A testosterone-secreting, gonadotropin-responsive pure thecoma and polycystic ovarian disease.

UNLABELLED: A 31-yr-old hirsute female with oligoamenorrhea since menarche had markedly elevated peripheral plasma testosterone (T) concentrations of 250-255 ng/100 ml (normal 20-60 ng/100 ml), which lacked a diurnal rhythm, were not suppressed by dexamethasone, were decreased by ACTH, and were massively increased to 2,530 ng/100 ml by human chorionic gonadotropin (hCG). The binding capacity of T-binding globulin (TeBG) was 0.2 mug/100 ml (normal = 1.1-3.3 mug/100 ml). Plasma delta 4-androstenedione (A) was elevated at 374-681 ng/100 ml (normal = 90-135 ng/100 ml). Plasma estrone (E1) and estradiol (E2) were normal. The endometrium was proliferative. A T-secreting tumor was suspected because the plasma T levels were higher than those observed in polycystic ovarian disease. Exploratory surgery revealed bilateral polycystic ovaries and a pure thecoma in the right ovary which was not visible on surface examination. The thecoma did not contain granulosa cells. Plasma T in the right ovarian vein, draining the tumor, was 28,200 ng/100 ml and in the left ovarian vein was 2,600 ng/100 ml. Plasma A was elevated in both ovarian veins: 11,170 ng/100 ml on the left and 8,360 ng/100 ml on the right. The thecoma contained 1.35 mug/g of T and only 0.014 mug/g and 0.007 mug/g of E2 and E1, respectively. Plasma A and T after bilateral oophorectomy and removal of the thecoma were normal at 184 ng/100 ml and 40 ng/100 ml, respectively. CONCLUSIONS: 1) This pure thecoma produced primarily T rather than E1 OR E2 and was gonadotropin-responsive. 2) A very high plasma androgen level in a female is an important clue to the presence of a tumor. A T-secreting tumor should be ssupected when the peripheral plasma T is over 250 ng/100 ml and when plasma T increases to over 1,000 ng/100 ml following hCG stimulation. 3) Tumors cannot be classified as estrogenic or androgenic on the basis of the character of the endometrium.

Adrenal function in hirsutism I. Diurnal change and response of plasma androstenedione, testosterone, 17-hydroxyprogesterone, cortisol, LH and FSH to dexamethasone and 1/2 unit of ACTH.

ACTH dependency of plasma androstenedione (A) and testosterone (T) was determined in normal and hirsute women by measuring the magnitude of change of A and T between the time of the cortisol (F) peak and F nadir in a diurnal study. There was a significant diurnal rhythm of A synchronous with F in both normal and hirsute women (P less than 0.01). Five of 12 hirsute women had a greater than normal diurnal swing of A (P less than 0.05), but only 2 of the 12 had a greater than normal diurnal swing of T. Responsiveness of A and T to 1/2 unit of intravenous ACTH was determined after dexamethasone 1 mg was given the night before. Plasma A and T were elevated in most of the hirsute women during acute ACTH suppression by dexamethasone, indicating ACTH-independent hypersecretion of androgens. Nine of 17 hirsute women had a greater than normal A response to ACTH (P less than 0.05). Those who had an exaggerated diurnal swing of A also had hyper-responsiveness of A secretion to ACTH. Only 2 hirsute women had an exaggerated T response to ACTH. Some T levels were decreased by ACTH. Seven of the 9 hiruste women who had an exaggerated A response to ACTH had a normal maximum F response, but a greater than normal 17-hydroxy-progesterone (17-OHP) response to ACTH with a high 17-OHP to F ratio, suggesting they have a mild but compensated reduction in 21-hydroxylase or 11beta-hydroxylase activity. Two women with hyper-responsiveness of A secretion had low F and 17-OHP responses to ACTH suggesting reduced C21 but intact C19 3beta-hydroxysteroid dehydrogenase-delta-5,-4 isomerase activity. These apparent reduced enzyme activity may not be congenital, but induced by an altered hormonal milieu such as an abnormal androgen-estrogen ratio. It is concluded that ACTH uniformly stimulated A secretion but not T secretion and that approximately 50% of the hirsute women had ACTH-dependent hypersecretion of A, but most of these also had concurrent ACTH-independent hypersecretion of androgens.

