AN ESTIMATED 27 MILLION Americans have been diagnosed with thyroid disease, and another 13 million have undiagnosed thyroid disorders.1 Clinicians may miss thyroid problems during routine assessments because many signs and symptoms, such as weight loss or gain, fatigue, thinning hair, and insomnia, are nonspecific and may mimic other disorders or age-related changes.
This article examines hyperthyroidism and hypothyroidism, including what causes these disorders and how they're diagnosed and treated. Let's start by reviewing normal anatomy and physiology.
Nestled in the neck
The thyroid gland lies in the neck, inferior to the thyroid cartilage and anterior to the trachea between the cricoid cartilage and the suprasternal notch. It comprises two lobes connected in the front by a narrow piece of tissue called the isthmus. The normal thyroid gland isn't visible on inspection (see Looking at the thyroid gland).
The thyroid gland produces two hormones. Almost 90% is thyroxine (T4); the remaining 10% is triiodothyronine (T3), the more potent and physiologically active of the two. Most T4 is converted into T3 in tissues.
Most (99%) of the thyroid hormones are bound to thyroid-binding globulins, thyroxine-binding prealbumin, and albumin.2 Bound hormone can't enter cells. Only about 1% is unbound. This "free" hormone enters cells and carries out thyroid functions, which fall into three categories: effects on metabolic rate, effects on growth, and effects on specific body mechanisms.3,4
Negative feedback maintains balance
Thyroid hormone production is regulated by the hypothalamic-pituitary-thyroid (HPT) axis in a negative feedback system, meaning that hormones in the HPT axis are secreted in response to need. Here's how the HPT axis works:
- The hypothalamus produces and secretes thyrotropin-releasing hormone (TRH).2
- TRH stimulates the anterior pituitary to secrete thyroid-stimulating hormone (TSH).
- TSH increases the production of T3 and T4.
If thyroid hormone levels are high, TRH secretion from the hypothalamus and TSH from the pituitary slows down to maintain homeostasis. Conversely, if thyroid hormone levels are low, secretion from the hypothalamus and pituitary increases.3
For a helpful analogy, think of the thyroid gland as a furnace and TSH as a thermostat. If the furnace (thyroid gland) is underactive or "cold" (hypothyroidism), the TSH level rises to increase thyroid hormone secretion and restore balance. If the thyroid gland is overactive or "hot" (hyperthyroidism), TSH levels drop to decrease thyroid hormone secretion. That's why low TSH levels indicate hyperthyroidism, and high TSH levels indicate hypothyroidism.
Primary causes of thyroid dysfunction include autoimmune problems such as Graves disease (hyperthyroidism) and Hashimoto thyroiditis (hypothyroidism). Secondary causes of thyroid dysfunction include pituitary tumors, surgery, or irradiation. Medications, such as glucocorticoids or lithium, can also cause thyroid dysfunction.1,3 (See What's behind thyroid dysfunction? for other possible causes of thyroid problems.)
Hypothyroidism is more common than hyperthyroidism, affecting 8% of women and 2% of men over age 50. By age 60, more than 20% of women are affected by hypothyroidism.4,5
Sorting out signs and symptoms
Because the thyroid gland affects nearly all body functions, thyroid dysfunction has head-to-toe consequences. Using the furnace analogy can help you distinguish signs and symptoms of hyperthyroidism from those of hypothyroidism.
- Hyperthyroidism turns the furnace up. The patient will report heat intolerance and diaphoresis, weight loss with increased appetite, nervousness, insomnia, tremulousness, and frequent bowel movements.
- Hypothyroidism turns the furnace down. The patient will report cold intolerance, dry, coarse skin, weight gain with poor appetite, fatigue, slow thinking, hypersomnia, and constipation.
For details on how thyroid dysfunction affects various body systems, see Manifestations of thyroid disease.
Patients with thyroid problems may visit their healthcare provider with complaints about signs and symptoms affecting their quality of life—for example, depression or anxiety, weight loss or gain, fatigue, or insomnia. Patients with these nonspecific complaints need a head-to-toe physical assessment and diagnostic testing to identify thyroid problems and rule out other disorders.
