A. Introduction. Thyroid hormone affects virtually all systems, and abnormal thyroid function may have protean manifestations. The first step is to decide whether the patient is hypothyroid or thyrotoxic based on clinical manifestations and the results of thyroid function tests. Treatment is then determined on the underlying cause, symptoms, and additional testing. Hypothyroidism and thyrotoxic states are most frequently encountered in the outpatient setting but in severe cases may require hospitalization.
B. Approach to the Patient. Because thyroid hormone affects virtually all systems, abnormal thyroid function has protean manifestations. The simplest approach is to:
a. Decide whether the patient is hypothyroid or hyperthyroid based on clinical manifestations and the results of thyroid function tests.
b. List the possible causes of the abnormal thyroid function and use the clinical and laboratory data available to begin a process of elimination.
c. Determining the etiology of thyrotoxicosis may require a radioactive iodine uptake study.
i. Primary hypothyroidism results from a thyroid abnormality. Common causes include:
1. Hashimoto’s disease (the most common cause and a chronic autoimmune process)
2. Thyroiditis (subacute, postpartum)
3. Drugs such as thionamides, lithium, amiodarone, iodide, interferon-α, tyrosine kinase inhibitors, and interleukin-2 (IL-2). Remember that drugs can cause either thyroiditis or thyrotoxicosis!
4. Surgical resection or radiation of the thyroid gland
ii. Secondary hypothyroidism results from pituitary disorders.
iii. Tertiary hypothyroidism results from disease affecting the hypothalamus.
b. Clinical manifestations of hypothyroidism
1. Weakness, fatigue, somnolence, and lethargy
2. Arthralgias or myalgias
3. Cold intolerance
4. Skin dryness or edema
5. Slow speech or hoarseness
6. Menorrhagia, galactorrhea, or both
7. Weight gain (usually no more than 10 lbs)
9. Decreased hearing
10. Carpal tunnel syndrome
1. Brittle nails or thin, coarse hair
2. Delayed return phase of deep tendon reflexes
3. Puffiness of the face and eyelids or thickened tongue
4. Pitting edema
5. Effusions (anywhere)
6. Hypothermia, bradycardia, or hypotension in severe cases
7. Goiter (enlargement of the thyroid gland) is variably present and can occur with both hypothyroidism and hyperthyroidism.
iii. Laboratory studies
1. Elevated levels of thyroid-stimulating hormone (TSH) and decreased levels of free thyroxine (T4) are diagnostic of primary hypothyroidism. Both tests are low in secondary and tertiary hypothyroidism.
2. Serum levels of cholesterol, creatine kinase, prolactin, and liver enzymes may be increased as a result of low thyroid hormone.
3. Anemia, usually normocytic or macrocytic, may occur with long-standing hypothyroidism.
4. Hyponatremia may occur with severe hypothyroidism.
5. Positive antithyroid antibodies (e.g., anti-TPO or antimicrosomal antibodies and antithyroglobulin antibodies) in patients with Hashimoto’s disease. However, antithyroid antibodies may also be present in a variety of other thyroid disorders (e.g., subacute and postpartum thyroiditis, Graves’ disease, and thyroid cancer).
6. Nonspecific EKG findings such as sinus bradycardia, low-voltage QRS complexes, and T wave abnormalities may occur.
i. Primary hypothyroidism. Replacement therapy with levothyroxine is the treatment of choice in all cases of primary hypothyroidism.
1. If the free T4 is normal and the patient has only mild symptoms, start therapy at just below the expected final replacement dose (1.5 μg/kg of lean body mass/day of l-thyroxine).
2. In older patients or those with heart disease, if free T4 is low or the patient is significantly symptomatic, start with a low dose of thyroxine (e.g., 25 μg given orally daily) and increase by 25 to 50 μg every 2–4 weeks until a maintenance dose level is achieved.
3. TSH levels should be monitored every 6–8 weeks until the patient is biochemically euthyroid. Thereafter, monitoring can take place on an as-needed basis.
ii. Secondary or tertiary hypothyroidism. Levothyroxine should be administered only after adrenal insufficiency has been excluded or treated.
d. Myxedema coma is a life-threatening manifestation of hypothyroidism; usually patients are stuporous, hypothermic, bradycardic, hypotensive, hypoxemic, and hypercapnic.
i. Approach to the patient. Because myxedema coma almost always results from longstanding hypothyroidism, make sure to search for, and treat, the precipitating cause of the acute decompensation (e.g., infection, ischemia, stroke, acute abdominal event, pulmonary embolus, myocardial infarction) in patients with hypothyroidism.
ii. Treatment. Patients often require care in the intensive care unit (ICU). A careful search for triggers and evaluation of glucocorticoid deficiency is necessary. Intravenous levothyroxine may be administered after adrenal insufficiency has been excluded or treated.
a. There are many causes of “thyrotoxicosis” (a term that simply implies symptoms and signs attributed to increased levels of thyroid hormones). The causes can be subdivided into those that are attributable to thyroid hyperfunction (hyperthyroidism) versus those that are not. A radioactive iodine uptake will reveal the functional status of the gland, expressed as the percentage of radioactive iodine captured by the thyroid.
i. Hyperfunctioning thyroid (hyperthyroidism). In these cases, high radioactive iodine uptake will be seen.
