Commentary
AUA Guideline on the Diagnosis and Treatment of Cryptorchidism
C
RYPTORCHIDISM
is one of the most common male
pediatric urological conditions, and one that can
have a lifelong effect if not managed appropriately.
The evaluation and treatment of cryptorchidism
have progressed significantly during the last several
decades, as the condition has been studied exten-
sively. While we now have a much better under-
standing of the pathogenesis and sequelae of
undescended testes (UDTs), our knowledge remains
incomplete. Given the breadth of studies performed
in the last 3 decades examining the many pathoge-
netic factors contributing to cryptorchidism, as
well as the availability of numerous hormonal
and surgical treatment options, a comprehensive
consensus statement was necessary. This consensus
document is now presented as the American Uro-
logical Association guideline on the evaluation and
treatment of cryptorchidism.
The purpose of this complementary commentary
is to inform the reader on progress in the evaluation
and treatment of cryptorchidism since March 2013,
the last time when studies pertinent to the devel-
opment of the guideline were evaluated. Addition-
ally, given that the risk of malignancy in men with
a history of cryptorchidism is not as high as previ-
ously thought, we briefly discuss considerations
in postpubertal males with a history of cryptorchi-
dism, which were not addressed in the guideline.
To identify salient studies to include in this com-
mentary, we searched PubMed
Ò
for articles related
to cryptorchidism in children and adults, limited
to humans, between March 2013 and April 2014. In
our review we focused on reports that provided addi-
tional data to enhance the conclusions of the AUA
guideline panel. We identified work in numerous
areas focused on in the guidelines about which addi-
tional findings had been reported, including epide-
miology, genetics, environmental factors, use of
imaging, hormonal and surgical treatment, natural
course of cryptorchidism and fertility.
EPIDEMIOLOGY
A clear distinction is now made between congenital
and acquired cryptorchidism. In the AUA guideline
several studies evaluated testicular ascent among
boys with descended testes at birth, finding that
approximately 23% of testes ascended, resulting
in acquired cryptorchidism. A more recent study
retrospectively evaluated the records 660 boys who
underwent orchiopexy after age 2 years, of whom
66% had a scrotal testis on 2 or more occasions and
suggesting a significantly higher ascent rate than
previously observed.
1
Furthering the relationship
between cryptorchidism and disorders of sexual
differentiation, a recent report identified a link be-
tween prematurity and intrauterine growth retar-
dation in boys with hypospadias and UDT, adding
to the list of risk factors for UDT and indications
for a multidisciplinary evaluation.
2
CRYPTORCHIDISM GENETICS
Evidence supporting genetic susceptibility in boys
with UDT is currently weak, although several genes
including
INSL3
,
LGR8
,
AR
and
ESR1
have been
implicated. More recently, the anti-m
€
ullerian hor-
mone (AMH) receptor type 2 has been correlated
with UDT, as it was found to be expressed in 100%
of 109 appendix testes from patients with UDT.
3
A recent case report describing a case of persistent
m
€
ullerian duct syndrome with an undetectable
AMH level demonstrated a novel T
>
G base substi-
tution in the
AMH
gene, resulting in a Leu
>
Arg
amino acid change.
4
Given that testicular descent
is affected by AMH, these findings suggest a role
for it and its receptor in the pathogeneses of UDT.
Novel work has also linked deletion of the distal
portion of chromosome 9p to cryptorchidism and
other urological anomalies, identifying
DMRT1
as
the likely responsible gene.
5
Finally, a new
AR
mutation (c.2214 T
>
G; Ile
>
Met) was identified in a
family with testicular dysgenesis syndrome which
was found to decrease AR transcriptional activity
by 50%, in line with the concept that reduced
androgen signaling might contribute to the devel-
opment of the syndrome.
6
Similar to the genes
discussed in the AUA guideline, the aforementioned
genes lack proof of causality in linking them
to UDT.
0022-5347/14/1922-0346/0
THE JOURNAL OF UROLOGY
®
©
2014 by A
MERICAN
U
ROLOGICAL
A
SSOCIATION
E
DUCATION AND
R
ESEARCH
,I
NC
.
Vol. 192, 346-349, August 2014
Printed in U.S.A.
346
j
www.jurology.com