In Children with 46, XY DSD; HCG Testing is not always the Best Answer for Testicular Function Assessment

Review Article

J Endocr Disord. 2022; 8(1): 1048.

In Children with 46, XY DSD; HCG Testing is not always the Best Answer for Testicular Function Assessment

Khater D* and Raafat S

Associate Professor of Pediatric Endocrine and Diabetes at Faculty of Medicine, Alexandria University, Egypt

*Corresponding author: Doaa Khater, Associate Professor of Pediatric Endocrine and Diabetes at Faculty of Medicine, Alexandria University, Egypt

Received: August 23, 2022; Accepted: September 24, 2022; Published: October 01, 2022

Abstract

Hormonal levels are the hallmark for the assessment of testicular function in XY DSD (Disorders of sex development). Traditionally, it has relied on testosterone level increment after hCG (human Chorionic Gonadotropin) stimulation testing. More recently role of Sertoli cell hormones is more emphasized.

Objectives: Evaluating the role of serum anti-mullerian hormone and inhibin B on function of the pre-pubertal testis without the need for hCG stimulation test.

Method: The study was conducted in the Endocrinology Clinic in Alexandria University Children’s Hospital. All patients who present with XY DSD were tested for Testosterone (T), Dihydrotestosterone (DHT), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Anti-Mullerian Hormone (AMH), inhibin B. All cases had hCG stimulation test.

Results: The hCG stimulation test was done for 32 cases. There was significant positive correlation between serum testosterone levels before and after hCG stimulation test (p <0.001). Similarly, significant correlation was identified between basal AMH and testosterone increment after hCG stimulation (p <0.001) and between basal levels of AMH and inhibin (MCp= 0.025).

Conclusion: Single measurement of basal AMH and/or inhibin B can detect the presence and function of testes by a reliable non-invasive way. Basal AMH assessment is an important tool to distinguish between cryptorchidism and anorchia. hCG test is needed in the work-up of patients with inconclusive results.

Keywords: Testosterone; Anti-mullerian hormone; Inhibin B; Testis

List of Abbreviation

AMH: Antimullerian Hormone; DHT: Dihydrotestosterone; DSD: Disorders of Sex Development; FSH: Follicle Stimulating Hormone; hCG: human Chorionic Gonadotropin; T: Testosterone; LH: Luteinizing Hormone; LCH: Leydig Cell Hypoplasia; PAIS: Partial Androgen Insensitivity Syndrome; TRS: Testicular Regression Syndrome

Introduction

The classification of 46, XY DSD includes defects in testicular development, testosterone biosynthetic defects or its action defect [1-4].

Traditionally, the standard endocrinological evaluation of 46, XY DSD cases is based on measurement of testosterone, dihydrotestosterone and androstenedione and their ratios either in mini-puberty or after human Chorionic Gonadotropin (hCG) stimulation which reflects the activity of the testicular Leydig cells. Although it leads to etiological diagnosis of XY DSD cases such as testosterone biosynthetic defects, 5-alpha reductase deficiency or abnormal androgen receptor activity, however, it is cumbersome and needs multiple sampling [5]. More recently, there has been growing evidence of the value of Sertoli cell function assessment as it secretes hormones like Anti-Mullerian Hormone (AMH) and inhibin B. Mullerian ducts have completely disappeared in the male 10 weeks after conception, but testes continue to churn out high amounts of AMH throughout childhood, when basal testosterone and gonadotropin levels have little clinical use. This makes AMH an appealing biomarker for pediatric endocrinologists, not to mention that prior gonadotropin stimulation is not required [6].

Moreover, it can be used in the evaluation of boys with nonpalpable gonads [7]. Inhibin B is another useful marker of normal testicular tissue; therefore, basal inhibin B measurement can be used as a reliable tool to assess both the existence and function of the testes and spermatogenesis afterwards [8-10].

However, the value of AMH and inhibin Bin evaluating cases with XY DSD has been challenged [2,11]. We report our experience of the role of serum AMH and inhibin Bin assessing the function of the pre-pubertal testis without the need for hCG stimulation test.

Methods

All cases of 46, XY DSD who were referred to Endocrinology Clinic in Alexandria University Children’s Hospital, Egypt for evaluation of atypical genitalia during the period from 1/1/2017- 31/12/2019 were included in the study. After informed consent and explanation of the study objectives, peripheral blood was collected for karyotyping, basal serum Testosterone (T), Dihydrotestosterone (DHT), Follicle Stimulating Hormone (FSH), luteinizing Hormone (LH), Antimullarian Hormone (AMH) and inhibin B [12]. All patients had a Human Chorionic Gonadotropin stimulation test using human chorionic gonadotropin (1500 IU/day) intra-muscular injections for three consecutive days. Venous samples were taken before the test and 24 hours after the third injection, then T/DHT ratio was calculated. We considered functioning testicular tissue when testosterone increment was more than twice the baseline value or absolute testosterone concentration above the upper limit of normal pre-pubertal range [1,13]. Patients with T/ DHT ratio >25 were diagnosed as 5 alpha reductase deficiency and below this value were diagnosed as androgen insensitivity syndrome [14]. Infants in the period of mini-puberty, testosterone and dihydrotestosterone were measured without stimulation and the T/ DHT ratio was calculated. The results of serum hormones were compared with normal reference ranges according to age [15].

Data were analyzed using IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp) [16]. The research has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the Ethics Committee of the College of Medicine, Alexandria University. Written informed consents were obtained from all patients’ legal guardians

Results

Forty cases were identified with XY DSD. Their age of presentation ranged between zero day to 13 years with a mean of 2.75 ± 3.45

Basal levels of FSH were within normal reference range for age and sex in 35 cases (87.5%) and higher than reference range in 5. Serum LH levels were within reference range for age in all cases. Basal AMH levels were within normal reference range for age in 29 cases (72.5%), 9 cases had low level of AMH and only 2 had high basal AMH. For basal inhibin B, 16 cases (40%) had normal serum level for age, 15 cases had high levels (37.5%), and 9 cases showed low level (22.5%) (Figure 1).