ACTA ENDOCRINOLOGICA (BUC)

The blood-CSF barrier (BCB), as a component of the blood-brain barrier, is protective for the maternal brain. This study assesses estradiol, prolactin, glycoproteic hormones (hCG, FSH, LH, TSH) and thyroxine across the BCB in pregnancy after 38 weeks. Method. 35 pregnant women were simultaneously sampled in serum and CSF during caesarian section and compared to 27 non-pregnant fertile women undergoing surgery for benign gynecological disorders. The study was approved by the local Ethics Committee. Results were analysed as nonparametric variables. Compared to non-pregnant controls, we found high serum estradiol levels at term, also reflected in the CSF, while the CSF/serum ratio was non-significantly modified (median ratio 0.1 versus 0.1, p=NS). Prolactin showed a similar proportional increase in serum and CSF levels at term, with unmodified CSF/serum ratio (median ratio 0.14 versus 0.18, p=NS). hCG showed a similar profile across the BCB. FSH was significantly lower at term, but still conserved the CSF/ serum ratio. LH was undetectable in pregnancy. In peripartum TSH showed a unique profile across the BCB as it was the only one showing an increased CSF/serum ratio compared to non-pregnant controls (median ratio 0.11 versus 0.04, p<0.0001). Thyroxine was significantly increased in both serum and CSF, and showed a CSF/serum ratio unmodified from non-pregnant women (median ratio 0.02 versus 0.02, p=NS). Conclusion. There is an increase of BCB permeablity for TSH in term pregnancy. The peripartum increase in estradiol and decrease in HCG could be involved. We suggest that the unique TSH profile maintains the necessary thyroxine levels in pregnancy at term.

Introduction. Estrogens are known to have a neuroprotective role and to influence the permeability of the blood brain barrier (BBB). An ongoing debate exists on the changing effects of estrogens on target tissues with advancing age and at menopause and on the potential disruptive role of increasing gonadotropin levels.\r\nThe aim of the present study was to assess the permeability of the BBB for estradiol, FSH and LH in three physiological states: early follicular phase, preovulatory phase and at menopause.\r\nMethod. Hormonal levels were assessed simultaneously in the serum and cerebrospinal fluid (CSF) of 15 women at menopause (mean age 60?8 years), 16 of reproductive age in early follicular phase and 11 in preovulatory phase (mean age 31?7 years), all undergoing surgery for benign gynecologic disorders. FSH, LH and estradiol levels were assessed using chemo luminescence and are expressed as median and 10-90 percentile interval. Statistical analysis assessed the serum-CSF correlation and the CSF/serum ratio for each hormone between groups.\r\nResults. Estradiol serum levels were 26.2 pg/ml (6.4-43.5) at menopause (n=15), 58.5 pg/ml (25.7-75.9) in early follicular phase (EFP, n=16) and 221.2 pg/ml (113.7-405.5) in preovulatory phase (PREOV, n=11). CSF estradiol is 18.5 pg/ml (0.4-30.5) at menopause, 5.4 pg/ml (2.2-10.2) in EFP (p<0.001) and 17.3 pg/ml (10.3-34.6) in PREOV patients. Estradiol serum and CSF levels correlate positively in the fertile cycle (r=0.72, p<0.0001) and negatively at menopause (r=-0.88, p<0.05). The CSF/serum ratio for estradiol is 0.8 (0.01-4.4) at menopause, 0.1 (0.04-0.13) in EFP and 0.1 (0.03-0.13) in PREOV patients. FSH serum levels were 75.8 mUI/ml (35.9-129.8) at menopause, 7.7 mUI/ml (3.5-11.4) in EFP and 7.3 mUI/ml (3.1-10.7) in PREOV patients. CSF FSH is 2.7 mUI/ml (0.4- 5.9) at menopause, significantly higher than 0.7 mUI/ml (0.3-1) in EFP (p<0.001) and 0.5 mUI/ml (0.2-1) in PREOV patients (p<0.05). FSH serum and CSF levels correlate positively in the fertile cycle (r=0.8, p<0.0001) and do not correlate at menopause (p=NS). The CSF/serum ratio for FSH is 0.03 (0.01-0.1) at menopause, significantly lower than 0.09 (0.06-0.16) in EFP (p<0.001) and is 0.06 (0.03-0.13) in PREOV phase. LH serum levels were 57.4 mUI/ml (27.5-84.8) at menopause, 4.7 mUI/ml (1.7-7.1) in EFP and 5.5 mUI/ml (4.9-8.02) in PREOV phase. CSF LH is 1.6 mUI/ml (0.7-2.6) at menopause, significantly higher than 0.4 mUI/ml (0.1-1) in EFP (p<0.001) and 0.5 mUI/ml (0.2-0.9) in preovulatory phase (p<0.05). The CSF/serum ratio for LH is 0.03 (0.01-0.07) at menopause, it is significantly lower than 0.09 (0.03-0.27) in EFP (p<0.001) and is 0.07 (0.03-0.14) in preovulatory phase.\r\nConclusions. This study shows the negative correlation of serum and CSF estradiol levels at menopause reflecting the need of constant estrogen levels within the CSF despite low chronic serum levels. Simultaneously, the CSF/serum ratio for gonadotrophins is\r\nreduced significantly at menopause and the positive correlation of serum and CSF levels is lost, reflecting a protective mechanism against rising levels of FSH and LH.

