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Hypothyroidism
is thyroid hormone deficiency. It is diagnosed by clinical features
such as a typical facies, hoarse slow speech, and dry skin, and
by low levels of thyroid hormones. Management includes treatment of
the underlying cause and administration of thyroxine.
Hypothyroidism occurs at any age but is particularly common in the elderly. It occurs in close to 10% of women and 6% of men > 65. Although typically easy to diagnose in younger adults, it may be subtle and present atypically in the elderly.
Primary hypothyroidism:
Primary hypothyroidism is due to disease in the thyroid; TSH is increased. The most common cause is probably autoimmune. It usually results from Hashimoto's thyroiditis and is often associated with a firm goiter or, later in the disease process, with a shrunken fibrotic thyroid with little or no function. 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.
Most patients with non-Hashimoto's goiters are euthyroid or have hyperthyroidism, but goitrous hypothyroidism may occur in endemic goiter. Iodine deficiency decreases thyroid hormonogenesis; in response, TSH is released, which causes the thyroid to enlarge and trap iodine avidly; thus, goiter results. If iodine deficiency is severe, the patient becomes hypothyroid, a rare occurrence in the US since the advent of iodized salt.
Iodine deficiency can cause endemic cretinism in children; endemic cretinism is the most common cause of congenital hypothyroidism in severely iodine-deficient regions and a major cause of mental deficiency worldwide.
Rare inherited enzymatic defects can alter the synthesis of thyroid hormone and cause goitrous hypothyroidism (see Endocrine and Metabolic Disorders in Children: Congenital Goiter).
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, and in patients taking interferon-α. Hypothyroidism can result from radiation therapy for cancer of the larynx or Hodgkin lymphoma (Hodgkin's disease). 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-mo intervals.
Secondary
hypothyroidism:
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.
Symptoms and Signs
Symptoms and signs of primary hypothyroidism are often subtle and insidious. Symptoms may include cold intolerance, constipation, forgetfulness, and personality changes. Modest weight gain is largely the result of fluid retention and decreased metabolism. Paresthesias of the hands and feet are common, often due to carpal-tarsal tunnel syndrome caused by deposition of proteinaceous ground substance in the ligaments around the wrist and ankle. Women with hypothyroidism may develop menorrhagia or secondary amenorrhea.
The facial expression is dull; the voice is hoarse and speech is slow; facial puffiness and periorbital swelling occur due to infiltration with the mucopolysaccharides hyaluronic acid and chondroitin sulfate; eyelids droop because of decreased adrenergic drive; hair is sparse, coarse, and dry; and the skin is coarse, dry, scaly, and thick. The relaxation phase of deep tendon reflexes is slowed. Hypothermia is common. Dementia or frank psychosis (myxedema madness) may occur. In the elderly, hypothyroidism may mimic dementia or parkinsonism.
Carotenemia is common, particularly notable on the palms and soles, caused by deposition of carotene in the lipid-rich epidermal layers. Deposition of proteinaceous ground substance in the tongue may produce macroglossia. A decrease in both thyroid hormone and adrenergic stimulation causes bradycardia. The heart may be enlarged, partly because of dilation but chiefly because of pericardial effusion. Pleural or abdominal effusions also may be noted. The pericardial and pleural effusions develop slowly and only rarely cause respiratory or hemodynamic distress.
Although secondary hypothyroidism is uncommon, its causes often affect other endocrine organs controlled by the hypothalamic-pituitary axis. In a woman with hypothyroidism, indications of secondary hypothyroidism are a history of amenorrhea rather than menorrhagia and some suggestive differences on physical examination. Secondary hypothyroidism is characterized by skin and hair that are dry but not very coarse, skin depigmentation, only minimal macroglossia, atrophic breasts, and low BP. 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 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 CO2 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 CNS, and exposure to cold.
Diagnosis
Serum TSH is the most sensitive test. In primary hypothyroidism, there is no feedback inhibition of the intact pituitary, and serum TSH is always elevated, whereas serum free T4 is low. In secondary hypothyroidism, free T4 and serum TSH are low (sometimes TSH is normal but with decreased bioactivity).
Many patients with primary hypothyroidism have normal circulating levels of T3, probably caused by sustained TSH stimulation of the failing thyroid, resulting in preferential synthesis and secretion of the biologically active hormone 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 folic acid. Anemia is rarely severe (Hb > 9 g/dL). As the hypometabolic state is corrected, anemia subsides, sometimes requiring 6 to 9 mo.
Serum cholesterol is usually high in primary hypothyroidism but less so in secondary hypothyroidism.
In addition to primary and secondary hypothyroidism, other conditions may produce decreased levels of total T4, such as serum thyroxine-binding globulin (TBG) deficiency, some drugs (see Thyroid Disorders: Primary hypothyroidism), and euthyroid sick syndrome (see Thyroid Disorders: Hashimoto's Thyroiditis).
Treatment
Various thyroid hormone preparations are available for replacement therapy, including synthetic preparations of T4 (l-thyroxine), T3 ( liothyronine ), combinations of the 2 synthetic hormones, and desiccated animal thyroid extract. l-Thyroxine is preferred; the average maintenance dose is 75 to 125 μg po once/day (see Endocrine and Metabolic Disorders in Children: Hypothyroidism during infancy and early childhood for pediatric doses). Therapy is begun with low doses, especially in the elderly, usually 25 μg once/day. The dose is adjusted q 6 wk until maintenance dose is achieved. The maintenance dose may need to be decreased in elderly patients and increased in pregnant women. Dose may also need to be increased if drugs that decrease T4 absorption or increase its biliary excretion are administered concomitantly. The dose used should be the lowest that restores serum TSH levels to the mid-normal range (though this criterion cannot be used in patients with secondary hypothyroidism).
Liothyronine 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 μg bid) results in rapidly increasing serum T3 to between 300 and 1000 ng/dL (4.62 to 15.4 nmol/L) within 4 h due to its almost complete absorption; these levels return to normal by 24 h. Additionally, patients receiving liothyronine are chemically hyperthyroid for at least several hours a day, potentially increasing cardiac risks.
Similar patterns of serum T3 occur when mixtures of T3 and T4 are taken po, 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 has been stable on such a preparation.
In patients with secondary hypothyroidism, l-thyroxine should not be given until there is evidence of adequate cortisol secretion (or cortisol therapy is given), because l-thyroxine could precipitate adrenal crisis.
Myxedema coma is treated with a large initial dose of T4 (300 to 500 μg IV) or T3 (25 to 50 μg IV). The maintenance dose of T4 is 75 to 100 μg IV once/day and of T3, 10 to 20 μg IV bid 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.
Subclinical
Hypothyroidism
Subclinical
hypothyroidism is elevated serum TSH in patients with absent or
minimal symptoms of hypothyroidism and normal serum levels of free
T4.
Subclinical thyroid dysfunction is relatively common; it occurs in nearly 15% of elderly women, particularly in those with underlying Hashimoto's thyroiditis.
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 in the next 10 yr. These patients are also more likely to have hypercholesterolemia and atherosclerosis. They should be treated with l-thyroxine, even if they are asymptomatic. For patients with TSH levels between 4.5 and 10 mU/L, a trial of l-thyroxine is reasonable if symptoms of early hypothyroidism (eg, fatigue, depression) are present. l-Thyroxine 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 who are not treated should have annual measurement of serum TSH and free T4 to assess progress of the condition.
Last full review/revision November 2005
Content last modified November 2005
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