Hyperthyroidism -- Overview and Analysis

Hyperthyroidism -- Overview and Analysis

Definition of the Disease

The thyroid is an organ located at the base of the human throat, involved in hormone regulation. Thyroid hormones regulate the human body's metabolic rate. The metabolism is how the body burns calories to produce energy. As the metabolism is connected to nutrition, thus the thyroid gland and its metabolic influence has an effect upon all bodily processes, including but not limited to heart rate, digestion, muscle and bone strength, and cholesterol. ("Hyperthyroidism: Topic Overview -- What is hyperthyroidism?" WebMD. Last updated 11 Nov 2003) Hyperthyroidism is when the body produces too much thyroid hormone, as opposed to hypothyroidism, when the body does not produce enough of the hormone.

Brief overview of pathophysiology

Hyperthyroidism is a term used to describe variety of diseases of known as "thyrotoxicositic" disorders of the endocrine system. Thyrotoxicosis are the clinical, physiologic and biochemical syndromes that result when tissues are exposed to, and respond to high levels of thyroid hormone. (Spector, 2005, "Graves Disease Part 1," MedStudents) The pathophysiology of the endocrine system has some of the most far-reaching yet diffuse effects of any bodily system.

Thyroid hormones are the primary endocrine secretion of the thyroid gland. Thyroid hormones affect three fundamental physiologic processes: cellular differentiation, growth, and metabolism. "Not many hormones can claim as diverse a set of target cells." (Bowen, 2003)

The thyroid gland also produces another hormone called "calcitonin," and the "parathyroid glands secrete parathyroid hormone. Parathyroid hormone and calcitonin participate in control of calcium and phosphorus homeostasis and have significant effects on bone physiology." (Bowen, 2003) Hence, the prevalence of osteoporosis and other bone disorders in patients with disorders of the thyroid.

Etiology/Prevalence and Incidence

Graves disease is the most common form of hyperthyroidism. In Graves' disease, "T lymphocytes become sensitized to antigens within the thyroid gland and stimulate B. lymphocytes to synthesize antibodies to these antigens. One such antibody is directed against the TSH receptor site in the thyroid cell membrane and has the capacity to stimulate the thyroid cell to increased growth and function." (Spector, 2005, "Graves Disease Part 1," MedStudents) Graves disease is usually the result of an inherited tendency to develop the disorder. Other causal factors that contribute to the development of the disorder may be a significant increase in the stress level of the patient with the tendency to develop Graves.

In general, life stresses that may incite the increased response of the thyroid may include pregnancy, particularly the postpartum period; iodine excess, particularly in areas of iodine deficiency; lithium therapy; viral or bacterial infections and glucocorticoid withdrawal in patients with diabetes. (Spector, 2005, "Graves Disease Part 1," MedStudents) Postpartum thyroiditis can occur in up to 5 to 10% of women in the first three to six months after delivery. (Reid & Wheeler, 2005) Additionally, many symptoms of thyrotoxicosis suggest a state of catecholamine excess in the patient's hormone levels.

Thus although Graves' disease, also known in Europe as "von Basedow's disease," is the most common cause of hyperthyroidism, there are many other causes. This is yet another reason for the difficulties in treating and diagnosing the illness. Graves disease's heritability makes it easier to diagnose in a patient with a known family history, but other non-genetic causes must be taken into consideration. These can include thyroid nodules -- growths in the thyroid gland -- and thyroiditis, inflammation of the thyroid gland, as well as the life stresses mentioned above. ("Graves Disease," WebMD, Last updated 2003)

In terms of prevalence, Graves's disease affects as many as 1.9 per cent of the female population. The ratio of women to men is as high as 7:1. It reaches its peak incidence between the third and forth decades and the reason for the female predominance in this as in all thyroid diseases remains unknown. All thyroid disorders, however, are much more common in women, including Hashimoto's thyroiditis as well as Graves disease, particularly in the two decades that precede menopause. Another thyroid disorder, "autoimmune hypothyroidism" is frequently is associated with infertility," while "hyperthyroidism during pregnancy presents special concerns because radioactive iodine is contraindicated and the standard antithyroid drugs are teratogenic," or in other words, toxic to the fetus. Pregnancy and postpartum hormone shifts thus can cause hyperthyroidism, while hypothyroidism can make it difficult for a woman to become pregnant at all. (AMA, 2000)

