by 3D4Medical.com, David Mack/Photo Researchers Inc

Hyperthyroidism refers to any condition in which there is too much thyroid hormone in the body. It is sometimes referred to as overactive thyroid.

  • Excess thyroid hormone levels can increase metabolism (how energy is used), and increase the risk of other health issues such as:
  • Graves' disease is a common cause of hyperthyroidism.
  • Radioactive iodine ablation is the most common treatment for overactive thyroid.

What Causes Hyperthyroidism?

Common causes of hyperthyroidism in adults include the following:

  • Diffuse Toxic Goiter (Graves' disease)
    • Overactivity of the entire thyroid gland caused by antibodies in the blood which stimulate the thyroid to grow and secrete excessive amounts of thyroid hormone
  • Toxic Adenoma ("hot nodule")
    • A dominant thyroid nodule, or lump, is overactive and secretes excess thyroid hormone
  • Toxic Multinodular Goiter (Plummer's disease)
    • One or more nodules or lumps in the thyroid becomes overactive
  • Subacute Thyroiditis
    • Hyperthyroid phase of subacute thyroiditis, caused by viral infection or postpartum inflammatory process
    • Due to thyroid inflammation, excess amounts of the hormone are released into the blood circulation
    • More than 90% of affected individuals will go back to normal thyroid function without treatment
  • Drug-Induced Hyperthyroidism
    • Iodine-induced hyperthyroidism, common in the older population, typically in the setting of preexisting nontoxic nodular goiter
    • Amiodarone (Cordarone)
    • Iodine-containing contrast material used in radiology studies

What Are Hyperthyroidism Symptoms and Signs?

Symptoms and their severity depend on the duration and extent of thyroid hormone excess, and the age of the individual. Individuals may experience:

  • Nervousness and irritability
  • Palpitations and tachycardia
  • Heat intolerance or increased sweating
  • Tremor
  • Weight loss or gain
  • Increase in appetite
  • Frequent bowel movements or diarrhea
  • Lower leg swelling
  • Sudden paralysis
  • Shortness of breath with exertion
  • Decreased menstrual flow
  • Impaired fertility
  • Sleep disturbances (including insomnia)
  • Changes in vision:
    • Photophobia, or light sensitivity
    • Eye irritation with excess tears
    • Diplopia, or double vision
    • Exophthalmos, or forward protrusion of the eyeball
  • Fatigue and muscle weakness
  • Thyroid enlargement
  • Pretibial myxedema (fluid buildup in the tissues about the shin bone; may be seen with Grave's disease)

How Do Doctors Diagnose Hyperthyroidism?

Characteristic symptoms and physical signs can suggest that hyperthyroidism may be present; however, laboratory evaluation is necessary to establish the diagnosis and cause of hyperthyroidism.

Diagnostic lab tests performed on a blood sample include:

  • Thyroid-stimulating hormone (TSH)
    • TSH level will be low in hyperthyroidism
    • TSH assay is the most sensitive test for the diagnosis of hyperthyroidism
  • Free T4 (free thyroxine)
    • The free or unbound thyroid hormone in the blood will be high in hyperthyroidism
    • In patients with unstable thyroid states, T4 levels are sometimes more accurate than TSH as indicators of thyroid status
    • With mild hyperthyroidism, the free T4 will remain in the normal range.
  • Triiodothyronine (T3) radioimmunoassay (RIA) or free T3
    • This form of thyroid hormone is 20 to 50 times more biologically active than T4
    • T4 is converted in many organs (i.e. liver, kidneys) to the more bioactive T3 with the removal of iodine by an enzyme called a deiodinase
    • T3 is often elevated to a relatively higher level than T4 in severe hyperthyroidism.
  • Thyroxine (T4)
    • Total T4 in the blood measures both free and bioactive protein-bound T4
  • Thyroid autoantibodies: TSH receptor antibodies (TRAb) or thyroid-stimulating immunoglobulins (TSI)
    • These antibodies are present in over half of patients with Graves' disease
    • TSI binds to the TSH receptor and activates the receptor, leading to increased production and release of thyroid hormone into the blood
    • TSI stimulates the thyroid gland to grow
    • TRAb binds to the TSH receptor and blocks TSH from binding, resulting in reduced THS receptor function and reduced thyroid hormone production.

If lab tests indicate hyperthyroidism, imaging tests may be used to further determine the cause.

