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Biomedical subjects

R Azziz

Publications and source records attributed to R Azziz.

At least 73 records · Page 4Linked to original sources
PubMed1996

Adrenal androgen production in response to adrenocorticotropin infusions in men.

The responses of several adrenal steroids to adrenocorticotropin (ACTH) were investigated in a group of healthy young men. The protocol consisted of overnight adrenal suppression with dexamethasone followed by 1 hr infusions of ACTH in increasing (4X) doses ranging from 30-30,720 ng/1.5M2 followed by 0.25 mg ACTH/1.5M2. Whereas cortisol, androstenedione and androstenediol concentrations tended to plateau at the higher ACTH infusion rates, those of dehydroepiandrosterone (DHEA) and 17-hydroxyprogesterone (17-OH P) did not. The cortisol concentration achieved after the highest dose of ACTH was over 50 fold higher than that at baseline. DHEA levels rose to values about 13 times baseline whereas the other steroids increased to lesser extents (3-5 fold). The ACTH infusion rate required to significantly increase each steroid over the baseline level was extrapolated from dose response curves and was considered to be an index of the sensitivity of each steroid to ACTH. Cortisol was the most sensitive, rising significantly at approximately 35 ng ACTH/1.5M2, followed by androstenediol, DHEA, androstenedione and 17-OH P.

17-alpha-Hydroxyprogesterone↗
PubMed1995

Molecular abnormalities of the 21-hydroxylase gene in hyperandrogenic women with an exaggerated 17-hydroxyprogesterone response to short-term adrenal stimulation.

OBJECTIVE: Our purpose was to establish the incidence of point mutations of the 21-hydroxylase gene (CYP21) in hyperandrogenic women with and without a 17-hydroxyprogesterone response to corticotropin stimulation above normal but below those levels associated with nonclassic adrenal hyperplasia. STUDY DESIGN: We studied 22 patients with hirsutism or hyperandrogenic oligoovulation: eight with an exaggerated net increase in 17-hydroxyprogesterone (i.e., change in 17-hydroxyprogesterone between 8.8 and 36 nmol/L) and 14 with a normal change in 17-hydroxyprogesterone. Large deletions of the 21-hydroxylase gene were evaluated by laser densitometry. Point mutations were detected with the polymerase chain reaction and dot blot hybridization analysis and included 30 Leu, intron-2 (G), 8 bp deletion exon-3, 172 Asn, 236-237-239 exon-6, 281 Leu, 318 stop, 339 His, 341 Trp, 356 Trp, and 453 Ser. RESULTS: Four patients with an increase in 17-hydroxyprogesterone carried a 281 Leu mutation, one patient had an intron-2 (G) mutation, and one had a complete deletion of CYP21. Only two of these patients demonstrated no obvious abnormality of CYP21. In contrast, only one of the control patients demonstrated a CYP21 abnormality, a significant difference (p < 0.001). CONCLUSIONS: These findings suggest that the majority of hyperandrogenic women with an exaggerated 17-hydroxyprogesterone response to corticotropin stimulation are heterozygotes (carriers) for inherited defects of CYP21. Whether these mutations are incidental to the androgen excess or predispose to the development of this disorder remains to be determined.

17-alpha-Hydroxyprogesterone↗
PubMed1995

Chronic hyperinsulinemia and the adrenal androgen response to acute corticotropin-(1-24) stimulation in hyperandrogenic women.

OBJECTIVE: Many women with androgen excess demonstrate elevated circulating insulin levels independent of obesity. In addition, in these women some investigators have demonstrated a negative correlation between the circulating levels of the adrenal androgens, dehydroepiandrosterone or dehydroepiandrosterone sulfate and insulin. The mechanism by which insulin decreases adrenal androgens is unclear. The objective of this study was to determine whether chronic hyperinsulinemia in hyperandrogenic women results in an alteration in the adrenocortical response to corticotropin, resulting in decreased androgen secretion. STUDY DESIGN: We studied seven hyperandrogenic women with severe chronic hyperinsulinemia and eight hyperandrogenic normoinsulinemic patients. Nine healthy women served as controls for the basal hormonal levels and the response to a 3-hour, 100 gm oral glucose tolerance test. In all subjects insulin and glucose were measured hourly during the oral glucose tolerance test and the baseline sample was assayed for total testosterone, dehydroepiandrosterone sulfate, dehydroepiandrosterone, androstenedione, sex hormone-binding globulin, and free testosterone. In hyperandrogenic women cortisol, dehydroepiandrosterone, and androstenedione were also measured, before and 60 minutes, after acute intravenous administration of 0.25 mg corticotropin (1-24). RESULTS: There was no difference in the response of cortisol, dehydroepiandrosterone, or androstenedione to corticotropin-(1-24) stimulation between normoinsulinemic and hyperinsulinemic hyperandrogenic patients. As defined, the hyperinsulinemic patients had higher basal and peak insulin levels and areas under the insulin response curve compared with the normoinsulinemic patients or controls. Total testosterone and dehydroepiandrosterone did not differ among study groups. As expected, hyperandrogenic patients demonstrated lower sex hormone-binding globulin activity and higher free testosterone, androstenedione, and dehydroepiandrosterone sulfate basal levels compared with controls. CONCLUSIONS: The results of this study do not support the hypothesis that chronic hyperinsulinemia in hyperandrogenic patients significantly inhibits the andrenocortical secretion of dehydroepiandrosterone or androstenedione in response to corticotropin stimulation or the basal circulating adrenal androgen levels. Additional studies, including a greater number of patients, may be needed to fully establish these conclusions.

