Utility of breast ultrasonography in the diagnostic work-up of precocious puberty and proposal of a prognostic index for identifying girls with rapidly progressive central precocious puberty.

OBJECTIVE: To determine the utility of breast ultrasono- graphy in the diagnostic work-up of precocious puberty and to create a prognostic index for early differentiation between non/slowly progressive or transient forms of precocious puberty and rapidly progressive central precocious puberty. METHODS: We recruited consecutively 60 girls with precocious pubertal development. In all the girls we evaluated Tanner stage, basal and gonadotropin-releasing hormone (GnRH)-stimulated follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, estradiol (E2) levels, and bone age, and performed pelvis and breast ultrasound examinations. Logistic regression models were fitted to identify possible diagnostic factors for rapidly progressive central precocious puberty and non/slowly progressive or transient forms. RESULTS: Ultrasound breast volume>or=0.85 cm3 was associated with rapidly progressive central precocious puberty (P=0.01). Uterine volume>or=5 cm3, LH peak>or=7 IU/L, presence of an endometrial echo, E2 levels>or=50 pmol/L and bone age>2 SD above expected were significantly associated with rapidly progressive central precocious puberty. A multivariate model including uterine volume, E2 level, bone age, presence of an endometrial echo and ultrasound breast volume revealed a strong ability to classify rapidly progressive forms. From this multivariate analysis a prognostic index for rapidly progressive central precocious puberty was defined. CONCLUSIONS: Ultrasound imaging allows better definition of the breast and the maturation stage than does use of Tanner's stages. Ultrasound breast volume>or=0.85 cm3 is an independent predicting factor of rapidly progressive central precocious puberty. A prognostic index that was created from a multivariate model including uterine volume, E2 level, presence of an endometrial echo, bone age and ultrasonographically determined breast volume, may help in the early differentiation between rapidly progressive central precocious puberty and non/slowly progressive or transient forms.

Unusual presentation of juvenile granulosa cell tumor of the ovary.

BACKGROUND: We present a case report of juvenile granulosa cell tumor of the ovary (JGCT) with an unusual clinical presentation and hormonal secretion. CASE: A 16-yr-old girl had developed spontaneous menarche at the age of 12 yr, but after this initial menstrual bleeding she had no further periods for 4 yr. She had no clinical signs of virilization. Endocrinological studies detected high levels of DHEA, 17 hydroxyprogesterone (17OH-P), insulin and PRL, an exaggerated DHEA response after ACTH stimulation, and low FSH and high LH values after GnRH. An ultrasound examination revealed an irregular structure and increased diameters of her right ovary, due to the presence of a cyst. Because exploratory laparoscopy revealed the presence of a right ovarian mass, her right ovary was removed. JGCT was diagnosed. Ten days after surgery, menstrual bleeding initiated. Endocrinological evaluation after the operation showed that 17OH-P, insulin and basal FSH and LH serum values had returned to normal, while DHEA levels had decreased to within the upper limit of the normal range. Only PRL levels remained unchanged. CONCLUSION: Our patient presented some unusual characteristics. She did not have precocious puberty, but secondary amenorrhea. Hormonal secretion consisted mainly of androgens, even though clinical signs of virilization were not present.

[Ethics in perinatology]. / Etica in perinatologia.

The perinatal phase coincides, at its onset (22nd-23rd week of gestation, according to common acknowledgment), with the possible beginning of a extrauterine life susceptible of protraction. The 1st, for some the 4th, week of neonatal life marks the conclusion of the perinatal phase. There are several reasons to burden this period, to which a complex World Health Organization (WHO) document for Europe was dedicated in November 2000, with ethical issues. The profound immaturity that characterizes these extremely low weight newborns, of an approximate weight of 500 g, influences the poor survival prognosis (especially for those born within the 24th week), as well as the limitations concerning quality of life, often severe. Neonates born earlier than the 23rd week are at extreme risk, and rouse critical considerations regarding the choice of a health care program. A close monitoring of pregnancies at risk of premature termination, and a careful program of medical care for these extremely pre-terms, progressively implemented in the last 10-15 years, have given consistent results, reported in surveys of recent publication. From an ethical point of view, the problem of limitations within or beyond which to stretch intensive care interventions in Neonatal Intensive Care Unit (NICU) is still crucial, being the orientation between rational and emotional a difficult issue. Guidelines or behaviour proposals, variable with time and manifold in different countries, are reported. Naturally, the communication of a severe diagnosis to parents of a newborn even if not preterm-born falls also under the ethical issues of the perinatal period.

