Gilvydas Verkauskas1, Dalius Malcius2, Audrone Eidukaite3, Juozas Vilimas4, Darius Dasevicius5, Vytautas Bilius4, Faruk Hadziselimovic6. 1. Faculty of Medicine, Vilnius University, Vilnius, Lithuania. Electronic address: gilvydas.verkauskas@vuvl.lt. 2. Lithuanian University of Health Sciences, Kaunas, Lithuania. 3. State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania. 4. Faculty of Medicine, Vilnius University, Vilnius, Lithuania. 5. National Centre of Pathology, Vilnius, Lithuania. 6. Institute for Cryptorchidism Research, Kindermedizinisches Zentrum, Liestal, Switzerland.
Abstract
INTRODUCTION: A transient increase in gonadotropins and testosterone during mini-puberty causes gonocytes to differentiate into Ad spermatogonia, which establish male germ cell memory and male-specific DNA methylation pathways. Over half of patients with unilateral cryptorchidism and the majority of patients with bilateral cryptorchidism display an abnormal spermiogram, which indicates that unilateral cryptorchidism is a bilateral disease; therefore, it represents a serious andrological problem. The aim of this study was to evaluate relationships between hormonal parameters and testicular biopsy findings in boys with cryptorchidism. METHOD: Seventy-one boys (median age 15 months; range 7-65 months) who underwent orchidopexy (24% had bilateral cryptorchidism) were tested for serum LH, FSH, and inhibin B. With ipsilateral testis biopsy histology, we determined the tubular fertility index (TFI), Ad spermatogonia counts, and Ad/tubular index (Ad/T). We compared age groups (<18 vs. >18 months old); groups with and without Ad spermatogonia; groups with unilateral and bilateral cryptorchidism; and extreme groups with high infertility risk (HIR; n = 12; TFI <0.2; Ad/T = 0) and low infertility risk (LIR; n = 9; TFI >0.9; Ad/T>0.02). RESULTS: Of the specimens, 38% had no Ad spermatogonia. Age was significantly negatively correlated with TFI and Ad/T, but positively correlated with FSH. Median LH values were significantly higher in LIR than in HIR groups. Unilateral and bilateral cryptorchidism showed similar TFI, Ad/T, and hormone concentrations. The areas under ROC curves for FSH, LH, and inhibin B (0.66, 0.601, and 0.599, respectively) showed low diagnostic value for predicting HIR (no Ad spermatogonia). CONCLUSION: Our observation of lower plasma LH levels in the group with the most pronounced testicular pathology was the opposite of what we would have expected if testicular pathological changes were caused by a primary gonadal defect. Therefore, low plasma LH levels in the HIR group confirmed the notion that this group of patients with cryptorchidism had hypogonadotropic hypogonadism. The estimated incidence of defective mini-puberty in boys with cryptorchidism could be as high as 50%. Testicular biopsies from boys with cryptorchidism lacked Ad spermatogonia. Fertility parameters worsened with age. Significantly lower basal LH in the HIR group indicated hypogonadotropic hypogonadism. Serum hormone levels could not predict histological biopsy findings.
INTRODUCTION: A transient increase in gonadotropins and testosterone during mini-puberty causes gonocytes to differentiate into Ad spermatogonia, which establish male germ cell memory and male-specific DNA methylation pathways. Over half of patients with unilateral cryptorchidism and the majority of patients with bilateral cryptorchidism display an abnormal spermiogram, which indicates that unilateral cryptorchidism is a bilateral disease; therefore, it represents a serious andrological problem. The aim of this study was to evaluate relationships between hormonal parameters and testicular biopsy findings in boys with cryptorchidism. METHOD: Seventy-one boys (median age 15 months; range 7-65 months) who underwent orchidopexy (24% had bilateral cryptorchidism) were tested for serum LH, FSH, and inhibin B. With ipsilateral testis biopsy histology, we determined the tubular fertility index (TFI), Ad spermatogonia counts, and Ad/tubular index (Ad/T). We compared age groups (<18 vs. >18 months old); groups with and without Ad spermatogonia; groups with unilateral and bilateral cryptorchidism; and extreme groups with high infertility risk (HIR; n = 12; TFI <0.2; Ad/T = 0) and low infertility risk (LIR; n = 9; TFI >0.9; Ad/T>0.02). RESULTS: Of the specimens, 38% had no Ad spermatogonia. Age was significantly negatively correlated with TFI and Ad/T, but positively correlated with FSH. Median LH values were significantly higher in LIR than in HIR groups. Unilateral and bilateral cryptorchidism showed similar TFI, Ad/T, and hormone concentrations. The areas under ROC curves for FSH, LH, and inhibin B (0.66, 0.601, and 0.599, respectively) showed low diagnostic value for predicting HIR (no Ad spermatogonia). CONCLUSION: Our observation of lower plasma LH levels in the group with the most pronounced testicular pathology was the opposite of what we would have expected if testicular pathological changes were caused by a primary gonadal defect. Therefore, low plasma LH levels in the HIR group confirmed the notion that this group of patients with cryptorchidism had hypogonadotropic hypogonadism. The estimated incidence of defective mini-puberty in boys with cryptorchidism could be as high as 50%. Testicular biopsies from boys with cryptorchidism lacked Ad spermatogonia. Fertility parameters worsened with age. Significantly lower basal LH in the HIR group indicated hypogonadotropic hypogonadism. Serum hormone levels could not predict histological biopsy findings.
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Authors: Katharina Gegenschatz-Schmid; Gilvydas Verkauskas; Philippe Demougin; Vytautas Bilius; Darius Dasevicius; Michael B Stadler; Faruk Hadziselimovic Journal: Basic Clin Androl Date: 2018-02-09