Log in

Suppressed thyroid-stimulating hormone secretion in patients treated with interleukin-2 and interferon-α2b for metastatic melanoma

  • Original Articles
  • Published:
The clinical investigator Aims and scope Submit manuscript

Abstract

Recent reports suggest that combined therapy with recombinant interleukin (IL)-2 and interferon (IFN) alb may result in autoimmune-induced thyroid dysfunction. We prospectively analyzed thyroid function for 6 weeks in two groups of patients with progressive metastatic melanoma treated according to two different protocols. In group I (n =17) three treatment cycles were given, each with three weeks of subcutanous administration of rIL-2 and INF-α2b at different doses. In group 11 (n=13) the chemotherapeutic agent dacarbazine was given in addition. In group 1 three patients developed frank hyperthyroidism, which required antithyroid drug therapy in one case. Autoantibodies against thyroid microsomal antigen, thyroglobulin, and the thyroid-stimulating hormone (TSH) receptor were not significantly elevated in any of these patients. However, the remaining 14 patients showed a significant decrease in TSH after 6 weeks of treatment, from 1.8 ± 0.9 to 0.7 ± 0.7 μU/ml (P < 0.02). Thyroid hormones (triiodothyronine, thyroxine, free thyroxine) also increased during the observation time, but this did not parallel the drop in TSH levels. Only thyroxine increased above the upper limit of normal, while triiodothyronine and free thyroxine stayed within the normal range. In group 11, 6 of 13 patients (46%) had a decreased TSH after 6 weeks of treatment. Mean TSH was 1.5±1.4 before and 0.8 ± 0.6 μU/ml after 6 weeks and was totally suppressed in three cases. None of these patients showed ouvert hyperthyroidism. Hypothyroidism was not observed in either group. We conclude that treatment with rIL-2 and INF-α2b may not only be associated with autoimmune thyroiditis and hyperthyroidism but also results in suppression of TSH levels while the patients remain euthyroid.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

IL:

interleukin

INF:

interferon

TSH:

thyroid-stimulating hormone

T3:

triiodothyronine

T4 :

thyroxine

fro:

free thyroxine

References

  1. Atkins MB, Mier JW, Parkinson DR, Gould JA, Berkman EM, Kaplan MM (1988) Hypothyroidism after treatment with interleukin-2 and lymphokine-activated killer cells. N Engl J Med 318:1557–1563

    Google Scholar 

  2. Atkins MB, Kaplan MM, Demchak PA, Robert NJ, Reichlin S, Mier JW (1991) Thyroid dysfunction after high-dose interleukin-2 therapy: un update. In: Scherbaum WA, Bogner U, Weinheimer B, Bottazzo GF (eds) Autoimmune thyroiditis. Springer, Berlin Heidelberg New York, pp 271–281

    Google Scholar 

  3. Atzpodien J, Korffer A, Franks CR, Poliwoda M, Kirchner M (1990) Home therapy with recombinat interleukin-2 and interferon-α2b in advanced malignancies. Lancet 335:1509–1512

    Google Scholar 

  4. Burman P, Tötterman TH, Oberg K, Karlsson FA (1986) Thyroid autoimmunity in patients on long term therapy with leukocyte-derived interferon. J Clin Endocrinol Metab 63:1086–1090

    Google Scholar 

  5. Castello G, Comella P, Manzo T, Napolitano M, Parziale AP, Galati MG, Daponte A, Casaretti R, Celentano E, Comella G (1993) Immunological and clinical effects of intramuscular rINFα2b and low dose subcutaneous rIL-2 in patients with advanced malignant melanoma. Melanoma Res 3:43–49

    Google Scholar 

  6. Denicoff KD, Durrkin TM, Lotze MT, Quinlan PE, Davis CL, Listwak SJ, Rosenberg SA, Rubinow DR (1989) The neuroendocrine effects of interleukin-2 treatment. J Clin Endocrinol Metab 69:4022–410

    Google Scholar 

  7. Dubuis JM, Dayer JM, Siegrist-Kaiser CA, Burger AG (1988) Human recombinant interleukin-1 beta decreases plasma thyroid hormone levels in rats. Endocrinology 123:2175–2181

    Google Scholar 

  8. Gemlo BT, Palladino Jr MA, Jaffe HS, Espevik TP, Rayner AA (1988) Circulating cytokines in patients with metastatic cancer treated with recombinant interleukin 2 and lymphokine-activated killer cells. Cancer Res 48:5864–5867

    Google Scholar 

  9. Kirchner H, Korfer A, Fraanks CR, Goldmann U, Evers P, Gessner S, Riechers H, Poliwoda H, Atzpodien J (1990) Thyroid toxicity in cancer patients receiving subcutaneeous recombinant interleukin-2 with and without interferon alpha-2B. J Cancer Res Clin Oncol 116 [Suppl]:345

    Google Scholar 

  10. Lyson K, McCann SM (1991) The effect of interleukin-6 on pituitary hormone release in vivo and in vitro. Neuroendocrinology 54:262–266

    Google Scholar 

  11. Masuhiro K, Matsuzaki N, Nishino E, Taniguchi T, Kameda T, Li Y, Saji F, Tanizawa O (1991) Trophoblast-derived interleukin-1 (IL-1) stimulates the release of human chorionic gonadotropin by activating IL-6 and IL-6 receptor system in first trimester human trophoblasts. J Clin Endocrinol Metab 72:594–601

    Google Scholar 

  12. Pichert G, Jost LM, Zöbeli L, Odermatt B, Pedio G, Stahel RA (1990) Thyroiditis after treatment with interleukin-2 and interferon a-2a. Br J Cancer 62:100–104

    Google Scholar 

  13. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Hinghausen SEE, Matory YL, Skibber JM, Shiloni E, Vetto JT Seipp CA, Simpson C, Reichert CM (1985) Observation on the systemic administration of autologous lymphokineactivated killer cells and recombinant interleukin 2 to patients with metastatic cancer. N Engl J Med 313:1485–1492

    Google Scholar 

  14. Scalzo S, Gengaro A, Boccoli G, Masciulli R, Giannella G, Salvo G, Marolla P, Carlini P, Masssimini G, Holdener EE, Testa U, Calabresi F, Peschle C (1990) Primary hypothyroidism associated with interleukin-2 and interferon alpha-2 therapy of melanoma and renal carcinoma. Eur J Cancer 26:1152–1156

    Google Scholar 

  15. Wiedermann CJ, Vogel W, Tillg H, Wiedermann FJ, Herold M, Zilian U, Wohlfarter T, Gruber M, Braunsteiner H (1991) Suppression of thyroid function by interferon-alpha 2 in man. Naunyn Schmiedebergs Arch Pharmacol 343:665–668

    Google Scholar 

  16. Zinzani PL, Clark JW, Wanebo HJ, Kouttab NM, Calabresi P (1990) Continuous intravenous infusion of interleukin-2 (IL-2) and α-INF therapy for melanoma with in vitro studies of combination cytokines for melanoma. Proc Am Soc Clin Oncol 9:279

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Correspondence to: H. Mönig

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mönig, H., Hauschild, A., Lange, S. et al. Suppressed thyroid-stimulating hormone secretion in patients treated with interleukin-2 and interferon-α2b for metastatic melanoma. Clin Investig 72, 975–978 (1994). https://doi.org/10.1007/BF00577739

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00577739

Key words

Navigation