Radioactive iodine thyroid scan-with either I-231 or 99mTc. In this test, if the patient's thyroid is scanned, they will swallow radioactive iodine or have an injection of 99mTc. The patient will then wait for the isotope to be taken up by the thyroid gland, and images will be taken to show the amount of isotope taken up by the thyroid.

  • This test helps to determine the cause of hyperthyroidism and to assess whether any thyroid lumps or nodules are actively producing thyroid hormone
  • Increased uptake of the isotope will be seen in a generalized pattern in Graves' disease (See Figure 1 below), and in a localized pattern in toxic nodular goiter (See Figure 2 below)
  • Overall decreased uptake of iodine will be seen in subacute thyroiditis (See Figure 3 below)
  • "Cold nodules" (swellings in the thyroid gland that do not take up the radioactive isotope on the thyroid scan) may require additional evaluation by fine needle aspiration biopsy to exclude a tumor.

False positive tests: high total T4 and total T3 levels or suppressed TSH levels

  • Estrogen administration or pregnancy can raise levels of TBG (thyroxine-binding globulin), resulting in high total T4 and total T3 levels, but there are normal free T4 and free T3 estimates and normal results on sensitive TSH assay
  • Euthyroid hyperthyroxinemia (another condition in which thyroid hormone levels appear to be elevated without an excess function of thyroid hormones) may also be attributable tan inherited conditions of other abnormal binding proteins-albumin and prealbumin
  • Thyroid hormone resistance states
    • Increased serum T4 levels without hyperthyroidism, usually from an inherited condition.
  • Administration of corticosteroids, severe illness, pituitary dysfunction
    • These conditions may suppress the TSH level in the absence of hyperthyroidism

What Is the Treatment for Hyperthyroidism?

The treatments discussed here are for all causes of hyperthyroidism except for subacute thyroiditis. Subacute thyroiditis typically gets better without any specific treatment.

Treatment options for hyperthyroidism caused by Graves' disease or nodular thyroid disease are divided into two categories:

  1. treatments that decrease thyroid hormone production, and
  2. symptomatic treatment to alleviate the effects of excess thyroid hormone.

Although the most common treatment of overactive thyroid disease is radioactive iodine ablation, many patients are initially treated with antithyroid medication to normalize thyroid hormone levels prior to either radioactive iodine ablation or thyroidectomy.

Surgery is used to treat hyperthyroidism if the patient requires a quick reduction in thyroid hormone levels such as during pregnancy.

What Are Antithyroid Medications?

Medications to treat hyperthyroidism include:

The effects, indications, and risks of these medications are as follows:

  • Effects: 
    • Decreased thyroid hormone production
  • Indications:
    • Hyperthyroidism from multiple causes
    • Low doses of methimazole (<10-15mg/day) are safe in pregnancy or postpartum in a woman breastfeeding
    • Elderly persons or cardiac patients requiring 'pretreatment' with antithyroid medications before radioiodine therapy
  • Risks:
    • Skin rashes, agranulocytosis (compromised immune system), and hepatitis
    • Increased risk of liver failure. FDA black box warnings restrict the use of PTU to those patients who cannot tolerate methimazole or are in the first trimester of pregnancy.

What Is Radioactive Iodine?

  • Effect:
    • Damages the thyroid cells that make thyroid hormone
    • Most common permanent treatment of hyperthyroidism in the U.S.
  • Indications:
    • Graves' disease
    • Toxic multinodular goiter
    • Toxic adenoma
  • Contraindications:
    • During pregnancy, radioactive iodine may destroy fetal thyroid tissue
    • Breastfeeding women may pass radioactive iodine through breast milk
    • A 6-month waiting period before pregnancy is suggested after therapy
  • Risks:
    • Most patients treated become hypothyroid and require lifelong thyroid hormone replacement therapy
    • Elderly patients and cardiac patients have an increased risk of 131I-(radioactive iodine)-induced thyroiditis

What Are Surgical Interventions for Hyperthyroidism?

Surgical options

  • Overactive nodule(s) of a toxic adenoma or toxic multinodular goiter: Removal of part of the thyroid gland containing an overactive nodule. The entire thyroid may be removed if there are multiple, bilateral overactive nodules or if the goiter is enlarged.
  • Generalized overactive thyroid gland of Graves' disease: Removal of the entire thyroid gland.

