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Signed in but can't access contentOxford Academic is home to a wide variety of products. The institutional subscription may not cover the content that you are trying to access. If you believe you should have access to that content, please contact your librarian. Institutional account managementFor librarians and administrators, your personal account also provides access to institutional account management. Here you will find options to view and activate subscriptions, manage institutional settings and access options, access usage statistics, and more. Hypothyroidism is thyroid hormone deficiency. Symptoms include cold intolerance, fatigue, and weight gain. Signs may include a typical facial appearance, hoarse slow speech, and dry skin. Diagnosis is with thyroid function tests. Management includes administration of thyroxine. Hypothyroidism occurs at any age but is particularly common among older adults, where it may present subtly and be difficult to recognize. Hypothyroidism may be
The 2nd most common cause is post-therapeutic hypothyroidism, especially after radioactive iodine therapy or surgery for hyperthyroidism or goiter. Hypothyroidism during overtreatment with propylthiouracil, methimazole, and iodide abates after therapy is stopped. Rare inherited enzymatic defects can alter the synthesis of thyroid hormone and cause goitrous hypothyroidism. Hypothyroidism may occur in patients taking lithium, perhaps because lithium inhibits hormone release by the thyroid. Hypothyroidism may also occur in patients taking amiodarone or other iodine-containing drugs, in patients taking interferon-alfa, and in patients taking checkpoint inhibitors or some tyrosine kinase inhibitors for cancer. Hypothyroidism can result from radiation therapy for cancer of the larynx or Hodgkin lymphoma. The incidence of permanent hypothyroidism after radiation therapy is high, and thyroid function (through measurement of serum TSH) should be evaluated at 6- to 12-month intervals. Secondary hypothyroidism occurs when the hypothalamus produces insufficient thyrotropin-releasing hormone (TRH) or the pituitary produces insufficient TSH. Sometimes, deficient TSH secretion due to deficient TRH secretion is termed tertiary hypothyroidism. Subclinical hypothyroidism is elevated serum TSH in patients with absent or minimal symptoms of hypothyroidism and normal serum levels of free thyroxine (T4). In patients with serum TSH > 10 mU/L, there is a high likelihood of progression to overt hypothyroidism with low serum levels of free T4 within the next 10 years. These patients are also more likely to have hypercholesterolemia and atherosclerosis. They should be treated with levothyroxine, even if they are asymptomatic. For patients with TSH levels between 4.5 and 10 mU/L, a trial of levothyroxine is reasonable if symptoms of early hypothyroidism (eg, fatigue, depression) are present. Levothyroxine therapy is also indicated in pregnant women and in women who plan to become pregnant to avoid deleterious effects of hypothyroidism on the pregnancy and fetal development. Patients should have annual measurement of serum TSH and free T4 to assess progress of the condition if untreated or to adjust the levothyroxine dosage. Symptoms and Signs of HypothyroidismSymptoms and signs of primary hypothyroidism are often subtle and insidious. The most common presenting symptoms are fluid retention and puffiness, especially periorbitally; tiredness; cold intolerance; mental fogginess. Various organ systems may be affected with many possible signs and symptoms, including:
Secondary hypothyroidism is characterized by skin and hair that are dry but not very coarse, skin depigmentation, only minimal macroglossia, atrophic breasts, and low blood pressure. Also, the heart is small, and serous pericardial effusions do not occur. Hypoglycemia is common because of concomitant adrenal insufficiency or growth hormone deficiency. Myxedema comaMyxedema coma is a life-threatening complication of hypothyroidism, usually occurring in patients with a long history of hypothyroidism. Its characteristics include coma with extreme hypothermia (temperature 24° to 32.2° C), areflexia, seizures, and respiratory depression with carbon dioxide retention. Severe hypothermia may be missed unless low-reading thermometers are used. Rapid diagnosis based on clinical judgment, history, and physical examination is imperative, because death is likely without rapid treatment. Precipitating factors include illness, infection, trauma, drugs that suppress the central nervous system, and exposure to cold.
