In the current study, both AMH and inhibin B levels were generally lower than normal reference ranges for age in cases with primary gonadal failure, and they were normal in partial androgen insensitivity syndrome (PAIS), and 5α-reductase deficiency. AMH was higher than reference ranges in 2 cases with androgen insensitivity syndrome while, Inhibin B was higher in 15 cases. Despite these variations, the results showed a positive correlation between mean basal levels of AMH and inhibin B which suggest a discriminatory value of the determination of AMH and inhibin B levels in the diagnosis of XY DSD cases.
Several previous reports [1, 2, 10, 17] have shown that AMH and inhibin B are low in dysgenetic testes, undetectable in patients with anorchia and normal or high in other causes of XY DSD (androgen biosynthesis or action defect, AIS, 5α-reductase deficiency and Leydig cell hypoplasia). A study in Denmark showed that the median serum levels of inhibin B hormone in patients with vanishing testes was markedly lower than those in cases of bilateral cryptorchidism. [18]
A significant correlation between AMH and inhibin B was demonstrated in older patients 1-13year-old in former studies, however, they were not correlated for 0.5-1year-old patients with XY DSD [2, 19, 20]
Our study found a strong correlation between basal AMH, inhibin B, and FSH levels and hCG induced testosterone increment (p < 0.001).
It worth mentioning that the need for hCG stimulation test in the work-up is controversial. Adding to that, there is an extensive range of regimens for hCG stimulation test performance and the definition of an adequate testosterone response to hCG stimulation is also unclear and may depend on the regimen and the age of the child. [15] Our data showed that a low AMH correlates well with a low hCG-stimulated level in most of the cases, however a normal AMH might not predict a normal HCG-stimulated testosterone value as in the cases with LCH. Similar findings were reported by Ahmed SF et al [1] while other investigators found that assessment of serum AMH confirms the testicular function without the need for hCG stimulation tests. [17] In our study, 32 cases -beyond the period of mini-puberty- had hCG stimulation test. Post stimulation testosterone level showed increment after stimulation in most of them (81.2%). There was a positive relation between serum testosterone level before and after hCG stimulation test indicating an adequate leydig cell function. Patients who did not show adequate post stimulation increment of testosterone (Leydig cell dysfunction) were 2 cases with studied testicular regression syndrome (TRS), 2 with gonadal dysgenesis, 1 with Leydig cell hypoplasia and 1 with 5 alpha reductase deficiency. Post stimulation inadequate testosterone response with lower level of AMH and inhibin B in the case with 5 alpha reductase deficiency is attributed to associated cryptorchidism.
The studied testicular regression syndrome (TRS) cases had very low basal levels of AMH and inhibin B. Stoppa-Vaucher S et al [21] concluded that undetectable AMH level and the absence of Müllerian structures on pelvic ultrasound strongly suggests a diagnosis of bilateral anorchia as early as 3 days of age. Weintraub A et al [22] reported that assessment of AMH can distinguish between cryptorchidism and anorchia. We can conclude that a single measurement of basal AMH and/or inhibin B is highly confirmative of the presence and function of testes. Therefore, basal AMH and inhibin B might substitute the need for
Serum FSH levels, were within normal reference ranges for age in all cases except 3 cases with TRS and 2patients with gonadal dysgensis. These cases had high FSH levels with low AMH and inhibin B levels. Assessment of basal FSH levels in patients with XY DSD might elucidate their etiology. High FSH with a low AMH and inhibin B can discriminate cases of defective testicular development from other causes of XY DSD. Moreover, the inverse relationship between circulating FSH and inhibin B levels observed in the current study adds to the current evidence that pre-pubertal Sertoli cells in humans can inhibit FSH release. [18, 23, 24]
On the contrary, basal LH levels were within the normal reference ranges in all cases. Cases with primary gonadal failure showed normal LH levels despite high serum FSH levels. Previous report of 395 cases of under-masculinized 46XY males suggests that FSH is a more useful indicator of testicular dysfunction in the pre-pubertal age group being an indirect measure of Sertoli cell function.
The limitations of this study include a single center experience and a small number of patients.
In conclusion, our study confirmed that a single measurement of basal AMH and/or inhibin B can detect the presence and function of testes. Basal AMH assessment is an important tool to distinguish between cryptorchidism and anorchia. Basal FSH level is an indirect indicator of the Sertoli cell function. Future prospective studies on larger number of patients may decide on the real need for hCG testing in the work-up of these patients.