Cryptorchidism
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Cryptorchidism | |
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Cryptorchidism on scrotal ultrasound | |
Specialty | Medical genetics |
Cryptorchidism, also known as undescended testis, is the failure of one or both testes to descend into the scrotum. The word is from Greek κρυπτός (kryptos) 'hidden' and ὄρχις (orchis) 'testicle'. It is the most common birth defect of the male genital tract.[1] About 3% of full-term and 30% of premature infant boys are born with at least one undescended testis.[2] However, about 80% of cryptorchid testes descend by the first year of life (the majority within three months), making the true incidence of cryptorchidism around 1% overall. Cryptorchidism may develop after infancy, sometimes as late as young adulthood, but that is exceptional.
Cryptorchidism is distinct from monorchism, the condition of having only one testicle. Though the condition may occur on one or both sides, it more commonly affects the right testis.[3]
A testis absent from the normal scrotal position may be:
- Anywhere along the "path of descent" from high in the posterior (retroperitoneal) abdomen, just below the inguinal ring
- In the inguinal canal
- Ectopic, having "wandered" from the path of descent, usually outside the inguinal canal and sometimes even under the skin of the thigh, the perineum, the opposite scrotum, or the femoral canal
- Undeveloped (hypoplastic) or severely abnormal (dysgenetic)
- Missing (also see anorchia).
About two-thirds of cases without other abnormalities are unilateral; most of the other third involve both testes. In 90% of cases, an undescended testis can be felt in the inguinal canal. In a small minority of cases, missing testes may be found in the abdomen or appear to be nonexistent (truly "hidden").
Undescended testes are associated with reduced fertility, increased risk of testicular germ-cell tumors, and psychological problems when fully-grown. Undescended testes are also more susceptible to testicular torsion (and subsequent infarction) and inguinal hernias.[citation needed] Without intervention, an undescended testicle will usually descend during the first year of life, but to reduce these risks, undescended testes can be brought into the scrotum in infancy by a surgical procedure called an orchiopexy.[4]
Although cryptorchidism nearly always refers to
Cryptorchidism, hypospadias, testicular cancer, and poor semen quality make up the syndrome known as testicular dysgenesis syndrome.
Signs and symptoms
Infertility
Many men who were born with undescended testes have reduced fertility, even after orchiopexy in infancy. The reduction with unilateral cryptorchidism is subtle, with a reported infertility rate of about 10%, compared with about 6% reported by the same study for the general population of adult men.
The fertility reduction after orchiopexy for bilateral cryptorchidism is more marked, about 38%, or six times that of the general population. The basis for the universal recommendation for early surgery is research showing degeneration of
Cancer risk
One of the strongest arguments for early orchiopexy is reducing the risk of testicular cancer. About one in 500 men born with one or both testes undescended develops testicular cancer, roughly a four- to 40-fold increased risk. The peak incidence occurs in the third and fourth decades of life. The risk is higher for intra-abdominal testes and somewhat lower for inguinal testes, but even the normally descended testis of a man whose other testis was undescended has about a 20% higher cancer risk than those of other men.[citation needed]
The most common type of testicular cancer occurring in undescended testes is seminoma.[5] It is usually treatable if caught early, so urologists often recommend that boys who had orchiopexy as infants be taught testicular self-examination, to recognize testicular masses and seek early medical care for them. Cancer developing in an intra-abdominal testis would be unlikely to be recognized before considerable growth and spread, and one of the advantages of orchiopexy is that a mass developing in a scrotal testis is far easier to recognize than an intra-abdominal mass.
Orchidopexy was originally thought to result in easier detection of testicular cancer, but did not lower the risk of actually developing cancer. However, recent data have shown a paradigm shift. The New England Journal of Medicine published in 2007 that orchidopexy performed before puberty resulted in a significantly reduced risk of testicular cancer than if done after puberty.[6]
The risk of malignancy in the undescended testis is 4 to 10 ten times higher than that in the general population and is about one in 80 with a unilateral undescended testis and one in 40 to one in 50 for bilateral undescended testes. The peak age for this tumor is 15–45 years old. The most common tumor developing in an undescended testis is a seminoma (65%); in contrast, after orchiopexy, seminomas represent only 30% of testicular tumors.[7]
Causes
Environmental hypotheses
In most full-term infant boys with cryptorchidism but no other genital abnormalities, a cause cannot be found, making this a common, sporadic, unexplained (
- Severely premature infants can be born before descent of testes. Low birth weight is also a known factor.[8]
- A contributing role of environmental chemicals called endocrine disruptors that interfere with normal fetal hormone balance has been proposed. The Mayo Clinic lists "parents' exposure to some pesticides" as a known risk factor.[8][9]
- Risk factors may include exposure to regular alcohol consumption during pregnancy (five or more drinks per week, associated with a three-fold increase in cryptorchidism when compared to nondrinking mothers.[10] Cigarette smoking is also a known risk factor.[8]
- Family history of undescended testicles or other problems of genital development[8]
- Cryptorchidism occurs at a much higher rate in a large number of congenital malformation syndromes. Among the more common are Down syndrome,[8] Prader–Willi syndrome, and Noonan syndrome.