Genetic and female hormonal factors play an important but still-unclear role in the illness. Ethnic background has an influence as well. With Graves, for example "is an increased frequency haplotypes HLA-B8 and -DRw3 in Caucasian, HLA-Bw36 in Japanese, and HLA-Bw46 in Chinese patients with the disease." (Spector, 2005, "Graves Disease Part 1," MedStudents) Again, however, although it influenced by genetics, Graves is an inherited tendency rather than a genetic disorder, unlike, for example, color blindness which is bound to the male chromosome, and one cannot always predict if and when it will manifest itself in a patient. Yet while Graves' disease may be triggered by severe emotional stress, such as the death of a loved one or being involved in an automobile accident, stress alone cannot cause the development of Graves' disease in a patient. ("Graves' Disease," WebMD, 2003)

The less common toxic multinodular goiter (two or more nodules) or toxic thyroid adenoma (a single nodule) can also cause the thyroid gland to produce too much thyroid hormone. Thyroid nodules are also more common in women than in men, although the proportion of nodules that are malignant in males is, again, double than in females. (AMA, 2000) Toxic multinodular goiter is also a more common cause of hyperthyroidism in older people. Thyroiditis can also be caused by a viral or bacterial infection or tumors. In rare cases, taking large amounts of iodine-containing substances can cause hyperthyroidism. Women also may be at increased risk of interferon-alpha induced thyroid dysfunction from exposure to radioactive interferons. (AMA, 2000)

Causes, Signs and Symptoms

The usual symptoms of hyperthyroidism, regardless of the cause, include nervousness, mood changes, weakness, and fatigue, and tremors; a rapid, pounding, and irregular heartbeat; and shortness of breath, even when resting, excessive sweating, and warm, flushed skin that may be itchy, an increased number of soft stools, fine, soft hair and hair loss, loss of appetite, weight loss. ("Hyperthyroidism: Topic Overview -- Symptoms?" WebMD. Last updated 6 Aug 2003) Graves' disease often causes the eyes to bulge. A goiter will cause a bulging at the patient's neck, although a goiter is not always present in hyperthyroidism.

The cause thus will affect the patient's symptoms, but even patients with the same cause of the disorder will not always exhibit similar manifestations and symptoms of hyperthyroidism. Also, hyperthyroidism symptoms and effects will vary by age and gender. Women, as noted before, exhibit endocrine disorders more than men, and genetics clearly exacerbates the tendency of older patients in particular to develop Graves disease. Symptoms may additionally vary with age. For example, children may have rapid growth with faster-than-expected bone maturation, while older adults may have a decreased appetite, weight loss, and atrial fibrillation. The severity of symptoms may also vary, and depression and fatigue may occur, otherwise known as apathetic hyperthyroidism, or hyperthyroidism with atypical signs, often caused by the malnutrition that occurs with the speeded metabolism of the disorder. ("Hyperthyroidism: Topic Overview -- Symptoms?" WebMD. Last updated 6 Aug 2003)

Lastly, it is important to note that lymphocytic thyroiditis and postpartum (subacute lymphocytic) thyroiditis may be transient inflammatory causes of hyperthyroidism that, in the acute stage, may be clinically indistinguishable from Graves' disease. A woman may exhibit a severe case of hyperthyroidism that 'balances itself out' as her prepregnancy hormone levels return to normal. (Spector, 2005, "Graves Disease Part 1," MedStudents)

Differential diagnosis

Thus, although Graves may be the most common suspect in diagnosing thyroid disorders, it is not the only one, especially given the relative commonality of thyrotoxicosis in endocrine medicine. Thyrotoxicosis affects, in all of its forms, approximately 2% of the adult population. Still other factors to consider besides patient profile and heritability are the geographical area the patient lives in, when conducting a differential diagnosis -- "the prevalence of toxic nodular goiter and toxic adenoma is increased in areas of limited iodine supply. Thyrotoxicosis in patients with multinodular goiter can be precipitated by iodinated radio contrast agents and the antiarrhythmic drug amiodarone." (Ch, 2003)

Doing a full reproductive, geographic, and life history of the patient is critical when differentiating a diagnosis as "transient hyperthyroidism" that may be caused by HCG-induced thyroiditis in pregnancy or de Quervain subacute thyroiditis," as a result of the hormonal influences before and after delivery, versus an individual with a history of Graves Disease, or thyroid nodules. (Ch, 2003)

Diagnostic workup

Hyperthyroidism is diagnosed based on a medical history, a physical exam, and medical tests. The most frequently used medical tests are: the thyroid-stimulating hormone (TSH) test, which measures the levels of TSH in the blood stream. "It is the most sensitive test to screen for hyperthyroidism." ("Hyperthyroidism: Topic Overview -- Exams and Tests," WebMD, Last updated 6 Aug 2003)

Thyroid hormone tests, which are generally done at the same time as the TSH test, help determine the cause of hyperthyroidism, distinguishing Graves Disease from some of the other potential differential diagnosis and causes of the disease.

