Hyperthyroidism PDF

Hyperthyroidism Hyperthyroid disease (HTD) or hyperthyroidism – which results in an accelerated metabolic state – is a clinical syndrome in which secretion of the thyroid gland hormones triiodothyronine (T3) and thyroxine (T4) is significantly increased and no longer under t...

Hyperthyroidism Hyperthyroid disease (HTD) or hyperthyroidism – which results in an accelerated metabolic state – is a clinical syndrome in which secretion of the thyroid gland hormones triiodothyronine (T3) and thyroxine (T4) is significantly increased and no longer under the regulation of hypothalamic-pituitary controls The causes of HTD are many and diverse and will be described in this chapter The term thyrotoxicosis refers to a constellation of clinical manifestations associated with serum concentrations of T3 and T4 that are both excessive and toxic The terms hyperthyroidism and thyrotoxicosis are often used interchangeably by medical professionals, however, they are not synonymous and should be distinguished from each other Increased serum concentrations of thyroid hormones and their effects can occur despite normal thyroid (Euthyroid) or hypothyroid function – for example, in cases of overdose with synthetic thyroid hormone medications or the release of preformed thyroid hormone from an inflamed but underactive thyroid gland (i.e., thyroiditis), respectively Under these selected circumstances, although thyrotoxicosis is present, hyperthyroidism is not. Primary hyperthyroidism is a from of hyperthyroidism in which excessive amounts of thyroid hormones are secreted by a thyroid gland that is not being overstimulated by hormones from the hypothalamus or pituitary gland Secondary hyperthyroidism is caused by benign tumors of the pituitary gland that secrete thyroid-secreting hormone (TSH) or thyrotropin Tertiary HTD is typically caused by noncancerous tumors of the hypothalamus that secrete thyrotropin-releasing hormone (TRH) Hyperthyroid disease is also commonly known by the public as hyperactive or overactive thyroid gland Prevalence: The overall frequency of HTD in the US is estimated between 0.05–1.3% with the majority of individuals demonstrating subclinical disease. Subclinical disease means that the condition is mild and produces no symptoms or represents an early stage in the evolution of the disease The prevalence of hyperthyroidism is only one-tenth to one-fifth that of hypothyroid disease. Caucasian and Hispanic populations in the United States have a slightly higher prevalence of HTD than do African-Americans. With the sole exception of Graves disease (GD), which is far more common in women than in men by an 8-to-1 ratio, other causes of HTD have no gender preponderance. Newly diagnosed HTD occurs in approximately 1 in 2000 pregnancies. Graves disease predominantly affects those 20–40 years of age.  Because GD accounts for 95% of childhood cases of HTD, the frequency of GD approximates the frequency of all pediatric cases of HTD. The prevalence of GD is approximately 0.02% in childhood. Females are affected three to six times more often than males. Incidence increases throughout childhood with a peak incidence between ages 10–15 years. Symptoms Muscle weakness, especially in shoulders and thighs Frequent and often loos bowel movements Sensation of a racing, pounding heartbeat (palpitations) Chest pain that occurs in the absence of coronary artery disease Scanty or absent menses (oligomenorrhea and amenorrhea, respectively) Lack of sexual desire and erectile dysfunction in males Inability to concentrate, which often interferes with school or work performances Temporary hair loss Hypokalemic (i.e., low serum potassium concentration) Paralysis occurs in approximately 15% of asian- and native-american males with HTD This complication often present abruptly following vigorous exercise with paralysis that lasts up to 72 hours Thyroid storm Thyrotoxic crisis (also known as thyroid storm): is a rapidly developing, life threatening complication that often presents with: ○ Extreme restlessness, agitation, exceedingly high body temperature, significant tachycardia, cardiac arrhythmia that may progress to heart failure, nausea, vomiting, diarrhea may also occur and deplete the intravascular fluid volume, and result in dehydration and hypovolemic shock Thyrotoxic crisis is caused by the sudden availability of large quantities of circulating free/unbound thyroid hormones and often occurs with serious infection or other period of extreme stress Chronic HTD can also contribute to the development of weak and brittle bones by increasing the risk for osteoporosis Furthermore, HTD may result in cardiomyopathy and in older patients Afib that can precipitate heart failure Hyperthyroidism has numerous causes, including autoimmunity, medications, infections, and both cancerous and non-cancerous tumors Graves disease is the most common cause of HTD, accounting for approximately 85% of all cases It is an autoimmune disorder that involves the synthesis of antibodies that bind with the TSH receptor within the cell membrane thyroid hormone producing cells Pathophysiologic mechanism of graves