- In vitro fertilization, use of cosmetics by the mother, and pre-eclampsia have also been recognized as risk factors for development of cryptorchidism.[11]
- PAIS, the testis are generally partially undescended. This also occurs with 5α-Reductase 2 deficiency (DHT insensitivity) however, the testis generally descend during puberty.
In 2008, a study was published that investigated the possible relationship between cryptorchidism and prenatal exposure to a chemical called
A 2010 study examined the prevalence of congenital cryptorchidism among offspring whose mothers had taken mild
New insight into the testicular descent mechanism has been hypothesized by the concept of a male programming window derived from animal studies. According to this concept, testicular descent status is "set" during the period from 8 to 14 weeks of gestation in humans. Undescended testis is a result of disruption in androgen levels only during this programming window.[14]
Sexually antagonistic epigenetic marker hypothesis
William R. Rice et al. propose that cryptorchidism arises as a result of un-erased sexually discordant epimarks. They propose that ontogeny is canalized with epigenetic marks (epimarks) that make XY fetuses sensitive to fetal androgens, and decrease sensitivity of XX fetuses. Sometimes these markers go unerased, carrying over generations, and produce mosaicism in opposite sex offspring. The hypothesis is testable with current technology.[15]
Mechanism
Normal development
The testes begin as an immigration of primordial
In many infants with inguinal testes, further descent of the testes into the scrotum occurs in the first six months of life. This is attributed to the postnatal surge of gonadotropins and testosterone that normally occurs between the first and fourth months of life.
Spermatogenesis continues after birth. In the third to fifth months of life, some of the fetal spermatogonia residing along the basement membrane become type A spermatogonia. More gradually, other fetal spermatogonia become type B spermatogonia and primary spermatocytes by the fifth year after birth. Spermatogenesis arrests at this stage until puberty.
Most normal-appearing undescended testes are also normal by microscopic examination, but reduced spermatogonia can be found. The tissue in undescended testes becomes more markedly abnormal ("degenerates") in microscopic appearance between two and four years after birth. Some evidence indicates early orchiopexy reduces this degeneration.
Pathophysiology
At least one contributing mechanism for reduced
The inhibition of spermatogenesis by ordinary intra-abdominal temperature is so potent that continual suspension of normal testes tightly against the inguinal ring at the top of the scrotum by means of special "suspensory briefs" has been researched as a method of
An additional factor contributing to infertility is the high rate of anomalies of the epididymis in boys with cryptorchidism (over 90% in some studies). Even after orchiopexy, these may also affect sperm maturation and motility at an older age.
Diagnosis
The most common diagnostic dilemma in otherwise normal boys is distinguishing a
In the minority of cases with bilaterally nonpalpable testes, further testing to locate the testes, assess their function, and exclude additional problems is often useful. Scrotal ultrasound or magnetic resonance imaging performed and interpreted by a radiologist can often locate the testes while confirming absence of a uterus. At ultrasound, the undescended testis usually appears small, less echogenic than the contralateral normal testis and usually located in the inguinal region.[citation needed] With color Doppler ultrasonography, the vascularity of the undescended testis is poor.[citation needed]
A
In the even smaller minority of cryptorchid infants who have other obvious birth defects of the genitalia, further testing is crucial and has a high likelihood of detecting an intersex condition or other anatomic anomalies. Ambiguity can indicate either impaired androgen synthesis or reduced sensitivity. The presence of a uterus by pelvic ultrasound suggests either persistent Müllerian duct syndrome (AMH deficiency or insensitivity) or a severely virilized genetic female with congenital adrenal hyperplasia. An unambiguous micropenis, especially accompanied by hypoglycemia or jaundice, suggests congenital hypopituitarism.
Treatment
Intersex topics |
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The primary management of cryptorchidism is
When the undescended testis is in the inguinal canal, hormonal therapy is sometimes attempted and very occasionally successful. The most commonly used hormone therapy is human chorionic gonadotropin (hCG). A series of hCG injections (10 injections over five weeks is common) is given and the status of the testis/testes is reassessed at the end. Although many trials have been published, the reported success rates range widely, from roughly 5% to 50%, probably reflecting the varying criteria for distinguishing retractile testes from low inguinal testes. Hormone treatment does have the occasional incidental benefits of allowing confirmation of Leydig cell responsiveness (proven by a rise of the testosterone by the end of the injections) or inducing additional growth of a small penis (via the testosterone rise). Some surgeons have reported facilitation of surgery, perhaps by enhancing the size, vascularity, or healing of the tissue. A newer hormonal intervention used in Europe is the use of
; the success rates and putative mechanism of action are similar to hCG, but some surgeons have combined the two treatments and reported higher descent rates. Limited evidence suggests that germ cell count is slightly better after hormone treatment; whether this translates into better sperm counts and fertility rates at maturity has not been established. The cost of either type of hormone treatment is less than that of surgery and the chance of complications at appropriate doses is minimal. Nevertheless, despite the potential advantages of a trial of hormonal therapy, many surgeons do not consider the success rates high enough to be worth the trouble, since the surgery itself is usually simple and uncomplicated.In cases where the testes are identified preoperatively in the inguinal canal, orchiopexy is often performed as an outpatient and has a very low complication rate. An incision is made over the inguinal canal. The testis with accompanying cord structure and blood supply is exposed, partially separated from the surrounding tissues ("mobilized"), and brought into the scrotum. It is sutured to the scrotal tissue or enclosed in a "subdartos pouch". The associated passage back into the inguinal canal, an inguinal hernia, is closed to prevent reascent. In patients with intra-abdominal maldescended testis, laparoscopy is useful to see for oneself the pelvic structures, position of the testis and decide upon surgery (single or staged procedure ).
