Tests
1st tests to order
chromosomal karyotype
Test
Definitive test if KS suspected. Usually from a blood lymphocyte sample - check your local laboratory protocol.
There is no clear consensus on the clinical symptoms/signs that warrant karyotype analysis for suspected KS.
The US Endocrine Society guideline on hypogonadism recommends karyotype analysis to diagnose KS in any individual who has primary hypogonadism confirmed based on low total serum testosterone (in two early-morning fasting samples) and high serum LH and FSH, especially if bi-testicular volume <6 mL.[32]
The 2021 European Academy of Andrology KS guideline states that karyotype analysis is indicated in the following scenarios: men with nonobstructive azoospermia or severe oligozoospermia (total sperm count <10 x 10⁶/ejaculate or sperm concentration <5 x 10⁶/mL); or men with primary hypogonadism (low serum testosterone level) and elevated serum gonadotropins (LH and FSH) combined with small testicular volume (<5 mL per testis); or boys born with cryptorchidism, especially if bilateral, who do not experience spontaneous descent of the testes by 1 year of age.[3]
Occasionally, KS may be identified unexpectedly when a karyotype analysis is performed to investigate developmental delay (e.g., in speech and/or walking) in a toddler over 2 years of age.[2]
In KS, karyotype analysis will confirm the presence of an extra X chromosome.[1][2][3]
Ensure counseling takes place prior to karyotype analysis.
Result
common result is non-mosaic 47,XXY; mosaic 46,XY/47,XXY may be found in milder cases
serum total testosterone
Test
Measure with an early-morning (8-9 a.m.) fasting sample.[32] Check the level on two different days before confirming a diagnosis of hypogonadism.[32]
Most useful in diagnosing hypogonadism in late adolescence and adulthood.[3] Hypogonadism is a key feature of KS.[1][4]
Testosterone levels are typically normal in childhood and the early stages of puberty but typically fail to rise in late puberty.[1]
This biochemical hypogonadism is generally detectable from around age 14 years (at Tanner stage 5 of puberty), when the usual accelerated nocturnal rise in testosterone becomes blunted.[2]
Testosterone in postpubertal boys and adult men with KS is typically in the low or low-normal range.[2][14][18] Be aware that a normal testosterone level therefore does not exclude KS.
If KS has been diagnosed prenatally, check testosterone levels in the first 2-3 months after birth.[3]
If KS is diagnosed in childhood, it is usual practice to start evaluating testosterone on a regular basis (e.g., annually) once puberty has started or when clinical signs of hypogonadism are seen
Result
subnormal or within the lower part of the age-related range from late puberty onward: in an adult man, an early-morning fasting serum total testosterone level <300 nanograms/dL (<10.4 nanomol/L) is generally accepted as being consistent with hypogonadism
serum LH/FSH
Test
In KS, serum LH and FSH levels are typically normal until puberty, after which they become elevated.[2][14][18]
If hypogonadism is confirmed as part of evaluation for infertility or for symptoms/signs of testosterone deficiency, it is essential to measure serum LH and FSH to confirm the hypogonadism is primary (i.e., due to testicular failure).[23]
KS is the most common cause of primary hypogonadism, in which low testosterone levels are accompanied by elevated gonadotropins.[1]
If KS is diagnosed in childhood, it may be helpful to monitor serum LH and FSH levels once clinical signs of puberty are seen and annually thereafter.
However, bear in mind that raised gonadotropins per se are not an indication to start testosterone therapy.[3]
If KS has been diagnosed prenatally, check LH levels in the first 2-3 months after birth.[3]
Result
usually raised from the start of puberty onward
Tests to consider
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