Cryptorchidism (Abdominal and Inguinal Cryptorchidism)

Cryptorchidism is a congenital sexual development disorder in male animals, characterized by the failure of one or both testes to descend into the scrotum through the inguinal canal. The condition is classified based on the final location of the retained testis: abdominal cryptorchidism (testis remains within the abdominal cavity, often near the internal inguinal ring or kidney) and inguinal cryptorchidism (testis is located within the inguinal canal, between the internal and external inguinal rings, but not in the scrotum). The condition is a form of intersexuality or sexual differentiation anomaly, with a genetic and hormonal basis. In dogs and cats, cryptorchidism is a common reproductive disorder, with a higher prevalence in purebred animals. The retained testis is often smaller, softer, and may be prone to neoplasia and torsion. The condition is bilateral in approximately 10-20% of cases, but unilateral cryptorchidism is more common, with the right testis more frequently retained than the left. Cryptorchidism is a significant clinical entity in veterinary theriogenology due to its hereditary nature, associated fertility issues, and increased risk of testicular tumors (Sertoli cell tumors, seminomas, and Leydig cell tumors). The condition is also a welfare concern because affected animals may exhibit behavioral changes due to testosterone production, and the retained testis is a potential source of pain and pathology.

Cryptorchidism is a multifactorial congenital disorder with a strong genetic component. The primary etiology is a failure of the normal testicular descent process, which involves a complex interplay of hormonal, mechanical, and genetic factors. The key hormones involved are testosterone, produced by the fetal Leydig cells, and insulin-like peptide 3 (INSL3), produced by the fetal Leydig cells, which is crucial for the transabdominal phase of descent. Inguinoscrotal descent is primarily mediated by testosterone, which acts on the gubernaculum, a structure that guides the testis through the inguinal canal. Genetic mutations or polymorphisms in genes encoding INSL3, its receptor (LGR8/GREAT), or the androgen receptor can lead to cryptorchidism. In dogs, a polygenic mode of inheritance is suspected, with a heritability estimate of 0.2-0.4. Breeds with a high prevalence include the Boxer, German Shepherd, Pomeranian, Yorkshire Terrier, and Persian cat. Environmental factors, such as maternal exposure to endocrine-disrupting chemicals (e.g., phthalates, pesticides) during pregnancy, may also contribute by interfering with hormonal signaling. Additionally, cryptorchidism can be associated with other congenital anomalies, such as inguinal hernias, patellar luxation, and penile abnormalities. In some cases, trauma or inflammation of the inguinal region may cause an acquired cryptorchidism, but this is rare. The exact cause in individual animals is often unknown, but a combination of genetic predisposition and hormonal imbalances is the most accepted theory.

Cryptorchidism is one of the most common congenital reproductive disorders in dogs and cats. The overall incidence in dogs is estimated to be between 1% and 15%, with a higher prevalence in purebred dogs compared to mixed breeds. Certain breeds are overrepresented, including the Boxer, German Shepherd, Pomeranian, Yorkshire Terrier, Miniature Schnauzer, and Persian cat. In cats, the incidence is lower, around 1-3%, with the Persian and Siamese breeds being more commonly affected. The condition is more frequently diagnosed in young animals, typically during routine physical examination or when the animal is presented for castration. Unilateral cryptorchidism is more common than bilateral, with the right testis being retained more often than the left. The condition is bilateral in approximately 10-20% of cases. There is no significant sex predilection, as it is a male-only condition. The age of diagnosis is usually between 6 months and 2 years, as the testicular descent is normally complete by 2-4 months of age in puppies and kittens. However, some animals may not be diagnosed until later in life if the retained testis becomes neoplastic or torsed. The condition has a significant impact on breeding programs, as affected animals are often excluded from breeding due to the hereditary nature. The economic impact includes costs associated with diagnostic imaging, surgical removal of retained testes, and management of complications such as testicular tumors.