Once a patient is being treated for hyperthyroidism, his or her health professional will usually test TSH and thyroid hormones several times each year to evaluate how well the patient is responding to treatment and to check for a worsening of the condition. ("Hyperthyroidism: Topic Overview -- Exams and Tests," WebMD, Last updated 6 Aug 2003) Other tests include an anti-thyroid antibody test, which may help specifically diagnose Graves' disease and autoimmune thyroiditis, if the patient is known to have a genetic history of Graves in particular. ("Hyperthyroidism: Topic Overview -- Exams and Tests," WebMD, Last updated 6 Aug 2003) radioactive thyroid scan and radioactive iodine uptake tests are also often performed to evaluate why the thyroid gland is overactive. "Radionuclide uptake and scan" can also easily distinguish the high uptake of Graves' disease from the low uptake of thyroiditis" and provide other useful anatomic information about failures in the patient's endocrine system due to iodine exposure. "Nonspecific laboratory findings can occur in hyperthyroidism, including anemia, granulocytosis, lymphocytosis, hypercalcemia, transaminase elevations, and alkaline phosphatase elevation," which may also show up in lab results. This is one reason why a full-lab workup is usually necessary in a patient with a thyroid complaint, or even in a patient with a suspected thyroid complaint. (Reid & Wheeler, 2005)

Treatment plan

Treatment options for hyperthyroidism include antithyroid medication, radioactive iodine, and surgery. The treatment course will depend upon the severity of the disorder, its cause, and also previous treatments that have been performed for complaints relating to the thyroid. "Antithyroid drugs act principally by interfering with the organification of iodine, thereby suppressing thyroid hormone levels. Methimazole usually is the drug of choice in nonpregnant patients because of its lower cost, longer half-life, and lower incidence of hematologic side effects." (Reid & Wheeler, 2002, p.2) In patients that initially used drugs, a randomized study indicated that "relapse can occur in up to fifty percent of patients who respond initially, regardless of the regimen used," and relapse was more likely in patients who smoked, had large goiters, or had elevated thyroid-stimulating antibody levels at the end of therapy." (Reid & Wheeler, 2002, p.2)

Surgery to remove the thyroid is usually only a last result, and even the use of radioactive iodine is avoided unless necessary, as this requires the patient to become dependant upon synthetic hormones for his or her life. "After obtaining baseline thyroid function tests, complete blood count and liver function tests," periodic reassessment must always be performed while "antithyroid agents are administered," and especially in older patients without support services, sustained compliance with the treatment plan must be monitored closely. (Shrier & Burman, 2002)

In most cases, one or more of these treatments cane reduce or eliminate the symptoms of hyperthyroidism. Because hyperthyroidism may return after successful treatment of drug therapy, it is important that patients undergoing such drug therapy to balance their hormones have their thyroid hormone levels be prepared for more invasive treatment if need be. Left untreated, a relapse of hyperthyroidism can lead to "atrial fibrillation, osteoporosis, and a life-threatening condition called thyroid storm." ("Hyperthyroidism: Topic Overview -- Symptoms?" WebMD, Last updated 11 Nov 2003

Beta blockers offer prompt relief of the adrenergic symptoms of hyperthyroidism such as tremor, palpitations, heat intolerance, and nervousness. (Reid & Wheeler, 2005) Currently, most endocrinologists in the United States recommend definitive treatment of patients with overt hyperthyroidism by ablating thyroid function first with drug treatment, then with radioactive iodine after the short-term use of antithyroid agents, then only last with surgery, and in the final stages of radioactive and surgical treatment then maintaining the patient on life-long thyroid hormone replacement therapy if all else fails, but in Japan, the preferred initial mode of treatment of patients with overt hyperthyroidism is the use of long-term antithyroid medications alone. (Shrier & Burman, 2002)