Thyroid Disorders
Thyroid disorders affect 1 in 200 adults but are more common in women and with advancing age. The incidence of hypothyroidism, for instance, is 0.3-5 cases per 1000 individuals per year, including 7% of women and 3% of men aged 60-89 years. Hypothyroidism is much more common than hyperthyroidism, nodular disease, or thyroid cancer. Thyroid nodules occur in 4%-8% of all individuals and, like other thyroid problems, increase in incidence with age.
Thyroid disease is more common in people who have conditions such as diabetes or other autoimmune diseases (eg, lupus); in those with a family history of thyroid disease or a history of head and neck irradiation; and in patients who use certain medications, including amiodarone and lithium. Recent guidelines from the American Thyroid Association suggest that all adults have their serum thyroid-stimulating hormone (TSH) concentrations measured, beginning at age 35 and every 5 years thereafter.
Causes of hypothyroidism are outlined in Table 36-1. The most common noniatrogenic condition causing hypothyroidism in the United States is Hashimoto thyroiditis. Other common causes are post–Graves disease, thyroid irradiation, and surgical removal of the thyroid. Hypothyroidism may also occur secondary to hypothalamic or pituitary dysfunction, most commonly in patients who have received intracranial irradiation or surgical removal of a pituitary adenoma. In addition, some patients may have mild elevations of TSH despite normal thyroxine levels, a condition termed subclinical hypothyroidism.
| Primary Hypothyroidism (95% of cases) |
|---|
| Idiopathic hypothyroidism (probably old Hashimoto thyroiditis) |
| Hashimoto thyroiditis |
| Post-thyroid irradiation |
| Postsurgical |
| Late-stage invasive fibrous thyroiditis |
| Iodine deficiency |
| Drugs (lithium, interferon) |
| Infiltrative diseases (sarcoidosis, amyloid, scleroderma, hemochromatosis) |
| Secondary Hypothyroidism (5% of cases) |
| Pituitary or hypothalamic neoplasms |
| Congenital hypopituitarism |
| Pituitary necrosis (Sheehan syndrome) |
Patients with hypothyroidism present with a constellation of symptoms that can involve every organ system. Symptoms include lethargy, weight gain, hair loss, dry skin, slowed mentation or forgetfulness, depressed affect, cold intolerance, constipation, hair loss, muscle weakness, abnormal menstrual periods (or infertility), and fluid retention. Because of the range of symptoms seen in hypothyroidism, clinicians must have a high index of suspicion, especially in high-risk populations. In older patients, hypothyroidism can be confused with Alzheimer disease or other conditions that cause dementia. In women, hypothyroidism is often confused with depression.
Physical findings that can occur with hypothyroidism include low blood pressure, bradycardia, nonpitting edema, generalized hair thinning along with hair loss in the outer third of the eyebrows, skin drying, and a diminished relaxation phase of reflexes. The thyroid gland in a patient with chronic thyroiditis may be enlarged, atrophic, or of normal size. Thyroid nodules are common in patients with Hashimoto thyroiditis.
The most valuable test for hypothyroidism is the sensitive TSH assay. Measurement of the free thyroxine (T4) level may also be helpful. TSH is elevated and free T4 decreased in overt hypothyroidism (Table 36-2). Other laboratory findings may include hyperlipidemia and hyponatremia. Hashimoto thyroiditis, an autoimmune condition, is one of the most common causes of hypothyroidism. Testing for thyroid autoantibodies (antiperoxidase, antithyroglobulin) is positive in 95% of patients with Hashimoto thyroiditis.