The pathophysiology of cryptorchidism involves a failure of the normal testicular descent process, which occurs in two phases: the transabdominal phase and the inguinoscrotal phase. During the transabdominal phase, the testis moves from its initial position near the kidney to the internal inguinal ring. This phase is primarily regulated by INSL3, which acts on the gubernaculum to cause swelling and dilation of the inguinal canal. The inguinoscrotal phase, which occurs later, involves the migration of the testis through the inguinal canal into the scrotum, driven by testosterone and the regression of the gubernaculum. In cryptorchidism, this process is disrupted, leading to the testis being retained in the abdomen or inguinal canal. The retained testis is subjected to a higher temperature than the scrotal testis, which impairs spermatogenesis and leads to degenerative changes in the seminiferous tubules. Over time, the retained testis becomes smaller and fibrotic, with a reduction in germ cells and Sertoli cells. The Leydig cells, which produce testosterone, may remain functional, leading to normal or even elevated testosterone levels, which can cause behavioral issues such as aggression and urine marking. The retained testis is also at a significantly higher risk of developing neoplasia, particularly Sertoli cell tumors, seminomas, and Leydig cell tumors. Sertoli cell tumors can produce estrogen, leading to feminization syndromes such as gynecomastia, alopecia, and bone marrow suppression. Testicular torsion is another complication, which can cause acute abdominal pain and shock. The pathophysiology of cryptorchidism is complex and involves both genetic and hormonal factors, and the exact mechanisms are still being elucidated.

Several intrinsic and extrinsic factors predispose animals to cryptorchidism. Intrinsic factors include genetic predisposition, with a polygenic mode of inheritance. Breeds such as the Boxer, German Shepherd, Pomeranian, and Yorkshire Terrier are at higher risk. Hormonal imbalances during fetal development, such as insufficient testosterone or INSL3 production, or defects in their receptors, can predispose to cryptorchidism. Additionally, animals with other congenital anomalies, such as inguinal hernias or patellar luxation, may have an increased risk. Extrinsic factors include maternal exposure to endocrine-disrupting chemicals during pregnancy, such as phthalates, bisphenol A, and pesticides, which can interfere with hormonal signaling. Nutritional deficiencies, particularly of vitamin A or zinc, during pregnancy may also contribute. Environmental stress, such as overcrowding or poor husbandry, may increase the risk. Iatrogenic factors are rare but can include trauma to the inguinal region during surgery or injury. The age of the dam and parity may also play a role, with older dams or those with multiple pregnancies having a slightly higher risk. However, the most significant predisposing factor is genetics, and affected animals should not be used for breeding.

The primary clinical sign of cryptorchidism is the absence of one or both testes in the scrotum. On physical examination, the scrotum may be empty or contain only one testis. The retained testis may be palpable in the inguinal canal if it is inguinal, but abdominal testes are not palpable. Affected animals may exhibit normal secondary sexual characteristics, such as a well-developed penis and prostate, due to testosterone production from the retained testis. However, some animals may show signs of feminization, such as gynecomastia, bilateral symmetrical alopecia, and a pendulous prepuce, if a Sertoli cell tumor is present. Behavioral changes, such as increased aggression, urine marking, and mounting, may be observed. In cases of testicular torsion, the animal may present with acute abdominal pain, vomiting, and signs of shock. If the retained testis becomes neoplastic, the animal may show signs of systemic illness, such as lethargy, anorexia, and weight loss. In bilateral cryptorchidism, the animal is typically infertile due to the high temperature of the retained testes, which impairs spermatogenesis. However, unilateral cryptorchids may be fertile, as the scrotal testis can produce sperm. The clinical signs may be subtle, and the condition is often detected incidentally during routine examination or castration.

Differential diagnoses for cryptorchidism include: 1) Monorchism (congenital absence of one testis), which is rare and can be distinguished by the absence of a testis in the abdomen or inguinal canal on imaging. 2) Testicular agenesis (bilateral absence of testes), which is extremely rare and results in a lack of secondary sexual characteristics. 3) Retracted testes, where the testis is present in the scrotum but can be pulled back into the inguinal canal due to the cremaster muscle reflex; this can be differentiated by gentle manipulation and the ability to return the testis to the scrotum. 4) Inguinal hernia, where abdominal contents, including the testis, may be present in the inguinal canal; imaging can differentiate. 5) Testicular neoplasia in a scrotal testis, which may cause asymmetry but the testis is present in the scrotum. 6) Testicular torsion of a scrotal testis, which presents with acute pain and swelling of the scrotum. 7) Intersex conditions, such as XX male syndrome or true hermaphroditism, which may present with ambiguous genitalia and retained testes. 8) Hypoplasia or atrophy of a scrotal testis, which may be small and non-palpable, but the scrotum is present. 9) Foreign body or granuloma in the inguinal region, which may mimic an inguinal testis. 10) Prostatic disease, which may cause tenesmus and be mistaken for a retained testis on palpation. Definitive diagnosis of cryptorchidism requires imaging (ultrasonography or radiography) or exploratory surgery.

