Abstract
Serial thyroid functions studies were carried out in patients with melanoma and renal cell carcinoma treated with interleukin-2 (3 MU m-2 by continuous infusion days 1-4) and interferon alpha-2a (6 MU m-2 subcutaneously on days 1 and 4), both given on alternate weeks. The results on eight patients who completed at least three cycles of treatment are described. Four patients developed thyroid dysfunction with a hyperthyroid phase of 2 weeks followed by a hypothyroid phase ranging from 12 to 24 weeks. Two patients became clinically symptomatic and required treatment. Fine-needle aspirates of the thyroid were obtained in three patients with thyroid dysfunction. The cytology revealed a mixed cellular infiltrate with lymphocytes and histiocytes, and immunocytochemical staining showed strong HLA-DR expression of all thyrocytes, both suggestive of an autoimmune thyroiditis. One patient with thyroiditis developed anti-thyroglobulin antibodies, the serology of all other patients was normal. Patients with thyroid dysfunction tended to have higher in vivo stimulated lytic activity of peripheral mononuclear blood cells and had significantly higher levels of CD16 positive blood cells as compared to euthyroid patients. The possibility of autoimmune thyroiditis should be anticipated in future trails combining interleukin-2 and interferon alpha-2a.
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- Atkins M. B., Mier J. W., Parkinson D. R., Gould J. A., Berkman E. M., Kaplan M. M. Hypothyroidism after treatment with interleukin-2 and lymphokine-activated killer cells. N Engl J Med. 1988 Jun 16;318(24):1557–1563. doi: 10.1056/NEJM198806163182401. [DOI] [PubMed] [Google Scholar]
- Bottazzo G. F., Pujol-Borrell R., Hanafusa T., Feldmann M. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet. 1983 Nov 12;2(8359):1115–1119. doi: 10.1016/s0140-6736(83)90629-3. [DOI] [PubMed] [Google Scholar]
- Burman P., Tötterman T. H., Oberg K., Karlsson F. A. Thyroid autoimmunity in patients on long term therapy with leukocyte-derived interferon. J Clin Endocrinol Metab. 1986 Nov;63(5):1086–1090. doi: 10.1210/jcem-63-5-1086. [DOI] [PubMed] [Google Scholar]
- Buscema M., Todd I., Deuss U., Hammond L., Mirakian R., Pujol-Borrell R., Bottazzo G. F. Influence of tumor necrosis factor-alpha on the modulation by interferon-gamma of HLA class II molecules in human thyroid cells and its effect on interferon-gamma binding. J Clin Endocrinol Metab. 1989 Aug;69(2):433–439. doi: 10.1210/jcem-69-2-433. [DOI] [PubMed] [Google Scholar]
- Cohen P. J., Lotze M. T., Roberts J. R., Rosenberg S. A., Jaffe E. S. The immunopathology of sequential tumor biopsies in patients treated with interleukin-2. Correlation of response with T-cell infiltration and HLA-DR expression. Am J Pathol. 1987 Nov;129(2):208–216. [PMC free article] [PubMed] [Google Scholar]
- Del Prete G. F., Tiri A., Mariotti S., Pinchera A., Ricci M., Romagnani S. Enhanced production of gamma-interferon by thyroid-derived T cell clones from patients with Hashimoto's thyroiditis. Clin Exp Immunol. 1987 Aug;69(2):323–331. [PMC free article] [PubMed] [Google Scholar]
- Doniach D., Bottazzo G. F., Russell R. C. Goitrous autoimmune thyroiditis (Hashimoto's disease). Clin Endocrinol Metab. 1979 Mar;8(1):63–80. doi: 10.1016/s0300-595x(79)80010-9. [DOI] [PubMed] [Google Scholar]
