Carme Valls

Polycystic ovary syndrome after precocious pubarche: ontogeny of the low-birthweight effect

OBJECTIVE Young girls with precocious pubarche (PP) are at increased risk of developing polycystic ovary syndrome (PCOS), including hyperinsulinism, dyslipidaemia and ovarian hyperandrogenism, particularly if PP itself was preceded by a low birthweight. Resistance to insulin is thought to be a key factor in the pathogenesis of this sequence. We aimed to elucidate the peripubertal ontogeny of the low birthweight effect on hyperinsulinism, dyslipidaemia and ovarian dysfunction after PP.

Multiple Endocrine Involvement in Two Pediatric Patients with Kearns-Sayre Syndrome

We present 2 cases of progressively severe Kearns-Sayre syndrome (KSS) with multisystemic affectation and atypical endocrine and cutaneous features, a 16-year-old patient (case 1) and a 5-year-old patient (case 2). Endocrine studies showed high glucose and glycohemoglobin concentrations with normal pancreatic reserve and low values of ACTH, cortisol, LH and FSH in case 1. Normal ACTH values with low concentrations of cortisol and PTH were observed in case 2. Southern blot analysis and PCR amplification revealed the presence of a deletion of approximately 6.7 kb in the mitochondrial DNA of both patients. Endocrinological studies suggest that adrenal insufficiency may be an additional feature of KSS that worsens the clinical evolution of the patients. In spite of a normal pancreatic reserve, insulin therapy should be considered in patients with diabetes mellitus of mitochondrial origin.

Heterotopic ovarian transplantation without vascular pedicle in syngeneic lewis rats: six-month control of estradiol and follicle-stimulating hormone concentrations after intraperitoneal and subcutaneous implants

OBJECTIVE To assess the recovery, maintenance, and quality of ovarian function by comparing the success of autotransplantation in intraperitoneal (IP) and SC locations over a 6-month period in syngeneic Lewis rats. DESIGN Experimental animal study. SETTING Unit of Experimental Research at the Barcelona University School of Medicine. ANIMAL(S) Female syngeneic Lewis rats. INTERVENTION(S) The animals were randomized to one of three groups: group A, control group with ovariectomy (n = 15); group B, ovariectomy and IP autologous heterotopic transplant of ovarian tissue without vascular pedicle (n = 14); and group C, ovariectomy and SC autologous heterotopic transplant (n = 15). MAIN OUTCOME MEASURE(S) Serum levels of FSH and 17beta-E2 and vaginal cytology. RESULT(S) In groups B and C, E2 serum concentrations from day 7 and day 10 onward remained comparable to basal levels, and significantly higher than in group A, throughout the 6-month period. In group B from day 7 after surgery onward, and in group C from day 10 after surgery onward, FSH concentrations remained low (comparable to basal levels) throughout the follow-up period. Vaginal cytology of groups B and C showed trophic maturation between days 4 and 10 after ovariectomy and insertion of the ovarian tissue implant, whereas the control group remained atrophic. There were no statistically significant differences between IP and SC implants. CONCLUSION(S) A heterotopic autotransplant of ovarian tissue without vascular pedicle in syngeneic Lewis rats is successful for > or =6 months.

Early menarche and subclinical ovarian hyperandrogenism in girls with reduced adult height after low birth weight.

In girls born small for gestational age (SGA), early onset of puberty tends to be followed by a swift progression to early menarche and to growth arrest below target height. We have now examined whether, conversely, girls born SGA with reduced final height experienced an early menarche, and also whether these girls present a subclinical variant of ovarian hyperandrogenism. The latter question was prompted by the emerging evidence that adolescent girls born SGA tend to present hyperinsulinism and adrenal hyperandrogenism. Pelvic ultrasound examination and assessment of ovarian function were performed in the follicular phase of the menstrual cycle (range: day 5 ± 3; duration of cycles 21-35 d) in 14 short, non-obese adolescents born SGA. Blood samples for measurement of serum gonadotropins were obtained before and 3 and 24 h after challenge with the GnRH-agonist leuprolide acetate (Procrin®, Abbott, Spain; 500 μg s.c.), while serum androstenedione, 17-hydroxyprogesterone (17-OHP) and estradiol were measured at 0 and 24 h. Serum glucose, insulin, lipid profile, dehydroepiandrosterone-sulfate (DHEAS), total testosterone and sex hormone-binding globulin (SHBG) were determined from baseline samples. Peak 17-OHP responses above 160 ng/dl (4.8 nmol/1) were considered elevated.

Pioglitazone (7·5 mg/day) added to flutamide-metformin in women with androgen excess: additional increments of visfatin and high molecular weight adiponectin

Background and aim  Low‐dose pioglitazone (Pio), flutamide (Flu), metformin (Met) plus an oestro‐progestagen is a novel polytherapy lowering total and visceral adiposity, and reducing carotid intima media thickness (IMT) in hyperinsulinaemic women with androgen excess, without changing their body mass index (BMI). In a search for mediators of PioFluMets actions, we measured serum levels of visfatin and high molecular weight (HMW) adiponectin.

