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Patients with hypothyroidism commonly complain of fatigue, constipation, or cold intolerance.


This discussion focuses on primary hypothyroidism in nonpregnant adults.

  1. Epidemiology

    1. Prevalence of overt hypothyroidism (elevated TSH with low free T4) is 0.1% in men and 1–2% in women (see below for a discussion of subclinical hypothyroidism).

    2. Prevalence increases with age.

    3. 10 times more common in women than men

    4. More common in patients with other autoimmune diseases.

  2. Etiology

    1. Primary hypothyroidism: failure of the thyroid gland to produce adequate thyroid hormone

      1. Most common cause in iodine sufficient areas is chronic autoimmune (Hashimoto) thyroiditis

        1. Both cell-mediated and antibody-mediated destruction of the thyroid gland

        2. Autoantibodies against thyroid peroxidase, thyroglobulin, and TSH receptor

        3. Patients may or may not have a goiter on presentation.

      2. Iodine deficiency is a common cause worldwide; patients have large goiters.

      3. Thyroidectomy or radioactive iodine therapy both cause hypothyroidism.

        1. Patients with partial thyroidectomy may not need replacement but should be monitored annually; hypothyroidism will develop in 20%.

        2. Postablative hypothyroidism develops several weeks after the radioactive iodine therapy in about 80% of patients.

      4. Can develop years later in patients who have undergone external neck radiation

      5. Amiodarone (14% of patients) and lithium (6% of patients) commonly cause hypothyroidism

      6. Less common etiologies include infiltrative diseases, such as sarcoidosis, and thyroid agenesis.

    2. Central hypothyroidism: reduction in TSH due to pituitary or hypothalamic disorder

      1. Accounts for < 1% of cases of hypothyroidism

      2. Pituitary adenoma is the most common cause; also can occur post neurosurgery or brain radiation or as a complication of postpartum hemorrhage

      3. Granulomatous diseases, especially sarcoidosis, can infiltrate the hypothalamus.

  3. Clinical manifestations

    1. Metabolic: Decreased metabolism that can lead to weight gain, cold intolerance, and increased total and low-density lipoprotein (LDL) cholesterol (due to decreased clearance)

    2. Cardiac: Reduction in myocardial contractility and heart rate

    3. Skin: Nonpitting edema, due to accumulation of glycosaminoglycans; dry skin; coarse, fragile hair

    4. Central nervous system: fatigue, delayed relaxation phase of the deep tendon reflexes

    5. Pulmonary: hypoventilation seen with severe hypothyroidism

    6. Gastrointestinal: reduced intestinal motility causes constipation

    7. Reproductive: menstrual abnormalities, reduced fertility, increased risk of miscarriage


  1. The signs and symptoms of hypothyroidism all lack sensitivity and specificity.

  2. The TSH is the best screening test for both primary hypothyroidism and hyperthyroidism; it is not necessary to measure thyroid hormone levels initially unless central hypothyroidism is suspected.

    1. TSH does have circadian fluctuations, with higher levels toward the evening.

    2. TSH levels tend to be higher in the winter and spring than in the summer and autumn.

  3. If the TSH is normal, no further testing is necessary (LR– for hypothyroidism is < 0.01).

  4. If the TSH is elevated (LR+ for hypothyroidism is > 99), the free T4 should be ordered next.

    1. Most of T4 is bound to thyroxine-binding globulin and albumin.

    2. The levels of these binding proteins are affected by a variety of medical conditions, thus altering the level ...

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