Human ovarian 17 beta-hydroxysteroid oxidoreductase activity: a comparison of normal and polycystic ovarian tissues.

Ovarian tissue and ovarian venous blood were obtained from women undergoing wedge resection, and ovarian tissue was obtained from normally menstruating women who had an oophorectomy for medical reasons. A morphological evaluation was made of the wedged tissue. 17 beta-Hydroxysteroid oxidoreductase levels were determined as the 17-ketoreductase (17-KR) and 17 beta-dehydrogenase activities in both normal and wedged tissue. Plasma androstenedione (A) and testosterone (T) levels were measured in the ovarian venous blood. Low, but measurable, 17 beta-hydroxysteroid oxidoreductase activity was found in the mitochondria, microsomes, and cytosol. With whole, cell-free homogenates, mean 17-KR activity was not significantly different in normal tissues and polycystic tissues; mean 17-KR activity of corpora lutea was significantly greater than that of the other tissues. Mean 17 beta-dehydrogenase activity was not significantly different from 17-KR activity in the tissues studied. Ovarian venous A levels were higher than the reported mean ovarian venous A levels of normal women with only one exception; approximately half of the ovarian venous T levels were higher than reported mean ovarian venous T levels of normal women. The morphology of the wedge sections did not correlate well with the biochemical data.

Comparative study of flurbiprofen and morphine for postsurgical gynecologic pain.

This single-dose, double-blind, randomized, placebo-controlled study assessed the efficacy and safety of 50 mg of flurbiprofen (Ansaid, Upjohn) in the relief of postoperative pain following cesarean section, as well as vaginal or abdominal hysterectomies. Results show that both 50 mg of oral flurbiprofen and 10 mg of intramuscular morphine sulfate were significantly superior to placebo in 161 patients with respect to pain intensity after medication, pain relief scores, need for additional analgesia, and overall clinical evaluation of pain relief. By two hours after treatment, there were no significant differences between morphine sulfate and flurbiprofen in terms of pain intensity or degree of pain relief. According to investigators' global evaluations of efficacy, both active treatments were statistically superior to placebo. The only adverse reaction occurred in the morphine treatment group. Flurbiprofen administered orally for the relief of moderate to severe pain following major gynecologic surgery appears to be equal to morphine sulfate and superior to placebo in efficacy and safety. Unlike morphine, flurbiprofen is a nonparenteral, uncontrolled substance, and thus patient acceptance is improved while nursing time is decreased.

A technique for uterine conservation in adolescents with vaginal agenesis and a functional uterus.

Vaginal agenesis in association with a functional uterus occurs infrequently, and usually presents in adolescents. To preserve reproductive function, the uterus must be conserved, and a vagina must be constructed in one operative procedure. The authors describe a surgical technique that combines a modified McIndoe vaginoplasty with uterine conservation in which a special stent is fabricated to insert in the uterine cervix and the neovagina. Factors that must be considered when choosing between a hysterectomy and a uterine conservation procedure also are discussed.

The use of prophylactic partial exchange tranfusion in pregnancies associated with sickle cell hemoglobinopathies.

Sickle cell anemia is associated with an alarming attrition rate during pregnancy. The maternal morbidity rate, perinatal wastage rate, and the incidence of severe morbidity in both mother and child are elevated above acceptable limits. In most cases, these statistics have been compiled using conservative therapeutic modalities. In contrast, this report utilizes prophylactic partial exchange transfusion therapy in patients with severe sickle cell hemoglobinopathies. The protocol involves the introduction of 750-1000 cc of buffy coat, poor washed red cells exchanged with 1000-1500 cc whole blood during phlebotomy at 28 weeks' gestation and again prior to term. Thirty-six consecutive pregnant patients with sickle cell anemia have been managed in this fashion. The one maternal mortality occurred in a patient who did not complete the protocol. Major maternal morbidity and perinatal wastage rates were significantly decreased. Two cases of serum hepatitis occurred. It appears from these data that the use of prophylactic partial exchange transfusion in pregnant patients with severe sickle cell hemoglobinopathies can be of benefit. Further trials of this method seem justified by these results to assess completely the benefit-risk ratio of this procedure.

