Προγνωστικοί δείκτες ατροφίας του όρχεως σε παιδιά με κρυψορχία

Abstract

The low fertility rates of formerly cryptorchid men underline the importance of the early diagnosis of future spermatogenic disorders in boys with cryptorchidism. This study aims at the introduction and the evaluation of specific parameters (clinical, ultrasonographic, hormonal) as early prognostic markers of testicular atrophy in boys with cryptorchidism, through the analysis of the anatomic, the pathophysiolgic and the endocrine environment, which affects the cryptorchid as well as the contralateral testis, in case of unilateral cryptorchidism, during their development. Toward this purpose, the size of the testes and the hormonic profile of boys with cryptorchidism were examined preoperatively, the effect of orchidopexy on these parameters was studied and an effort took place in order the response of the testes, and particularly of the Sertoli cells, by measuring the serum levels of Inhibin B (Inh B), to the r-FSH stimulation test, a procedure that offers a dynamic evaluation of the function of the Sertoli cells, to be evaluated. The study group consisted of 36 boys with cryptorchidism (mean age 41,86 months), whereas the control group consisted of 30 boys with normally descended testes (mean age 50,5 months). The study group The study group underwent clinical, ultrasonographic and hormonal evaluation, preoperatively. The hormones measured were FSH, LH, Ιnh B, AMH, PRL, T, fr-T, DHEA, TSH, T3, T4 (ELISA). The control group also underwent hormonic evaluation for comparison reasons. After orchidopexy, the study group was followed up clinically and ultrasonographically (mean time 17,71 months, 4-54 months). A subgroup (22/36 boys), underwent also postoperative harmonic evaluation, mean time 20,54 months after orchidopexy, followed by the r-FSH stimulation test (200 i.u. r-FSH s.c.) and re-evaluation at 24h and 48h after the stimualtion. The results were statistically analyzed (SPSS, Mann-Whitney and Wilcoxon tests, Monte Carlo p<0,05). 43 cases of undescended testes were recognized at the study group (38,8% right-sided, 41,6% left-sided, 19,4% bilateral). 42 orchidopexies were performed (mean age 41,86 months). The cryptorchid testes were found atrophic in 30,9% of the cases, and in all of the nonpalpable cases (23,7%). Epidymal anomalies were reported in 40,4% of the cases. The size of the cryptorchid testes was significantly smaller both pre- and postoperatively compared with the normal contralateral testes (p=0,009 και p=0,007 respectively). Preoperatively, high levels of FSH (p1-tailed=0,000) and AMH (p=0,004) in association with low levels of fr-T (P=0,011) and DHEA (p=0,035) were reported in boys with cryptorchidism. Postoperatively, the levels of Inh B (p1-tailed=0,036) and AMH (p=0,019) declined significantly, whereas the levels of fr-T (p=0,018) rose. After the r-FSH stimulation test, the highest levels of FSH (p=0,000), Inh B (p=0,000) and AMH (p=0,011) were recorded at 24h after the stimulation, whereas the ratio Inh B / FSH resulted in its lowest values at this time-point. In conclusion, the small nonpalpable cryptorchid testes show greater predisposition to atrophy, especially when involved in bilateral cryptorchidism. Delay of the surgical treatment is another aggravating factor. Moreover, the presense of epidymal anomalies raise significantly the risk of future fertility problems. The harmonic evaluation showed that both the cryptorchid and the contralateral testes develop under the influence of a disturbed endocrine environment, characterized by high levels of FSH in association with low levels of fr-T and DHEA. The orchidopexy seems to normalize this environment, at least as far as fr-T is concerned. On the other hand, the decline in the levels of Inh B and AMH reflects the impaired function of the Sertoli cells, due to their continuing degeneration, despite orchidopexy. Inh B and AMH, as exclusive products of the Sertoli cells, are considered to be unique markers for the evaluation of the function of the Sertoli cells, especially when supported by the r-FSH stimulation test, which was introduced in the peadiatric population by this study. The above markers (clinical, ultrasonographic, hormonal) can contribute to the early diagnosis of future spermatogenic disorders in boys with cryptorchidism, bypassing more invasive methods, such as the biopsy of the testis, which is considered the gold standard in the diagnosis of these disorders, thus offering the opportunity of early treatment.

Σκοπός της μελέτης είναι η ανεύρεση προγνωστικών δεικτών ατροφίας του όρχεως σε παιδιά με κρυψορχία. Μελετήθηκαν ορμονικές παράμετροι και το μέγεθος των όρχεων προεγχειρητικά, η επίδραση της ορχεοπηξίας και η ανταπόκριση των όρχεων στη δοκιμασία διέγερσης με r-FSH. Ως αρνητικοί δείκτες αξιολογήθηκαν το μικρό προεγχειρητικά μέγεθος του κρυψόρχεως, η εντόπιση του ενδοκοιλιακά, ή στο έσω στόμιο του βουβωνικού πόρου, η αμφοτερόπλευρη κρυψορχία, η καθυστερημένη χειρουργική αντιμετώπιση, ανατομικές ανωμαλίες (διαχωρισμός όρχεως-επιδιδυμίδας). Τα προεγχειρητικά υψηλά επίπεδα FSH σε συνδυασμό με τα χαμηλά επίπεδα Fr-t και DHEA ομαλοποιήθηκαν εν μέρει μετά την ορχεοπηξία, ενώ οι Inh B και AMH μειώθηκαν, αντανακλώντας την ελαττωμένη λειτουργικότητα των κυττάρων Sertoli. Η Inh B σε συνδυασμό με τη δοκιμασία διέγερσης με r-FSH αποτελεί ιδανικό δείκτη αξιολόγησης της λειτουργικότητας των κυττάρων Sertoli. Οι παραπάνω κλινικοί, υπερηχογραφικοί και ορμονικοί δείκτες μπορούν να συμβάλλουν στην πρώϊμη διάγνωση μελλοντικών διαταραχών σπερματογένεσης στα παιδιά με κρυψορχία, αντικαθιστώντας έτσι τη βιοψία του όρχεως, και επιτρέποντας την έγκαιρη αντιμετώπισή τους.