Many patients with primary hypothyroidism have normal circulating levels of triiodothyronine (T3), probably caused by sustained TSH stimulation of the failing thyroid, resulting in preferential synthesis and secretion of biologically active T3. Therefore, serum T3 is not sensitive for hypothyroidism. Anemia is often present, usually normocytic-normochromic and of unknown etiology, but it may be hypochromic because of menorrhagia and sometimes macrocytic because of associated pernicious anemia or decreased absorption of folate. Anemia is rarely severe (hemoglobin is usually > 9 g/dL [> 90 g/L]). As the hypometabolic state is corrected, anemia subsides, sometimes requiring 6 to 9 months. Serum cholesterol is usually high in primary hypothyroidism but less so in secondary hypothyroidism. Screening for hypothyroidism is warranted in select populations (eg, neonates, older adults with risk factors) in which it is relatively more prevalent, especially because it can cause significant morbidity and its manifestations can be subtle. Screening is done by measuring TSH levels. In patients with heart disease, therapy is begun with low doses, usually 25 mcg once a day. The dose is adjusted every 6 weeks until maintenance dose is achieved. The maintenance dose may need to be increased in pregnant women. Dose may also need to be increased if drugs that decrease T4 absorption or increase its metabolic clearance are administered concomitantly. The dose used should be the lowest that restores serum TSH levels to the midnormal range (though this criterion cannot be used in patients with secondary hypothyroidism). In secondary hypothyroidism the dose of levothyroxine should achieve a free T4 level in the midnormal range. Liothyronine (L-triiodothyronine) should not be used alone for long-term replacement because of its short half-life and the large peaks in serum T3 levels it produces. The administration of standard replacement amounts (25 to 37.5 mcg twice a day) results in rapidly increasing serum T3 to between 300 and 1000 ng/dL (4.62 to 15.4 nmol/L) within 4 hours due to its almost complete absorption; these levels return to normal by 24 hours. Additionally, patients receiving liothyronine are chemically hyperthyroid for at least several hours a day, potentially increasing cardiac risks. Similar patterns of serum T3 changes occur when mixtures of T3 and T4 are taken orally, although peak T3 is lower because less T3 is given. Replacement regimens with synthetic T4 preparations reflect a different pattern in serum T3 response. Increases in serum T3 occur gradually, and normal levels are maintained when adequate doses of T4 are given. Desiccated animal thyroid preparations contain variable amounts of T3 and T4 and should not be prescribed unless the patient is already taking the preparation and has normal serum TSH. In patients with secondary hypothyroidism, levothyroxine should not be given until there is evidence of adequate cortisol secretion (or cortisol therapy is given), because levothyroxine could precipitate adrenal crisis. Myxedema coma is treated as follows:
Patients require a large initial dose of T4 (300 to 500 mcg IV) or T3 (25 to 50 mcg IV). The intravenous maintenance dose of T4 is 75 to 100 mcg once a day and of T3, 10 to 20 mcg twice a day until T4 can be given orally. Corticosteroids are also given because the possibility of central hypothyroidism usually cannot be initially ruled out. The patient should not be rewarmed rapidly, which may precipitate hypotension or arrhythmias. Hypoxemia is common, so PaO2 should be monitored. If ventilation is compromised, immediate mechanical ventilatory assistance is required. The precipitating factor should be rapidly and appropriately treated and fluid replacement given carefully, because hypothyroid patients do not excrete water appropriately. Finally, all drugs should be given cautiously because they are metabolized more slowly than in healthy people.
Hypothyroidism is particularly common among older adults. It occurs in close to 10% of women and 6% of men > 65. Although typically easy to diagnose in younger adults, hypothyroidism may be subtle and manifest atypically in older adults. Older patients have significantly fewer symptoms than do younger adults, and complaints are often subtle and vague. Many older patients with hypothyroidism present with nonspecific geriatric syndromes—confusion, anorexia, weight loss, falling, incontinence, and decreased mobility. Musculoskeletal symptoms (especially arthralgias)
occur often, but arthritis is rare. Muscular aches and weakness, often mimicking polymyalgia rheumatica
Polymyalgia Rheumatica Polymyalgia rheumatica is a syndrome closely associated with giant cell arteritis (temporal arteritis). It affects adults > 55. It typically causes severe pain and stiffness in proximal muscles... read more or
polymyositis
Autoimmune Myositis Autoimmune myositis is characterized by inflammatory and degenerative changes in the muscles (polymyositis, necrotizing immune-mediated myopathy) or in the skin and muscles (dermatomyositis)... read more
In older patients, levothyroxine therapy is begun with low doses, usually 25 mcg once a day. Maintenance doses may also need to be lower in older patients.
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A nurse in a clinic is reviewing the laboratory values of a client who has primary hypothyroidism
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