The incidence of preterm labor and specific risk factors.

A retrospective review of patients at high risk for preterm delivery because of twin gestation, uterine malformation, incompetent cervix, or previous preterm delivery was carried out to assess the rates of preterm labor and spontaneous preterm birth. Among the 119 patients with multifetal gestation, 46% had preterm labor and 36% delivered before 37 weeks' gestation. In the 58 patients with an anomalous uterus, the rate of preterm labor was 19%, and 14% had early deliveries. Of those with incompetent cervices (115), one-fourth had preterm labor and 17% had an early birth. When a history of one or more preterm deliveries was present, the preterm labor rate ranged from 41-68%, with an early delivery rate of 30-47%. Prophylactic tocolytic therapy did not prolong gestations significantly. Maternal smoking did not have an adverse effect on the incidence of preterm labor except in twin pregnancies, for which early delivery was more likely. The percentages for preterm delivery are slightly lower than those found in the literature; this may be attributable to improvement in preterm birth prevention efforts including patient education, more frequent examinations, home uterine activity monitoring, and daily nursing contact.

Female gonorrhea: its relation to abnormal uterine bleeding, urinary tract symptoms, and cervicitis.

Data are presented from an investigation of the assocation of presenting complaints with gonococcal infection in females seeking primary care in an urban emergency room. Over 27% of patients in the study had cultures positive for Neisseria gonorrhoeae (GC). The GC positivity rates which were significantly higher than expected were found in patients with abnormal uterine bleeding, urinary tract symptoms, and cervicitis, as well as acute PID. Clinical findings suggest an etiologic role for the gonococcus in the pathogenesis of these disorders. Where the incidence of gonorrhea is high, new approaches in the managment of patients with these presenting complaints are necessary in order to prevent the more serious complications of gonorrhea and further spread of the disease.

Fetal health assessment in pregnancies complicated by sickle hemoglobinopathies.

The contraction stress test (CST) and nonstress test (NST) are used as fetal health assessments. Severe sickle hemoglobinopathies in the parturient have been shown to place the fetus significantly at risk. This study correlates these fetal health assessment tests with outcome data in 58 pregnancies occurring in women with sickle cell disease. There were 30 patients with homozygous sickle cell anemia (HbS-S), 19 with hemoglobin S-C disease (HbS-C), and nine with hemoglobin S-thalassemia (HbS-Thal). All received prophylactic partial exchange transfusions as part of their antepartal care. At 34 weeks' gestation, NSTs followed by CSTs were begun in each patient. A total of 255 tests were performed. Of these, 19 NSTs and 24 CSTs were unsatisfactory or questionably abnormal and were repeated. There were no nonreactive NSTs, and no patient demonstrated a positive CST. The neonatal outcome revealed one infant who was small for gestational age and two infants who were of low birth weight but appropriate for gestational age. All infants survived and were normal. These data suggest that the fetal reactivity and placental reserve among these parturients with severe sickle hemoglobinopathies were uncompromised, as these tests have been shown to be relatively sensitive assessments of fetal well-being in other maternal disorders.

Clinical findings and hormonal responses in patients with polycystic ovarian disease with normal versus elevated LH levels.

The clinical features, ovarian pathology, and hormonal responses to dexamethasone (Dex), Dex + ethinyl estradiol (EE), and Dex + hCG were compared in 5 women with polycystic ovarian disease (PCOD) who have normal 24-hr urinary luteinizing hormone (LH levels to 5 who had elevated urinary LH levels. No differences were noted in the clinical features. There was no correlation between ovary size and LH levels. Three in the normal-LH group had hyperthecosis. Plasma androstenedione (A) was more frequently elevated in the high-LH group. Dex + EE markedly increased LH secretion in the high-LH group, suggesting increased responsiveness of the positive feedback control mechanism of LH secretion in the high-LH group. There was a greater response of A, testosterone (T), and 17-ketosteroids to Dex + hCG in the normal-LH group. Those with high-LH levels did not exhibit a significant increase in A, T, and 17-KS with hCG. The limitations and usefulness of the Dex + hCG test are discussed. The hypothesis is advanced that the increased LH secretion in the high-LH group is due at least in part to positive feedback resulting from the increased A levels. The amount of 17beta-oxidoreductase activity in the ovary may influence LH secretion in PCOD.

