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Systemic lupus erythematosus with membranous glomerulonephritis and transverse myelitis associated with anabolic steroid use.

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ARTHRITIS Rr RHEUMATISM
Vol. 40, No. 10, October 1997, pp 1899-1902
0 1997, American College of Rheumatology
1899
SYSTEMIC LUPUS ERYTHEMATOSUS WITH MEMBRANOUS
GLOMERULONEPHRITIS AND TRANSVERSE MYELITIS
ASSOCIATED WITH ANABOLIC STEROID USE
CHARLES D. RADIS and KRISTINA P. CALLIS
This report describes a 29-year-old bodybuilder
taking anabolic steroids who presented with urinary
retention, arthralgias, and peripheral edema, subsequently developed acute lower-extremity paralysis, and
was diagnosed as having transverse myelitis and membranous glomerulonephritis secondary to systemic lupus erythematosus (SLE). The association of anabolic
steroid use and hyperprolactinemia, and their possible
link to the development of SLE, are reviewed.
Systemic lupus erythematosus (SLE) is a heterogeneous disorder in which sex hormone abnormalities
are common and may, via immunomodulation, play a
role in the development of disease or in some cases lead
to SLE flares. Both male and female SLE patients
demonstrate relative hyperestrogenism with altered
estradiol-to-testosterone ratios (1-3). Elevated levels of
prolactin have also been associated with SLE in some
but not all studies (4-8). There is increasing evidence that prolactin may function as an immunostimulatory hormone either directly through immunocompetent cells or through its effect on testosterone
levels. In supraphysiologic amounts, prolactin inhibits
gonadotropin-releasing hormone, leading to suppression
of both estrogens and androgens. This may be particularly important in male SLE patients, in whom lower
levels of circulating androgens may tip the balance in
favor of activation of disease.
This report describes a male bodybuilder who
developed SLE soon after taking a 6-week cycle of
nandrolone (19-nortestosterone), a synthetic anabolic
steroid frequently used by bodybuilders. It is postulated
that the ingestion of nandrolone led to a reduction in
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Charles D. Radis, DO, Kristina P. Callis, MD: Rheumatology
Associates, Portland, Maine.
Address reprint requests to Charles D. Radis, DO, Rheumatology Associates, 51 Sewall Street, Portland, ME 04102.
Submitted for publication December 19, 1996; accepted in
revised form May 27, 1997.
endogenous testosterone and that this, in association
with mild hyperprolactinemia, triggered SLE.
CASE REPORT
The patient, a 29-year-old male bodybuilder, was
admitted to the hospital with a 1-month history of
arthralgias, lower-extremity edema, and anemia and a
3-day history of lower thoracic back pain and urinary
retention. There was no previous significant medical
history except for a positive purified protein derivative
reaction 2 years previously, for which he had been
treated with a 6-month course of isoniazid. There was no
family history of SLE or other connective tissue disorder. He had recently completed a 6-week cycle of oral
nandrolone, 75 mg daily. He denied using any other
medications or drugs.
Physical examination revealed a temperature of
38.5"C, a pulse of 95 beats per minute, and a blood
pressure of 128/60 mm Hg. Bilateral flank pain in
response to palpation was present, along with pitting
edema of the legs midway to the knees. The findings of
rheumatologic examination were remarkable only for
bilateral knee effusions.
Laboratory studies revealed a mild normocytic
anemia (hemoglobin 12.2 gm/dl; normal 14.0-18.0),
normal white blood cell count, and a platelet count of
351,000/mm3. The serum creatinine level was 1.2 mgidl
(normal 0.5-1.4). The serum albumin value was low at
2.1 mg/dl (normal 3.5-5.0), and the cholesterol level was
mildly elevated at 228 mgidl. Urinalysis demonstrated
4+ proteinuria and 1-3 white blood cells and 1-3 red
blood cells per high power field. A 24-hour urine
collection revealed 2.6 gm of creatinine and 1.97 gm of
protein, with a creatinine clearance rate of 97 mliminute.
Antinuclear antibodies (ANA) were positive at a titer of
1:1,024, and anti-DNA antibodies elevated at a titer of
1:32. Antihistone antibodies were not detected, but SS-A
1900
RADIS AND CALLIS
and SS-B antibodies were present. The levels of C3 and
C4 complement were 99 mg/dl (normal 83-180) and 19.1
mg/dl (normal 9.5-4.9, respectively. The testosterone
level was 4.7 ngiml (normal 3.0-11.O), the thyroid-
stimulating hormone (TSH) level was 7.0 pU/ml (normal 3.6-5.O), and the prolactin level was 18.1 ngiml
(normal 1.O-12.5).
On the second hospital day, the patient awoke
with a flaccid paralysis of his lower extremities. Reflexes
were absent, and pain sensation diminished without a
definite sensory level. Magnetic resonance imaging
(MRI) of the spine revealed an abnormal hyperintense
signal of the cord from T6 to the conus medullaris,
consistent with transverse myelitis (Figure 1). SLE was
diagnosed based on clinical findings consistent with the
American College of Rheumatology 1982 criteria (9).
Methylprednisolone, 1,000 mg intravenous bolus,
was infused immediately and on 2 subsequent days.
Intravenous cyclophosphamide (500 mg/m2) was administered on the fourth hospital day. Intravenous heparin
was administered until the results of antiphospholipid
antibody and VDRL testing were normal. An open renal
biopsy was performed on the sixteenth hospital day. The
results of light microscopy, immunofluorescence staining, and electron microscopy studies were consistent
with a diagnosis of type V lupus membranous glomerulonephritis according to the World Health Organization
classification. The patient was treated with pulse intravenous cyclophosphamide for a total of 4 monthly doses,
and a regimen of prednisone at a tapering dosage.
Prednisone was discontinued 12 months after presentation. Azathioprine, 100 mg daily, was initially substituted
Figure 2. Magnetic resonance imaging of the pituitary gland (coronal
view), demonstrating an area of hypointensity consistent with a
prolactinoma.
Figure 3. Magnetic resonance imaging of the pituitary gland (sagittal
view), demonstrating an area of hypointensity consistent with a
prolactinoma.
Figure 1. Magnetic resonance imaging of the spine, demonstrating an
abnormal hyperintense signal of the cord from T6 to the conus
medullaris (area between the dashed lines), consistent with transverse
myelitis.
1901
SLE AND ANABOLIC STEROID USE
for monthly cyclophosphamide, but currently the patient
is taking hydroxychloroquine, 400 mg daily.
Eight months post-hospitalization, the prolactin
level was 31.6 ngiml (normal 2.1-17.1) and the testosterone level was 4.5 ng/ml (normal 2.8-11.0) (normal
values different from those reported above because
testing performed at a different laboratory). The TSH
level was normal. MRI of the pituitary gland demonstrated an area of hypointensity consistent with prolactinoma (Figures 2 and 3). The patient’s neurologic
function has improved progressively, and 2 years posthospitalization he is able to walk without assistive devices. He has no proteinuria or hematuria, but mild
urinary retention and sexual dysfunction persist. The
ANA titer has decreased to 1:64 (normal), and antiDNA antibodies are absent. He is currently taking
bromocriptine, 5 mg daily, with suppression of his prolactin level to 1.5 ngiml. His testosterone level has
increased to 5.93 ng/ml.
DISCUSSION
The present case is of interest due to a combination of factors that may have led to the development of
SLE in a predisposed host. Although relatively little has
been written regarding the effect of anabolic steroids on
the immune response in humans, significantly elevated
ANA titers and increased natural killer cell activity have
been demonstrated in 4 of 13 bodybuilders utilizing
cyclical anabolic steroids (10). Background, lowspecificity ANA were also seen in a significant proportion of bodybuilders who claimed never to have taken
anabolic steroids. None of the bodybuilders exhibited
any symptoms of overt immunologic disease. Of note,
the most common synthetic androgen used by bodybuilders in that series was nandrolone, the same agent
taken by our patient.
There have been several studies on the use of
androgens in the clinical setting of SLE. Nandrolone was
first investigated by Hazelton et a1 (11) as a potential
treatment for SLE, based on the findings in animal
studies that suggested improvement with this agent
combined with gonadectomy (12). In the pilot study by
Hazelton and colleagues, patients were given monthly
nandrolone in 150-mg injections. There was no clinical
benefit overall in the 8 female patients, while 2 male
patients developed complications including subcutaneous nodules and a rash. In another open trial, 4 women
and 3 men were given weekly nandrolone in 100-mg
injections for 3-24 months (13). There was no significant
change in SLE activity in the women; however, all 3 men
had clinical flares of disease despite early subjective
improvement. Manifestations of disease included development of Raynaud’s phenomena, increased arthralgias,
pleuropericardial disease, rash, and progressive dementia. At baseline, the male SLE patients had low-normal
testosterone levels. Within 4 weeks of the initiation of
nandrolone treatment, native testosterone levels markedly declined, presumably through a negative feedback
effect of nandrolone on luteinizing hormone (LH) production. These observations are consistent with the
hypothesis that in male SLE patients, lower levels of
circulating androgens may favor activation of SLE.
Hyperprolactinemia has also been linked with
SLE flares in several reports (4-8). Via the hypothalamicpituitary-gonadal axis, hyperprolactinemia suppresses
LH, resulting in decreased testosterone levels. Prolactin,
as an immunostimulating hormone, is also thought to
contribute to lupus activity directly through prolactin
receptors on B and T lymphocytes (14). It seems reasonable to suggest that our patient’s modestly elevated
prolactin levels secondary to a prolactinoma, coupled
with exogenous androgen administration, may have provided a permissive environment for the development of
SLE. His subjective clinical improvement with bromocriptine, with resulting normalization of the prolactin
level and rise in the testosterone level, is consistent with
the clinical improvement seen in an open-label trial of
bromocriptine treatment in SLE (15).
This report is the first to suggest an association
between the ingestion of a synthetic anabolic steroid,
nandrolone, and the onset of SLE. We suggest that our
patient’s condition may have provided an endocrinologic
and immunologic milieu that, in the setting of exogenous
androgen use, led to clinical disease. This case lends
further support to the existence of the complex interaction between the neuroendocrine and immune systems.
Furthermore, drug-induced SLE may represent a new
addition to the growing list of health hazards associated
with anabolic steroid use.
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anabolic, steroid, lupus, associates, membranous, systemic, erythematosus, myelitis, use, transverse, glomerulonephritis
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