Postmenopausal hyperandrogenism: the under-recognized value of inhibins.

We report a 70-year-old female presenting with increased libido and mild but rapid onset virilism. Investigations showed markedly elevated androstenedione and 17 hydroxyprogesterone misdirecting to possible late-onset congenital adrenal hyperplasia. High serum testosterone and oestrogens with suppressed gonadotrophins, however, indicated an androgen-secreting tumour. A normal dehydroepiandrosterone sulphate and elevated inhibins A and B indicated the tumour was ovarian in origin, which was confirmed on pelvic examination and imaging. At laparotomy, a right ovarian sertoliform endometrioid carcinoma was removed, following which the patient developed menopausal vasomotor symptoms and improvement of her virilism. Serum testosterone, oestradiol, inhibins A and B became undetectable, gonadotrophins appropriately increased and 17 hydroxyprogesterone and androstenedione normalized. We propose that inhibins may be of diagnostic value and should be included in investigative algorithms of females with virilization and hyperandrogenaemia, especially if postmenopausal. Androgen-secreting tumours must be excluded before raised 17 hydroxyprogesterone concentrations are used to diagnose late-onset congenital adrenal hyperplasia in females with new-onset virilization.

Laparoscopic pelvic lymphadenectomy: experience of a Gynaecological Cancer Centre in the UK.

INTRODUCTION: The role of laparoscopic lymphadenectomy in the management of gynaecological cancers has been established over the last two decades, having been first described in Dargent and Selvat (L'envahissement ganglionnaire pelvin. Medsi-Mcgraw Hill, Paris, 1989). It has been shown that laparoscopic lymphadenectomy can be performed in the majority of patients and is associated with a low complication rate. However, the technique continues to be undertaken in only a relatively small number of Gynaecological Cancer Centres in the UK owing to the long learning curve and wide variations in training. MATERIALS AND METHODS: At the Royal Wolverhampton NHS Trust Gynaecological Cancer Centre in the Greater Midlands Cancer Network laparoscopic lymphadenectomy has been performed since 1999 in the management of early cervical and high grade endometrial cancers. We have undertaken a retrospective audit (1999-2009) of these 42 cases to assess the feasibility of the procedure as well as to assess the complication rate. CONCLUSION: We are presenting the first reported series of exclusive laparoscopic transperitoneal lymphadenectomies from a Gynaecological Cancer Centre in the UK.

Malignant transformation of residual endometriosis after hysterectomy: a case series.

OBJECTIVE: To explore the role of long-standing hormone replacement therapy (HRT) in the malignant transformation of endometriosis. DESIGN: Short case series. Three cases of women with pelvic clearance receiving long-standing HRT studied in detail. SETTING: Teaching hospital in the United Kingdom (Gynaecological Cancer Centre) (Institutional Review Board approval was not obtained as it was not deemed necessary, this being a case series). PATIENT(S): Women with a history of pelvic clearance for endometriosis and longstanding HRT. INTERVENTION(S): HRT. MAIN OUTCOME MEASURE(S): Malignant transformation of endometriosis. RESULT(S): Long-standing HRT in all three women with pelvic clearance for endometriosis resulted in malignant transformation of residual endometriosis many years after the initial surgery. All cases presented with a new pelvic lesion. CONCLUSION(S): The diagnosis of malignant transformation needs to be considered in women with a history of endometriosis and with long-term HRT use in whom a new pelvic lesion is detected. The risk of malignant transformation in women with endometriosis after pelvic clearance receiving HRT needs to be explored further. Surveillance with CA-125 and imaging in such cases to predict recurrence or malignant transformation needs to be studied further in a research setting.

Lipopolysaccharide induces nitric oxide synthase expression and platelet-activating factor increases nitric oxide production in human fetal membranes in culture.

BACKGROUND: Platelet-activating factor and nitric oxide may be involved in the initiation of human labour as inflammatory mediators. The aim of this study was to test whether platelet-activating factor and lipopolysaccharide were able to induce nitric oxide synthase expression and stimulate the production of nitric oxide in human fetal membrane explants in culture. METHODS: Fetal membranes were collected from Caesarean sections at term. RNA was extracted from membranes and subjected to a qualitative RT-PCR to assess the baseline expression of iNOS. Discs of fetal membranes were cultured for 24 hours in the presence of platelet-activating factor at a dose range of 0.1 nanomolar--1 micomolar or 1 microgram/ml lipopolysaccharide. Nitric oxide production was measured via nitrite ions in the culture medium and mRNA for iNOS was detected by RT-PCR. RESULTS: Culturing the membrane discs in medium containing serum induced nitric oxide synthase expression and platelet-activating factor significantly stimulated the production of nitric oxide under these conditions. When cultured without serum inducible nitric oxide synthase expression was induced by lipopolysaccharide, but not by platelet-activating factor. CONCLUSION: Platelet-activating factor may have a role in the initiation of labour, at term or preterm, via the increased local production of nitric oxide as an inflammatory mediator. In this model of intrauterine infection, lipopolysaccharide was found to induce iNOS expression by fetal membranes, and this mechanism could be involved in preterm labour.