When obtaining the patient's health history, routinely ask about changes that might signal a thyroid problem. Without specific questioning, the patient may not think to report unintentional weight gain or loss, fatigue, thinning hair, insomnia, or other subtle clues suggesting thyroid dysfunction.
Getting a feel for the thyroid
It's important to keep in mind that some thyroid problems, such as thyroid cancer, may be asymptomatic initially, so inspection and palpation of the thyroid gland should be performed routinely.
To inspect the neck for the thyroid gland, tip the patient's head back slightly. Using tangential lighting directed downward from the tip of the patient's chin, inspect the region below the cricoid cartilage for the gland. Ask the patient to sip some water and extend the neck again and swallow. Watch for upward movement of the thyroid gland, noting its contour and symmetry. The thyroid cartilage, the cricoid cartilage, and the thyroid gland all rise with swallowing and then fall to their resting positions.
To palpate the thyroid gland, stand behind the patient and ask the patient to flex the neck slightly forward to relax the sternomastoid muscle. Lightly place the second through fourth fingers of both hands on the patient's neck so your index fingers are just below the cricoid cartilage. (See Palpating the neck for the thyroid gland.) Instruct the patient to sip and swallow water while you feel for the thyroid isthmus rising up under your finger pads. It's often but not always palpable.
Displace the trachea to the right with the fingers of your left hand; use your right-hand fingers to palpate laterally for the thyroid's right lobe in the space between the displaced trachea and the relaxed sternomastoid. Then palpate the left lobe in a similar fashion. Note the gland's size, shape, and consistency, as well as the presence of any tenderness or nodules.6 If you find a nodule, reassure the patient that most thyroid nodules (90% to 95%) are benign.7
The size of normal thyroid glands varies slightly based on a patient's height and weight, sex, and age, but they're typically small, weighing less than an ounce. The anterior surface of a lateral lobe is approximately the size of the distal phalanx of the thumb.6 Enlarged thyroid glands (goiters) vary in size from barely palpable to a visible goiter.
Each lobe should feel slightly firm and rubbery, approximately the same size, and without nodules or tenderness. The thyroid gland usually feels soft in Graves disease and firm in Hashimoto thyroiditis and malignancy.
Some conditions such as acute thyroiditis (inflammation of the thyroid gland), especially if associated with a viral disease, may cause tenderness.
Document all your assessment findings and notify the healthcare provider of any abnormalities.
The most sensitive test available to determine thyroid function is measurement of serum TSH. As discussed earlier, decreased TSH indicates hyperthyroidism and increased TSH indicates hypothyroidism. To differentiate overt and subclinical disease (mild thyroid hormone excess or deficiency), T4 is also measured (see Interpreting lab findings).
Some healthcare providers also test for thyroid antibodies to detect autoimmune thyroid disease, the most specific being antithyroid peroxidase (anti-TPO) antibody. Anti-TPO is an indirect enzyme-linked immunosorbent assay (ELISA) for the quantitative measurement of immunoglobulin-G class of autoantibodies against TPO. In almost all patients with autoimmune hypothyroidism and up to 80% of patients with Graves disease, anti-TPO levels are usually elevated.8 Because anti-TPO levels can be elevated in patients without thyroid disease, this test can't be relied upon as a screening or predictive tool.
Other diagnostic studies include:
- imaging studies, especially when nodules are found or suspected. An ultrasound can help distinguish whether a nodule is solid or cystic and may also help differentiate whether the nodule appears benign or malignant by looking at border edges, vascularity, and presence of microcalcifications. Radioactive iodine uptake scans can be useful in determining whether a nodule is hot (favors benign) or cold (favors malignancy).9
- fine needle aspiration to obtain cells from thyroid nodules to determine whether the nodule is benign or malignant.9
- a complete blood cell count, lipid profile, and complete metabolic profile may be ordered to discover any concomitant medical concerns. Patients with hypothyroidism may have iron deficiency anemia, dyslipidemia, hyponatremia, and a decreased glomerular filtration rate.9
Once a diagnosis is made, treatment is tailored to the disorder. Thyroid hormone replacement is indicated for patients with an underactive thyroid. If the thyroid is working overtime, treatments aim to slow it down. Cancerous thyroid glands are removed entirely; these patients will need thyroid replacement drug therapy after surgery. Let's examine treatment options more closely.