disease  These antibodies, in turn, stimulate thyroid follicular cells to secrete T3 and T4 Mechanisms of B-cell activation may be indirect – that is, they may involve activation of helper T lymphocytes in conjunction with genetic factors that inhibit suppressor T lymphocytes The two pathways differ with respect to the mechanism of help T-cell activation Antibodies formed against anti-TSH antibodies cross reaction with the TSH receptors Hyperthyroid disease: Pathophysiologic mechanisms by which B lymphocytes are activated to produce antibodies to GD The result is persistent stimulation of thyroid cells with synthesis and secretion of thyroid hormones at a high rate Graves disease tends to run in families and studies have shown an associated with human leukocyte antigens (HLA) HLA-B8 and HLA-DR3, suggesting a genetic susceptibility Benign tumors of the thyroid gland known as adenomas that secrete TSH also cause HTD When tumors are solitary, the condition is known as: Plummer disease When multiple, toxic multinodular goiter Mutations of the TSH receptor have been associated with Plummer disease Toxic multinodular goiter is the second most common cause of HTD in the US overall but he most common cause of HTD among the elderly Subacute thyroiditis is believe to be the result of viral infection If the thyroid gland is tender, the condition is known as painful thyroiditis; when it is not tender, silent thyroiditis Jod-Basedow disease (also known as iodine-induced HTD) occurs in patients with a multinodular goiter who are exposed to large amounts of iodine (a key element in the synthesis of thyroid hormones), either in the diet, in the form of iodinated radiographic contrast dyes used for diagnostic purposes, or iodine-containing medications. Thyrotoxicosis factitia results from ingestion of excessive amounts of thyroid hormone. For example, isolated epidemics of thyrotoxicosis have been caused by the consumption of ground beef that was contaminated with bovine thyroid tissue. In other cases, individuals have abused synthetic thyroid hormone to achieve weight loss Struma ovarii is a condition in which a small percentage of certain ovarian tumors (especially ovarian teratomas) contain thyroid tissue that actively secretes thyroid hormone Hashimoto thyroiditis (also known as chronic lymphocytic thyroiditis) is an autoimmune disease, the most common cause of hypothyroid disease, and the most common thyroid disorder overall in the United States However, this condition may cause transient thyrotoxicosis early during its clinical course when preformed thyroid hormones are released from thyroid cells by the destructive nature of inflammation  Postpartum thyroiditis is common, occurring in up to 9% of women during the first 6 months after delivery. Transient thyrotoxicosis may last as long as 3 months and results from the release of stored thyroid hormone following damage to the thyroid gland by antibodies to thyroperoxidase, a key enzyme in the synthesis of thyroid hormones Subsequent to injury, the thyroid gland is unable to produce thyroid hormone and hypothyroid disease ensues. Mild gestational HTD may occur during the first 4 months of pregnancy. Human chorionic gonadotropin (HCG, a hormone produced by the placenta) generally has a low affinity for stimulating TSH receptors in the thyroid and causing the synthesis of thyroid hormone. However, very high serum levels of HCG in some pregnant women may cause sufficient receptor activation to result in HTD. Hyperthyroid disease may also be caused by high serum levels of HCG secreted by some types of testicular cancer. Amiodarone is a medication used for the treatment of cardiac arrhythmias. The drug becomes concentrated in the thyroid and other tissues and is composed of 38% iodine by weight. The drug is eliminated very slowly from the human body, and its half-life may be as long as 100 days. Among patients in the United States who take amiodarone, approximately 3% develop HTD. Amiodarone-induced HTD may occur as soon as 4 months after initiating therapy or months after discontinuing therapy. Type I amiodarone-induced HTD results when iodine contained in the drug causes toxic multinodular goiter or GD. Type II amiodarone induced HTD results when the drug causes a destructive thyroiditis and releases stored hormone from injured cells. Thyrotoxicosis can last up to 3 months and may be followed by hypothyroidism Pathophysiology There are three basic pathophysiologic mechanisms that cause the majority of conditions associated with hyperthyroidism and/or thyrotoxicosis: ○ 1. increased synthesis and secretion of T3 and T4 ○ 2. injury to thyroid follicular cells (i.e., cells that synthesize the thyroid hormones) with release of preformed T3 and T4 ○ 3. ingestion of excessive amounts of thyroid hormone or iodine salt-containing preparations. Many of the clinical manifestations of HTD are related to an increase in oxygen consumption and use of metabolic fuels (glucose, lipids, proteins) associated with a  hypermetabolic state, as well as an increase in sympathetic nervous system (SNS) activity. Hyperthyroid disease: unbound sex hormone levels Enlarged