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Exp Clin Endocrinol Diabetes 1999; 107(3): 177-182
DOI: 10.1055/s-0029-1212094
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Unique alterations of thyroid function parameters after i.v. administration of alkylating drugs (cyclophosohamide and ifosfamide)

W. Reinhardt, V. Sauter, F. Jockenhövel4 , G. Kummer3 , M. Uppenkamp1 , O. Witzke2 , T. Philipp2 , D. Reinwein, K. Mann
  • 1University of Essen, Department of Medicine, Div. of Endocrinology, Hematology, Germany
  • 2University of Essen, Department of Medicine, Div. of Nephrology, Germany
  • 3Clinic of Bone Marrow Transplantation, Germany
  • 4Essen, 2nd Medical Clinic University of Cologne, Germany
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Publication Date:
14 July 2009 (online)

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Summary

Alkylating drugs (cyclophosphamide and ifosfamide) have been in clinical use for the treatment of malignant diseases in the past. They are most useful anticancer agents and cyclophos-phamide is also widely used for its immunosuppressive properties. However the effect of alkylating drugs on thyroid hormone param-eters have not been evaluated so far.

Three groups of patients were prospectively evaluated:

Group I: 15 patients with Wegener's granulomatosis and 4 patients with severe scleritis received a single dose cyclophosphamide (15 mg/kg bw/day) and 250 mg prednisone i.v. Group II: 9 patients with malignant lymphomas were treated according to the I MVP 16-protocol. Patients received daily ifosfamide 1000 mg/m2 from day 0 to 4 and vepesid from day 0 to 2. Patients did not receive corticosteroids additionally. Group III: 6 patients with a relapse of malignant lymphomas received ifosfamide 1.500 mg/m2/day from day 0 to 4 i.v. and dexamethasone 40 mg/m2 as well as ara-c and etoposid.

All patients received mesna to prevent hemorrhagic cystitis and odansetran or metoclopramide as antiemetic drugs. Alkylating drugs were given as a one hour infusion. Thyroid hormone param-eters were determined before and on day 1, 2, 3, 4 after drug ad-ministration. We observed a significant increase in T4 and fT4 concentrations and a concomitant fall in TSH in either group one day after the administration of alkylating drugs. The effect was most pronounced in group III: T4 increased from 113 ± 8 nmol/L to 175 ± 8 (normal: 58-154) and fT4 from 14.0 ± 0.8 to 24.8 ± 2.5 pmol/L (normal 10-25). TSH dropped from 1.27 ± 0.16 to 0.33 ± 0.07 mU/L (normal 0.3—4). All changes were significant: p < 0.001. Two of the six patients displayed biochemical hyper-thyroidism. Also reverse T3 increased significantly. Two days after drug administration a gradual normalization occurred. However, T3, Tg, TBG, Transthyretin and albumin levels did not change throughout the study period. One patient with coexisting hypothyroidism, who received his last thyroxine substitution ther-apy one day before the administration of cyclophosphamide (as in group I), also demonstrated an increase in T4, fT4 and rT3 and a fall in TSH concentrations.

Iv. administrations of cyclophosphamide and ifosfamide induce a transient increase in T4 and fT4 concentrations and a concomi-tant fall of TSH in the presence of normal Tg, T3 and thyroid binding protein concentrations. These data suggest, that the changes are not due to a release of thyroid hormones from the thyroid itself, but is likewise related to a release of thyroxine from cellular pools such as the liver.

Key words

Alkylating drugs - cyclophosphamide - ifosfamide - thyroid function - thyroid hormones