1. TSH-secreting tumor. This pituitary tumor is rare and should be considered in thyrotoxic patients with normal (or moderately elevated) TSH levels.
2. Autonomous toxic adenomas. Hyperthyroidism may be caused by a single adenoma or by a toxic multinodular goiter. There are no associated Graves’-specific findings, such as infiltrative ophthalmopathy, antithyroid antibodies, or thyroid-stimulating immunoglobulins (TSIs).
MNEMONIC: Causes of Thyrotoxicosis/Hyperfunctioning Gland (“TAG”)
Autonomous toxic adenoma (younger patients) or multinodular goiter (older patients)
ii. Damaged or nonfunctioning thyroid. The thyroid uptake will reveal low radioactive iodine uptake.
1. Factitious thyrotoxicosis results from the ingestion of large amounts of exogenous thyroid hormone.
2. Iodine-induced thyrotoxicosis (Jod-Basedow disease) occurs when a patient with a multinodular goiter receives a large iodine load (e.g., following radiographic contrast studies or amiodarone therapy).
3. Struma ovarii. An exceedingly small percentage of ovarian dermoid tumors and teratomas contain thyroid tissue, which may autonomously secrete thyroid hormone. In these cases, low uptake in association with a thyrotoxic state may be observed.
4. Thyroiditis (subacute, painless, postpartum) is an autoimmune disease resulting in thyroid destruction. In the early phase, thyrotoxicosis can result from leakage of intracellular thyroid hormone as cells are destroyed. Hypothyroidism typically follows and may be transient or permanent.
MNEMONIC: Causes of Thyrotoxicosis—Decreased or Absent Thyroid Function (“FIST”)
b. Clinical manifestations of thyrotoxicosis
1. Nervousness, emotional lability, and restlessness
2. Heat intolerance and increased sweating
3. Fatigue, weakness, and muscle cramps
4. Palpitations and angina
5. Weight loss (despite hyperphagia) and hyperdefecation (not diarrhea)
1. Agitation and anxiety
2. Warm, moist palms
3. Stare and lid lag
4. Fine tremor and hyperreflexia
5. Irregularly irregular pulse (a sign of atrial fibrillation), widened pulse pressure, and, occasionally, evidence of high-output heart failure
iii. Laboratory studies
1. Serum free T4 and free T3 are usually increased, and serum TSH is suppressed (except with a TSH-secreting tumor).
2. Hypercalcemia, anemia, and increased alkaline phosphatase levels may occur in thyrotoxicosis.
c. Treatment. There are many ways to treat thyrotoxic patients—with the choice depending on the cause and clinical setting.
i. Symptomatic relief is provided by β-blockers (e.g., propranolol). β-blockers do not decrease thyroid hormone secretion but help reduce adrenergic stimulation and associated side effects.
ii. Reduction of thyroid hormone secretion (in true hyperthyroidism) can be accomplished using thionamide drugs (methimazole, propylthiouracil), radioactive iodine, or thyroid surgery.
iii. Thyroiditis. Patients with thyrotoxicosis secondary to thyroiditis are best treated symptomatically (typically with β-blockers) until the condition resolves spontaneously. As the acute phase resolves, treatment for hypothyroidism, either transiently (if thyroid function returns) or permanently, may be required. For painful thyroiditis, nonsteroidal antiinflammatory drugs (NSAIDs) and steroids can be considered for symptomatic relief.
d. Thyroid storm is a life-threatening exacerbation of thyrotoxicosis.
i. Approach to the patient. Always look for a precipitating cause of clinical decompensation as well as the etiology of thyrotoxicosis (e.g., myocardial infarction, infection, surgery).
ii. Clinical manifestations include the usual features of thyrotoxicosis and the precipitating event, plus fever and psychosis (hallmarks of thyroid storm), nausea, vomiting, and seizures.
iii. Treatment goals include suppression of the effects of thyroid hormone and rapid reduction of circulating thyroid hormone levels.
1. These goals are usually accomplished by a combination of β-blockade, thionamide therapy, corticosteroids, and radioactive iodide treatment (following thionamide administration). Aspirin should be avoided because it displaces thyroid hormone from its binding protein.
2. Definitive treatment occurs after the patient is rendered euthyroid.
Suggested Further Readings
Burch HB, Wartofsky L. Life-threatening thyrotoxicosis: thyroid storm. Endocrinol Metab Clin North Am 1993;22:263–77. (Classic Article.)Find this resource:
De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet 2016;388:906–18.Find this resource:
Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003;348:2646–55.Find this resource:
Peeters RP. Subclinical hypothyroidism. N Engl J Med 2017;376:2556–65.Find this resource:
Smith TJ, Hegedüs L. Graves’ disease. N Engl J Med 2016;375:1552–65.Find this resource:
Stott DJ, Rodondi N, Kearney PM, et al. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med 2017;376:2534–44.Find this resource: