Systemic lupus erythematosus associated with klinefelter's syndrome

Stern, Richard; Fishman, Jack; Brusman, H. P.; Kunkel, Henry G.

doi:10.1002/art.1780200103

Cited by 152 publications

(43 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Elevated 16a-hydroxyestrones are the only shared abnormalities between men and women with SLE. No clinical or phenotypic characteristics were observed in this group of men with SLE, suggesting exaggerated feminine characteristics like those evident in previously described patients (2). Increased 16a-hydroxyestrone has previously been described only in patients with cirrhosis (8,13) and probably reflects the consequences of severe liver disease.…”

Section: Discussionsupporting

confidence: 40%

Alterations of estrogen metabolism in systemic lupus erythematosus

Lahita

Bradlow

Kunkel

et al. 1979

Arthritis & Rheumatism

220

View full text Add to dashboard Cite

Estradiol metabolism in 10 patients with systemic lupus erythematosus (SLE) and 29 normal controls was studied by measurement of urinary metabolites after injection of labeled 'Hestradiol. Patients with SLE manifested increased l&hydroxylation of estrone. Diseased men differed from diseased women to the extent that only 16a-hydroxyestrone was elevated in men, whereas women had elevations of both 16a-hydroxyestrone and estriol. These data suggest that patients with SLE have abnormal patterns of estradiol metabolism, leading to increased estrogenic activity.The female susceptibility to most connective tissue diseases is well known. The incidence of systemic lupus erythematosus (SLE) in women after puberty is 9 : 1, women to men (1). The recent finding of elevated estriol levels in SLE patients with manifestations of Klinefelter's syndrome suggested that chronic estrogenic stimulation plays an important role in female prevalence (2). These data are supported by the finding that castration of a single female monozygotic twin prevented the possible development of SLE (3). Studies in murine models of SLE implicate sex hormones in the origin of autoantibodies (4) and overall morbidity (5,6).Previous studies (7) also indicated that, although the total estrogens recovered were normal, the pattern of metabolism might result in increased estrogenic activity. This article reports a study of estrogen metabolism in normal controls and patients with SLE. Specifically, the pattern of urinary metabolites excreted as glucuronide was studied as a measure of overall estrogen metabolism. PATIENTS AND METHODS Subjects.Five men with SLE aged 17 to 43 and 5 women with SLE aged 18 to 53 were hospitalized at the Rockefeller University Clinical Research Center. Written informed consent was obtained and all procedures were approved by the Rockefeller Human Research Committee. These patients had SLE by the ARA criteria. No patients were selected solely on the basis of clinical activity. Women were studied in the midfollicular phase of their menstrual cycle. Normal subjects and patients with SLE were excluded if they were receiving thyroid therapy, had liver disease, or were pregnant. All men studied were karyotyped by Dr. James German (New York Blood Center) and found to be normal. Patients on low dose corticosteroids were not excluded from the study.Methods. The administration of the tracer and the analysis of the urine were camed out as previously described from this laboratory (8). Briefly, the procedure is as follows:Each subject studied received approximately 3 pCi of estradiol -6,7-3H by intravenous injection of a weighed amount of a solution of the steroid in freshly redistilled pyrogen-free propylene glycol. A weighed aliquot of propylene glycol solution from which the individual tracer doses were obtained was used for calculation of the administered dose of radioactivity. Complete urine collections as judged from the consistency of creatinine measurements were obtained for 3 days after each injection. The specimens were refrigerate...

show abstract

Section: Discussionsupporting

confidence: 40%

Alterations of estrogen metabolism in systemic lupus erythematosus

Lahita

Bradlow

Kunkel

et al. 1979

Arthritis & Rheumatism

220

View full text Add to dashboard Cite

show abstract

“…In the late 1970s, investigators made the important observation that estrogen metabolism is altered in patients with systemic lupus erythematosus (24,25). Lahita et al (25) showed elevated serum levels of 16␣-hydroxylated estrogens in these patients.…”

Section: Discussionmentioning

confidence: 99%

Estrone/17β‐estradiol conversion to, and tumor necrosis factor inhibition by, estrogen metabolites in synovial cells of patients with rheumatoid arthritis and patients with osteoarthritis