Amniotic fluid tests for fetal maturity in normal and abnormal pregnancies.

The lecithin-sphingomyelin (L/S) ratio is acknowledged to be superior to most procedures for predictinf fetal lung maturity in normal pregnancy. In complicated gestations, however, errors have been reported. This study involves 686 normal gestations and 389 pregnancies complicated by fetomaternal diseases. The L/S ratio, creatinine level, and percent of fat-staining cells were measured in samples of amniotic fluid from these patients. The results showed good correlation of all three tests with fetal maturity as measured by weight, Dubowitz criteria, and incidence of respiratory distress syndrome in the normal patients. In the complicated pregnancies, however, the creatinine was unacceptable in up to 30% of the cases. The L/S ratio likewise decreased in accuracy for all parameters of fetal maturity measured. The Nile blue staining of the fetal cells appeared to be the most consistent technic in these cases. A fetal maturity battery comprised of these three assays and other methods of assessing fetal health is advocated in pregnancies complicated by certain disease states.

Nile blue and fetal maturity. Further investigations.

The consistency of results using Nile blue staining of fetal cells in amniotic fluid to estimate fetal maturity has been demonstrated. Recently, evidence to support this method has been published from this laboratory. Several biochemical and technical factors were cited as important to the success of the method. This report deals with further testing of several Nile blue dyes (hydrochloride and sulfate) necessitated by changes in production and federal regulation of this compound. The results show Nile blue hydrochloride (HCl) to be the most superior dye regardless of color index. Buffered solutions (6.6) of Nile blue A (sulfate) improve its performance, but not to levels demonstrated by the HCl preparation. Storage at room temperature adversely affects each dye; however, the sulfate variety appears to be the most unreliable under these circumstances. For best results, it is recommended that Nile blue HCl be used and the solution (buffered or normal) be kept refrigerated.

Pregnancy after successful vaginoplasty and cervical stenting for partial atresia of the cervix.

We previously reported surgical correction of vaginal agenesis and partial cervical atresia in an 11-year-old girl with amenorrhea and a pelvic mass. This patient, the subject of this report, conceived 7 years later and delivered at term. An abdominal cerclage was placed at 12 weeks' gestation to protect the cervix, and delivery was by cesarean.

Features of Turner's syndrome in women with polycystic ovaries.

Four women with phenotypic features of Turner's syndrome and with poly cystic ovaries (PCO) are describe. In addition to the phenotypic features, Case 1 had primary amenorrhea and small PCO, Case 2 had a 46, XX/45, X karyotype (lumphocytes), Case 3 had enlarged PCO which contained a decreased number of oocytes, and Case 4 had enlarged PCO and was short in statute. These cases support the concept of a relation between PCO and the X chromosome. Some PCO may represent an intermediate condition in a spectrum that extends from the streak gonad of Turners syndrome to the normal ovary. Evidience for X chromosome involvement in PCO is summarized. The concept is advanced that at least some cases of OCO may be due to X chromosomal factors causing an abnormal follicular appartus.

Danazol in the management of ureteral obstruction secondary to endometriosis.

Ureteral obstruction caused by endometriosis is uncommon. It is, however, an important complication that imposes a 25% chance for permanent loss of renal function on the affected side. The standard management is surgical; however, three cases have been reported in which regression of obstruction followed medical therapy. This case report concerns a patient with long-standing partial ureteric obstruction due to endometriosis who was treated for 2 months with danazol. Clinical response of the endometriosis was excellent, but the obstruction persisted, a retroperitoneal ureteroneocystotomy was therefore performed. The ureter was found to be obstructed by dense fibrous tissue that contained endometrial glands. It seems therefore that a trial of danazol may be attempted in selected cases, but that the drug is unlikely to relieve endometriotic ureteric obstruction once dense fibrosis has occurred.

Mumps oophoritis: a cause of premature menopause.