Surgery becomes more complicated if the blood supply is not ample and elastic enough to be stretched into the scrotum. In these cases, the supply may be divided, some vessels sacrificed with expectation of adequate collateral circulation. In the worst case, the testis must be "autotransplanted" into the scrotum, with all connecting blood vessels cut and reconnected (anastomosed).
When the testis is in the abdomen, the first stage of surgery is exploration to locate it, assess its viability, and determine the safest way to maintain or establish the blood supply. Multistage surgeries, or autotransplantation and anastomosis, are more often necessary in these situations. Just as often, intra-abdominal exploration discovers that the testis is nonexistent (
The principal major complication of all types of orchiopexy is a loss of the blood supply to the testis, resulting in loss of the testis due to ischemic atrophy or fibrosis.
Other animals
Cryptorchidism is seen in all domestic animals, most commonly in stallions, boars, and canines.[16] The prevalence of this condition can vary depending on species and breed. Evidence of this condition is more likely in companion animals and swine than ruminants.[17] The cause of this condition can vary from a combination of genetics, environment, and epigenetics.[16]
Dogs
Cryptorchidism is common in
Commonly affected breeds include:[21]
- Alaskan Klee Kai
- Boxer
- Chihuahua
- Dachshund (miniature)
- Bulldog
- Maltese
- Miniature Schnauzer
- Pekingese
- Pomeranian
- Poodle (toy and miniature)
- Pug
- Shetland Sheepdog
- Siberian Husky
- Whippet
- Yorkshire Terrier
Cats
Cryptorchidism is rarer in cats than it is in dogs. In one study, 1.9% of intact male cats were cryptorchid.
Horses
In horses, cryptorchidism is sufficiently common that affected males (ridglings) are routinely gelded.
Rarely, cryptorchidism is due to the presence of a
References
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- ^ "Cryptorchidism". Lecturio. Retrieved 11 July 2021.
- ISBN 978-0-8036-2505-1.)
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: CS1 maint: location missing publisher (link - ^ "Undescended testicle". A.D.A.M. Medical Encyclopedia. Johns Creek, Georgia, USA: Ebix. 31 July 2019. Retrieved 9 February 2022.
- ^ Dähnert, Wolfgang (2011). Radiology Review Manual. 995.
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: CS1 maint: location (link) CS1 maint: location missing publisher (link) - PMID 17476009.
- PMID 29261861. Retrieved 11 July 2021.
- ^ a b c d e "Undescended testicle - Symptoms and causes". Mayo Clinic. Retrieved 2018-03-31.
- PMID 18414644.
- ^ Rehmeyer, Julie (2 January 2007). "Drinking During Pregnancy Emerges As a Possible Male-Infertility Factor". Science News. Archived from the original on 30 March 2008. Retrieved 8 January 2007.
- PMID 21115274.
- doi:10.1021/on.2008.11.12.154968 (inactive 31 January 2024). Retrieved 2019-01-20.)
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- ^ a b "Congenital and Inherited Anomalies of the Reproductive System - Merck Veterinary Manual". Merck Veterinary Manual. Retrieved 2017-12-05.
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- ^ PMID 15070057.
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- ^ ISBN 978-0-87605-551-9.
- ^ ISBN 978-0-7216-6795-9.
- ^ a b Meyers-Wallen, V.N. "Inherited Abnormalities of Sexual Development in Dogs and Cats". Recent Advances in Small Animal Reproduction. Retrieved 2006-08-10.
- PMID 12387382.
- ISBN 978-0-7216-0423-7.
- ^ Eldredge, Debra M.; Carlson, Delbert G.; Carlson, Liisa D.; Giffin, James M. (2008). Cat Owner's Home Veterinary Handbook. Howell Book House. p. 421.
- ^ Memon, M.; Tibary, A. (2001). "Canin and Feline Cryptorchidism" (PDF). Recent Advances in Small Animal Reproduction. Retrieved 2007-02-09.
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- ISBN 978-0-683-04481-2. p. 1210.