Diagnostic and management challenges from childhood,puberty through to transition in severe insulin resistance due to insulin receptor mutations

Two Caucasian girls, both of normal weight and body mass indices, were diagnosed with type A insulin resistance (IR) in childhood. Case 1 presented with premature adrenarche aged 7 years, then by age 12 years had hirsutism, acne, acanthosis nigricans, and asymptomatic diabetes. Subsequent investigation revealed raised adiponectin (15.3 mg/L) and heterozygous p.Pro1205Leu mutation in the INSR gene encoding the insulin receptor. She experienced postprandial hypoglycaemia on metformin; acarbose was trialled and discontinued aged 16 years, as she became normoglycaemic. Hirsutism was treated with topical eflornithine, oral spironolactone and flutamide, and laser therapy. Unfortunately, diabetes reemerged in young adulthood with obesity. Case 2: during an emergency admission for acute abdominal pain aged 11 years, hyperglycaemia was noted which led to further investigation. An oral glucose tolerance test showed diabetes and ultrasound showed polycystic ovaries. Further investigations revealed raised adiponectin (18 mg/L) and compound heterozygous mutations in the INSR gene: p.Pro1263Ala and p.Ser748Leu (latter probable normal variant). She was treated with metformin and experienced postprandial hypoglycaemia. Symptoms of hyperandrogenism were controlled by flutamide. She maintained a healthy weight and reassessment at young adulthood showed resolution of diabetes. Type A IR may present in childhood with overlapping features of common endocrine entities such as premature adrenarche and polycystic ovarian syndrome. Patients with abnormal glucose tolerance yet normal weight merit screening with adiponectin; raised adiponectin levels prompt insulin receptor mutational analysis. Postprandial hypoglycaemia is characteristic. Management includes optimization of glycaemic control with oral hypoglycaemic agents and maintenance of healthy weight, and controlling the effects of hyperandrogenism.     

Massive cystic degeneration of a pedunculated leiomyoma

A 51-year-old woman presented with a large abdominopelvic mass suspicious on preoperative imaging for ovarian malignancy. At laparotomy, a large cystic mass was found originating from the uterus and adherent to the proximal ileum. Pathologic evaluation confirmed the diagnosis of cystic leiomyoma.     

Topical gabapentin in the treatment of localized and generalized vulvodynia

OBJECTIVE: To evaluate the clinical efficacy and tolerability of topical gabapentin in the treatment of women with vulvodynia. METHODS: A retrospective study was designed to ascertain clinical responses to topical gabapentin. Patient demographic and medical characteristics, including present and prior treatment for vulvodynia, were routinely collected. The final outcome was defined by a comparison between pretreatment and posttreatment mean pain scores based on a discrete visual analog scale of 0 to 10. Categorical data were compared by Fisher exact test, continuous variables between groups by the Wilcoxon rank sum test, and mean change in pain score between pretreatment and posttreatment by paired Student t test. RESULTS: Between January 2001 and December 2006, 51 women with vulvodynia (19 or 37% with generalized vulvodynia, 32 or 63% with localized) were treated with 2% to 6% gabapentin. After a minimum of 8 weeks of therapy, the mean pain score among the 35 evaluable women was significantly reduced from 7.26 to 2.49 (mean change -4.77, 95% confidence interval -5.47 to -4.07). Overall, 28 of 35 (80%) demonstrated at least a 50% improvement in pain scores. Among patients with localized vulvodynia, sexual function improved in 17 of 20 with evaluable results (6 of 9 reinstituted vaginal intercourse, whereas all 11 patients experiencing decreased frequency of intercourse reported increased frequency after treatment). Discontinuations occurred in 7 of 50 (14%) treated. CONCLUSION: Topical gabapentin seems to be well-tolerated and associated with significant pain relief in women with vulvodynia. LEVEL OF EVIDENCE: III.     

Long-term effects of neovaginal reconstruction with sigmoid loop technique on sexual function and self image in patients with gynecologic malignancies: results of a prospective study

ObjectiveWe evaluated the long-term results of sigmoid vaginoplasty in women with gynecologic malignancies after radical pelvic surgery, with specific focus on safety and effects of the procedure on patients' sexuality and self image.MethodsThis prospective study included women with gynecologic malignancies who underwent partial or complete colpectomy as part of the cancer treatment. In all cases a pedicled sigmoid loop was used for the neovaginal reconstruction. Systematic clinical examination was performed and validated questionnaires about sexuality (Female Sexual Function Index), quality of life (SF-12) and susceptibility to depression (ADSk-15) were answered by all patients at the earliest 6 months after vaginoplasty.ResultsSeven patients with sigmoid vaginoplasty, recruited between 11/2003 and 02/2008, were evaluated in the present analysis. Mean patients age was 48 ± 8.49 years. Mean neovaginal length was 6.4 cm (range: 2–12 cm). The mean Female Sexual Function Index (FSFI)-score of all patients was 16.6 ± 12.6. In the subset of sexually active patients the mean FSFI-score was 22.5 ± 9.4 higher. Regarding early operative morbidity and complications, sigmoid vaginal reconstruction appears to be a safe procedure, though in a long-term assessment 85% of the patients developed a vaginal stenosis with the need for operative bougienage.ConclusionsThe vaginal reconstruction using a sigmoid loop is a safe and well accepted procedure in patients with gynecologic malignancies. However lower sexuality scores seem to be achieved than in non-cancer patients after equivalent vaginoplasty. Cancer-related physical and psychological comorbidity seem to have negative effects on the overall outcome and patient's satisfaction.     

Antenatal testing--benefits and costs

Antenatal testing is a common component of care for the high-risk pregnancy. The goals of antenatal testing include the prevention of stillbirth and the detection of the hypoxic fetus to allow intervention before acidosis and long-term damage. Data regarding the efficacy of antenatal testing are limited by a lack of randomized controlled trials. The majority of available data hinge on observational studies with the inherent potential for bias. There is also a paucity of data comparing the various testing modalities and addressing the issue of the optimal timing of initiation of testing. As well, data are limited regarding the various conditions most likely to benefit from testing and the frequency with which testing should be performed. The issue of cost relating to antenatal testing is an important one. Central to the issue of estimating cost is an understanding of the efficacy of the test. Given our current limitations, we have significant difficulty accurately estimating the cost of antenatal testing; however, rough estimates of cost are made.     

Hypophosphatasia: molecular testing of 19 prenatal cases and discussion about genetic counseling

OBJECTIVE: We studied hypophosphatasia (HP) mutations in 19 cases prenatally detected by ultrasonography without familial history of HP. We correlated the mutations with the reported ultrasound signs, and discussed genetic counseling with regard to the particular dominantly inherited prenatal benign form of HP. METHOD: The coding sequence of the tissue nonspecific alkaline phosphatase (TNSALP) gene was analyzed by DNA sequencing, and 3D modeling was used to locate the mutated amino acids with regard to the functional domains of TNSALP. RESULTS: Although reported ultrasound signs were heterogeneous, two mutated alleles were found in 18 of the 19 cases studied, indicating recessive transmission of the disease. Functional domains of TNSALP were affected by 74% of missense mutations. In all the cases, including one with only a heterozygous mutation, molecular, biological, and familial data do not corroborate the hypothesis of prenatal benign HP. The mutation c.1133A>T observed in the prenatal benign form of HP and common in USA was not found in this series. CONCLUSION: The results point out the prenatally detectable allelic heterogeneity of HP. The nature of the detected mutations and the evidence of recessive inheritance do not support these cases being affected with prenatal benign HP.