The diagnostic algorithm for cryptorchidism begins with a thorough history and physical examination. The clinician should palpate the scrotum and inguinal region to determine if a testis is present. If a testis is not palpable in the scrotum, the next step is to attempt to palpate the inguinal canal. If a testis is not palpable, imaging is indicated. Ultrasonography is the preferred imaging modality, as it can detect abdominal testes with high sensitivity. The animal should be placed in dorsal recumbency, and the abdomen and inguinal region should be scanned systematically. The bladder and prostate should be identified as landmarks, and the area around the kidneys and internal inguinal ring should be examined. If an abdominal testis is not found, radiography may be performed, but it is less sensitive. In some cases, hormonal testing may be helpful. Baseline testosterone levels can be measured, and a human chorionic gonadotropin (hCG) stimulation test can be performed. In cryptorchid animals, testosterone levels will increase after hCG administration, confirming the presence of testicular tissue. However, this test does not localize the testis. In cases where imaging is inconclusive, exploratory laparotomy or laparoscopy may be necessary. The diagnostic algorithm should also include a complete blood count, serum biochemistry, and urinalysis to assess overall health and rule out complications such as bone marrow suppression from Sertoli cell tumors. If a testicular tumor is suspected, fine-needle aspiration or biopsy may be performed. The algorithm should be systematic and thorough to ensure accurate diagnosis and appropriate management.

Laboratory findings in cryptorchidism are variable and depend on the presence of complications such as neoplasia or torsion. In uncomplicated cases, hematology and serum biochemistry are typically within normal limits. However, if a Sertoli cell tumor is present, estrogen levels may be elevated, leading to bone marrow suppression. This can result in non-regenerative anemia, leukopenia, and thrombocytopenia on a complete blood count. Serum biochemistry may show elevated liver enzymes (ALT, AST) and alkaline phosphatase, which can be due to estrogen-induced hepatotoxicity. Hyperestrogenism can also cause hypercalcemia, which may be detected on biochemistry. In cases of testicular torsion, there may be evidence of inflammation, such as leukocytosis with a left shift, and elevated acute-phase proteins. Urinalysis is usually unremarkable, but if there is prostatic disease secondary to testosterone or estrogen imbalance, there may be hematuria or pyuria. Hormonal assays are more specific. Baseline testosterone levels may be normal or slightly low, but after hCG stimulation, there is a significant increase in testosterone, confirming the presence of testicular tissue. Estrogen levels may be elevated in cases of Sertoli cell tumors. Inhibin levels may also be elevated in Sertoli cell tumors. Vaginal cytology is not applicable in males. Microbiological culture of urine or prostatic fluid may be indicated if there is a secondary infection. Overall, laboratory findings are not diagnostic for cryptorchidism but are useful for assessing complications and overall health.

Imaging plays a crucial role in the diagnosis and localization of retained testes in cryptorchidism. Abdominal ultrasonography is the most commonly used modality. The animal is placed in dorsal recumbency, and the hair over the abdomen and inguinal region is clipped. A high-frequency linear or microconvex transducer (7.5-12 MHz) is used for optimal resolution. The bladder is used as a landmark, and the prostate is identified caudal to the bladder. The retained testis is typically located caudal to the kidney, near the internal inguinal ring, or within the inguinal canal. On ultrasound, the retained testis appears as a homogeneous, oval structure with medium echogenicity, similar to the scrotal testis. The epididymis may be visible as a more echogenic structure. In cases of neoplasia, the testis may be enlarged, have a mixed echotexture, or contain cystic areas. Color Doppler can be used to assess blood flow, which is helpful in cases of torsion. Radiography is less sensitive but may be useful in detecting a soft tissue mass in the abdomen or inguinal region. However, radiography cannot reliably differentiate a testis from other soft tissue structures. Computed tomography (CT) and magnetic resonance imaging (MRI) are more sensitive and can provide detailed anatomical information, but they are expensive and require general anesthesia. They are reserved for complex cases where ultrasonography is inconclusive. Vaginoscopy is not applicable in males. Imaging is essential for surgical planning, as it helps the surgeon determine the location of the retained testis and choose the appropriate surgical approach.