- Dutcher J. P., Creekmore S., Weiss G. R., Margolin K., Markowitz A. B., Roper M., Parkinson D., Ciobanu N., Fisher R. I., Boldt D. H. A phase II study of interleukin-2 and lymphokine-activated killer cells in patients with metastatic malignant melanoma. J Clin Oncol. 1989 Apr;7(4):477–485. doi: 10.1200/JCO.1989.7.4.477. [DOI] [PubMed] [Google Scholar]
- Fentiman I. S., Balkwill F. R., Thomas B. S., Russell M. J., Todd I., Bottazzo G. F. An autoimmune aetiology for hypothyroidism following interferon therapy for breast cancer. Eur J Cancer Clin Oncol. 1988 Aug;24(8):1299–1303. doi: 10.1016/0277-5379(88)90219-2. [DOI] [PubMed] [Google Scholar]
- Fisher R. I., Coltman C. A., Jr, Doroshow J. H., Rayner A. A., Hawkins M. J., Mier J. W., Wiernik P., McMannis J. D., Weiss G. R., Margolin K. A. Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. A phase II clinical trial. Ann Intern Med. 1988 Apr;108(4):518–523. doi: 10.7326/0003-4819-108-4-518. [DOI] [PubMed] [Google Scholar]
- Flynn S. D., Nishiyama R. H., Bigos S. T. Autoimmune thyroid disease: immunological, pathological, and clinical aspects. Crit Rev Clin Lab Sci. 1988;26(1):43–95. doi: 10.3109/10408368809105889. [DOI] [PubMed] [Google Scholar]
- Gemlo B. T., Palladino M. A., Jr, Jaffe H. S., Espevik T. P., Rayner A. A. Circulating cytokines in patients with metastatic cancer treated with recombinant interleukin 2 and lymphokine-activated killer cells. Cancer Res. 1988 Oct 15;48(20):5864–5867. [PubMed] [Google Scholar]
- Hanafusa T., Pujol-Borrell R., Chiovato L., Russell R. C., Doniach D., Bottazzo G. F. Aberrant expression of HLA-DR antigen on thyrocytes in Graves' disease: relevance for autoimmunity. Lancet. 1983 Nov 12;2(8359):1111–1115. doi: 10.1016/s0140-6736(83)90628-1. [DOI] [PubMed] [Google Scholar]
- Hartmann L. C., Urba W. J., Steis R. G., Smith J. W., 2nd, VanderMolen L., Creekmore S. P., Longo D. L. Hypothyroidism after interleukin-2 therapy. J Clin Oncol. 1989 May;7(5):686–687. doi: 10.1200/JCO.1989.7.5.686. [DOI] [PubMed] [Google Scholar]
- Massa P. T., ter Meulen V., Fontana A. Hyperinducibility of Ia antigen on astrocytes correlates with strain-specific susceptibility to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4219–4223. doi: 10.1073/pnas.84.12.4219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenberg S. A., Lotze M. T., Muul L. M., Chang A. E., Avis F. P., Leitman S., Linehan W. M., Robertson C. N., Lee R. E., Rubin J. T. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med. 1987 Apr 9;316(15):889–897. doi: 10.1056/NEJM198704093161501. [DOI] [PubMed] [Google Scholar]
- Stahel R. A., Sculier J. P., Jost L. M., Delforge A., Bron D., Gmür J., Oelz O., Sauter C., Stryckmans P., Klastersky J. Tolerance and effectiveness of recombinant interleukin-2 (r-met Hu IL-2 [ala-125]) and lymphokine-activated killer cells in patients with metastatic solid tumors. Eur J Cancer Clin Oncol. 1989 Jun;25(6):965–972. doi: 10.1016/0277-5379(89)90155-7. [DOI] [PubMed] [Google Scholar]
- Todd I., Pujol-Borrell R., Hammond L. J., Bottazzo G. F., Feldmann M. Interferon-gamma induces HLA-DR expression by thyroid epithelium. Clin Exp Immunol. 1985 Aug;61(2):265–273. [PMC free article] [PubMed] [Google Scholar]
- Zamvil S. S., Mitchell D. J., Lee N. E., Moore A. C., Waldor M. K., Sakai K., Rothbard J. B., McDevitt H. O., Steinman L., Acha-Orbea H. Predominant expression of a T cell receptor V beta gene subfamily in autoimmune encephalomyelitis. J Exp Med. 1988 May 1;167(5):1586–1596. doi: 10.1084/jem.167.5.1586. [DOI] [PMC free article] [PubMed] [Google Scholar]