Adrenal Cortex↗
PubMed1995

Leuprolide and estrogen versus oral contraceptive pills for the treatment of hirsutism: a prospective randomized study.

The administration of long-acting GnRH analogs (GnRH-a) results in gonadotropin and androgen suppression in hyperandrogenic women. Nonetheless, no randomized studies are available comparing GnRH-a with currently used treatments for hirsutism. We have hypothesized that the greater degrees of androgen suppression achieved with GnRH-a therapy could result in a more rapid improvement in hirsutism compared to oral contraceptive (OCP) administration. To test this hypothesis, we studied 17 hirsute women before and during 6 months of randomized treatment with 1) leuprolide depot (3.75 mg/month) plus conjugated estrogen (0.625 mg/day) and medroxyprogesterone acetate (10 mg; days 1-12; n = 9; leuprolide+ERT), or 2) an OCP containing ethynodiol diacetate (1 mg) and ethinyl estradiol (35 micrograms; n = 8). LH, FSH, estradiol, dehydroepiandrosterone sulfate, androstenedione (A4), sex steroid-binding globulin, and total and free testosterone (T) were measured at weeks 0, 2, 4, 8, 12, and 28. At 0 and 28 weeks of treatment, hirsutism was evaluated subjectively by patient self-evaluation and by the Ferriman-Gallwey score, and objectively by determination of facial hair density, outer hair shaft diameter, and growth rate, determined both photographically and in plucked hairs. In the leuprolide+ERT, but not OCP, groups, there was a significant decrease in the circulating LH and FSH levels. In both groups, T and A4 decreased with treatment, although the decrease in A4 levels did not reach significance in OCP-treated women. The circulating sex steroid-binding globulin level increased in both treatment groups, but the changes in the OCP-treated women was greater. Consequently, although the calculated percent free T decreased significantly in both treatment groups, the decrease was greater in the OCP-treated women. The dehydroepiandrosterone sulfate level did not change with either therapy. A significant percent decrease in the Ferriman-Gallwey score was noted in the leuprolide+ERT, but not OCP, patients, and by self-evaluation, seven (78%) and five (55%) of leuprolide+ERT patients, compared to two (25%) and two (25%) OCP-treated women, noted an improvement in hair growth and texture, respectively. No significant difference in mean facial hair density or outer hair diameter was noted with either therapy. Patients treated with leuprolide+ERT demonstrated a decrease in the actual hair growth rate, using the photographic method, or percent decrease in growth rate, using plucked hair. In conclusion, treatment with leuprolide plus cyclic estrogen/progestin appears to provide a more rapid, and possibly greater, improvement in hirsutism, compared to a standard OCP regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Adrenal androgen excess in women: lack of a role for 17-hydroxylase and 17,20-lyase dysregulation.