Risks of thyroid surgery

  • Most patients will remain euthyroid (having normal thyroid function) after thyroid lobectomy.
  • Patients will become hypothyroid after total thyroidectomy and require thyroid hormone replacement therapy
  • There is a small risk of recurrent hyperthyroidism if a large amount of remaining thyroid gland is left after the surgery.
  • There is a small risk of damage to structures near the thyroid, including the nerve to the voice box, and the glands that regulate calcium levels in the blood.

What Therapies Decrease Hyperthyroid Symptoms and Signs?

Beta-adrenergic blocking agents

Can Hyperthyroidism Be Caused by Other Medical Treatments?

Amiodarone therapy

  • Amiodarone is a drug used in the treatment of abnormal heart rhythms.
  • Amiodarone tablets (Cordarone, Pacerone) contain iodine, and up to 10% of people taking this medication develop abnormalities in thyroid function.
    • Patients taking amiodarone should have baseline thyroid function tests before starting amiodarone therapy
    • Type 1 amiodarone-induced hyperthyroidism (Jod-Basedow phenomenon) causes an increased production of thyroid hormones due to the iodine portion of amiodarone
    • Type 2 amiodarone-induced hyperthyroidism resembles destructive thyroiditis, where increased amounts of thyroid hormone are released

IV contrast agents for CT scans

  • Excess iodine in the contrast material used for CT scans may cause increased production of thyroid hormone.

What Is the Prognosis of Hyperthyroidism?

Hyperthyroidism is typically treatable and rarely fatal. However, complications can arise with untreated hyperthyroidism. Untreated hyperthyroidism may have the following complications:

Complications may also arise from side effects of therapies, including radioactive iodine, surgery, and thyroid hormone replacement therapy.

Pictures of Hyperthyroidism

X=Ray Image of Radioactive Scan of Toxic Multinodular Goiter

Figure 1 Above: Radioactive iodine scan of a patient with toxic multinodular goiter. Note the patchy and darker appearance of the nodules that are producing excess amounts of thyroid hormone. Compare this to the normal scan shown in Figure 3.

Radioactive Iodine Scan Image of Subacute Thyroiditis

Figure 2 Above: Radioactive iodine scan of a patient with subacute thyroiditis during the hyperthyroid phase. Note that there is very little iodine uptake in the thyroid. This is due to inflammation of the thyroid causing release of stored thyroid hormone (causing elevated thyroid hormone levels in the blood) and reduced iodine uptake.

Radioactive Iodine Thyroid Scan Image of Normal Thyroid and Image of Patient with Grave's Disease

Figure 3 Above: Radioactive iodine thyroid scan. Comparison between scans from the normal patient and a patient with Graves' disease. Note the overall increased uptake throughout the enlarged thyroid gland in a patient with Graves' disease.

Thyroidectomy (Thyroid Surgery) Definition

Thyroidectomy: The surgical removal of part or all of the thyroid gland.

Subtotal thyroidectomy, the more commonly performed operation, involves removal of only a part of the gland. This procedure may be done to:

  • Remove a tumor from the thyroid,
  • Reduce the mass of a goitrous (enlarged) thyroid gland, or
  • Treat hyperthyroidism (excess production of thyroid hormone).

The goal in the case of hyperthyroidism is to leave just enough thyroid tissue to make a normal amount of thyroid hormone. If too much thyroid is removed, the patient will produce too little thyroid hormone (hypothyroidism) and need treatment to return the thyroid status to normal (euthyroid) status. The possible complications of thyroid surgery include vocal cord paralysis and accidental removal of the parathyroid glands (located behind the thyroid gland), resulting in low calcium levels (the parathyroid glands regulate calcium).

Subtotal thyroidectomy is appropriate in some people with hyperthyroidism, especially those with a large goiter, and it may also be indicated in cases with a coexistent thyroid nodule whose nature is unclear. The patient is treated with an antithyroid drug until euthyroidism has been achieved and inorganic iodide is also usually administered for seven days before surgery to "cool down" the overactive thyroid gland. In surgical centers with the most experience, hyperthyroidism is cured in more than 98% of cases with low rates of complications. Surgery is more costly than nonsurgical therapy of hyperthyroidism (with an antithyroid drug or radioactive iodine).

SOURCE:
MedTerms.com. Thyroidectomy.

Reviewed on 9/29/2022
References
MedscapeReference.com. "Hyperthyroidism, Thyroid Storm, and Graves' Disease."