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Decreased Levothyroxine Requirement in Women with Hypothyroidism during Androgen Therapy for Breast Cancer

Baha M. Arafah, MD
[+] Article and Author Information

From the University Hospitals of Cleveland, Cleveland, Ohio. Requests for Reprints: Baha M. Arafah, MD, Division of Clinical and Molecular Endocrinology, University Hospitals of Cleveland, 11100 Euclid Avenue, Room 3128 Lakeside, Cleveland, OH 44106. Acknowledgments: The author thanks all referring physicians and the nursing staff at the Clinical Research Center, Cancer Center, and the outpatient facility for their help in conducting the study; Dr. F. Ismail-Beigi for reviewing the manuscript; and Robert Meyers for technical assistance.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1994;121(4):247-251. doi:10.7326/0003-4819-121-4-199408150-00002
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Objective: To determine the effects of androgen administration on measures of thyroid function and thyroid hormone replacement doses in women with breast cancer.

Design: Consecutive patients with metastatic, hormone-dependent breast cancer who were eligible for androgen treatment.

Interventions: Androgen therapy (fluoxymesterone, 10 mg orally twice daily) was continued for as long as it was effective in controlling tumor growth.

Patients: 7 patients with no known thyroid disease and 4 others receiving long-term treatment for hypothyroidism.

Measurements: Serum levels of total and free thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin were determined before and every 4 weeks after androgen therapy was initiated.

Results: Within 4 weeks of androgen administration to the seven patients without thyroid disease, serum levels of total T4 and T4-binding globulin decreased (P < 0.001), whereas the calculated free thyroxine index and measured free hormone levels remained unchanged. Six to 12 weeks after androgen therapy was discontinued, all seven patients remained clinically euthyroid, and serum levels returned to baseline values.

In contrast, clinical hyperthyroidism developed shortly after androgen was administered to four patients who received long-term thyroid hormone replacement therapy. Within 4 weeks of treatment, the serum free T4 level increased in each of the four patients, whereas the TSH level decreased. Thyroid hormone doses had to be reduced by 25% to 50% to maintain euthyroidism.

Conclusions: The study documents the reversible effects of androgens on thyroid hormone levels and indicates the need to reduce thyroid replacement doses in women during androgen therapy. Monitoring thyroid hormone levels in patients receiving replacement therapy and perhaps in those with autonomous thyroid function is necessary after androgen therapy.

Figures

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Figure 2.
Free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels in four women who received long-term treatment for primary hypothyroidism measured before, during, and after androgen therapy for breast cancer.

The upper portion of each graph shows the levothyroxine dose used; the arrows indicate the beginning and duration of androgen therapy. Levothyroxine dose was not altered in patient 1 but was reduced during androgen administration to patients 2, 3, and 4 to maintain euthyroidism.

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Figure 1.
Serial measurements of total thyroxine (T4) and free thyroxine (fT4), T4-binding globulin (TBG), triiodothyronine resin uptake (T3RU), free thyroxine index (fT4I), and thyroid-stimulating hormone (TSH) levels obtained during androgen administration to seven women with no history of thyroid disease.PP

Each point represents the mean ±SD (error bars). * = < 0.001 compared with levels before treatment. + = < 0.001 compared with values before treatment.

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[Thyroid hormone profile in breast cancer patients in postmenopause]. Arq Bras Endocrinol Metabol 2012;56(4):238-43.
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