Introduction
Background
Thyrotoxicosis is the hypermetabolic condition associated with elevated levels of free thyroxine (FT4) and/or free triiodothyronine (FT3). Hyperthyroidism includes diseases that are a subset of thyrotoxicosis, that are caused by excess synthesis and secretion of thyroid hormone by the thyroid; they are not associated with exogenous thyroid hormone intake and subacute thyroiditis. Most clinicians, exclusive of endocrinologists, use the terms hyperthyroidism and thyrotoxicosis interchangeably. This article discusses the causes of thyrotoxicosis associated with hyperthyroidism (excess synthesis and release of thyroid hormone) and surreptitious use of thyroid hormone. Subacute thyroiditis is discussed in the article Subacute Thyroiditis.
The most common forms of hyperthyroidism include diffuse toxic goiter (Graves disease), toxic multinodular goiter (Plummer disease), and toxic adenoma. Together with subacute thyroiditis, these conditions constitute 85-90% of all causes of thyrotoxicosis. Table 1 contains a list of hyperthyroid conditions associated with thyrotoxicosis.
Table 1. Common, Less Common, and Uncommon Forms of Thyrotoxicosis and Hyperthyroidism
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Table
Common Forms (85-90% of cases) Radioactive iodine uptake over neck
Diffuse toxic goiter (Graves disease) Increased
Toxic multinodular goiter (Plummer disease) Increased
Thyrotoxic phase of subacute thyroiditis Decreased
Toxic adenoma Increased
Less Common Forms
Iodide-induced thyrotoxicosis Variable
Thyrotoxicosis factitia Decreased
Uncommon Forms
Pituitary tumors producing thyroid-stimulating hormone Increased
Excess human chorionic gonadotropin (molar pregnancy/choriocarcinoma) Increased
Pituitary resistance to thyroid hormone Increased
Metastatic thyroid carcinoma Decreased
Struma ovarii with thyrotoxicosis Decreased
Common Forms (85-90% of cases) Radioactive iodine uptake over neck
Diffuse toxic goiter (Graves disease) Increased
Toxic multinodular goiter (Plummer disease) Increased
Thyrotoxic phase of subacute thyroiditis Decreased
Toxic adenoma Increased
Less Common Forms
Iodide-induced thyrotoxicosis Variable
Thyrotoxicosis factitia Decreased
Uncommon Forms
Pituitary tumors producing thyroid-stimulating hormone Increased
Excess human chorionic gonadotropin (molar pregnancy/choriocarcinoma) Increased
Pituitary resistance to thyroid hormone Increased
Metastatic thyroid carcinoma Decreased
Struma ovarii with thyrotoxicosis Decreased
Pathophysiology
The hypermetabolic effect of thyrotoxicosis affects every organ system. The pituitary gland stimulates the thyroid to make thyroid hormone, which is released into the circulation to reach every cell in the body. Thyroid hormone is necessary for normal growth and development, and it regulates cellular metabolism. Excess thyroid hormone causes an increase in the metabolic rate that is associated with increased total body heat production and cardiovascular activity (increased heart contractility, heart rate, vasodilation).
Graves disease
The most common cause of thyrotoxicosis is Graves disease (50-60%). Graves disease is an organ-specific autoimmune disorder characterized by a variety of circulating antibodies, including common autoimmune antibodies, as well as anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-TG) antibodies. The most important autoantibody is thyroid-stimulating immunoglobulin (TSI). TSI is directed toward epitopes of the thyroid-stimulating hormone (TSH) receptor and acts as a TSH-receptor agonist. Similar to TSH, TSI binds to the TSH receptor on the thyroid follicular cells to activate thyroid hormone synthesis and release and thyroid growth (hypertrophy). This results in the characteristic picture of Graves thyrotoxicosis, with a diffusely enlarged thyroid, very high radioactive iodine uptake, and excessive thyroid hormone levels compared with a healthy thyroid. See the images below.
Iodine 123 (123I)...
Iodine 123 (123I) nuclear scintigraphy: 123I scans of a normal thyroid gland (A) and common hyperthyroid conditions with elevated radioiodine uptake, including Graves disease (B), toxic multinodular goiter (C), and toxic adenoma (D).
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Iodine 123 (123I)...
Iodine 123 (123I) nuclear scintigraphy: 123I scans of a normal thyroid gland (A) and common hyperthyroid conditions with elevated radioiodine uptake, including Graves disease (B), toxic multinodular goiter (C), and toxic adenoma (D).
Color flow ultrasonogram in a patient with Graves...
Color flow ultrasonogram in a patient with Graves disease. Generalized hypervascularity is visible throughout the gland, which often can be heard as a hum or bruit with a stethoscope.
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Color flow ultrasonogram in a patient with Graves...
Color flow ultrasonogram in a patient with Graves disease. Generalized hypervascularity is visible throughout the gland, which often can be heard as a hum or bruit with a stethoscope.
Thyroid hormone levels can be extremely elevated in this condition. Clinical findings specific to Graves disease include thyroid ophthalmopathy (periorbital edema, chemosis [conjunctival edema], injection, proptosis) and, rarely, dermopathy over the lower extremities. This autoimmune condition may be associated with other autoimmune diseases, such as pernicious anemia, myasthenia gravis, vitiligo, adrenal insufficiency, and type 1 diabetes mellitus.
Subacute thyroiditis
The next most common cause of thyrotoxicosis is subacute thyroiditis (approximately 15-20%), a destructive release of preformed thyroid hormone. A typical nuclear scintigraphy scan shows no radioactive iodine uptake in the thyrotoxic phase of the disease. (See images below.) Thyroid hormone levels can be extremely elevated in this condition. This topic is discussed and a typical nuclear scintigraphy scan is shown in the article Subacute Thyroiditis.
Absence of iodine 123 (123123123I)...
Iodine 123 (123I) nuclear scintigraphy: 123I scans of a normal thyroid gland (A) and common hyperthyroid conditions with elevated radioiodine uptake, including Graves disease (B), toxic multinodular goiter (C), and toxic adenoma (D).
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Iodine 123 (123I)...
Iodine 123 (123I) nuclear scintigraphy: 123I scans of a normal thyroid gland (A) and common hyperthyroid conditions with elevated radioiodine uptake, including Graves disease (B), toxic multinodular goiter (C), and toxic adenoma (D).
* A toxic multinodular goiter demonstrates an enlarged thyroid with multiple nodules and areas of increased and decreased isotope uptake, as in the image above.
* Subacute thyroiditis usually demonstrates very low123 I isotope uptake.
* A toxic adenoma demonstrates a solitary hot nodule with suppression of function in the surrounding normal thyroid tissue, as shown above.
* If a dominant nodule is found upon examination of a patient with thyrotoxicosis, obtain an123 I thyroid scan to assure that the dominant nodule is functioning. If the nodule is cold, perform a biopsy on the nodule by fine-needle aspiration to exclude concomitant malignancy.
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Absence of iodine 123 (123123100.5°F) or a severe sore throat.
* The use of radioisotopes to diagnose and treat thyroid disease exposes the practitioner to certain risks. Examples of potential problems include the administration of isotopes to patients who are pregnant or may become pregnant in the near future. The Nuclear Regulatory Commission and specific state agencies maintain specific regulations on the proper use of radioisotopes, and practitioner noncompliance may lead to fines and other disciplinary actions.
