For many years the American Thyroid Association has recommended close monitoring of all patients treated with thyroid hormone (1). The reason for this recommendation is that many patients are either overtreated or undertreated based on their blood TSH (thyroid stimulating hormone) levels (2), which may lead to adverse effects .
This problem has been found to be especially important in post menopausal women and older men (3) who are at increased risk for fractures from worsening osteoporosis when overtreated with thyroid hormones (4). Thyroid hormones have a direct action on bone cells leading to bone loss (5) . TSH, which may play a role in protecting bone (6), is also low in overtreated patients. On the other hand, patients with hypothyroidism treated with doses of thyroxine that keep TSH within the normal range, do not appear to be at increased risk of fracture (4,7). For this reason, regular monitoring of thyroid replacement therapy every 6-12 months once stabilized, using serum TSH as a gauge, is the current standard of care (1).
This issue is again emphasized by a new study from Toronto, Canada published in the British Medical Journal examining the health records of 213,511 patients over the age of 70 years who were taking thyroxine over a 3.8 year period (8). 10.4% had a fracture during this time and 88% of the fractures were in women. The risk of fracture was almost double for those currently taking thyroid hormone as compared to those who only used it years ago. Those patients taking higher doses of thyroxine were more likely to have had a fracture than those taking lower doses. Unfortunately serum TSH data were not available so it is not certain which patients were properly treated, but it is plausible that many patients were overtreated, especially those who received higher doses. This supports the importance of avoiding overtreatment with thyroxine by adjusting the dose carefully through TSH monitoring.
Age itself is a risk factor for osteoporosis and fracture (9). Additionally, older patients need less thyroxine to maintain a euthyroid state (10,11). Failure to recognize the relationship of age and thyroxine requirements will lead to over dosage if the dose of thyroxine is not titrated down as patients age. Unnecessary treatment of elderly patients adds to this danger. The diagnosis of thyroid failure in the elderly needs to be carefully evaluated with the knowledge that the upper normal value for TSH in people over 80 yrs is ~7.5 uU/ml, compared to 4.0 uU/ml in young adults (12). Therefore careful selection of which elderly patients should be treated with thyroxine is critical. Thyroid hormone overtreatment of elderly patients is an avoidable problem.
Individuals vary in their absorption of thyroxine, sometimes because of use of interfering medications, higher thyroxine doses may be required for some patients to achieve normal TSH levels. This should not contribute to bone loss as long as overtreatment is avoided. Further, some patients with thyroid cancer need to have a lower TSH levels to prevent cancer recurrence (13). In these selected patients the risk of bone loss is outweighed by beneficial effects on control of the cancer. Hence, it is important is to adjust the dose of thyroxine to achieve TSH levels that are appropriate for each individual patient.
- Singer PA, Cooper DS, Levy EG, Ladenson PW, Braverman LE, Daniels G, Greenspan FS, McDougall IR, Nikolai TF 1995 Treatment guidelines for patients with hyperthyroidism and hypothyroidism. Standards of Care Committee, American Thyroid Association. J A M A 273:808-812
- Canaris GJ, Manowitz NR, Mayor G, Ridgway EC 2000 The Colorado thyroid disease prevalence study. Arch Int Med 160:526-534
- Sheppard MC, Holder R, Franklyn JA 2002 Levothyroxine treatment and occurrence of fracture of the hip. Arch Int Med 162:338-343
- Bauer DC, Ettinger B, Nevitt MC, Stone KL 2001 Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Int Med 134:561-568
- Murphy E, Williams GR 2004 The thyroid and the skeleton. Clinical Endocrinology 61:285-298
- Imam A, Iqbal J, Blair HC, Davies TF, Huang CL, Zallone A, Zaidi M, Sun L 2009 Role of the pituitary-bone axis in skeletal pathophysiology. Curr Op Endocrinol Diab 16:423-429
- Flynn RW, Bonellie SR, Jung RT, MacDonald TM, Morris AD, Leese GP 2010 Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab 95:186-193
- Turner MR, Camacho X, Fischer HD, Austin PC, Anderson GM, Rochon PA, Lipscombe LL 2011 Levothyroxine dose and risk of fractures in older adults: nested case-control study. BMJ 342:d2238
- Syed FA, Ng AC 2010 The pathophysiology of the aging skeleton. Curr Osteoporos Rep 8:235-240
- Kabadi UM 1997 Influence of age on optimal daily levothyroxine dosage in patients with primary hypothyroidism grouped according to etiology. Southern Medical Journal 90:920-924
- Sawin CT, Herman T, Molitch ME, London MH, Kramer SM 1983 Aging and the thyroid. Decreased requirement for thyroid hormone in older hypothyroid patients. Am J Med 75:206-209
- Boucai L, Hollowell JG, Surks MI 2011 An approach for development of age-, gender-, and ethnicity-specific thyrotropin reference limits. Thyroid 21:5-11
- Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM 2009 Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19:1167-1214
The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis and treatment of thyroid disorders and thyroid cancer. ATA is an international individual membership organization with over 1,400 members from 43 countries around the world. Celebrating its 88th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, THYROID, Clinical Thyroidology and Clinical Thyroidology for Patients; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators, support of online professional, public and patient educational programs; and the development of guidelines for clinical management of thyroid disease.
More information about ATA is found at www.thyroid.org