Complications common in phenotypically normal male 45,X/46,XY patients

By Eleanor McDermid
Eur J Endocrinol 2018; doi:10.1530/EJE-18-0309
01 October 2018

medwireNews: Boys who have normal or minor abnormalities of their external genitalia despite a 45,X/46,XY karyotype have complications including reduced fertility, report researchers.

“Therefore, it seems essential to identify these patients by considering the systematic evaluation of karyotype in patients referred for growth failure especially among those who have associated gonadal malfunction or Turner syndrome features”, write Laetitia Martinerie (CHU Robert Debré, Paris, France) and study co-authors.

Twenty of the 40 patients in the study had a postnatal diagnosis, and most of these were initially referred for short stature during childhood or puberty. Three had Müllerian duct derivatives discovered during testicular surgery and four presented in adulthood with infertility.

External genitalia were outwardly normal in 45.0% of the patients, and the other patients had mild abnormalities, most commonly unilateral cryptorchidism or asymmetry of testicular volume (in 27.5%).

However, the patients had a range of Turner-syndrome–like abnormalities, including media otitis or conductive deafness (45%), dysmorphism (28%), cardiac malformations (26%), autoimmunity (20%), orthopaedic defects (20%) and renal malformations (16%).

Also, 47% had short stature, with the average height standard deviation score (SDS) being –1.47 in infancy and –2.32 during puberty after correction for target height. Sixteen patients received growth hormone therapy, resulting in a 0.92 gain in height SDS over 2 years in 11 evaluated patients.

However, this did not equate to a significant final height difference relative to untreated patients, and the researchers note that treatment “did not seem to modify pubertal stunting in patients free of testosterone treatment.”

Puberty occurred spontaneously in 14 of 15 patients monitored from infancy, with the 15th requiring testosterone therapy. However, five patients monitored throughout puberty showed signs of declining fertility, mostly in the form of decreased Sertoli cell function, but also with some evidence of decreased Leydig cell function. Patients who were diagnosed in adulthood had preserved Leydig cell function, but half had reduced Sertoli cell function and all had azoospermia.

One youth was diagnosed with testicular embryonal carcinoma at the age of 17 years, Martinerie and team report in the European Journal of Endocrinology.

They say that “the current prevalence of these findings is difficult to specify given the absence of prospective follow-up studies.”

Nevertheless, they stress that, even if they have no or mild abnormalities, 45,X/46,XY patients “must be followed throughout their life, with particular attention paid to growth, testicular function and testicular tumor screening and fertility preservation should eventually be considered.”

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