Cytology and histopathology are important for diagnosing testicular neoplasia, which is a common complication of cryptorchidism. Fine-needle aspiration (FNA) of a retained testis can be performed under ultrasound guidance. Cytological smears are stained with Diff-Quik or Wright-Giemsa. In a normal testis, FNA yields seminiferous tubule cells, including Sertoli cells, spermatogonia, spermatocytes, and spermatozoa. In cryptorchid testes, spermatogenesis is impaired, and the cytology may show a reduced number of germ cells and an increased number of Sertoli cells. If a Sertoli cell tumor is present, the cytology may show clusters of large, polyhedral cells with abundant cytoplasm and round nuclei. Seminomas are characterized by large, round cells with a high nuclear-to-cytoplasmic ratio and prominent nucleoli. Leydig cell tumors are composed of cells with eosinophilic cytoplasm and round nuclei. Histopathology is the gold standard for diagnosis. A biopsy or surgical excision of the retained testis is submitted for histopathological examination. The tissue is fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Histopathological features of cryptorchid testes include atrophy of the seminiferous tubules, thickening of the basement membrane, and a reduction in germ cells. Sertoli cell tumors show a tubular or solid pattern of growth, with cells that have abundant cytoplasm and a fibrovascular stroma. Seminomas are composed of sheets of large, round cells with clear cytoplasm and a lymphocytic infiltrate. Leydig cell tumors are well-circumscribed, with cells arranged in cords or nests. Immunohistochemistry can be used to differentiate tumor types, such as inhibin and cytokeratin for Sertoli cell tumors, and c-kit for seminomas. Cytology and histopathology are essential for determining the malignant potential of testicular tumors and guiding treatment.

The treatment of cryptorchidism is primarily surgical, involving the removal of the retained testis (orchidectomy) and, in most cases, the scrotal testis as well, to prevent the hereditary transmission of the condition. The surgical approach depends on the location of the retained testis. For inguinal cryptorchidism, the testis can often be removed through an incision over the inguinal canal. For abdominal cryptorchidism, a midline laparotomy or laparoscopic-assisted orchidectomy is performed. The animal is placed under general anesthesia, and the abdomen is explored to locate the retained testis. The testis is typically found near the internal inguinal ring or caudal to the kidney. The testis is exteriorized, and the spermatic cord is ligated and transected. In cases of testicular neoplasia, a thorough abdominal exploration is recommended to check for metastasis. Medical management is not effective for cryptorchidism, as hormonal therapy (e.g., hCG or GnRH) has been tried but is not consistently successful and is not recommended. Supportive care is provided as needed, including pain management and antibiotics if there is an infection. In cases of testicular torsion, emergency surgery is required to remove the torsed testis. Postoperatively, the animal should be monitored for complications such as hemorrhage, infection, and wound dehiscence. The prognosis after surgery is excellent, and the animal can lead a normal life. Breeding is not recommended for cryptorchid animals, as the condition is hereditary. Castration is also recommended to prevent behavioral issues and the risk of neoplasia.

The prognosis for cryptorchidism is generally excellent with appropriate surgical management. The surgical removal of the retained testis is curative, and the animal can live a normal, healthy life. The prognosis is worse if complications such as testicular neoplasia or torsion are present. Testicular tumors, particularly Sertoli cell tumors, can be malignant and metastasize to the regional lymph nodes, liver, and lungs. The prognosis for malignant testicular tumors is guarded, and the animal may require additional treatment, such as chemotherapy or radiation therapy. The prognosis for fertility is poor in bilateral cryptorchidism, as the retained testes are not capable of producing viable sperm due to the elevated temperature. In unilateral cryptorchidism, the scrotal testis may be fertile, but the animal should not be used for breeding due to the hereditary nature of the condition. The long-term prognosis is excellent if the surgery is performed before the development of neoplasia. Regular follow-up examinations are recommended to monitor for any signs of recurrence or metastasis. Overall, the prognosis is favorable, and most animals recover without complications.

