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