Pelvic ultrasound evaluation in patients with Turner syndrome during treatment with growth hormone.

OBJECTIVES: Treatment with growth hormone (GH), alone or in combination with oxandrolone, is used in patients affected by Turner syndrome to improve growth velocity and adult height. Since GH interacts with gonadotropins in the stimulation of the human ovary, the aim of our study was to evaluate the possible effects of GH administration on uterine and ovarian characteristics. METHODS: We performed pelvic ultrasound assessment in 29 patients with Turner syndrome aged 7.5-16.6 years (19 with 45,X karyotype; 10 with variant karyotypes) before and during treatment with GH alone. Uterine volume and ovarian size and morphology were compared to those of 23 age-matched girls with Turner syndrome not treated with GH. Both patients and controls were divided into prepubertal and pubertal groups. Cross-sectional and longitudinal studies (before and every 6 months during GH treatment for 2 years) were performed. RESULTS: We observed a significantly higher uterine anteroposterior diameter and volume in younger (< or = 11 years) GH-treated Turner syndrome girls than in those who were untreated. Also visualization and heterogeneous echopattern of the ovaries were significantly more frequent in treated than in untreated Turner syndrome patients, particularly before the age of 11 years. The longitudinal study showed a significant increase in uterine volume, more related to treatment than to age. Spontaneous breast development and menarche were found more frequently in GH-treated Turner syndrome girls. CONCLUSION: Growth hormone therapy can have a co-gonadotropin role in patients with Turner syndrome.

[Transvaginal ultrasonic evaluation of the thickness of the section of the uterine wall in previous cesarean sections]. / Valutazione ecografica transvaginale dello spessore del segmento uterino inferiore in tagli cesarei pregressi.

BACKGROUND: The aim of this study is to evaluate accuracy of transvaginal sonographic examination of the lower uterine segment in pregnant women with previous cesarean section. METHODS: Sixty-one pregnant women between 37 and 40 weeks of gestation, with previous cesarean section underwent transvaginal ultrasonography. Wall thickness of the lower uterine segment, the length of cervix, dilation of the isthmus uteri were measured. On the basis of the surgical findings (in 53 patients) and outcome of the trial of labor (in 8 patients) a Score was assigned to the pregnant women: Score 1 to the women who had good healing or a trial of labor without complications; Score 2 to the women with a thin or discontinued scar and in case of threatened rupture of the uterus in the trial of labor. RESULTS: The mean thickness of the lower uterine segment is 3.82 mm +/- 0.99 mm. The Score 1 group shows a mean thickness of 4.2 mm +/- 2.5 mm, and the Score 2 group a mean thickness of 2.8 mm +/- 1.06 mm. The transvaginal sonographic examination provides a sensitivity and a specificity respectively of 100 and 75%, for a thickness cut-off of 3.5 mm, and a positive and negative predictive values of 60.7% and 100% respectively. CONCLUSIONS: The transvaginal sonographic evaluation of the lower uterine segment improves therefore the obstetrical decision-making regarding the trial of labor in women with previous cesarean section.

Effects of valproate, phenobarbital, and carbamazepine on sex steroid setup in women with epilepsy.

Serum levels of sex-hormones, sex-hormone binding globulin, gonadotropin, and prolactin were evaluated during the follicular and the luteal phases in 65 women with epilepsy and in 20 healthy controls. Twenty-one patients were treated with sodium valproate (VPA), 21 with phenobarbital (PB), and 23 with carbamazepine (CBZ). VPA does not stimulate liver microsome enzymes, whereas PB and CBZ do. Patients on VPA therapy showed higher body weight and body mass index, but no significant differences in hirsutism score, or in ovary volume or polycystic ovary prevalence (at ultrasound examination). Estradiol levels were lower in all patient groups than in healthy controls in the follicular but not in the luteal phases. VPA affected luteal progesterone surge in 63.6% of cases. This effect was significantly lower in the CBZ and PB groups. Furthermore, increases in testosterone and delta 4-androstenedione levels and in free androgen index, along with a higher luteinizing hormone-follicle-stimulating hormone ratio in the luteal phase, were observed in women treated with VPA. Although sex-hormone binding globulin levels were higher in CBZ and PB than in VPA-treated patients, the differences were not significant because of the wide dispersion of the carrier protein levels. Inducer antiepileptic drugs decreased dehydroepiandrosterone sulfate levels, which remained unchanged during VPA treatment. No significant differences occurred in basal gonadotropin and prolactin levels.

Menstrual cycle and ovary alterations in women with epilepsy on antiepileptic therapy.