One cause of secondary oligomenorrhea is ovarian infection. A rare type of infection related to the disturbance of menstrual function is mumps oophoritis. Three patients with premature menopause presumably caused by this agent were described. In one patient the symptoms coincided with a subclinical infection during the perinatal period, with subsequent infertility. Another patient seemed to have had a clinically mild oophoritis during the pubertal period, and the third patient became symptomatic following parturition. It appears that this aberration in menstrual function and fertility may be related to the time during which the infection occurs as well as to the severity of the infection. In addition, it is apparent that mumps oophoritis may be a more frequent cause of premature menopause than has heen previously suspected.

Polycystic ovarian disease, maturation arrest of spermiogenesis, and Klinefelter's syndrome in siblings of a family with familial hirsutism.

A family with hirsutism in five generations in which polycystic or bilaterally enlarged ovaries were documented in three different sibships of two generations is described. Two brothers of one of the women with polycystic ovaries had a low or low-normal plasma follicle-stimulating hormone level and one of these had oligospermia due to maturation arrest of spermiogenesis. A third brother had Klinefelter's syndrome. Other abnormal features in the family included precocious adrenarche, beardless males, eunuchoidism, and prepubertal grand mal seizures.

Vaginal birth after cesarean section: the demise of routine repeat abdominal delivery.

In light of the abundant very favorable data and considerable published patient experience regarding vaginal birth after cesarean for selected gravidas, the authors are moved to repeat with emphasis the question asked by Dr. Danforth in his recent treatise on cesarean delivery: "The question now is not whether the dictum of automatic repeat cesarean section is still valid, but rather why we continued to adhere to it for more than 60 years, as though it had been carved in stone." From recently published American data, it is obvious that more providers and more patients must be convinced of the safety, efficacy, and cost effectiveness of a selective program of trial of labor and vaginal delivery following previous cesarean birth if we are to effect a significant reduction in this nation's cesarean birth rate. The policy of "once a cesarean section, always a cesarean section" should be applied correctly only to its intended group of patients with previous uterine fundal or upper-segment incisions. As the advisability of insisting on a trial of labor for all parturients who have no contraindications becomes a signal part of the fabric of obstetric practice in the United States and the remainder of the world, we shall witness the demise of routine repeat abdominal delivery.

A program of uterine activity monitoring and its effect on neonatal morbidity.

In a recent study 34 patients at high risk for preterm delivery who received uterine activity monitoring were compared with 33 similar patients who attempted to detect contractions by palpation. The incidence of preterm delivery was significantly reduced among those using the uterine activity detection device, although all patients in both groups had the same prenatal care and educational intervention. When short-term neonatal morbidity associated with preterm delivery was compared between the two groups, adverse effects decreased significantly among those in the monitored group (p = 0.001). The majority of short-term morbidity in both groups was noted in those delivering preterm and thus was gestational age related. No significant difference was found in neonatal morbidity between the groups when the infants were delivered at less than 37 weeks' gestation. Uterine activity monitoring, which is effective in preventing preterm birth, is also efficacious in decreasing short-term neonatal morbidity.

Meperidine and normeperidine distribution in the rhesus monkey.

Previous work has shown that both meperidine and normeperidine are transferred across the placenta to the fetus. Little is known in primates, however, about the tissue deposition of these compounds. Four pregnant, dated rhesus monkeys within one week of term were anesthetized for cesarean delivery. An equal mixture of meperidine and normeperidine was administered as an intravenous bolus 10 minutes before delivery (1.25 mg/kg). The infants were then sacrificed at 20 minutes after birth and the concentration of the compounds in various organ systems were analyzed by gas-liquid chromatography and mass spectroscopy (GLC-MS). The infant serum 20 minutes after delivery revealed a meperidine concentration of 2.23 micrograms/ml and a normeperidine level of 0.67 micrograms/ml (3:1). In contrast, the tissues analyzed showed a much higher concentration of the metabolite in the liver (1:7), gallbladder (1:3), and brain (1:2). Other tissues, such as muscle and kidney, demonstrated equal levels of the two compounds. The authors conclude that normeperidine is quickly transferred to fetal tissues and to a greater degree than the parent compound in certain organs. The increased distribution, particularly in the brain, could account for the toxic actions in the cerebrum of the derivatives of meperidine.