What is the best test for cryptorchidism?

Abstract

Cryptorchidism is a common heritable condition in horses and ponies and while retained testicles rarely release viable sperm, Leydig cells produce testosterone leading to undesirable stallion-like behaviour. Endocrine assays are frequently required to definitively diagnose retained testicular tissue. A literature search of the Medline database was performed using the PubMed search engine. The search term ‘equine cryptorchidism’ was entered and the results filtered using the contents of the abstracts to retain articles relating specifically to diagnostic testing for cryptorchidism. The initial search yielded 139 articles which after filtering were reduced to 6 articles included for analysis. Retrospective analysis of clinical cases comprising level IV evidence was used to evaluate the use of serum oestrone sulphate and serum testosterone (alone and after human chorionic gonadotropin (hCG) administration) for the detection of cryptorchidism (Cox et al. 1986). Leung et al. (2011) also analysed a large number of normal horses but few cryptorchid animals (n = 25, only 18 confirmed) were diagnosed using urine steroid profiling. The remaining prospective experimental studies evaluated the use of serum testosterone following administration of hCG (Silberzahn et al. 1989), serum anti-Müllerian hormone (AMH) (Claes et al. 2013), serum androstenedione (Illera et al. 2003) and faecal oestrogens (Palme et al. 1994) to distinguish between gelded, entire and cryptorchid horses. This data was then variably extrapolated to provide inferred relevance for the use of each test for the detection of suspected cryptorchid animals. Of the 4 prospective experimental studies those by Silberzahn et al. (1989) and Palme et al. (1994) lack sufficient numbers or appropriate methodology to provide quality evidence. Illera et al. (2003) evaluated the use of serum androstenedione but inconsistency in their results significantly weakens the evidence provided by this paper. The most recent experimental study by Claes et al. (2013) provides the strongest evidence for the use of serum AMH. The quality of the evidence provided by the retrospective studies (Cox et al. 1986; Leung et al. 2011) is weak as the cryptorchid status of all the animals in the study, particularly those testing negative, was not confirmed. Testosterone may be measured directly but serum levels vary greatly between individuals and fluctuate with age and season (Cox et al. 1986; Claes et al. 2013) making it unsuitable as a definitive test. Measurement of testosterone pre and 30 min post administration of hCG was reported to be more reliable with an accurate diagnosis achieved in 95% of cases (Cox et al. 1986). However, other studies have questioned the reliability of this elevation in testosterone so soon after hCG administration (Silberzahn et al. 1989; Illera et al. 2003) and accuracy may be improved by testosterone measurement up to 72 h post hCG (Silberzahn et al. 1989). This claim has not been validated and such a time delay is less suitable for use in clinical practice. Measurement of serum oestrone sulphate in horses and ponies (not donkeys) >3-years-old was 96% accurate in weak early retrospective studies (Cox et al. 1986). However, evaluation of serum oestrone sulphate in a more clearly defined population yielded reduced positive predictive values (PPV) and negative predictive values (NPV) of 85% and 91% respectively for this test (Illera et al. 2003). Illera et al. (2003) reported serum androstenedione to have increased accuracy (92%) compared with both oestrone sulphate (86%) and testosterone pre and post hCG stimulation (88%) for the detection of cryptorchids. However, this finding is weakened by anomalies in the results of the study and, on the basis of this, evidence serum androstenedione cannot be recommended. Anti-Müllerian hormone (AMH) is produced in elevated amounts from Sertoli cells in cryptorchid testes (Ball et al. 2008) making it a potentially reliable and specific test for the presence of testicular tissue. Claes et al. (2013) evaluated the serum AMH concentrations in stallions, geldings and cryptorchids. Serum AMH concentrations were significantly higher in cryptorchid stallions (32.7 ± 5.3 ng/ml) compared with intact stallions (14.7 ± 2.4 ng/ml); geldings were below or fractionally above the lower limit of detection for the test. Only animals of >2 years of age were included in the study and AMH levels require investigation in cryptorchid pubertal animals. The calculated biological half-life was 1.5 days (Claes et al. 2013) making AMH a useful test if there is doubt over the success of a recent castration procedure. The evidence for many of the available endocrine assays is based on poor quality retrospective or experimental studies. Currently, the strongest evidence exists for the use of AMH for the detection of cryptorchidism, although the test warrants validation in a large number of confirmed cryptorchid animals and in animals <2 years of age. No conflicts of interests have been declared.