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Treatment of Hyper- and Hypothyroidism
Committees from AACE and ATA are currently working on updating the hyper- and hypothyroidism treatment guidelines.
Reviewed by Jeffrey R. Garber, MD; By Conni Bergmann Koury, Editor-in-Chief
Diagnosing thyroid disease can be challenging. According to the American Association of Clinical Endocrinologists (AACE), the sensitive thyroid-stimulating hormone (TSH or thyrotropin) assay has become the single best screening tool for hyper- and hypothyroidism. Additionally, serum TSH is the most sensitive test for detecting mild thyroid hormone excess or deficiency.1
Committees from AACE and the American Thyroid Association (ATA) are currently working on updated guidelines for the diagnosis and treatment of both hyper- and hypothyroidism. Jeffrey R. Garber, MD, Associate Professor of Medicine at Harvard Medical School and Chief of Endocrinology at Harvard Vanguard Medical Associates, spoke to Review of Endocrinology and provided a preview of what will be addressed by the new guidelines.
BACKGROUND
Hyper- and hypothyroidism are highly prevalent conditions that usually come to the attention of the primary care physician first.2 Hyperthyroidism develops when the body produces too much thyroxine.3 This disorder occurs in almost 1% of Americans and affects women five to ten times more often than men. In its mildest form hyperthyroidism may not cause recognizable symptoms, otherwise the symptoms can be discomforting, disabling, or even life-threatening. The condition can significantly accelerate the body's metabolism, causing sudden weight loss, a rapid or irregular heartbeat, sweating, and nervousness or irritability.
Several treatment options exist for patients with hyperthyroidism, such as antithyroid medications and radioactive iodine to slow the production of thyroid hormones. Treatment can include surgery. Graves' disease, the most common cause of hyperthyroidism, occurs when the immune system mistakenly attacks the thyroid gland and causes it to overproduce thyroxine. Graves' disease is rarely life-threatening, and can develop at any age in either men or women. It is, however, more common in women and usually begins after age 20 years.
Hypothyroidism—underactivity of the thyroid gland—occurs when the thyroid gland produces less than the normal amount of thyroid hormone. The result is the slowing down of many bodily functions, and although it may be temporary, it is usually a permanent condition.
Estimates of Americans with thyroid dysfunction vary from 10 to 12 million to as high as 25 to 30 million. Most have hypothyroidism. The overwhelming majority of cases are due to chronic immune (Hashimoto's) thyroiditis, radioactive iodine therapy, or surgery.
HYPERTHRYOIDISM
Causes of hyperthyroidism include:
- Graves' disease (toxic diffuse goiter)
- toxic adenoma
- Plummer's disease (toxic multinodular goiter)
- painful subacute thyroiditis
- silent thyroiditis
- iodine-induced hyperthyroidism
- excessive pituitary TSH or trophoblastic disease
- excessive ingestion of thyroid hormone
The signs of hyperthyroidism are attributable to the effects of excess thyroid hormone, and the severity of the symptoms can vary (Table 1). To diagnose the condition (Table 2), a comprehensive history should be performed and a laboratory evaluation must be made (Table 3). Although the diagnosis of overt Graves' disease with ophthalmopathy is obvious, it may be more difficult in elderly patients.
SCREENING and TREATMENT FOR HYPERTHYROIDISM
New guidance emerging from the upcoming AACE/ATA clinical guidelines regarding hyperthyroidism will address:
- Subclinical hyperthyroidism: who, when, and how? "The approach to elderly patients, postmenopausal women, and those with heart disease or osteoporosis will differ from the approach to healthy, younger patients," Dr. Garber said.
- Stratification of patients with subclinical hyperthyroidism, meaning those with very low TSH as opposed to those who are just below the normal limit.
- The optimal choice for antithyroid drugs and the optimal monitoring of patients on antithyroid drugs. "We are also going to address about some of the issues surrounding propylthiouracil and its potential for toxicity," he said.
- What types of surgery should be performed and what patients should receive which procedures.
- Who should perform thyroid surgery.
- The use of radioiodine.