Synthetic thyroid hormone, levothyroxine, is prescribed to restore normal thyroid hormone levels in patients with hypothyroidism. Dosing is based on age, weight, and cardiac status. The drug takes full effect in 4 to 6 weeks.
Levothyroxine is available in various strengths, is well absorbed, and has a long half-life (about 7 days). When starting therapy, patients will need assessment and blood monitoring every 6 to 8 weeks until the TSH is within the normal range and signs and symptoms have improved. After that, TSH testing can be done annually.10
Drug components may vary slightly depending on the manufacturer, so tell patients to continue to take levothyroxine from the same manufacturer, whether generic or branded, unless otherwise instructed by their healthcare provider. If a new drug manufacturer is used, TSH levels should be reevaluated until stable.
Certain foods such as dietary fiber, certain drugs including antacids, and many other substances such as iron and calcium can interfere with levothyroxine absorption. Advise patients to take the drug at the same time each day on an empty stomach (preferably ½ hour to 1 hour before breakfast) with at least 8 ounces of water.10 Taking the drug at the same time each day will help to maintain constant hormone levels and help prevent insomnia. Tell them to consult their healthcare provider before taking any other medications, including over-the-counter products.
The biggest problem with thyroid hormone replacement is overreplacement and the development of signs and symptoms of hyperthyroidism. Long-term therapy causes bone loss in premenopausal and postmenopausal women and may increase osteoporosis risk.
Make sure patients understand that replacement therapy is lifetime therapy. Warn them not to stop taking it abruptly and to consult their healthcare provider about any problems or new signs and symptoms. Older adults with preexisting cardiovascular (CV) disease may experience chest discomfort, palpitations, sweating, nervousness, or shortness of breath, which could indicate overdose or aggravated CV disease. In patients taking warfarin, levothyroxine may increase anticoagulant effects. Advise patients to report any unusual bleeding or bruising.
Treatment for hyperthyroidism is more complicated than that for hypothyroidism, so it's best managed by an endocrinologist. Radioactive iodine therapy is the treatment of choice because it's easily administered orally as a single dose, in capsule or liquid form, and associated with fewer complications than other options.11
Radioactive iodine concentrates in the thyroid, interfering with thyroid hormone synthesis and gradually destroying thyroid tissue. Consequently, most patients develop hypothyroidism within 3 months after receiving this therapy and then need levothyroxine therapy. The effectiveness of radioactive iodine is monitored by measuring thyroid hormone levels, with or without TSH levels, every 4 to 6 weeks.1,11,12
Radioactive iodine is contraindicated during pregnancy because it can cross the placental barrier and disable the baby's thyroid gland. Advise women to use effective contraception while on this therapy and to delay pregnancy for at least 6 months after ending treatment. The treatment is contraindicated in breastfeeding women because radioactive iodine can be transmitted in breast milk.
Radioactive iodine is shed in stool, urine, and other body secretions. Tell patients to avoid body fluid contact with others, especially children and pregnant women, for 48 to 72 hours after treatment, and teach them to double-flush the toilet during this time.
Surgery to remove the thyroid gland is usually indicated only when treatment with radioactive iodine is contraindicated. Possibly serious complications to surgery include hemorrhage, hypoparathyroidism, laryngeal edema, and vocal cord paralysis. If surgery is necessary, the surgeon may perform only a subtotal thyroidectomy to prevent hypothyroidism requiring thyroid hormone replacement.1
Antithyroid drugs (thionamides) such as propylthiouracil (PTU) and methimazole may be prescribed for patients with mild disease in which remission may be easier to achieve or for those with contraindications to radioactive iodine. They may also be used to reduce thyroid levels before radioactive iodine treatment.
Antithyroid drugs are usually administered for 12 to 18 months. Patients are assessed every 3 months for the first year. Fifty to 60% of patients relapse within the first 3 to 6 months after stopping the drug, indicating that the drug should be reinstituted or another form of treatment considered.1
Iodine products may be given to inhibit thyroid hormone release.10 Because of its rapid onset, iodine is often used to treat thyrotoxicosis or thyroid storm. To stabilize the thyroid gland, it may also be used as an adjunct to radioactive iodine or be given before thyroidectomy. Two commonly used iodine products are saturated solution of potassium iodide and Lugol solution.10
Iodine has its disadvantages. Some patients don't respond at all or only minimally. Iodine's effects last only for a few weeks, and T4 levels can rise quickly when iodine treatment stops. In patients with multinodular disease, nodules may take up the iodine and produce more thyroid hormone, actually increasing the severity of hyperthyroidism.