thyroid gland (goiter) Hyperplasia and/or hypertrophy of thyroid follicular cells Infiltration of thyroid with lymphocytes and edema (thyroiditis) Warm skin ↑ body heat production ↑ cardiac output → ↑ blood flow to skin Hypercalcemia and hypercalciuria Thyroid hormones stimulate resorption/breakdown of bone by osteoclasts Decreased blink response with a staring quality Hyperactivity of Müller muscle in upper eyelid SNS hyperactivity Shortness of breath May be related, in part, to respiratory muscle fatigue from increased metabolism of muscle proteins Onset of cardiac arrhythmia or heart failure → fluid in lungs Compression of trachea by enlarged thyroid High serum TSH concentrations TSH-secreting pituitary tumor Low serum TSH concentrations Negative feedback on pituitary and hypothalamus by high serum T3 and T4 concentrations Complications and prognosis The most serious potential and often life-threatening complications of thyrotoxicosis include thyrotoxic crisis, hypokalemic paralysis, atrial fibrillation, cardiomyopathy, and heart failure. If untreated, thyrotoxic crisis usually is fatal. Depending on the precipitating factor and even with prompt, aggressive intervention, the overall mortality rate is 10–30% but has been reported as high as 75%. A major serious complication of the use of thionamides is suppression of white blood cell production in the bone marrow—a condition known as agranulocytosis—with development of serious infections. There may also be serious complications related to thyroid surgery, such as hoarseness from nerve damage to the larynx and permanently low serum calcium concentrations from injury to the parathyroid glands (i.e., hypoparathyroid disease). Although HTD can be fatal if it is ignored, most patients respond well when the condition is diagnosed, treated, and monitored, and the outcome is usually good. Approximately one third to one half of patients will go into remission after taking thionamides for 1–2 years. Recurrences of HTD are common following thionamide therapy but also occur after lowdose RAI treatment or thyroid surgery. On rare occasions, GD may spontaneously resolve. Ocular, cardiac, and psychological complications can become very serious and persistent even following treatment.  Patients with atrial fibrillation experience a spontaneous remission rate of 56% as thyroid hormone levels decline with treatment. Posttreatment hypothyroidism is common and may occur from a few weeks to years after RAI therapy or surgical removal of thyroid tissue. thyroid gland. Appropriate therapy Methods used to treat thyrotoxicosis vary according to the cause and severity of the condition, the patient’s age, clinical circumstances (e.g., pregnancy), and the patient’s desires. Treatment is directed at relieving symptoms and reducing levels of circulating T3 and T4. These goals can be accomplished by blocking the effects of high levels of circulating thyroid hormones, inhibiting new thyroid hormone synthesis, preventing the release of preformed thyroid hormone from the thyroid gland, and preventing the conversion in peripheral tissues of T4 to T3. T3 is the more biologically potent of the two hormones. There are 5 basic treatments for thyrotoxicosis: 1. Propanol 2. Thioamides (methimazole and propylthiouracil) 3. Iodinated contrast agents (iopanoic acid and ipodate sodium) 4. Radioactive iodine (131I) 5. Thyroid surgery a. For some patients, more than one kind of treatment is required Causes of Thyrotoxicosis Potential Cause of Thyrotoxicosis Distinguishing Clinical Features Graves disease* Serum antibodies to TSH receptor (75–80% of patients) Eye abnormalities that include protrusion of the eye(s), double vision, loss of color vision/visual acuity, and corneal drying (50–70% of patients) Red, thickened skin over shin bone Swelling of fingers and toes High radioactive iodine uptake Generalized enlargement of thyroid Hypervascular thyroid with ultrasound Hyperthyroid state persists Subacute thyroiditis Markedly increased erythrocyte sedimentation rate Often follows upper respiratory infection Low radioactive iodine uptake Low-grade fever Usually painful enlargement of thyroid Transient thyrotoxicosis followed by hypothyroid state Plummer disease and toxic multinodular  One or more distinct nodules observed with ultrasound of thyroid goiter High radioactive iodine uptake Hyperthyroid state persists Hashimoto thyroiditis Generalized enlargement of thyroid High serum levels of antibodies to thyroid peroxidase (90% of patients) and/or thyroglobulin (40% of patients) Low radioactive iodine uptake Transient thyrotoxicosis followed by hypothyroid state Postpartum thyroiditis High serum levels of antibodies to thyroid peroxidase in first trimester of pregnancy or immediately after delivery Transient thyrotoxicosis followed by hypothyroid state Hyperthyroid disease Restoration of a euthyroid state may take up to 2 months. Propranolol is generally used for symptomatic relief until thyrotoxicosis can be controlled. It acts by both reducing SNS hyperactivity and inhibiting the conversion of T4 to T3. The drug effectively relieves tachycardia, tremors, diaphoresis, and