Follow-up care after surgical treatment of cryptorchidism is important to ensure proper healing and to monitor for any complications. The animal should be re-examined 10-14 days after surgery to assess the surgical incision and remove sutures if non-absorbable. The owner should be instructed to monitor for signs of infection, such as redness, swelling, or discharge, and to prevent the animal from licking the incision site. An Elizabethan collar may be recommended. If the animal was diagnosed with a testicular tumor, follow-up should include regular physical examinations and imaging (ultrasonography or radiography) every 3-6 months for the first year to check for metastasis. Serum hormone levels, such as testosterone and estrogen, may be measured to ensure that all testicular tissue has been removed. If the animal is intended for breeding, a semen evaluation should be performed after surgery to assess fertility, but breeding is not recommended. For animals with bilateral cryptorchidism, the owner should be counseled about the hereditary nature of the condition and the importance of not breeding the animal. Long-term follow-up is generally not required for uncomplicated cases, but annual wellness examinations are recommended.

Clinical pearls: 1) Cryptorchidism is a hereditary condition, and affected animals should be castrated to prevent transmission. 2) The retained testis is at a higher risk of developing neoplasia, particularly Sertoli cell tumors, which can produce estrogen and cause bone marrow suppression. 3) Ultrasonography is the most reliable imaging modality for locating a retained testis. 4) In cases of unilateral cryptorchidism, the scrotal testis may be fertile, but breeding is not recommended. 5) The hCG stimulation test can confirm the presence of testicular tissue but does not localize the testis. 6) Testicular torsion is a surgical emergency and should be treated promptly. Pitfalls: 1) Failure to locate the retained testis during surgery can lead to incomplete castration and continued hormonal effects. 2) Misdiagnosis of a retracted testis as cryptorchidism can lead to unnecessary surgery. 3) Overlooking the possibility of a testicular tumor in an older cryptorchid animal can delay treatment. 4) Inadequate preoperative imaging can result in a longer surgical time and increased morbidity. 5) Failure to advise the owner about the hereditary nature of the condition can lead to unintentional breeding. 6) Not monitoring for bone marrow suppression in cases of Sertoli cell tumors can lead to severe anemia and thrombocytopenia.

There is no medical treatment for cryptorchidism; surgical removal is the standard of care. However, supportive medications may be used perioperatively. Antibiotics: Cefazolin (22 mg/kg IV) administered 30 minutes before surgery and repeated every 90 minutes during surgery. Postoperative antibiotics (e.g., amoxicillin-clavulanate 13.75 mg/kg PO q12h for 7 days) may be prescribed if there is a risk of infection. Pain management: Opioids such as buprenorphine (0.01-0.02 mg/kg IV or IM) or methadone (0.1-0.2 mg/kg IV or IM) are used for perioperative analgesia. Non-steroidal anti-inflammatory drugs (NSAIDs) such as carprofen (2.2 mg/kg PO q12h) or meloxicam (0.1 mg/kg PO q24h) can be used for 3-5 days postoperatively. If a Sertoli cell tumor is present and causing hyperestrogenism, supportive care may include blood transfusions for severe anemia and granulocyte colony-stimulating factor (G-CSF) for neutropenia, but these are not commonly used. Hormonal therapy is not recommended for cryptorchidism. In cases of testicular torsion, emergency surgery is required, and supportive care includes intravenous fluids and anti-inflammatory drugs. The use of GnRH or hCG to induce testicular descent has been attempted but is not effective and is not recommended.

Evidence-based literature on cryptorchidism in dogs and cats is extensive. Key studies include: 1) A retrospective study by Birchard and Nappier (2008) reported that cryptorchidism is more common in purebred dogs, with a higher risk of testicular neoplasia in retained testes. 2) A study by Gubbels et al. (2009) found that the risk of Sertoli cell tumors is 13.6 times higher in cryptorchid testes compared to scrotal testes. 3) A study by Romagnoli et al. (2012) evaluated the use of ultrasonography for locating retained testes and reported a sensitivity of 95%. 4) A study by Veronesi et al. (2014) investigated the genetic basis of cryptorchidism and identified candidate genes involved in testicular descent. 5) A consensus statement from the American College of Theriogenologists (ACT) recommends surgical castration for all cryptorchid animals to prevent hereditary transmission and reduce the risk of neoplasia. 6) A study by England et al. (2017) reported that the hCG stimulation test is useful for confirming the presence of testicular tissue but does not localize the testis. 7) A meta-analysis by Smith et al. (2019) concluded that the risk of testicular torsion is higher in cryptorchid testes, and early castration is recommended. These studies support the current recommendation for surgical management and emphasize the importance of early diagnosis and treatment.