Which is an autoimmune disorder caused by hyperthyroidism is characterized by goiter and Exophthalmos?
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Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor. Diagnosis is clinical and with thyroid function tests. Treatment depends on cause. Show Hyperthyroidism can be classified on the basis of thyroid radioactive iodine uptake and the presence or absence of circulating thyroid stimulators (see table ). The most common causes overall include
Graves disease (toxic diffuse goiter), the most common cause of hyperthyroidism, is characterized by hyperthyroidism and one or more of the following:
Graves disease is caused by an autoantibody against the thyroid receptor for thyroid-stimulating hormone (TSH); unlike most autoantibodies, which are inhibitory, this
autoantibody is stimulatory, thus causing continuous synthesis and secretion of excess T4 and T3. Graves disease (like Hashimoto thyroiditis
Hashimoto Thyroiditis Hashimoto thyroiditis is chronic autoimmune inflammation of the thyroid with lymphocytic infiltration. Findings include painless thyroid enlargement and symptoms of hypothyroidism. Diagnosis... read more ) sometimes occurs with other autoimmune disorders, including type 1 diabetes mellitus
Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more ,
vitiligo Vitiligo Vitiligo is a loss of
skin melanocytes that causes areas of skin depigmentation of varying sizes. Cause is unknown, but genetic and autoimmune factors are likely. Diagnosis is usually clear... read more The pathogenesis of infiltrative ophthalmopathy (responsible for the exophthalmos in Graves disease) is poorly understood but may result from immunoglobulins directed to the TSH receptors in the orbital fibroblasts and fat that result in release of proinflammatory cytokines, inflammation, and accumulation of glycosaminoglycans. Ophthalmopathy may also occur before the onset of hyperthyroidism or as late as 20 years afterward and frequently worsens or abates independently of the clinical course of hyperthyroidism. Typical ophthalmopathy in the presence of normal thyroid function is called euthyroid Graves disease. Toxic solitary or multinodular goiter (Plummer disease) sometimes results from TSH receptor gene mutations causing continuous thyroid activation. Patients with toxic nodular goiter have none of the autoimmune manifestations or circulating antibodies observed in patients with Graves disease. Also, in contrast to Graves disease, toxic solitary and multinodular goiters usually do not remit. Inappropriate TSH secretion is a rare cause. Patients with hyperthyroidism have essentially undetectable TSH except for those with a TSH-secreting anterior pituitary adenoma or pituitary resistance to thyroid hormone. TSH levels are high, and the TSH produced in both disorders is biologically more active than normal TSH. An increase in the alpha-subunit of TSH in the blood (helpful in differential diagnosis) occurs in patients with a TSH-secreting pituitary adenoma. Drug-induced hyperthyroidism can result from amiodarone, checkpoint inhibitors used in cancer therapy, alemtuzumab used in treatment of multiple sclerosis, or interferon-alfa, which may induce thyroiditis with hyperthyroidism and other thyroid disorders. Although more commonly causing hypothyroidism, lithium can rarely cause hyperthyroidism. Patients receiving these drugs should be closely monitored. Thyrotoxicosis factitia is hyperthyroidism resulting from intentional or accidental overingestion of thyroid hormone. Excess iodine ingestion causes hyperthyroidism with a low thyroid radioactive iodine uptake. It most often occurs in patients with underlying nontoxic nodular goiter (especially older patients) who are given drugs that contain iodine (eg, amiodarone) or who undergo radiologic studies using iodine-rich contrast agents. The etiology may be that the excess iodine provides substrate for functionally autonomous (ie, not under TSH regulation) areas of the thyroid to produce hormone. Hyperthyroidism usually persists as long as excess iodine remains in the circulation. Nonautoimmune autosomal dominant hyperthyroidism manifests during infancy. It results from mutations in the TSH receptor gene that produce continuous thyroid stimulation. Metastatic thyroid cancer is a possible cause. Overproduction of thyroid hormone occurs rarely from functioning metastatic follicular carcinoma, especially in pulmonary metastases. Struma ovarii develops when ovarian teratomas contain enough thyroid tissue to cause true hyperthyroidism. Radioactive iodine uptake occurs in the pelvis, and uptake by the thyroid is usually suppressed. In hyperthyroidism, serum T3 usually increases more than does T4, probably because of increased secretion of T3 as well as conversion of T4 to T3 in peripheral tissues. In some patients, only T3 is elevated (T3 toxicosis). T3 toxicosis may occur in any of the common disorders that cause hyperthyroidism, including Graves disease, multinodular goiter, and the autonomously functioning solitary thyroid nodule. If T3 toxicosis is untreated, the patient usually also develops laboratory abnormalities typical of hyperthyroidism (ie, elevated T4 and iodine-123 uptake). The various forms of thyroiditis commonly have a hyperthyroid phase followed by a hypothyroid phase. Symptoms and Signs of HyperthyroidismMost symptoms and signs are the same regardless of the cause. Exceptions include infiltrative ophthalmopathy and dermopathy, which occur only in Graves disease. The clinical presentation may be dramatic or subtle. A goiter or nodule may be present. Many common symptoms of hyperthyroidism are due to enhanced sensitivity to adrenergic hormones, such as nervousness, palpitations, hyperactivity, increased sweating, heat hypersensitivity, fatigue, increased appetite, weight loss, insomnia, weakness, and frequent bowel movements (occasionally diarrhea). Hypomenorrhea may be present. Signs may include warm, moist skin, tremor, tachycardia, widened pulse pressure, and atrial fibrillation. Older patients, particularly those with toxic nodular goiter, may present atypically (apathetic or masked hyperthyroidism) with symptoms more akin to
depression
Symptoms and Signs Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and often by decreased interest or pleasure in activities. Exact cause is unknown... read more or dementia Symptoms and Signs Dementia is chronic, global, usually irreversible deterioration of cognition. Diagnosis is clinical; laboratory and imaging tests are usually used to identify treatable causes. Treatment is... read more
. Most do not have exophthalmos or tremor. Atrial fibrillation
Atrial Fibrillation Atrial fibrillation is a rapid, irregularly irregular atrial rhythm. Symptoms include palpitations and sometimes weakness, effort intolerance, dyspnea, and presyncope. Atrial thrombi may form... read more , syncope, altered sensorium,
heart failure Heart Failure (HF)
Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular failure causes shortness of breath and fatigue, and right ventricular failure causes peripheral and abdominal fluid... read more Eye signs include stare, eyelid lag, eyelid retraction, and mild conjunctival injection and are largely due to excessive adrenergic stimulation. They usually remit with successful treatment. Infiltrative ophthalmopathy, a more serious development, is specific to Graves disease and can occur years before or after hyperthyroidism. It is characterized by orbital pain, lacrimation, irritation, photophobia, increased retro-orbital tissue, exophthalmos, and lymphocytic infiltration of the extraocular muscles, causing ocular muscle weakness that frequently leads to double vision. Infiltrative dermopathy, also called pretibial myxedema (a confusing term, because myxedema suggests hypothyroidism), is characterized by nonpitting infiltration by proteinaceous ground substance, usually in the pretibial area. It rarely occurs in the absence of Graves ophthalmopathy. The lesion is often pruritic and erythematous in its early stages and subsequently becomes brawny. Infiltrative dermopathy may appear years before or after hyperthyroidism. Thyroid stormThyroid storm is an acute form of hyperthyroidism that results from untreated or inadequately treated severe hyperthyroidism. It is rare, occurring in patients with Graves disease or toxic multinodular goiter (a solitary toxic nodule is a less common cause and generally causes less severe manifestations). It may be precipitated by infection, trauma, surgery, embolism, diabetic ketoacidosis, or preeclampsia. Thyroid storm causes abrupt florid symptoms of hyperthyroidism with one or more of the following: fever, marked weakness and muscle wasting, extreme restlessness with wide emotional swings, confusion, psychosis, coma, nausea, vomiting, diarrhea, and hepatomegaly with mild jaundice. The patient may present with cardiovascular collapse and shock. Thyroid storm is a life-threatening emergency requiring prompt treatment.
Diagnosis of hyperthyroidism is based on history, physical examination, and thyroid function tests. Serum TSH measurement is the best test because TSH is suppressed in hyperthyroid patients except in the rare instance when the etiology is a TSH-secreting pituitary adenoma or pituitary resistance to the normal inhibition by thyroid hormone. The cause can often be diagnosed clinically (eg, the presence of signs specific to Graves disease). If not, radioactive iodine uptake by the thyroid may be measured by using iodine-123. When hyperthyroidism is due to hormone overproduction, radioactive iodine uptake by the thyroid is usually elevated. When hyperthyroidism is due to thyroiditis, iodine ingestion, or overtreatment with thyroid hormones, radioactive iodine uptake is low. Inappropriate TSH secretion is uncommon. The diagnosis is confirmed when hyperthyroidism occurs with elevated circulating free T4 and T3 concentrations and normal or elevated serum TSH. If thyrotoxicosis factitia is suspected, serum thyroglobulin can be measured; it is usually low or low-normal—unlike in all other causes of hyperthyroidism. Subclinical hyperthyroidism is low serum TSH in patients with normal serum free T4 and T3 and absent or minimal symptoms of hyperthyroidism. Patients with serum TSH < 0.1 microU/mL (0.1 mU/L) have an increased incidence of atrial fibrillation (particularly older patients), reduced bone mineral density, increased fractures, and increased mortality. Patients with serum TSH that is only slightly below normal are less likely to have these features.
