Impaired Sertoli Cell Function in Males Diagnosed with Noonan Syndrome

Abstract

In order to study male gonadal function in Noonan syndrome, clinical and laboratory data, including inhibin B, were gathered in nine pubertal males diagnosed with Noonan syndrome. Bilateral testicular maldescent was observed in four, and unilateral cryptorchidism occurred in two. Puberty was delayed in three patients. Luteinising hormone (LH) levels were normal in all patients in our series, while follicle stimulating hormone (FSH) levels were raised in seven. Inhibin B was low in six males and just above the lower limit of normal in two. Importantly, all three men with normal testicular descent displayed signs of Sertoli cell dysfunction, indicating, in contrast to earlier reports, that bilateral cryptorchidism does not seem to be the main contributing factor to impairment of testicular function in Noonan syndrome. These findings suggest different mechanisms of disturbance in male gonadal function, which is frequently associated with Sertoli dysfunction.

Testicular size development and reproductive hormones in boys and adult males with Noonan syndrome: a longitudinal study

“…However, although hormonal abnormities are observed more frequently in those patients with UT, we still found some abnormal results in the DT group. This is in accordance with previous findings (10).…”

“…In our study, about 50% of the subjects have the PTPN11 mutation, which is as expected in the NS population (30), but we did not find any correlations between this genotype and gonadal function. The lack of an association between gonadal function and the PTPN11 mutation was also shown in a previous study in nine males (10).…”

“…As adults, those with a history of bilateral UT had azoospermia, elevated FSH levels and normal or elevated LH levels, whereas all of the men with descended testes (DT) had normal hormone levels. Unexpectedly, Marcus et al (10) studied nine males and observed raised FSH and subnormal inhibin B concentrations in all three men with DT, indicating a primary gonadal dysfunction in males with NS.…”

“…UT are associated with impaired fertility (6,7). A small number of males with NS have had assessment of gonadal function in prepubertal period (2) as well as adulthood (8)(9)(10).…”

Noonan’s Syndrome Diagnosed at Second Decade of Life

“…Cryptorchidism will be present around 80% of the Noonan patients. 13 Our patient had unilateral cryptorchidism for which he underwent surgical correction. Juvenile myelomonocytic leukemia, myeloproliferative disease with coagulation defects and increased bleeding tendency are not uncommon.…”