[Cytokine therapy and the endocrine system: is it necessary to monitor more than the thyroid gland?].
Cytokines and Endocrine System: Is it Meaningful to Monitor More than the Thyroid Gland?


OBJECTIVE
It was the aim of this study to evaluate the occurrence, the degree, and clinical relevance of immunological phenomena in endocrine and non-endocrine organs as seen under therapy with interferon-alpha (IFN-alpha) and/or interleukin-2 (Il-2).


METHODS
In 61 patients (age: 50.2 +/- 12.8 years) receiving cytokines as treatment for hepatological or hemato-oncological diseases, parameters of the thyroid gland, the gonadal system, the adrenal gland the pituitary gland, parameters of water and electrolyte-balance, and of bone metabolism were measured. All patients were treated with interferon in a mean dosage of 15.3 +/- 10.5 mio U subcutaneously per week. Additionally, 15 patients were treated with interleukin-2 (36.5 +/- 22.3 mio U subcutaneously per week). Among other assays, patients "sera were screened for the existance of autoantibodies against 30 different antigenic substrates using an indirect immunofluorescence technique (IIF).


RESULTS
Pts, treated with IFN-alpha and IL-2 (n = 13) showed a significant induction of thyroid antibodies against thyroglobulin (anti-TG): 61 +/- 82 U/ml vs. 1000 +/- 2352 U/ml (p < 0.05) and against thyroid-peroxidase (anti-TPO): 162 +/- 538 vs. 468 +/- 1071 U/ml (p < 0.05). In pts, only treated with IFN-alpha (n = 26), the increase of anti-TG from 69 +/- 97 to 134 +/- 178 U/ml and of anti-TPO from 20 +/- 21 to 21 +/- 19 U/ml was insignificant. Patients with a combined treatment of IFN-alpha and Il-2 were mainly affected: 2 patients developed hypo- and 5 hyperthyroidism. Thus, regular controls of thyroid function during the entire duration of therapy is justified. We were unable to show any influence of the duration of treatment or dosage of cytokines on the endocrine and non-endocrine parameters investigated. In addition, 8 different AAB (against smooth/striated muscles, parietal cells, nuclear parts, myelin, keratin, endothel, and neuroendothel) were detected by IIF which did not change under therapy. Two patients newly developed AAB during therapy, however none of them suffered from clinical symptoms. AAB against endocrine organs other than the thyroid gland were not detected. No other endocrine system showed alterations of its function.


CONCLUSIONS
Based on the data of this study we conclude that the thyroid gland should be regularly monitored for immunological and functional changes during cytokine therapy. The results do not support a general recommendation for a routine screening of other, non-thyroidal endocrine systems for autoimmune phenomena and alterations of function in each patient.
Schuppert
F
F
Abteilung Klinische Endokrinologie, Zentrum Innere Medizin und Dermatologie der Medizinischen Hochschule Hannover.
Müller-Kunert
E
E
Stöcker
W
W
Bokemeyer
C
C
Schmoll
H J
HJ
von zur Mühlen
A
A
Rambusch
E G
EG
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D016903:Drug Monitoring; D005260:Female; D006728:Hormones / Q000097:blood*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D013961:Thyroid Gland / Q000276:immunology*; D013963:Thyroid Hormones / Q000097:blood*; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology
D001323:Autoantibodies; D006728:Hormones; D016898:Interferon-alpha; D007376:Interleukin-2; D013963:Thyroid Hormones