anxiety that occur from thyrotoxicosis of any cause. The therapeutic effects are dramatic and results may be seen within 10 minutes. Propranolol is also the initial treatment of choice for thyrotoxic crisis. In patients who cannot tolerate the drug or in whom the drug is contraindicated, other β-adrenergic blocking agents can be tried. Thionamides prevent new hormone synthesis in the thyroid. Propylthiouracil (PTU) has the additional benefit of inhibiting conversion of T4 to T3. These medications are generally used to treat young adults or patients with mild thyrotoxicosis, small goiters, or a fear of radioactive agents. They are also beneficial for preparing patients for thyroid surgery or radioactive iodine (RAI) therapy. When used long term for GD, remission rates up to 70% occur after 2 years. Thionamides do not cause permanent damage to thyroid tissue Hyperthyroid Disease and are associated with a lower risk for post treatment hypothyroidism than RAI therapy or thyroid surgery. Symptoms usually improve in 6–12 weeks, but the drugs are usually continued for at least 1 year before being discontinued. Methimazole has the advantage of requiring less frequent dosing and fewer pills than PTU, so that taking the medication is more convenient. Furthermore, patients treated with methimazole have a lower risk for developing serious liver complications and hepatic failure. PTU is considered the drug of choice during breastfeeding and pregnancy because it causes fewer complications in the fetus and newborn.  Iodinated contrast agents provide effective temporary treatment for thyrotoxicosis of any cause. These agents prevent the release of stored thyroid hormones from the thyroid and prevent conversion of circulating T4 to the more metabolically active T3 form. Within 24 hours after administration, serum T3 concentrations decrease by 62% on average. These agents are particularly useful for patients who are highly thyrotoxic and offer a therapeutic option for patients with subacute thyroiditis or type II amiodarone-induced thyroiditis and for those who are intolerant to thionamides. The administration of radioactive iodine is an excellent method for permanently eradicating overactive thyroid tissue—either generalized or nodular goiter. RAI damages all cells that concentrate the isotope, and a positive result may be seen in as few as 2 months. This form of therapy is the treatment of choice for recurring GD, patients with severe cardiac involvement, those with multinodular goiter or toxic adenoma, and patients who cannot tolerate thionamides. Furthermore, this method is often recommended for hyperthyroid patients older than 50 years of age. Since radiation is harmful to the human fetus, RAI is contraindicated in pregnant women. Most patients receive 131I after being symptomatically treated with propranolol—which is reduced in dosage as serum thyroid hormone levels decrease. However, elderly patients and those with severe HTD are usually rendered euthyroid with a thionamide while the dosage of propranolol is reduced. To increase the rate of successful RAI therapy, thionamides are discontinued for approximately 1 week prior to delivery of 131I. More than 80% of patients respond positively to a single dose of RAI. There is a high incidence of hypothyroidism (50–80%) years after RAI treatment, even when small doses are administered. Thyroid surgery for GD is being performed less frequently as RAI treatment becomes more widely accepted. Surgery is generally reserved for patients with large goiters that make swallowing or breathing difficult or if a single thyroid nodule is releasing excessive amounts of thyroid hormone. If surgery is required, the Hartley-Dunhill operation is the surgical procedure of choice for patients with GD. This operation consists of total removal of one lobe of the thyroid and partial removal of the other lobe, leaving approximately 4 g of thyroid tissue. When this procedure is performed by a competent, experienced neck surgeon, surgical complications are uncommon. Diagnosis  Hyperthyroid disease is definitively diagnosed from a medical history of the patient that includes a thorough description of clinical symptoms, a physical examination that focuses on eye, skin, cardiac, and neurologic findings, and blood tests. In most cases, determining the patient’s serum TSH concentration is the single most reliable and beneficial laboratory test for diagnosing HTD. With the rare exception that a TSH-secreting pituitary adenoma is causing HTD, serum TSH levels usually will be low or undetectable. Serum T3, T4, and free T4 (FT4) levels are generally all increased above normal. In some cases, serum T4 is normal but serum T3 is high. Elevation of serum FT4 with low to undetectable TSH levels is diagnostic. Hypercalcemia is often present. An electrocardiogram most commonly reveals sinus tachycardia and, occasionally, atrial fibrillation. Although blood tests can confirm the presence of excessive amounts of thyroid hormone, they do not identify a specific cause. Patients with GD who smoke are more likely to develop serious eye problems; therefore, smoking cessation is strongly advised