Some investigators have suggested that "dysregulation" of cytochrome P450c17 alpha may result in the exaggerated secretion of ovarian androgens in hyperandrogenism. Although the majority of hyperandrogenic (HA) patients demonstrate an ovarian source for their androgens, approximately 50% also display adrenocortical hyperactivity and adrenal androgen excess. To determine whether 17-hydroxylase (17-OH) and/or 17,20-lyase dysregulation is responsible for the adrenocortical abnormalities noted in many HA patients, we studied 92 consecutive women with hirsutism and/or HA oligomenorrhea; 26 healthy eumenorrheic nonhirsute women served as controls. The basal levels of total and free testosterone (T), sex hormone-binding globulin, and dehydroepiandrosterone sulfate were measured, and pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone, and androstenedione were measured 0 and 60 min after the acute iv administration of ACTH-(1-24). Controls and HA patients did not differ in mean age or body mass, but HA women had higher basal T, free T, dehydroepiandrosterone sulfate, androstenedione, and LH/FSH and lower sex hormone-binding globulin levels. The mean estimated basal 17-OH activity was higher among HA patients than in controls. Although 52 HA patients demonstrated solely an exaggerated basal delta 5-17-OH activity estimate, few HA patients had an exaggerated estimate for either basal delta 4-17-OH or ACTH-stimulated 17-OH activity. No HA patient demonstrated an exaggerated 17,20-lyase basal activity, whereas 14 demonstrated an exaggerated delta 4-17,20-lyase ACTH-stimulated activity only. There was no association between these estimates of 17-OH and 17,20-lyase activities and the circulating adrenal androgen levels in HA women. Importantly, none of the patients demonstrated an increase in the basal activities of both 17-OH and 17,20-lyase, and only 4 patients demonstrated an exaggerated ACTH-stimulated activity of both 17-OH and 17,20-lyase. In conclusion, the steroidogenic profile observed in this population of HA women before and after ACTH-(1-24) stimulation is not consistent with dysregulation of cytochrome P450c17 alpha and probably represents a generalized alteration of adrenocortical control or biosynthesis.

Adrenal Glands↗
PubMed1995

Advances in the diagnosis and treatment of the hirsute patient.

Most patients with hirsutism demonstrate hyperandrogenemia, which may be caused by polycystic ovary syndrome, nonclassic congenital adrenal hyperplasia, insulin resistance and, occasionally, neoplasms. In this review, current methods of diagnosis and recent advances in the medical treatment of hirsutism and hyperandrogenemia are discussed, including the use of gonadotropin-releasing hormone analogs, flutamide, spironolactone, finasteride, and ketoconazole.

Hirsutism↗
PubMed1994

delta 5-Androstene-3 beta,17 beta-diol in healthy eumenorrheic women: relationship to body mass and hormonal profile.

OBJECTIVE: To determine whether delta 5-Androstene-3 beta,17 beta-diol or androstenediol secretion increases with body mass. DESIGN: A prospective study. SETTING: University-based clinical research center. PATIENTS: Twenty healthy, nonhirsute, eumenorrheic women, 10 with a body mass index (BMI) < 31 kg/m2 and 10 with a BMI > 31 kg/m2 were studied. INTERVENTIONS: All patients had blood sampled before (0 minute) and 60 minute after acute administration of 1 mg ACTH-(1-24) i.v. Body circumferences were obtained, and the BMI and waist-hip ratio was calculated. MAIN OUTCOME MEASURES: Total T, androstenedione (A), E2, sex hormone binding globulin, DHEA, DHEAS, and androstenediol were measured at 0 minutes (steroid 0): and DHEA, A and androstenediol were also measured after stimulation (steroid 60). The net steroid increment (delta) from 0 to 60 minute was calculated. RESULTS: Compared with thin women, obese subjects had higher levels of androstenediol 60 (95.8 +/- 20.3 versus 130.7 +/- 40.7 ng/dL, respectively [conversion factor to SI units, 0.03443]) and delta androstenediol (17.4 +/- 8.7 versus 37.8 +/- 29.0 ng/dL, respectively [conversion factor to SI units, 0.03443]). Neither the BMI, height, nor the body circumference measures correlated with any of the steroid levels or responses to adrenal stimulation, except for a weak positive correlation between BMI and estrone (E1) (r = 0.38) and a negative correlation between waist-hip ratio and delta androstenediol (r = -0.51). The basal level of T, E1, and DHEA0, but not A or DHEAS, correlated with androstenediol 0 (r = 0.65, 0.62, and 0.67, respectively) and delta androstenediol (r = 0.66, 0.63, and 0.63 to 0.005, respectively). CONCLUSIONS: Although the unstimulated morning androstenediol level did not differ between obese and thin euandrogenic healthy women, the response of androstenediol to ACTH-(1-24) stimulation was greater in obese individuals. The present findings, together with our previous data demonstrating an increased adrenal secretion of the E1 precursor A in response to ACTH in obese women, suggests that the adrenal cortex in overweight women may further enhance the estrogenic milieu of these women.

Adrenal Glands↗
PubMed1994

Regulation of extragonadal insulin-like growth factor-binding protein-3 by testosterone in oophorectomized women.

Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is the principal carrier protein of IGF-I in the circulation. IGF-I has been postulated to play a role in the genesis and maintenance of the polycystic ovary syndrome. Regardless of the exact mechanism of action of IGF-I on ovarian steroidogenesis, alterations in the level of IGFBP-3 may play a significant role in regulating the concentration of IGF-I in hyperandrogenism. We have postulated that androgens reduce the circulating IGFBP-3 concentration through a mechanism similar to its suppression of the hepatic production of sex hormone-binding globulin (SHBG), thereby increasing bioavailable IGF-I and amplifying its impact on ovarian steroidogenesis. To test this hypothesis, we studied seven oophorectomized women (aged 39-51 yr; body mass, 20.9-35.8 kg/m2) during 3 weeks of testosterone (T) propionate administration (20 mg, three times weekly). All subjects were receiving 0.625 or 1.25 mg conjugated estrogens/day. Blood was sampled before (week 0), during (weeks 1-3), and after (week 4) T administration. Serum was assayed for total T, GH, and SHBG, and plasma was assessed for IGF-I, insulin (INS), and IGFBP-3. IGFBP-3 was measured by both RIA and Western ligand blotting; (expressed as a percentage of the control value). Circulating T increased from 1.51 +/- 1.06 to 30.8 +/- 13.8 mmol/L by week 2 (P < 0.001). During T administration, IGF-I increased (from 55 +/- 23 ng/mL at week 0 to 124 +/- 37 ng/mL at week 4; P < 0.05); INS did not change, with the exception of a higher fasting level 1 week after discontinuing therapy, and GH decreased (from 1.7 +/- 2.3 micrograms/L at week 0 to 0.4 +/- 0.4 microgram/L at week 4; P < 0.03), as did the circulating SHBG concentration (397 +/- 205 to 273 +/- 93 nmol/L by week 2; P < 0.01). IGFBP-3 levels determined by Western ligand blot were higher during the second and third weeks of T administration (265 +/- 28% and 218 +/- 43% of control values, respectively; P < 0.05) compared to that at week 0 (165 +/- 44% of control values). However, there was no difference in the circulating concentration of IGFBP-3, determined by RIA, at weeks 0, 1, 3, and 4 (3.59 +/- 0.35, 4.00 +/- 0.79, 3.48 +/- 0.56, and 3.65 +/- 0.52 microgram/mL, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

The hyperandrogenic-insulin-resistant acanthosis nigricans syndrome: therapeutic response.

The hyperandrogenic-insulin-resistant acanthosis nigricans syndrome affects between 2% and 5% of hirsute women and is characterized by INS resistance, elevated INS levels, acanthosis nigricans, and androgen excess. These patients' response to therapy is unclear, although long-acting GnRH-a suppression has been proposed. The objective of this study was to determine the success of OC in suppressing the hyperandrogenemia of five patients with the hyperandrogenic-insulin-resistant acanthosis nigricans syndrome and the subsequent response to GnRH-a suppression of those women failing initial therapy. After 6 months of OC and SPA therapy, four patients experienced adequate suppression of free T, an increase in SHBG levels, and a subjective improvement in hair growth rate. Two also reported an improvement in hair texture. The total and free T levels in the fifth patient did not suppress after 8 months of OC therapy. Nevertheless, in this patient the administration of a GnRH-a along with hormonal replacement and SPA adequately suppressed free and total T, increased SHBG, and dramatically decreased the shaving interval. In conclusion, although GnRH-a suppression and hormonal replacement can be helpful in patients not responding to standard therapy, the majority of patients with the hyperandrogenic-insulin-resistant acanthosis nigricans syndrome will respond favorably to OC treatment. It is also clear that although hyperinsulinemia augments LH-stimulated androgen biosynthesis in vivo, it does not appear to be able to initiate or maintain androgen production in the absence of adequate gonadotropin stimulation.

Acanthosis Nigricans↗
PubMed1993

3 beta-hydroxysteroid dehydrogenase deficiency in hyperandrogenism.

