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Menopause Matters

Thyroid Disease: A Primer for the Care of Midlife Women

Cynthia A. Stuenkel, MD

Thyroid disorders become more prevalent with age, and many of the symptoms mimic those of menopause. Given the potential for confusion, the physician must exercise great care to diagnose and treat the appropriate condition.

Symptoms common to the menopausal transition can be confused with symptoms of thyroid dysfunction—including altered menstrual cycle (frequency, length, amount of bleeding), sleep disruption, fatigue, mood swings, forgetfulness, heat intolerance, and palpitations. Indeed, in a subset of more than 3,000 multiethnic women aged 42 to 52 years, almost 10% had a thyroid-stimulating hormone (TSH) level outside the normal range—66% higher than normal, and 33% below normal. 1

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HYPOTHYROIDISM

Hypothyroidism is the most common thyroid disorder in women; by age 60 years, up to 17% of women have an underactive thyroid.2 A hypothyroid woman might complain of fatigue, dry skin, and heavier, longer menstrual cycles. If a woman has a family history of thyroid disorders or a personal history of postpartum thyroiditis, radioactive iodine treatment for Graves disease, diabetes, polycystic ovary syndrome, or other endocrine disorders, her risk of hypothyroidism increases. An elevated triglyceride level on a lipid panel may also suggest the diagnosis.

Diagnosis

The serum TSH determination is the current “gold standard” for diagnosing hypothyroidism. The normal range is 0.45 to 4.5 mIU/L.3 If the TSH value is elevated, free thyroxine (FT4) should be measured to confirm the diagnosis. Elevated TSH and FT4 levels may be suggestive of a rare TSH-producing pituitary adenoma. More likely, the patient has already been diagnosed with hypothyroidism but been noncompliant with her thyroid medication, and she was trying to “catch up” prior to her office visit.

Contrary to recommendations by the American Thyroid Association (ATA) (ie, screen all adults beginning at age 35 years and every 5 years thereafter),4 the US Preventive Services Task Force recently concluded that the evidence is insufficient to recommend for or against routine screening for thyroid disease in adults.5 The Canadian Task Force’s Periodic Health Examination seems more prudent; it recommends maintaining a high index of clinical suspicion for nonspecific symptoms consistent with hypothyroidism when examining perimenopausal and postmenopausal women.6

Treatment

Recent guidelines recommend reserving treatment for patients with TSH levels > 10 mIU/L,3,7 but identifying appropriate candidates for therapy remains a subject of some debate. An asymptomatic woman with no history of thyroid disease who has a TSH value of 4.5 to 10 mIU/L with a normal FT4 value would qualify for a diagnosis of mild thyroid failure (previously called “subclinical hypothyroidism”), and would merit close annual monitoring—particularly if she has positive findings for antithyroperoxidase antibodies, which portend a higher likelihood of overt hypothyroidism.

The usual replacement dose of synthetic thyroxine (levothyroxine) averages 1.6 mcg/kg body weight per day. Therapy should be initiated at 50 to 100 mcg/d and titrated at 6-week intervals by 25 to 50 mcg depending on TSH levels (more gingerly if the patient is older or at substantial risk for coronary heart disease).8 In treated patients, the target range for TSH is 0.5 to 2.0 mIU/L, with FT4 falling in the upper third of the normal range. Once the replacement dose is established, TSH values should be checked every 6 to 12 months, or if the patient changes thyroid hormone preparations (eg, insurance or pharmacy change). The patient should be cautioned that concurrent administration of thyroxine with food, vitamins, calcium, or iron may significantly interfere with its absorption.

If the patient starts estrogen therapy (ET) to alleviate menopausal symptoms, her TSH levels should be assessed at 6 weeks, as the dose of thyroid hormone may need to be increased.9 Oral estrogens, in particular, increase thyroid-binding globulin levels, which in turn reduce FT4 values. A normally functioning thyroid gland compensates by increasing thyroid hormone production to maintain FT4 values, but a hypoactive thyroid cannot do this. When the patient discontinues ET, her thyroid function should be reevaluated and her thyroxine dose decreased if necessary. Several case reports have also described the need to increase the dose of thyroxine when raloxifene10,11 or soy supplements12 are initiated in hypothyroid women.

There has been some speculation that thyroid-hormone replacement therapy may increase the risk of osteoporosis. In the Study of Osteoporotic Fractures,13 use of thyroid hormone itself did not increase fracture risk if the TSH was maintained in the normal range. However, suppressed TSH levels ( 0.1 mIU/L)—either as a result of excess endogenous thyroid hormone production or exogenous thyroid hormone use—were associated with a 3-fold increase in hip fractures and a 4-fold increase in vertebral fractures in women aged 65 years. As assessed by TSH measurements, approximately 20% of patients receiving thyroxine therapy may be overtreated.3 If the patient has been hyperthyroid, or using thyroxine therapy for many years (possibly at a higher dose than currently recommended), her bone mineral density should be tested—preferably at a cortical site such as the hip.14

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HYPERTHYROIDISM

Diagnosis

ymptoms of hyperthyroidism—especially anxiety, palpitations, lighter and less frequent periods, and heat intolerance—may also mimic menopausal symptoms. The initial diagnostic test of choice remains the TSH level. If the TSH value is < 0.1 mIU/L, FT4 should be measured to assess the degree of thyroid hormone excess. If the FT4 value is normal, the triiodothyronine level should be measured and, if elevated, might point to the presence of an autonomously functioning thyroid nodule. When the FT4 value is above the normal range, a radioactive iodine thyroid uptake scan can be used to confirm the diagnosis of hyperthyroidism and define thyroid anatomy. Markedly increased uptake in a homogenous distribution is consistent with Graves disease, while a heterogeneous distribution is consistent with multinodular goiter. A lack of uptake points to a diagnosis of thyroiditis.