Schmidt

Hartung

Capellino

et al. 2009

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. The role of estrogens in rheumatoid arthritis (RA) is debated since both proinflammatory and antiinflammatory effects have been reported. Important evidence of the dual role of estrogens is conversion to various proinflammatory or antiinflammatory metabolites. This study was undertaken to examine the downstream conversion of estrogens in synovial cells from patients with RA or osteoarthritis (OA).Methods. We studied serum levels of estrone, estrone sulfate, and estrone sulfate membrane transporters, intracellular interconversion of estrone and 17␤-estradiol, and conversion of estrone/17␤-estradiol to various estrogen metabolites in RA and OA synovial cells. The effect of estrogen metabolites on tumor necrosis factor (TNF) secretion was also studied in RA and OA synovial cells.Results. Serum levels of estrone sulfate were similar in healthy controls and RA patients. Estrone sulfate transporters were present in synovial tissue. Interconversion of estrone and 17␤-estradiol and the expression of converting enzymes of the cytochrome P450 family were similar in RA and OA cells. Using estrone and 17␤-estradiol as substrates, RA and OA synovial cells produced 16␣-, 4-, and 2-hydroxylated estrogens and their 4-and 2-methylation products. The levels of 16␣-hydroxylated estrone/17␤-estradiol (16␣OH-estrone/16␣OH-17␤-estradiol) were higher than the levels of all other estrogen metabolites. RA synovial cells produced more 16␣OH-estrone than did OA synovial cells. Importantly, the 16␣OH estrogens did not inhibit TNF secretion, whereas all other estrogen metabolites had marked inhibitory effects.Conclusion. Our findings indicate that precursor estrogens are converted to proinflammatory metabolites, particularly in RA synovial cells. RA synovial cells mainly produce the proproliferative 16␣OH-estrone, which, in addition to 16␣OH-17␤-estradiol, is one of the only 2 estrogens studied that does not inhibit TNF secretion. A preponderance of 16␣-hydroxylated estrogens is an unfavorable sign in synovial inflammation.

show abstract

“…Subsequently, Stern and colleagues studied the urinary estrogen levels in KS and SLE. One patient had elevated levels of all three urinary estrogens (estrone, estradiol, and estriol) with markedly increased estriol values (Stern et al, 1977). Moreover, some authors pointed to the fact that estradiol levels are frequently elevated in KS, reaching values as measured in women with the normal menstrual cycle, whereas androgen levels are similar to those found in prepubertal age males.…”

Section: Ks and Systemic Lupus Erythematosus (Sle)mentioning

confidence: 85%

Autoimmune rheumatic diseases and Klinefelter syndrome Autoimunitné reumatické choroby a Klinefelterov syndróm

Lazúrová

Rovenský

Imrich

et al. 2016

European Pharmaceutical Journal

View full text Add to dashboard Cite

The article summarizes data on the association of Klinefelter syndrome (KS) with autoimmune rheumatic diseases, that is rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polymyositis/dermatomyositis, systemic sclerosis (SSc), mixed connective tissue diseases (MCTD), Sjogren’s syndrome and antiphospholipid syndrome (APS). Recently, a higher risk for RA, SLE and Sjogren’s syndrome in patients with KS has been clearly demonstrated. However, the association of other autoimmune rheumatic disorders such as dermatomyositis/polymyositis, SSc, MCTD and APS is reported only casually. Based on the hormonal changes in KS, there are suggestions that low androgen and higher estrogen levels might be a predisposing factor for the development of autoimmune diseases, but evidence for the association is poor. Epidemiologic studies on larger cohorts of patients are required.

show abstract

Systemic lupus erythematosus associated with klinefelter's syndrome

Cited by 152 publications

References 24 publications

Alterations of estrogen metabolism in systemic lupus erythematosus

Alterations of estrogen metabolism in systemic lupus erythematosus

Estrone/17β‐estradiol conversion to, and tumor necrosis factor inhibition by, estrogen metabolites in synovial cells of patients with rheumatoid arthritis and patients with osteoarthritis

Autoimmune rheumatic diseases and Klinefelter syndrome Autoimunitné reumatické choroby a Klinefelterov syndróm

Contact Info

Product

Resources

About