Beta-blockers may be used as adjunctive therapy in patients with hyperthyroidism accompanied by atrial fibrillation to slow the ventricular response rate. They may also help lower the patient's body temperature and decrease diaphoresis, tremors, palpitations, and anxiety.
Watch out for complications
Life-threatening complications of thyroid disease include myxedema coma with hypothyroidism and thyroid storm with hyperthyroidism. They can result from undiagnosed or incorrect treatment of thyroid disease, or a precipitating factor such as trauma, infection, or surgery. Fortunately, both are rare.
Extreme hypothyroidism, or myxedema coma, is caused by a precipitous drop in thyroid hormone levels, usually from the patient not taking enough hormone replacement, or stopping therapy abruptly. Other risk factors include new-onset heart failure, recent stroke, and use of certain drugs such as amiodarone, lithium, phenothiazines, and tranquilizers. Myxedema coma can also occur in a patient with undiagnosed hypothyroidism.13
Signs and symptoms of impending myxedema coma are similar to those of hypothyroidism but more exaggerated, and include weakness, confusion, hypothermia, edema, and breathing difficulties. If left unchecked, confusion can change to coma. Myxedema coma often occurs in older adult women in the winter months; altered mental status is an important warning sign.13
To treat myxedema coma, administer supplemental oxygen and provide ventilatory support as indicated. Levothyroxine will be ordered to replenish the lack of thyroid hormone available and can be given I.V. at first and orally later.
Thyroid storm results from too much thyroid hormone. The patient will present with exaggerated signs and symptoms of hyperthyroidism, including an extremely high body temperature (up to 105.3° F [40.7° C]), severe tachycardia with heart failure and shock, restlessness and agitation, nausea and vomiting, diarrhea, weakness, and confusion or disorientation. The cardinal sign is an extremely high fever that's not consistent with other signs and symptoms.14
To treat thyroid storm, initiate continuous cardiac monitoring, administer supplemental oxygen, and establish vascular access for possible aggressive fluid resuscitation. A patient experiencing thyroid storm can deteriorate to hypovolemic shock, so monitor fluid intake and output to help gauge the exact amount of fluid replacement needed.14
As ordered, administer an antithyroid drug such as PTU or methimazole and large amounts of iodine to decrease thyroid hormone production.
Beta-blockers may be indicated to help prevent CV collapse. Propanolol can help inhibit the peripheral conversion of T4 to T3, but it's contraindicated in patients with bronchospastic disease.14 For these patients, administer a selective beta-blocker such as esmolol, a beta 1-specific antagonist with a short duration of action, with caution.11
Aggressively control hyperthermia by applying ice packs and cooling blankets and by administering acetaminophen.11 Avoid aspirin because it increases free T3 and T4 levels.14 Closely monitor the patient's cardiac rhythm, vital signs, and intake and output.
Make sure your patients with thyroid disease understand that their condition is lifelong, so they need frequent and regular follow-up, including blood work.
Teach patients with hypothyroidism the signs and symptoms of not only that disease, but also of hyperthyroidism, which may develop from overtreatment. The same is true for those with hyperthyroidism.
Besides monitoring the thyroid and anterior pituitary gland that releases TSH, the healthcare provider will also want to monitor other changes that can occur with the disease. These include anemia, dyslipidemia, depression, menstrual changes, BP abnormalities, electrolyte disturbances, and changes in blood glucose levels. Help your patient understand the importance of annual checkups and lab tests for other conditions and situations that may have been uncovered during thyroid disease assessment.
Discuss with your patients the signs and symptoms of the serious complications of each disease, specifically myxedema coma and thyroid storm. Emphasize that they should call 911 if they experience any signs or symptoms associated with either condition.
Thyroid diseases are manageable if they're diagnosed correctly and treated promptly. With your help, your patients can gain a better understanding of their disease and how to best control it.