| TSH | Free T4 | Free T3 | Likely Diagnosis |
|---|---|---|---|
| High | Low | Low | Primary hypothyroidism |
| High (> 10 μIU/mL) | Normal | Normal | This is not consistent with the AACE guidelinementioned previously. Subclinical hypothyroidism with high risk for future development of overt hypothyroidism |
| High (6–10 μIU/mL) | Normal | Normal | Subclinical hypothyroidism with low risk for future development of overt hypothyroidism |
| High | High | Low | Congenital absence of T4–T3-converting enzyme or amiodarone effect |
| High | High | High | Peripheral thyroid hormone resistance |
| Low | Low | Low | Pituitary thyroid deficiency or recent withdrawal of thyroid replacement after excessive replacement |
Patients with associated subclinical hypothyroidism have a high TSH level (usually in the 5-10 μIU/mL range) in conjunction with normal free T4 level. Between 3% and 20% of these patients will eventually develop overt hypothyroidism. Patients who test positive for thyroid antibodies are at increased risk.
In patients with primary hypothyroidism, therapy should begin with thyroid hormone replacement. In patients with secondary hypothyroidism, further investigation with provocative testing of the pituitary can be performed to determine if the cause is a hypothalamic or pituitary problem.
Most healthy adult patients with hypothyroidism require about 1.6 μg/kg of thyroid replacement, with requirements falling to 1 μg/kg for the elderly. The initial dosage may range from 12.5 μg to a full replacement dose of 100-150 μg of levothyroxine (0.10-0.15 mg/d). Doses will vary depending on age, weight, cardiac status, duration, and severity of the hypothyroidism. Therapy should be titrated after at least 6 weeks following any change in levothyroxine dose. The serum TSH level is the most important measure to gauge the dose, and a free T4 estimate may be included as well.
Treatment of subclinical hypothyroidism remains controversial. The American Association of Clinical Endocrinologists (AACE) guidelines suggest treating patients with TSH levels higher than 10 μIU/mL as well as those with TSH levels between 5 and 10 μIU/ mL in conjunction with goiter or positive antithyroid peroxidase antibodies, or both. (Level of evidence for American Thyroid Association recommendations: level 3 or 4, clinical consensus based on the literature).
Once the TSH level reaches the normal range, the frequency of testing can be decreased. Each patient’s regimen must be individualized, but the usual follow-up after TSH is stable is at 6 months; the history and physical examination should be repeated on a routine basis thereafter.
Thyroid hormone absorption can be affected by malabsorption, age, and concomitant medications such as cholestyramine, ferrous sulfate, sucralfate, calcium, and some antacids containing aluminum hydroxide. Drugs such as anticonvulsants affect thyroid hormone binding, whereas others such as rifampin and sertraline hydrochloride may accelerate levothyroxine metabolism, necessitating a higher replacement dose. The thyroid dose may also need to be adjusted during pregnancy. There has been some interest in using a combination of T4 and triiodothyronine (T3) or natural thyroid preparations in pregnant women with hypothyroidism, but studies to date have been small and findings inconsistent.
Hyperthyroidism has several causes. The most common is toxic diffuse goiter (Graves disease), an autoimmune disorder caused by immunoglobulin G (IgG) antibodies that bind to TSH receptors initiating the production and release of thyroid hormone. Other causes include toxic adenoma; toxic multinodular goiter (Plummer disease); painful subacute thyroiditis; silent thyroiditis, including lymphocytic and postpartum thyroiditis; iodine-induced hyperthyroidism (eg, related to amiodarone therapy); oversecretion of pituitary TSH; trophoblastic disease (very rare); and excess exogenous thyroid hormone secretion.
Patients with hyperthyroidism usually present with progressive nervousness, tremor, palpitations, weight loss, dyspnea on exertion, fatigue, difficulty concentrating, heat intolerance, and frequent bowel movements or diarrhea. Physical findings include a rapid pulse and elevated blood pressure, with the systolic pressure increasing to a greater extent than the diastolic pressure, creating a wide pulse-pressure hypertension. Exophthalmos (in patients with Graves disease), muscle weakness, sudden paralysis, dependent low-extremity edema, or pretibial myxedema may also be present. Cardiac arrhythmias such as atrial fibrillation may be evident on physical examination or electrocardiogram, and a resting tremor may be noted on physical examination.