The Value of Interleukin-8, Interleukin-6 and Interleukin-1β in Vaginal Wash as Predictors of Preterm Delivery

Aims: To study the value of interleukin (IL)-8, IL-6 and IL-1β in vaginal wash as predictors of preterm delivery. Methods: A prospective analysis of a study group of 200 pregnant women between 24 and 34 weeks of gestation with intact membranes and preterm labor and a control group of 50 pregnant women during the same period of gestation. The controls had uncomplicated pregnancies and subsequently delivered at term. Samples of vaginal secretions were collected from both groups and analyzed for IL-1β, IL-6 and IL-8 concentrations. Results: Of the women in the study group, 70 had preterm deliveries, while all women in the control group had full-term deliveries. Compared with the control group, the study group had significantly higher concentrations (p < 0.021) of IL-1β, IL-6 and IL-8. The women in the study group delivering preterm also had IL-1β, IL-6 and IL-8 concentrations significantly greater (p < 0.001) than those of the same group delivering full term. ROC curves were used to establish cut-off points for the three interleukins to predict preterm delivery. We did not find a cut-off point with an appropriate sensitivity and specificity. Conclusion: The concentrations of interleukins in vaginal wash were significantly higher both in the women with preterm labor and in those delivering preterm. While values differed between controls and those with the preterm labor, no cut-off can be obtained to use the results of IL-1β, IL-6 and IL-8 as a predictor clinically.

Persisting benefits 12-18 months after discontinuation of pubertal metformin therapy in low birthweight girls.

Background  Discontinuation of metformin therapy, if started beyond menarche in adolescents or young women with hyperinsulinaemia following low birthweight, is rapidly followed by rebound deteriorations in body fat, insulin resistance and blood lipid profile.

Cord serum visfatin at term birth: maternal smoking unmasks the relation to foetal growth

Objective  Visfatin is an adipocytokine involved in insulin action and oxidative stress. The regulation of circulating concentrations in the human foetus is unknown. We studied whether, at term birth, the serum concentrations of visfatin are related to foetal size, both in the absence and in the presence of maternal smoking during pregnancy.

Inhibin and follicular development in heterotopical ovary transplants without vascular pedicle in syngeneic Lewis rats

OBJECTIVE To evaluate the role of inhibin in elevated base levels of FSH and follicular hyperplasia in ovarian autotransplantation in rats. DESIGN Experimental animal study. SETTING Unit of Experimental Research at the Barcelona University School of Medicine. ANIMAL(S) Female syngeneic Lewis rats aged 16 weeks. INTERVENTION(S) The animals were randomized into two groups: group A, control group undergoing only laparotomy (n = 5) and group B, oophorectomized with SC autologous heterotopic transplant (n = 5). The animals were killed and their ovaries removed for histologic, morphometric, and immunohistochemical analysis at 28 days after surgery in both groups. MAIN OUTCOME MEASURE(S) Serum levels of E2 and FSH were determined on day 0 (the day of surgery or baseline) and days 4, 7, 14, 21, and 28. Morphometric analysis of ovarian structure for evaluation of antral follicles and their granulosa cell area and immunohistochemistry for inhibin staining were also done. RESULT(S) The endocrinological function recovered at 28 days, and the FSH levels for the transplant group were significantly higher than for the group with normoinsert ovary. Morphometric analysis showed that the mean granulosa cell area was greater in group B when compared with the control group. Immunohistochemistry revealed almost null inhibin staining of the stroma in transplanted ovarian tissue. CONCLUSION(S) Tissue damage brought on by ischemia in the transplant of nonvascularized ovaries may bring about an inhibin deficit in the ovarian stroma, which might explain the increased levels of FSH. These increased levels, in turn, would be responsible for the follicular hyperplasia seen in this tissue when it recovers its function.

Relationship between Foetal Growth Restriction and Maternal Nutrition Status Measured by Dual-Energy X-Ray Absorptiometry, Leptin, and Insulin-Like Growth Factor

Aims: The aim of this study was to determine if maternal nutritional status, as defined by body composition, leptin, and insulin-like growth factor (IGF)-I levels, relates to foetal growth. Methods: In this prospective study, mothers of foetuses with foetal growth restriction (FGR; cases; n = 46) and mothers of appropriate-for-gestational-age (AGA) foetuses (controls; n = 81) were consecutively recruited over a 14- month period. A maternal blood sample was obtained during the third trimester (between 32 and 34 weeks of gestation) for the assessment of IGF-I and leptin. Body composition was assessed by dual-energy X-ray absorptiometry within the first 15 days after delivery. The study used the SPSS-PC statistical package, version 19.0, and p < 0.05 was considered statistically significant. Results: Mean serum IGF-I levels were lower in the cases than in the controls (p < 0.05), whereas leptin concentrations were higher in the cases after adjusting for age, body mass index and cigarette consumption (p < 0.05). Cases had less lean and fat tissue than controls (p < 0.05) but a relatively higher fat percentage. Conclusions: The mothers of foetuses with FGR have a body composition pattern characterized by a slightly increased fraction of fat mass, lower IGF-I concentrations, and increased serum leptin levels. Optimization of maternal nutritional status should be considered, as the nutritional status may be involved in the pathogenesis of FGR.