Hypothyroidism PDF

Hypothyroidism Hypothyroidism disease is a multi-symptom complex with many causes and is characterized by a deficiency (either absolute or relative) of circulating triiodothyronine (T3) and thyroxine (T4) Thyroid hormone deficiency may affect virtually all bodily functions, w...

Hypothyroidism Hypothyroidism disease is a multi-symptom complex with many causes and is characterized by a deficiency (either absolute or relative) of circulating triiodothyronine (T3) and thyroxine (T4) Thyroid hormone deficiency may affect virtually all bodily functions, with the extent and severity of clinical manifestations closely related to the degree of hormone deficiency The majority of patients have primary hypothyroidism (i.e. thyroid gland failure) Pituitary failure, hypothalamic failure, and resistance of peripheral tissues to thyroid hormone (i.e., relative deficiency of thyroid hormone) are far less common, secondary types of hypothyroid disease Community studies use slightly different criteria for defining hypothyroidism; therefore female-to-male ratios vary In general, however, thyroid disease is much more common in females than in males, with reports of prevalence 2 to 8 times higher in females The frequency of hypothyroidism increases with age and is most prevalent in elderly populations Among adults older than 60 years, hypothyroidism was reported in 5.9% of women and 2.4% of men Approximately 1 in 3,000-5,000 babies in the United States is born with hypothyroid disease due to a small or completely absent thyroid gland. Significance Death caused by hypothyroidism is uncommon in the United States and other developed countries The significance of hypothyroidism lies primarily in the many troublesome clinical manifestations that result from low thyroid hormone levels These include: ○ Weakness, fatigue, intolerance to cold, constipation, weight gain, dry, flaky skin The most serious complication is myxedema coma, a medical emergency with an extremely high mortality rate Other serious complications include psychosis with paranoid delusions, dilation of the colon (megacolon), infertility and miscarriage Causes of risk factors There are many causes of hypothyroid disease which may be either reversible or permanent condition Hypothyroidism has traditionally been divided into primary (i.e., thyroid function failure) and secondary (i.e., cause is external to the thyroid gland) based on etiology Major causes of primary hypothyroidism includ: ○ Hashimoto thyroiditis (an autoimmune disease of the thyroid gland in which the person’s immune system targets the thyroid for destruction and the single most common cause of hypothyroidism nationally)  ○ Loss of viable thyroid gland tissue due to surgery ○ External beam radiation (e.g., in thyroid cancer patients) ○ 131I therapy (i.e., in patients with graves disease) ○ bacterial or viral thyroiditis ○ congenital or acquired iodide deficiency (because iodide is a major component for synthesizing T3 and T4) ○ genetic thyroid enzyme defects ○ medications that impair thyroid hormone synthesis (e.g., lithium, amiodarone, interferon-α, and interferon-β) ○ foods that interfere with thyroid hormone synthesis in iodide-deficient geographic regions (e.g., cabbage and turnips) Causes of secondary hypothyroidism include: ○ deficient pituitary thyroid-stimulating hormone (TSH) secretion (e.g., following a pituitary infarction) ○ deficient hypothalamic thyroid-releasing hormone (TRH) secretion (e.g., as seen with some genetic hypothalamic abnormalities in which TRH synthesizing enzymes are deficient) ○ peripheral resistance to thyroid hormones (in which the patient has normal to high levels of T3 and T4, but thyroid hormones are not effective in target tissues) Pathophysiology Thyroid gland hormones affect many body tissues and have multiple physiologic effects These include: ○ Regulation of metabolic rate in all cells and the use of glucose, fat and proteins ○ Regulation of body heat production (i.e., thermogenesis) ○ Maintenance of growth hormone secretion and skeletal growth ○ Development of the CNS ○ Synthesis of β-adrenergic receptors and Ca2-ATPase (which are important in maintaining normal heart rate and cardiac contractility) ○ Maintenance of normal respiratory rate ○ Maintenance of muscle tone and vigor Diagnosis of hypothyroid disease: Is its based on patient history, physical examination findings, and most importantly laboratory thyroid function test results There are many clinical signs and symptoms associated with hypothyroid disease and include the following: ○ Fatigue, lethargy, weakness, joint pain (arthralgia), muscle pain (myalgia), muscle cramps, intolerance to cold, constipation, dry skin, headaches menstrual abnormalities, such as amenorrhea (i.e., absence of menses) or menorrhagia (i.e., excessive blood loss at menses), thin and brittle nails, thinning of the hair and eyebrows, slow speech and thought, pallor, low body temperature, hoarseness ,  decreased sense of hearing, taste, and smell, difficulty breathing (dyspnea), increase in weight, enlarged thyroid gland (i.e., goiter), slow heart rate, lactation