Journal of Andrology, Vol. 24, No. 1, January/February 2003
Copyright © American Society of Andrology
Editorial Commentary
Robert D. Oates, MD, Associate Professor of Urology
Boston University School of Medicine
Department of Urology
Boston,
Massachusetts
Kamischke A, Baumgardt A, Horst J, Nieschlag E. Clinical and diagnostic
features of patients with suspected Klinefelter syndrome. J Androl.2002
;23:41-48.
The article by Kamischke et al entitled "Clinical and Diagnostic
Features of Patients With Suspected Klinefelter Syndrome" makes several
interesting points relevant to the clinical practice of andrologists,
endocrinologists, and urologists as well as primary care physicians. As is
widely known, Klinefelter syndrome occurs in 1:600 males, and the
characteristics of those presenting as teenagers with failure of pubertal
development are well described. These tall, eunichoid boys have small, firm
testes, often have gynecomastia, and may have learning difficulties as well.
They have scant public hair, may not shave on a daily basis, and are not
muscular. Their phenotype is a reflection of their poor androgenic axis,
itself a result of the slow but steady pathological destruction of the
intratesticular architecture. This leaves seminiferous tubules sclerosed and
the Leydig cell compartment either hyperplastic and dysfunctional or fibrosed
altogether. These young men reside on the most severely affected end of the
phenotypic Klinefelter spectrum. However, there are many men who are virilized
well enough at or around puberty that they escape detection and may only be
recognized when presenting for an infertility evaluation many years hence.
Kamischke et al retrospectively reviewed 10 134 new male patients presenting
to their clinic from 1984 to 1999 for evaluation of infertility or
hypogonadism. Sixty-five (65) had been diagnosed previously with Klinefelter
syndrome and were appropriately excluded from the study. The authors selected
311 patients who, on the basis of clinical symptoms, physical examination, and
previous laboratory assays, were suspected of having Klinefelter syndrome. In
each of these patients, a Barr body examination, followed by a peripheral
lymphocyte karyotype, was performed. Body size, hair distribution, and body
composition were recorded. The presence of gynecomastia was noted. Testis size
was measured both clinically and by scrotal ultrasound. Most patients had
semen analyses and hormonal measurements (follicle-stimulating hormone [FSH],
luteinizing hormone [LH], testosterone, sex hormone—binding globulin
[SHBG], and estradiol). The group of Klinefelter men (47,XXY: n = 85) was then
compared to the group whose karyotype turned out to be normal (46,XY; n =
224). Therefore, all of these men had at least a single feature that might
suggest Klinefelter syndrome, but none had had a prior karyotype. The clinical
predictive abilities of the authors were quite good actually, with 28% of the
patients who they thought might have Klinefelter syndrome turning out to be
positive for that diagnosis.
The authors show us that a Barr body examination is sensitive (82%) and
specific (95%) and can be performed in about 1 hour in a clinical laboratory.
This can provide a rapid diagnosis for patients, although confirmation with a
karyotype is still necessary to be definitive. Barr body analysis may,
therefore, be a useful screening tool for those in whom the diagnosis is much
less likely based on clinical features but still possible (men with severe
oligospermia, low normal LH, and normal testosterone). However, in the
severely oligospermic or azoospermic male with elevated FSH indicative of
spermatogenic dysfunction, a karyotype is still required to demonstrate other
etiologic anomalies such as translocations or Y chromosomal macrodeletions.
Thus, Barr body analysis cannot stand alone as a diagnostic tool. Most
interestingly, the authors' comparison of those with and without Klinefelter
syndrome (all were suspected to have Klinefelter syndrome) revealed that there
is no way to definitively distinguish the groups. That is, there is such
overlap in the clinical features of the 2 groups that it is impossible to
accurately predict their karyotype results on the basis of these clinical
features. For example, parental age and incidence of cryptorchidism were the
same for both cohorts, while the Klinefelter group tended to be taller and had
smaller testis size. While these two latter findings were significantly
different between the groups, one could not simply look at the height of an
individual or measure the testis size and place an individual into one of the
2 groups with any level of certainty. A Barr body analysis or karyotype should
be carried out in any man with spermatogenic compromise of a severe degree and
hypogonadal features or endocrine results. The authors' last point is a
provocative one. Their data suggest that the younger a Klinefelter patient is,
the more likely he is to have sperm production, albeit at markedly reduced
levels compared to the norm. Will earlier diagnosis and cryopreservation of
ejaculated sperm (or even testis sperm) lead to the preservation of future
fertility? The answer is unknown at this time but is worthy of further
study.
This article has been cited by other articles:
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M. R. Maduro, K. C. Lo, W. W. Chuang, and D. J. Lamb
Genes and Male Infertility: What Can Go Wrong?
J Androl,
July 1, 2003;
24(4):
485 - 493.
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