Impaired reproductive function is thought to frequently affect women with epilepsy, mainly when seizures originate in the temporal lobe. In this study, we evaluated menstrual cycle features and assessed ovulation by determining luteal progesterone (Pg) levels in 101 consecutive women with epilepsy (36 with idiopathic generalized epilepsy -IGE; 65 with partial epilepsy -PE), aged between 16 and 50 years, treated with various antiepileptic drugs (AED). PE originated in the temporal lobe (TLE) in 40 subjects, in the frontal lobe in 13, in the parietal lobe in 2, while the origin of focal seizures remained undetermined in 10 patients. In all patients, menstrual and reproductive history, body mass index, hair distribution and hormonal pattern were assessed. Suprapubic ovary ultrasound (US) examination was carried out in 83 patients (28 with IGE, 55 with PE). Three patients with IGE and one with PE were amenorrheic. Oligomenorrhea occurred in 16 patients, polymenorrhea in 2. Changes in menstrual cyclicity were independent from epilepsy type (19.4% in IGE; 23.1% in PE) and from origin of focal discharges (22.5% of patients with TLE; 20.0% with origin in other brain areas). Luteal Pg levels remained below 2 ng/ml in 30 patients independently of epilepsy type. Corpus luteum dysfunction was combined with hyperandrogenism in 15 of these patients. In the other cases different alterations of hypothalamus-pituitary-ovary axis were observed. Valproic acid blunted luteal Pg surge more frequently than other AED. Polycystic ovaries (PCO) were observed in 14 (16.9%) patients (21.0% with IGE: 14.5% with PE). These prevalences are not higher than those reported in the general population. Among PE patients, PCO was found in 1 case with undetermined focal origin and in 7 TLE cases, who also had ovary volume significantly larger than patients with seizures originating from the frontal or parietal lobe. Epileptic women exhibited an increased occurrence of multifollicular ovaries (MFO) found in 12 cases (14.4% vs 5% in the general population). However, no defined hormonal or clinical pictures were associated with this US alteration in most patients. These findings reappraise the impact of ovary alterations in women mainly affected by mild to moderate epilepsy, on differing AED regimens, with the exception of more frequent ovulatory dysfunction and PCO occurrence in patients taking VPA.

Ultrasonography endometrial patterns in different hormonal treatments to induce ovulation.

As several studies report that transvaginal ultrasound of endometrial thickness may help distinguish fertile from infertile cycles, we assessed endometrial growth and morphology in 124 infertile women. The patients underwent different ovulation induction treatments: clomiphene citrate (CC), human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG), analogous Gn-RH and hMG (aGn-RH+hMG). CC administration is followed by a slackening of endometrial maturation. The US pattern H (typical of the ovulatory phase) appears on day 13 (76.9% of the cases) in spontaneous cycles and on day 16 (75% of the cases) in CC-induced cycles. The H pattern on day 20 in CC-induced cycles persisted in the patients who did not conceive. In aGn-RH-stimulated cycles the endometrial pattern H appears on days 13 (41.66%) and 16 (83.33%), not preceded by a Hi image. The endometrial pattern Hi was always observed in the patients who did not conceive. Our retrospective study of endometrial US morphology shows that the different ovulation induction treatments may affect the day of appearance of the various endometrial patterns. These results, which need further confirmation, can allow the changes of conceiving to be investigated during the stimulation protocol of every single stimulated cycle.

Balanced autosomal translocations and ovarian dysgenesis.

We report two unrelated women with gonadal dysgenesis, and a (6;15)(p21.3;q15) and a (8;9)(p11.2;q12) balanced translocation, respectively. The patients were of normal stature and showed no phenotypic abnormality or malformation other than ovarian failure. We are not aware of other reports of balanced autosomal translocations associated with gonadal dysgenesis in women. The occurrence of chromosome anomaly and sterility in the two females may be coincidental. However, studies on mouse gametic progression indicate that balanced autosomal translocations can cause oocyte degeneration and reduction of reproductive lifespan. On the basis of these observations, we cannot exclude that the ovarian failure in our patients is the result of oocyte degeneration because of as yet unidentified consequences of the balanced translocations.

Precocious signs of polycystic ovaries in obese girls.