not associated with pregnancy (galactorrhea), somnolence and delayed return of deep tendon reflexes ○ With advanced disease, fluid retention is prominent and results from an accumulation of hydrophilic mucopolysaccharides between cells (myxedema). ○ Fluid retention is most noticeably manifested by puffiness of the face and eyelids and swelling of the hands, feet, and tongue. ○ Major head and facial manifestations of hypothyroidism. Hair dry, coarse, sparse Lateral eyebrows thin Periorbital edema Puffy dull face with dry skin The patient with severe hypothyroidism has a puffy facies. Edema, often most pronounced around the eyes, does not pit with pressure. The hair and eyebrows are dry, coarse, and thinned. The skin is dry. ○ Laboratory tests may show the following results: low or low-normal serum-free thyroxine concentration (i.e., FT4, the only metabolically active fraction of T4 that freely enters cells to produce an effect) low serum total thyroxine (T4) high serum TSH level with primary hypothyroidism and low or low-normal serum TSH with pituitary or hypothalamic failure low serum sodium concentration (hyponatremia due to impaired renal tubular sodium reabsorption, the result of a deficiency of Na-K ATPase) high serum prolactin concentration (because TRH stimulates pituitary gland synthesis and secretion of this hormone in primary hypothyroid disease) low hematocrit ○ Presentation of the rare pathophysiologic occurrence of a primary hypothalamic failure would show a decreased TRH, decreased TSH, decreased T3 and decreased T4. ○ Titers of antibodies against the thyroid gland proteins thyroperoxidase and thyroglobulin are high if hypothyroid disease is due to Hashimoto thyroiditis. ○ The American College of Physicians recommends screening all women older than age 50 years who have one or more clinical features of thyroid disease. ○ Patients may present with fatigue, goiter as well as other hypothyroid symptoms. Laboratory studies in this case scenario may show a T4 which is low, TSH which is high and a T3 resin uptake is decreased. ○ Thyroid antimicrobial antibodies would be increased  Serious complications and prognosis: ○ Inadequate treatment leads to disease progression with gradual worsening of symptoms and more metabolic derangements ○ Furthermore, progressive hypothyroid disease may result in life threatening myxedema coma ○ This serious complication is characterized by marked hypothermia, hypoventilation, and hypotension with the development of hypercapnia (i.e., elevated PaCO2 levels) and respiratory acidosis. ○ The mortality rate for myxedema coma is as high as 60% This serious complication is characterized by marked hypothermia, hypoventilation, and hypotension with the development of hypercapnia (i.e., elevated PaCO2 levels) and respiratory acidosis. This serious complication is characterized by marked hypothermia, hypoventilation, and hypotension with the development of hypercapnia (i.e., elevated PaCO2 levels) and respiratory acidosis. Because most brain growth occurs during the first 2 years of life, untreated hypothyroidism in infants can cause mental retardation. Appropriate Therapy: The primary goal of therapy is to return patients to a normal thyroid (euthyroid) state characterized by a serum TSH level in the normal range. Levothyroxine is the treatment of choice for hypothyroid disease. The drug is partially converted in the body to T3, the more active thyroid hormone. Significant increases in serum thyroxine levels are seen within 2 weeks and near-maximum levels within 4 weeks Levothyroxine is best taken in the morning with water. Drugs that may interfere with its absorption should not be taken at the same time. These include iron preparations, sucralfate, aluminum hydroxide antacids, calcium supplements, and cholestyramine. Poor absorption of the drug may also occur with diarrhea or any condition that causes gastrointestinal malabsorption (e.g., sprue or regional enteritis). Striking transformations in the patient’s appearance, exercise tolerance, and mental state often occur within several days after initiating therapy. Replacement therapy that is too rapid can cause anxiety and insomnia. Levothyroxine therapy must be continued. Doses can be increased by 25 µg every 1–3 weeks until the patient’s thyroid status is normal. Although each patient’s dose must be based on a careful clinical assessment, most patients require 100–250 µg daily. Older children are spared nervous system damage but often demonstrate slowed physical and linear bone growth.  They may also show delayed dental development. On the whole, response to levothyroxine therapy is very satisfactory and the prognosis is excellent. Return to an euthyroid state is often the rule, but relapses will occur if treatment is interrupted or the dose is not optimal. Although still possible, patients rarely die from myxedema coma. Chronic maintenance therapy with large doses of levothyroxine can lead to bone demineralization (osteomalacia) and should be avoided. Long-term maintenance therapy with unduly large doses of levothyroxine can also cause symptomatic hyperthyroidism.