OBJECTIVE: Deficient adrenocortical 3 beta-hydroxysteroid dehydrogenase activity has been reported in 5% to 30% of hyperandrogenic women. Our objective was to determine the incidence and degree of 3 beta-hydroxysteroid dehydrogenase deficiencies in hyperandrogenism. STUDY DESIGN: A prospective study of adrenal function in patients with hyperandrogenism was performed in a tertiary care university medical center. Eighty-six consecutive patients with hirsutism or hyperandrogenic oligomenorrhea were studied; 26 healthy eumenorrheic women served as controls. All subjects underwent serum sampling at rest and a 1-hour adrenal stimulation test with 1 mg of intravenously corticotropin-(1-24). Dehydroepiandrosterone sulfate, androstenedione, sex hormone-binding globulin, total and free testosterone, and luteinizing and follicle-stimulating hormones were measured in basal serum; dehydroepiandrosterone, 17-hydroxyprogesterone, and 17-hydroxypregnenolone were measured in basal and corticotropin-stimulated serum. On the basis of experience with genetically defined 21-hydroxylase late-onset adrenal hyperplasia, patients were presumed to suffer from 3 beta-hydroxysteroid-deficient late-onset adrenal hyperplasia if they demonstrated a dehydroepiandrosterone or 17-hydroxypregnenolone response to corticotropin-(1-24) stimulation (absolute poststimulation level or net increment) greater than threefold the upper 95th percentile of controls. RESULTS: Three women of two families (2.3%) had a 17-hydroxyprogesterone response consistent with 21-hydroxylase-deficient late-onset adrenal hyperplasia and were excluded from further study. Eighteen (21%) of the remaining patients had a 17-hydroxypregnenolone poststimulation increment above the upper 95th percentile of controls (13.9 nmol/L), and two had an elevated dehydroepiandrosterone increment (> 19.5 nmol/L). However, no patient exceeded threefold the upper control limit for either steroid response. Patients with an exaggerated dehydroepiandrosterone or 17-hydroxypregnenolone increment had higher circulating dehydroepiandrosterone sulfate levels but similar basal total and free testosterone, sex hormone-binding globulin, luteinizing and follicle-stimulating hormone concentrations, basal or stimulated androstenedione, dehydroepiandrosterone/androstenedione, and 17-hydroxypregnenolone/17-hydroxyprogesterone than their less responsive counterparts. CONCLUSIONS: Although an exaggerated response of 17-hydroxypregnenolone to adrenal stimulation is common in hyperandrogenism, a response severe enough to merit consideration as 3 beta-hydroxysteroid dehydrogenase-deficient late-onset adrenal hyperplasia was not encountered in this unselected patient population, suggestive of the rarity of this disorder.

17-alpha-Hydroxypregnenolone↗
PubMed1993

Laparoscopic surgery for ectopic pregnancies: technology assessment and public health implications.

OBJECTIVES: To review the process by which technology is assessed in the United States and to use the principles elicited to compare laparotomy versus laparoscopy for the treatment of ectopic pregnancies (EPs). PARTICIPANTS: Patients with an EP documented in 1987 in the United States. METHODS: Determining and reviewing the applicability, safety, efficacy, cost-effectiveness, cost-benefit, and availability of laparoscopic surgery for an EP. RESULTS: Laparoscopic surgery is applicable to at least 80% of patients, representing some 70,400 women in 1987. Safety and efficacy of laparoscopy are comparable with laparotomy, with the exception of a possible increase in the frequency of persistent EPs, if a conservative procedure is performed endoscopically. Dollar for dollar laparoscopy is more cost-effective than laparotomy for the treatment of EPs, with reduced hospitalization and recovery time, and improved cosmesis. Cost-benefit analysis indicates a savings of $105,600,000.00 in direct hospitalization costs and $65,000,000.00 in increased employer or patient income, because of a more rapid return to work time. Furthermore, savings in decreased home care requirements could not be calculated. The use of laparoscopic surgery in all potential candidates with an EP in 1987 would have resulted in an increased expenditure of $28,160,000.00 annually for additional equipment and $3,520,000.00 for the repeat laparotomies required to treat the excess number of persistent EPs. The expense of training physicians and operating room staffs in this technique could not be quantified. Overall, availability of this procedure was felt to be considerably less than 30% of affected patients. CONCLUSIONS: Overall, the use of laparoscopic surgery in all eligible (> or = 80%) patients with an EP in 1987 in the United States would have resulted in a savings of approximately $138,920,000.00 for that year alone. Currently, there is a tremendous deficiency in the availability of this cost-effective procedure, contributing to the escalating costs of medical care.

Cost-Benefit Analysis↗
PubMed1993

Microsurgery alone or with INTERCEED Absorbable Adhesion Barrier for pelvic sidewall adhesion re-formation. The INTERCEED (TC7) Adhesion Barrier Study Group II.