As several studies have reported that 35% of patients with polycystic ovary syndrome are obese and that this syndrome seems to originate during the early phase of sexual maturation, we undertook a study of such subjects. We studied ultrasound and hormonal findings in 49 obese girls aged from 7.9 to 19.10 years, with a mean excess weight of 44%; 23 premenarcheal girls and 26 postmenarcheal girls with mean gynecological age of 2.5 years. As controls, we studied 18 girls in the pubertal phase and 17 healthy girls with regular menses, matched for age and gynecological age. Pelvic ultrasonography was carried out in all girls and estrone, estradiol, progesterone, prolactin, follicle stimulating hormone, luteinizing hormone, sex hormone binding globulin (SHBG), testosterone, free testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), androstenedione and 17-hydroxyprogesterone (17-OHP) were measured by radioimmunoassay in 11 of the 18 postmenarcheal girls. Five girls (10.2%) with excess weight of > 40% presented with mild or severe hirsutism based on Ferriman and Gallway scores; six (12.2%) presented with acne and 14 (28.5%) presented with acanthosis nigricans.Hormonal evaluation showed elevated levels of estrone (p < 0.005) and testosterone (p < 0.01) but lower than normal levels of SHBG (p < 0.05) and estradiol (p <0.05). On the basis of our results, 23%) of the postmenarcheal obese subjects showed clinical, hormonal and ultrasonographic signs of polycystic ovaries, and 23% of postmenarcheal obese girls showed multifollicular ovaries. Six of these, at 1 year after menarche, showed a uterine cross-sectional area larger than normal for gynecological age (21.92 +/- 5.64 cm(2) vs. 16.36 +/- 2.34 cm(2)). Further serial echographic studies and a careful follow-up will demonstrate if both multifollicular ovaries and increased uterine cross-sectional area in obese girls are precocious signs of polycystic ovaries.

Hypogonadism in a patient with balanced X/18 translocation and pituitary hormone deficiency.

The case of a girl carrying a balanced X/autosome translocation: 46,X,t(X;18)(q22.3;q23),inv(9)(p11q13) and pituitary hormone deficiency (growth hormone and gonadotropin) is described. The patient had a doll-like facies, with frontal bossing and poor development of the nasal bridge, increased adipose tissue especially of the trunk, short stature and absence of pubertal development without Ullrich-Turner stigmata apart from urinary tract malformation. The lack of spontaneous puberty seems related both with gonadotropin deficiency, as suggested by hormonal data and MRI of the pituitary region, and with gonadal dysgenesis, due to the X/autosome translocation, involving the critical region of the X chromosome essential for normal ovarian function. Growth velocity was unsatisfactory during growth hormone treatment; a higher dose of growth hormone similar to that used in Ullrich-Turner patients, would probably have improved her growth rate.

Transdermal estradiol substitution therapy for the induction of puberty in female hypogonadism.

Fifteen patients aged 14.5-27.3 years (mean +/- SE 18.8 +/- 0.9) with pubertal development failure underwent replacement therapy with estradiol (E2) using a transdermal therapeutic system (TTS). Fourteen of them were affected by hypogonadotropic hypogonadism (11 with thalassemia major, 3 with multiple pituitary hormone deficiency), the 15th patient had an asymmetric gonadal dysgenesis (karyotype 45, X 0/46, XY). Two sizes (5 and 10 cm2) of E2 TTS, delivering respectively 25 and 50 micrograms of E2 a day for 3 1/2 days, were used in this study. All patients were initially given the lower dose of 25 micrograms, twice weekly for 3 weeks each month; 6 months after starting therapy, 5-10 mg oral medroxyprogesterone acetate (MPA) daily was added during the third week. Later, the following sequence was used: 25 micrograms E2 TTS (twice weekly), on days 1 through 14, and 50 micrograms E2 TTS (twice weekly), on days 15 through 25 of each month. On days 15 through 25, 5 mg daily of MPA were administered orally. The period of treatment ranged from 0.5 to 3 years. Breast development was obtained in all cases. The vaginal maturation index rose. Ultrasonography showed an increase of uterine size and uterine shape became of pubertal type. Withdrawal bleeding occurred in all patients. Plasma E2 levels rose to normal levels, estrone (E1) levels increased slightly. No change in plasma SHBG levels was observed. Urinary E2, E1 and estriol rose to maximum levels the 3rd day after the application of each system. Neither systemic side effects nor adverse metabolic effects were observed except for an increased sensitivity to the platelet aggregating agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypopituitarism and stalk agenesis: a congenital syndrome worsened by breech delivery?