Treatment

Treatment of hyperthyroidism usually includes transient “cooling” with β-blockers for symptomatic relief. In addition, if the diagnosis is Graves disease or multinodular goiter, concurrent antithyroid drugs (propylthiouracil or methimazole) should be used as well. Radioactive iodine thyroid ablation is the definitive therapy for Graves disease and toxic multinodular goiter. Patients with TSH levels of 0.1 to 0.45 mIU/L and normal FT4 levels meet the criteria for “subclinical hyperthyroidism,” for which the potential risks and benefits of treatment are less certain.3 Most hyperthyroid women should be referred to an endocrinologist for consultation and therapeutic intervention.

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THYROID NODULES

Ultrasonographic examinations in asymptomatic persons suggest that nodules occur in as many as 19% to 67% of the population.15 The majority of nodules are benign, but 5% to 10% are malignant. The risk of thyroid cancer increases with age, a history of radiation, a positive family history, rapid growth of the nodule, and hoarseness. The ATA has issued new guidelines for evaluation and management of thyroid nodules and thyroid cancers.15 If a thyroid nodule is suspected on physical examination, the next step is thyroid ultrasonography to define the anatomy of the gland and accurately measure the nodule—an important parameter for management decisions and long-term follow-up. If the patient's TSH level is low, a radioactive iodine uptake test should be performed to ascertain whether the nodule is functioning autonomously. Because “hot nodules” are rarely malignant, therapy for hyperthyroidism can be considered. If the TSH value is normal or elevated and the nodule is > 1 to 1.5 cm in diameter, the patient should be referred to an endocrinologist for fine-needle aspiration. The cytology of the cellular aspirate will dictate further management.

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CONCLUSION

An awareness of common thyroid disorders will enable physicians to take the necessary steps to diagnose and manage these conditions as they arise in midlife. Distinguishing thyroid dysfunction from normal menopausal changes will expedite diagnosis and ensure prompt, effective treatment..

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Cynthia A. Stuenkel, MD, is a member of The North American Menopause Society Board of Trustees; and clinical professor of medicine, Division of Endocrinology and Metabolism, University of California at San Diego, La Jolla.

References

1. Sowers M, Luborsky J, Perdue C, et al. Thyroid stimulating hormone (TSH) concentrations and menopausal status in women at the mid-life: SWAN. Clin Endocrinol (Oxf). 2003;58(3):340-347.
2. American Association of Clinical Endocrinologists. Thyroid Fact Sheet, 2005. Available at: http://www.aace.com/public/awareness/tam/2006/pdfs/ThyroidFactSheet.pdf. Accessed October 10, 2006.
3. Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291(2):228-238.
4. Ladenson PW, Singer PA, Ain KB, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med. 2000;160(11):1573-1575.
5. US Preventive Services Task Force. Screening for thyroid disease: recommendation statement. Ann Intern Med. 2004;140(2):125-127.
6. Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa, Canada: Canada Communication Group; 1994:611-618.
7. Col NF, Surks MI, Daniels GH. Subclinical thyroid disease: clinical applications. JAMA. 2004;291(2):239-243.
8. Demers LM, Spencer CA. Laboratory support for the diagnosis and monitoring of thyroid disease. In: The National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines, 2002. Available at: http://www.nacb.org/lmpg/thyroid_lmpg_pub.stm. Accessed October 10, 2006.
9. Arafah BM. Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med. 2001;344(23):1743-1749.
10. Garwood CL, Van Schepen KA, McDonough RP, Sullivan AL. Increased thyroid-stimulating hormone levels associated with concomitant administration of levothyroxine and raloxifene. Pharmacotherapy. 2006;26(6):881-885.
11. Siraj ES, Gupta MK, Reddy SS. Raloxifene causing malabsorption of levothyroxine. Arch Intern Med. 2003;163(11):1367-1370.
12. Bell DS, Ovalle F. Use of soy protein supplement and resultant need for increased dose of levothyroxine. Endocr Pract. 2001;7(3):193-194.
13. Bauer DC, Ettinger B, Nevitt MC, Stone KL; Study of Osteoporotic Fractures Research Group. Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med. 2001;134(7):561-568.
14. Greenspan SL, Greenspan FS. The effect of thyroid hormone on skeletal integrity. Ann Intern Med. 1999;130(9):750-758.
15. Cooper DS, Doherty GM, Haugen BR, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006;16(2):109-142.

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