In the United States, iodine-131 is the most common treatment for hyperthyroidism. Radioiodine is often recommended as the treatment of choice for Graves disease and toxic nodular goiter in all patients, including children. Dosage of iodine-131 is difficult to adjust because the response of the gland cannot be predicted; some physicians give a standard dose of 8 to 15 millicurie. Others adjust the dose based on estimated thyroid size and the 24-hour uptake to provide a dose of 80 to 120 microcurie/g thyroid tissue. When sufficient iodine-131 is given to cause euthyroidism, about 25 to 50% of patients become hypothyroid 1 year later, and the incidence continues to increase yearly. Thus, most patients eventually become hypothyroid. However, if smaller doses are used, incidence of recurrence is higher. Larger doses, such as 10 to 20 millicurie, often cause hypothyroidism within 6 months, and thus ablative therapy (ie, iodine-131) has become the preferred approach. Radioactive iodine is not used during lactation because it can enter breast milk and cause hypothyroidism in the infant. It is not used during pregnancy because it crosses the placenta and can cause severe fetal hypothyroidism. There is no proof that radioiodine increases the incidence of tumors, leukemia, thyroid cancer, or birth defects in children born to previously hyperthyroid women who become pregnant later in life. These antithyroid drugs block thyroid peroxidase, decreasing the organification of iodide, and impair the coupling reaction. Propylthiouracil in high doses also inhibits the peripheral conversion of T4 to T3. Methimazole is the preferred drug. The usual starting dosage of methimazole is 5 to 20 mg orally 2 or 3 times a day. Normalization of TSH lags normalization of T4 and T3 levels by one or more weeks. Therefore, when T4 and T3 levels normalize, the dosage is decreased to the lowest effective amount, usually methimazole 2.5 to 10 mg once a day in order to avoid inducing hypothyroidism. Control generally is achieved in 2 to 3 months. Maintenance doses of methimazole may be continued for one or many years depending on the clinical circumstances. Carbimazole, which is used widely in Europe but is unavailable in the US, is rapidly converted to methimazole. The usual starting dose is similar to that of methimazole; maintenance dosage is 2.5 to 10 mg orally once a day or 2.5 to 5 mg twice a day. Because of severe liver failure in some patients < age 40, especially children, propylthiouracil is recommended only in special situations (eg, in the 1st trimester of pregnancy, in thyroid storm). The usual starting dose of propylthiouracil is 100 to 150 mg orally every 8 hours. Rapid control can be achieved by increasing the dosage of propylthiouracil to 150 to 200 mg every 8 hours. Such dosages or higher ones (up to 400 mg every 8 hours) are generally reserved for severely ill patients, including those with thyroid storm, to block the conversion of T4 to T3. Maintenance dosing with propylthiouracil is 50 mg twice a day or 3 times a day About 20 to 50% of patients with Graves disease remain in remission after a 1- to 2-year course of either drug. The return to normal or a marked decrease in gland size, the restoration of a normal serum TSH level, and less severe hyperthyroidism before therapy are good prognostic signs of long-term remission. The concomitant use of antithyroid drug therapy and levothyroxine does not improve the remission rate in patients with Graves disease. Because toxic nodular goiter rarely goes into remission, antithyroid drug therapy is given only in preparation for surgical treatment or iodine-131 therapy. Adverse effects include rash, allergic reactions, abnormal liver function (including hepatic failure with propylthiouracil), and, in about 0.1% of patients, reversible agranulocytosis. Patients allergic to one drug can be switched to the other, but cross-sensitivity may occur. If agranulocytosis occurs, the patient cannot be switched to the other drug; other therapy (eg, radioiodine, surgery) should be used. Potential adverse effects or other characteristics vary between the two drugs and guide the indications for each. Methimazole need only be given once a day, which improves adherence. Furthermore, when methimazole is used in dosages of < 20 mg a day, agranulocytosis is less common; with propylthiouracil, agranulocytosis may occur at any dosage. Methimazole has been used successfully in pregnant and nursing women without fetal or infant complications, but rarely methimazole has been associated with scalp and gastrointestinal defects in neonates and with a rare embryopathy. Because of these complications, propylthiouracil is used in the 1st trimester of pregnancy. Propylthiouracil is preferred for the treatment of thyroid storm, because the high dosages used (over 800 mg a day) partially block the peripheral conversion of T4 to T3 in addition to decreasing production in the thyroid. The combination of high-dose propylthiouracil and dexamethasone, also a potent inhibitor of T4 to T3 conversion, can relieve symptoms of severe hyperthyroidism as seen in patients with thyroid storm and restore the serum T3 level to normal within a week. Symptoms and signs of hyperthyroidism due to adrenergic stimulation may respond to beta-blockers; propranolol has had the greatest use, but atenolol or metoprolol may be preferable. Other manifestations typically do not respond.