Thirty-seven patients with idiopathic hypopituitarism, of whom 12 had multiple pituitary hormone deficiencies (MPHD) and 25 isolated growth hormone deficiency (IGHD), were evaluated by magnetic resonance imaging (MRI). Twenty-two of the 37 showed congenital anterior pituitary hypoplasia, stalk agenesis and ectopic posterior pituitary gland at the infundibular recess (group A), while the remaining 15 presented isolated anterior pituitary hypoplasia (group B). Perinatal histories obtained from all patients demonstrated that 18/22 children of group A (81.81%) had histories of adverse perinatal events, with breech presentation in 15 (68.18%). Twelve of 12 children of group A born by breech delivery developed MPHD; 3 born by cesarean section for breech presentation had only IGHD. Patients of group B had also a high incidence of perinatal insults (12/15, 80%), but breech delivery was markedly less frequent (13.33 vs. 68.18% of group A) and responsible for only IGHD. Group B had also higher percentages of maternal spontaneous abortion and low birth weight. Our study suggests that several factors may play a role in the development of growth hormone deficiency. Some patients had severe perinatal insults apparently leading to hypopituitarism. We were able to define by MRI a group of patients with congenital abnormalities, such as anterior pituitary hypoplasia, stalk agenesis and posterior pituitary ectopia, among whom breech presentation was very common. In this group, breech delivery was always followed by MPHD while cesarean or normal delivery in such patients was followed by IGHD only.

[Contribution of pelvic ultrasonography in the diagnosis and follow-up of Turner's syndrome]. / Apport de l'échographie pelvienne dans le diagnostic et dans le follow-up du syndrome de Turner.

Between 1983 and 1988, 40 patients with Turner's syndrome, aged 8 to 26 years, underwent serial pelvic ultrasonography, in order to evaluate the morphofunctional parameters of the internal genital apparatus and correlate them with the karyotype and gonadotropin levels. Correlation of uterine and gonadal sonograms (site, size and echogenic potential) with the karyotype and the gonadotropin assays, permits the definition of each case and a personalized therapeutic approach as well as a control of its efficacy and/or its side-effects.

Laparoscopy in obstetrics and gynecological emergencies.

The Authors underline the importance of the laparoscopy in the Obstetrical and Gyneacological emergencies. For this purpose, 74 consecutive laparoscopies, performed as emergencies at the Department of Obstetrics and Gynaecology of the University of Pavia, are considered and analyzed. The Authors stress that the celioscopy has allowed a precise diagnosis in all the cases examined, and, even thanks to percelioscopic surgery, has avoided some useless laparotomies. Even more, when it was necessary to perform a major surgical act, the right laparoscopic diagnosis has addressed the therapy in several cases to conservative surgery.

Is perlaparoscopic bacteriological analysis sufficient for establishing the etiology of P.I.D.?

The Authors have studied the usefulness and the limits of laparoscopy in the etiologic diagnosis of P.I.D.; for this purpose 21 patients affected with P.I.D. underwent microbiological sampling from cervix and/or vagina and from Fallopian tube during laparoscopy. The findings have shown a discrepancy between the microbiological isolation from vagina/endocervix and from salpinx and remarkably the loss of evidence of S.T.D. agents from tuba with, conversely, frequent isolation of these agents (34.7%) from cervical swabs. Therefore, the Authors believe that the percelioscopic microbiologic study of endosalpinx is essential for the correct etiologic diagnosis of P.I.D., especially in anaerobic germ infections; yet the technical problems of percelioscopic samples and the biological features of S.T.D. agents require the simultaneous bacteriological sampling from the cervix and/or vagina.

Echography in obstetrics and gynecological emergencies: the ectopic pregnancy.

Sonographic findings suggestive of ectopic pregnancy in 23 patients are reported by the Authors. In accordance with the data from the literature the real time sonography has shown in this study a diagnostic accuracy of 76%.

[Histophysiology of the uterine isthmus]. / Histophysiologie de l'isthme utérin.

The uterine isthmus is morphologically defined as a topographic zone between the uterine corpus and the cervix, in very close association with the vasomusculary afferences. Architecturally isthmus corresponds to the connective-muscular function which is different by its thickness (from 2 mm to 10 mm) and by its morphology (digited, undulating sharp and regular). Histologically isthmus is made up by collagen fibers myometrial muscle cells, irregularly directed. The relationship of these two components reveal their functional synergy between the predominance of the connective tissue and the weakners of the muscle cells. The specific function of the isthmus and its autonomy depend: of the type and direction of the collagen fibers, and the quantity and arrangement the muscle cells, of the biochemical modifications and the variability of the ground substance moreover of the relations with the nervovascular endings. The isthmus incontinence is associated with these structural anomalies (muscular components, elastic fibers defects, connective tissue pathology, activity of the nerve endings, enzymatic troubles under hormonal control).