In patients with subacute thyroiditis, symptoms of hyperthyroidism are generally transient and resolve in a matter of weeks. There may be a recent history of a head and neck infection, fever, and severe neck tenderness. Postpartum thyroiditis may occur in the first few months after delivery. Both types of thyroiditis may have a transient hyperthyroid phase, a euthyroid phase, and occasionally a later hypothyroid phase.
Hyperthyroidism is detected by a decreased sensitive TSH assay and confirmed, if necessary, by the finding of an elevated free T4 level. Testing for thyroid autoantibodies, including TSH receptor antibodies (TRAb) or thyroid-stimulating immunoglobulins (TSI), may be done as necessary. Once hyperthyroidism is identified, radionucleotide uptake and scanning of the thyroid, preferably with iodine-123, is useful to determine whether hyperthyroidism is secondary to Graves disease, an autonomous nodule, or thyroiditis (ie, by showing activity and anatomy of the thyroid). In scans of patients with Graves disease, there is increased uptake on radionucleotide imaging with diffuse hyperactivity. In contrast, nodules demonstrate limited areas of uptake with surrounding hypoactivity, and in subacute thyroiditis, uptake is patchy and decreased overall.
Thyroid storm represents an acute hypermetabolic state associated with the sudden release of large amounts of thyroid hormone. This occurs most often in Graves disease but can occur in acute thyroiditis. Individuals with thyroid storm present with confusion, fever, restlessness, and sometimes with psychotic-like symptoms. Physical examination shows tachycardia, elevated blood pressure, and sometimes fever. Cardiac dysrhythmias may be present or develop. Patients will have other signs of high-output heart failure (dyspnea on exertion, peripheral vasoconstriction) and may exhibit signs of cardiac or cerebral ischemia. Thyroid storm is a medical crisis requiring prompt attention and reversal of the metabolic demands from the acute hyperthyroidism.
Radioactive iodine is the treatment of choice for Graves disease in adult patients who are not pregnant. It has also been used on an individual basis in patients younger than 20 years of age. To date, studies have shown no evidence of adverse effects on fertility, congenital malformations, or increased risk of cancer in women who were treated with radioactive iodine during their childbearing years or in their offspring. Patients should be advised to postpone pregnancy for at least 6 months postablation therapy.
Radioactive iodine should not be used in breast-feeding mothers. There is also concern that the administration of radioactive iodine in patients with active ophthalmopathy may accelerate progression of eye disease. For this reason, some experts initially treat Graves disease with oral suppressive therapy until the ophthalmologic disease has stabilized.
Antithyroid drugs are well tolerated and successful at blocking the production and release of thyroid hormone in patients with Graves disease. These drugs work by blocking the organification of iodine. Propylthiouracil (PTU) also prevents peripheral conversion of T4 to the more active T3. PTU must be given in divided doses (two or three times a day), whereas methimazole and carbimazole can be administered once a day. PTU can be used during pregnancy. The most serious side effect of these drugs is agranulocytosis, which occurs in 3 per 10,000 patients per year. Antithyroid drugs are especially useful in adolescents, in whom Graves disease may go into spontaneous remission after 6-18 months of therapy.
If it has been determined that symptoms of hyperthyroidism are due to thyroiditis, symptomatic treatment with a β-blocker can be used temporarily with little need for long-term therapy.
Surgery is reserved for patients in whom medication and radioactive iodine ablation are not acceptable treatment strategies or in whom a large goiter is present that compresses nearby structures or is disfiguring.
For patients with thyroid storm, aggressive initial therapy is essential to prevent complications. Treatment should include the administration of high doses of PTU (100 mg every 6 hours) to quickly block thyroid release and reduce peripheral conversion of T4 to T3. In addition, high doses of β-blockers (propranolol, 1-5 mg intravenously or 20-80 mg orally every 4 hours) can be used to control tachycardia and other peripheral symptoms of thyrotoxicosis. Hydrocortisone (200-300 mg/d) is used to prevent possible adrenal crisis.
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