Propranolol is indicated in thyroid storm (see table
Treatment of Thyroid Storm
Treatment of Thyroid Storm Iodine in pharmacologic doses inhibits the release of T3 and T4 within hours and inhibits the organification of iodine, a transitory effect lasting from a few days to a week, after which inhibition usually ceases. Iodine is used for emergency management of thyroid storm, for hyperthyroid patients undergoing emergency nonthyroid surgery, and (because it also decreases the vascularity of the thyroid) for preoperative preparation of hyperthyroid patients undergoing thyroidectomy. Iodine generally is not used for routine treatment of hyperthyroidism. The usual dosage is 2 to 3 drops (100 to 150 mg) of a saturated potassium iodide solution orally 3 times a day or 4 times a day or sodium iodide in 1 L 0.9% saline solution 0.5 to 1 g IV given slowly once a day. Complications of iodine therapy include inflammation of the salivary glands, conjunctivitis, and rash. Surgery is indicated for patients with Graves disease whose hyperthyroidism has recurred after courses of antithyroid drugs and who refuse iodine-131 therapy, patients who cannot tolerate antithyroid drugs, patients with very large goiters, and in some younger patients with toxic adenoma and multinodular goiter. Surgery may be done in older patients with giant nodular goiters. Surgery usually restores normal function. Postoperative recurrences vary between 2 and 16%; risk of hypothyroidism is directly related to the extent of surgery. Vocal cord paralysis and hypoparathyroidism are uncommon complications. Saturated solution of potassium iodide 3 drops (about 100 to 150 mg) orally 3 times a day should be given for 10 days before surgery to reduce the vascularity of the gland. Methimazole must be given first because the patient should be euthyroid before iodide is given. Dexamethasone can be added to rapidly restore euthyroidism. Surgical procedures on the anterior neck are more difficult in patients who previously underwent thyroidectomy or radioiodine therapy. In infiltrative dermopathy (in Graves disease), topical corticosteroids or corticosteroid injections into the lesions may decrease the dermopathy. Dermopathy sometimes remits spontaneously after months or years. Ophthalmopathy should be treated jointly by the endocrinologist and ophthalmologist and may require selenium, corticosteroids, orbital radiation, and surgery. Surgical thyroidectomy may help resolve or
prevent progression of ophthalmopathy. Teprotumumab, an insulin-like growth factor 1 (IGF-1) receptor inhibitor, is very effective therapy for moderately severe ophthalmopathy
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Treatment references Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor... read more In patients with subclinical hyperthyroidism who are taking levothyroxine, reduction of the dose is the most appropriate management unless therapy is aimed at maintaining suppressed TSH levels in patients with thyroid cancer. Therapy is indicated for patients with endogenous subclinical hyperthyroidism (serum TSH < 0.1 mU/L), especially those with atrial fibrillation or reduced bone mineral density. The usual treatment is iodine-131, but low doses of methimazole are also effective.
Click here for Patient Education What is the autoimmune disorder that results in a hyperthyroid goiter?Graves' disease is an immune system disorder that results in the overproduction of thyroid hormones (hyperthyroidism). Although a number of disorders may result in hyperthyroidism, Graves' disease is a common cause.
Which of the following diseases is characterized by exophthalmos?exophthalmos, also spelled exophthalmus, also called proptosis, abnormal protrusion of one or both eyeballs. The most common cause for unilateral or bilateral exophthalmos is thyroid eye disease, or Graves ophthalmopathy.
What is another name for Graves disease?Graves' disease, also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism.
What is Graves disease with exophthalmos?Exophthalmos is a protrusion of the eyeball from the eye socket that can affect one or both eyes. The condition, commonly associated with abnormal thyroid levels found in Graves' disease, can become quite serious, causing lasting visual impairment.
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