Le Syndrome des Ovaires Polykystiques (SOPK): rôle de l’Endocrinologue dans le diagnostic et la prise en charge

info:eu-repo/semantics/publishe

Secondary amenorrhoea associated with high serum 17-hydroxyprogesterone levels revealing a heterozygous CYP21A2 mutation in a woman with Addison disease

SCOPUS: le.jFLWINinfo:eu-repo/semantics/publishe

Testicular histological and immunohistochemical aspects in a post-pubertal patient with 5 alpha-reductase type 2 deficiency: case report and review of the literature in a perspective of evaluation of potential fertility of these patients.

International audienceBACKGROUND: Testicular morphology and immunohistochemical studies have never been reported in genetically documented adult patients with 5 alpha-reductase type 2 deficiency (5α-R2 deficiency). CASE PRESENTATION: We describe the testicular histopathology of a 17-year-old XY subject with 5α-R2 deficiency caused by the recurrent homozygous Gly115Asp loss of function mutation of the SRD5A2 gene.We also performed an immunohistochemical analysis in order to further study the relationship between seminiferous tubules structure, Sertoli cell differentiation and androgenic signaling impairment in this case. We thus evaluated the testicular expression of the anti-Müllerian hormone (AMH), androgen receptor (AR) and 3β-hydroxysteroid dehydrogenase (3βHSD). Histological analysis revealed a heterogeneous aspect with a majority (92%) of seminiferous tubules (ST) presenting a mature aspect but containing only Sertoli cells and devoid of germ cells and spermatogenesis. Focal areas of immature ST (8%) were also found. Testicular AR and 3βHSD expression were detected in adult male control, 5α-R2 deficiency and CAIS subjects. However, AMH expression was heterogeneous (detectable only in few AR negative prepubertal ST, but otherwise repressed) in the 5α-R2 deficiency, conversely to normal adult testis in which AMH was uniformly repressed and to an adult CAIS testis in which AMH was uniformly and strongly expressed. CONCLUSION: Intratesticular testosterone can repress AMH by itself, independently of its metabolism into dihydrotestosterone. We also compare our results to the few post pubertal cases of 5α-R2 deficiency with available histological testicular description, reported in the literature. We will discuss these histological findings, in the more general context of evaluating the fertility potential of these patients if they were raised as males and were azoospermic

Ovarian macrocysts and gonadotrope-ovarian axis disruption in premenopausal women receiving mitotane for adrenocortical carcinoma or Cushing's disease

Context: Mitotane is an adrenolytic and anticortisolic drug used in adrenocortical carcinoma (ACC), Cushing's disease (CD), and ectopic ACTH syndrome. Its effects on the ovaries are unknown. Objective: To evaluate the ovarian and gonadotrope effects of mitotane therapy in premenopausal women. Patients: We studied 21 premenopausal women (ACC: n=13; CD: n=8; median age 33 years, range 18-45 years) receiving mitotane at a median initial dose of 3 g/day (range 1.5-6 g/day). Methods: Gynecological history was collected and ovarian ultrasound was performed. Four women also underwent ovarian CT or magnetic resonance imaging. Serum gonadotropin, estradiol (E2), androgens, sex hormone-binding globulin (SHBG), and circulating mitotane levels were determined at diagnosis and during mitotane therapy. Results: In the women included, ovarian macrocysts (bilateral in 51%) were detected after a median 11 months (range: 3-36) of mitotane exposure. The median number of macrocysts per woman was two (range: 1-4) and the median diameter of the largest cysts was 50 mm (range: 26-90). Menstrual irregularities and/or pelvic pain were present in 15 out of 21 women at macrocyst diagnosis. In two women, the macrocysts were revealed by complications (ovarian torsion and hemorrhagic macrocyst rupture) that required surgery. Mitotane therapy was associated with a significant decrease in androstenedione and testosterone levels and a significant increase in LH levels. Serum FSH and E2 levels were also increased, and SHBG levels rose markedly

TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans.

CONTEXT: Missense loss-of-function mutations in TAC3 and TACR3, the genes encoding neurokinin B and its receptor NK3R, respectively, were recently discovered in kindreds with nonsyndromic normosmic congenital hypogonadotropic hypogonadism (CHH), thus identifying a fundamental role of this pathway in the human gonadotrope axis. OBJECTIVE: The objective of the study was to investigate the consequences on gonadotrope axis of TAC3 deletion and TACR3 truncation in adult patients with normosmic complete CHH. RESULTS: We identified three unrelated patients with the same homozygous substitution in the TAC3 intron 3 acceptor splicing site (c.209-1G>C) and three siblings who bore a homozygous mutation in the TACR3 intron 2 acceptor splicing site (c.738-1G>A). We demonstrated that these two mutations, respectively, deleted neurokinin B and truncated its receptor NK3R. We found in three patients with TAC3 mutation originating from Congo and Haiti a founding event in a more distant ancestor by means of haplotype analysis. We calculated that time to this common ancestor was approximately 21 generations. In several patients we observed a dissociation between the very low LH and normal or nearly normal FSH levels, this gonadotropin responding excessively to the GnRH challenge test. This particular hormonal profile, suggests the possibility of a specific neuroendocrine impairment in patients with alteration of neurokinin B signaling. Finally, in these patients, pulsatile GnRH administration normalized circulating sex steroids, LH release, and restored fertility in one subject. CONCLUSION: Our data demonstrate the hypothalamic origin of the gonadotropin deficiency in these genetic forms of normosmic CHH. Neurokinin B and NK3R therefore both play a crucial role in hypothalamic GnRH release in humans