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Letters to the Editor |
Department of Endocrinology, Research Institute for Endocrinology, Reproduction and Metabolism (E.J.G., C.P.-S., L.J.G.G.), and Department of Rheumatology (D.v.S., B.A.C.D.), University Hospital Vrije Universiteit; and Department of Rheumatology (J.C.v.D., D.v.S., B.A.C.D.), Jan van Breemen Institute 1007 MB Amsterdam, The Netherlands
To the editor:
Ankylosing spondylitis (AS) is a disease with a strong male preponderance. Reports that AS patients show somewhat elevated serum testosterone/17ß-estradiol ratios have supported the view that testosterone may be relevant in the pathogenesis of AS (1, 2). In a recent study, we have shown, however, that elevations of serum testosterone in both male and female patients with AS are probably spurious (3). In our study levels of serum testosterone, when measured directly in serum by a RIA, as is routinely done, were elevated in patients with AS compared with controls. But after serum extraction removing water-soluble substances potentially interfering with the RIA of testosterone, these differences with controls were no longer demonstrable. Although other substances may also be the cause, such interference in RIAs is most often caused by circulating endogenous antibodies (4). It seemed that the highest serum testosterone values were found in both male and female patients currently treated with phenylbutazone. We now have extended our observations to determine: 1) whether serum testosterone measurements in unextracted serum spuriously increase after starting treatment with phenylbutazone in patients with AS; and, if so, 2) the length of time to reach such elevations.
Blood was collected in five consecutive patients [four males
(range, 27–51 yr old) and one female (28 yr old)] fulfilling the New
York 1984 criteria for AS, who started treatment with
phenylbutazone (200–300 mg/day). None of the patients had endocrine or
neoplastic disease, nor did they use sex steroid hormones,
antiandrogenic medication, or corticosteroids. Informed consent was
obtained from all subjects, and the study was approved by the
Ethical Review Board. Total testosterone (bound and unbound) levels
were assayed in duplicate, both directly in serum and in
diethylether serum extracts, using a commercially available RIA
(Diagnostic Products, Los Angeles, CA). This solid-phase
assay is based on antibody recognition of testosterone molecules in
serum and in competitive conditions with the purified tracer
testosterone-19lsqb]125I] histamine. This
tracer is a widely used indicator in testosterone RIAs. The intra-assay
and interassay coefficients of variation were 6% and 7%,
respectively. The difference between the testosterone levels of each
subject measured before and after extraction was considered to be
statistically significant (two-tailed P < 0.05) when
the percentage difference was larger than 1.96
2*CV (coefficient of
variation, 19.4%) (5).
The assay results for serum testosterone before and after extraction
are shown in Fig. 1
. At baseline,
testosterone assay results were similar in serum without
extraction compared with after extraction, except for one male patient
who showed a 22% higher result without extraction. In all five
patients the use of phenylbutazone resulted in an increase in
testosterone levels assayed in serum before extraction, as opposed to
after extraction. All these differences were statistically
significant. These spurious elevations (by a mean of 232%) were
already observable after 4 days of treatment with phenylbutazone (Fig. 1).
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Received February 15, 2000.
References
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