- The role of long-term antithyroid therapy.
- Special considerations will be discussed, such as surgery for thyroid disease in pediatric patients and the treatment of those with Graves' ophthalmopathy, and the role of TSH receptor antibodies in certain cases.
HYPOTHYROIDISM
In the United States, the most common form of primary hypothyroidism is chronic autoimmune thyroiditis (Hashimoto's disease). Other causes include surgical removal of the thyroid gland, thyroid gland ablation with radioactive iodine, external irradiation, a biosynthetic defect in iodine organification, lymphoma, and drugs such as lithium or interferon. Central causes can include pituitary and hypothalamic disease.
Symptoms of hypothyroidism typically relate to the duration and severity of the condition (Table 4). Usually any physician can make the diagnosis of hypothyroidism, however, a clinical endocrinologist may be needed in certain situations (Table 5). To diagnose the condition, an appropriate laboratory evaluation of TSH level is critical (Table 6).
SCREENING AND TREATMENT FOR HYPOTHYROIDISM
According to Dr. Garber, the new AACE/ATA hypothyroid guidelines will include more than 30 recommendations. Specific areas that the guidelines will address are thyroid antibodies—including TSH receptor antibodies: Under what circumstances and in which patients should these measurements be used? The guidelines will also discuss the role of clinical scoring systems in the evaluation of patients with hypothyroidism, the role of diagnostic tests apart from serum TSH and serum thyroid hormone levels in patients with hypothyroidism (for example, cholesterol and muscle enzymes), and the preferred thyroid hormone measurements that should be made in addition to TSH in patients with hypothyroidism.
Other questions to answered by the new guidelines include:
- Should different tests be used in pregnant patients?
- When should thyroid testing be performed in hospitalized patients?
- When should TSH levels be measured in patients being treated for hypothyroidism?
A controversial area to be covered in the upcoming guidelines is defining the upper normal of TSH. For example, Dr. Garber said, should patients with a TSH between 2.5 µIU/L and the upper limit of normal for a given lab test be considered for treatment with thyroid hormone? How can we identify these patients, and which of these patients who have TSH levels above the given laboratory reference should be considered for treatment?
"A very interesting area of discussion that will be covered in the guidelines," Dr Garber said, "is when should patients with normal thyroid levels be considered for treatment?" Specifically this speaks to euthyroid women who are pregnant or planning to get pregnant, and who have a history of positive thyroid peroxidase antibodies. "Can miscarriages and premature delivery be reduced by treating these women with thyroid hormone?"
The upcoming AACE/ATA guidelines will address the patient populations that should be evaluated for hypothyroidism and if screening has a role in this disease. "Or, if you do not believe in screening, which patients, such as those with certain comorbid conditions, should be evaluated for aggressive case findings that indicate evaluation and potential treatment," Dr. Garber said.
The new guidelines will look at the role of desiccated thyroid hormone and T3 and T4 combinations, and special concerns in pregnancy for either of these. More questions to be addressed include:
- How should older people with hypothyroidism be treated?
- How should people with adrenal insufficiency be treated?
- How is hypothyroidism best managed during pregnancy?
"Physicians who are not necessarily endocrinologists but are familiar with the diagnosis and treatment of hypothyroidism should be able to take care of most patients with primary hypothyroidism," Dr. Garber said. "Some, however, fall into separate categories and should be seen by endocrinologists, for example pregnant women." The experts will also make recommendations regarding which patients should not be treated with thyroid hormone; the use of thyroid hormone in treating obesity and depression; and the roles of iodine supplementation and selenium, an emerging area of research.
The AACE/ATA guidelines will highlight the complexity of thyroid disease. It is important to note, said Dr. Garber, that "subclinical disease often remains undiagnosed, but through sound judgment, timely intervention, and patient involvement, an optimal level of care is attainable."
Jeffrey R. Garber, MD, is Associate Professor of Medicine at Harvard Medical School and Chief of Endocrinology at Harvard Vanguard MedicalAssociates. He may be reached at jgarber@bidmc.harvard.edu.
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