Introduction: Prolactinomas may grow during pregnancy. Dopamine agonists (DA) prevent tumor growth, but usually suppress prolactin (PRL) both in mother and fetus. Possible long-term consequences on fetal development remain unknown.\r\nAim: to assess whether DA treatment throughout pregnancy in a dosage able to maintain physiological gestational serum levels of prolactin (PRL) still prevents prolactinoma growth.\r\nPatients and methods: We evaluated 68 pregnancies in 49 women with prolactinoma (PRM) and 46 pregnancies in healthy women as controls. Thirty-three pregnancies were recorded in 27 women treated throughout pregnancy with bromocriptine (BRC) (n = 25) or cabergoline (CAB) (n = 2) divided in 2 groups: group A (22 pregnancies in 18 patients) had suppressed serum PRL (below the 5th percentile of the control group Z during the last trimester); group B (11 pregnancies in 10 patients) had physiological serum PRL levels. Other 26 pregnancies in 21 patients were incompletely evaluated and included only in the pregnancy outcome and cure rate analysis. Treated patients were compared with the control group Y 8 women with PRM who discontinued DA after pregnancy induction (9 pregnancies) and a control group Z of 46 healthy pregnant women, randomly selected from two departments of Obstetrics. Patients with multiple pregnancies were recorded in each corresponding study group.\r\nResults: In the control group Y, tumor size showed an increase in 2 (intrasellar macroPRM) out of 8 cases (25%). DA treatment throughout gestation in 27 women with PRM prevented the growth in all cases and induced a shrinkage of more than 30% of tumor mass in 8/14 macroPRM (57.1%), i.e., in 4/7 (57.1%) of macroPRM with physiological serum PRL levels during pregnancy, and in 5/8 (62.5%) of macroPRM with suppressed PRL levels (p = NS) (1 patient had pregnancies in both groups). Low dose DA (BRC 2.5 ? 5 mg/day or CAB 0.5 mg/week) maintains physiological PRL levels in 6/12 (50%) macroPRM, but suppressed PRL in 80% of microPRM. Cure was recorded in 6/49 (12.2%) of patients. Two patients with PRM-induced neuroophthalmic syndrome were successfully treated with DA throughout 1 and respectively 3 pregnancies.\r\nConclusions: Some women with prolactinomas showed a tumour size increase if they were not treated with dopamine agonists throughout pregnancy. Maintaining physiological serum PRL levels during pregnancy (frequently with low doses of DA) prevented tumor growth, avoiding a PRL suppression that may have subtle influence on long-term foetal development.

Introduction: In Turner Syndrome (45XO) and Turner mosaicism, fertility is reported to be extremely low. We encounter premature menopause, due to premature ovarian failure. When these patients conceive spontaneously, such pregnancies have an increased percentage of abortions, malformations and stillbirths. These patients should be counseled for prenatal genetic testing.\r\nMaterial and Methods: We discuss the case of a patient with Turner mosaicism (45XO,46XX), who successfully conceived due to IVF procedures.\r\nResults: The patient, a women with Turner mosaicism encountered secondary amenorrhea due to premature menopause. Because of her diagnosis she was proposed for IVF with egg-donation. She was on HRT for two years before. At the time of embryotransfer her endometrium was prepared with estrogens and progesterone. The embryotransfer was done at 48 hours and the patient received two of the four embryos; the other two embryos were frozen. An HCG done at 14 days after embryo-transfer revealed no pregnancy. After two months she decided to have another embryo-transfer with the frozen embryos.The endometrium was prepared in the same manner. This time an intrauterine pregnancy was reveled on vaginal ultrasound. The patient denied genetic tests; she had an uneventful pregnancy and delivered a healthy baby at term.\r\nConclusion: The new techniques of in vitro fertilization have proved very useful for patients with Turner syndrome and Turner mosaic syndrome. Oocyte donation can be an optimal alternative. This can be a way to manage infertility in these cases.