Adhesion re-formation after a reproductive operation, particularly involving the pelvic sidewall, is a prominent cause of failure in the surgical treatment of infertility. This study was done to evaluate the impact of standard microsurgery through laparotomy and the additional benefit of an oxidized regenerated cellulose adhesion barrier (INTERCEED [TC7] Absorbable Adhesion Barrier [Ethicon Inc.]), in reducing pelvic sidewall adhesion re-formation. One hundred and thirty-four patients with bilateral pelvic sidewall adhesions undergoing adhesiolysis by standard microsurgical techniques through laparotomy were treated during a prospective randomized trial involving 13 centers. After adhesiolysis, the deperitonealized surface of one pelvic sidewall was randomly assigned to be covered with INTERCEED Barrier, the contralateral sidewall serving as control. A second-look laparoscopy was performed ten days to 14 weeks postoperatively. Microsurgical adhesiolysis alone resulted in 24 percent of the sidewalls becoming free of adhesions and a 55.6 percent reduction in the area of adherent peritoneum. With microsurgery alone, 60 and 39 percent of adhesions initially characterized as filmy or severe, respectively, were not seen at second-look laparoscopy. The use of INTERCEED Barrier increased the incidence of adhesion-free sidewalls twofold. The treatment was also associated with a statistically significant reduction in the area of peritoneum affected by adhesion re-formation, compared with the control wall. Of the adhesions originally graded as severe, 61 percent of those treated with INTERCEED Barrier did not re-form at all. When evaluated on filmy adhesions, the use of the barrier was associated with a 72 percent reduction in adhesion re-formation. A measurable reduction in adhesion re-formation was found, depending on the initial adhesion type, with microsurgery alone. The addition of INTERCEED Barrier further reduced the incidence, extent and severity of postoperative adhesion re-formation. In this study, 90 percent of the patients benefited from the use of INTERCEED Barrier.

Cellulose, Oxidized↗
PubMed1993

Concordance of 21-hydroxylase gene ratio, human leukocyte antigen haplotyping and adrenal testing results in a family with late-onset adrenal hyperplasia.

Late-onset adrenal hyperplasia (LOAH) due to 21-hydroxylase (21-OH) deficiency is one of the most common autosomal recessive disorders. There appear to be two 21-OH genes, CYP21A (a pseudogene) and CYP21B (the functional gene), which lie in close proximity to the human leukocyte antigen (HLA) encoding region on the short arm of chromosome 6. While the CYP21A/CYP21B ratio is normally 1:1, ratio abnormalities are frequent in LOAH, suggesting gene deletion, duplication or conversion. The objective of this study was to determine whether an abnormal CYP21A/CYP21B ratio could predict carriers of LOAH, as determined by endocrine and HLA results. The probands appear to be compound heterozygotes carrying a 21-OH gene for LOAH and a deletion of the homologous gene. However, concordance between an abnormal 21-OH gene ratio and the inheritance of the LOAH gene does not appear to be complete, as demonstrated by this family study. Further studies of the feasibility of screening carriers for 21-OH deficiencies with the CYP21A/CYP21B ratio or other molecular probes must be performed.

Adolescent↗
PubMed1992

Pro-453 to Ser mutation in CYP21 is associated with nonclassic steroid 21-hydroxylase deficiency.

Steroid 21-hydroxylase deficiency is the leading cause of impaired cortisol synthesis in congenital adrenal hyperplasia (CAH), with the nonclassic form (NC) comprising approximately 1% of the Caucasian population. The structure of the CYP21 gene was studied in 13 unrelated NC-CAH patients, three affected siblings, and 55 blood donors using polymerase chain reaction. In addition to the Leu-281 and Leu-30 mutations previously associated with NC-CAH, the finding of a Pro-453 to Ser mutation in exon-10 of CYP21 in the NC-CAH patients is reported. Ser-453 was found in 46.2% of unrelated NC-CAH patients, but only 7.7% and 3.6% of salt-wasting CAH patients and blood donors, respectively. In contrast to the Leu-281 and Leu-30 mutations, Ser-453 has not been previously detected in the CYP21 pseudogene (CYP21P) and, therefore, has not likely arisen by gene conversion.

Adrenal Hyperplasia, Congenital↗
PubMed1992

Elevated interleukin-6 levels in peritoneal fluid of patients with pelvic pathology.

OBJECTIVE: To determine if interleukin 6 (IL-6) is a normal constituent of peritoneal fluid (PF), and if various types of pelvic pathology influence its presence within the PF microenvironment. STUDY DESIGN: Peritoneal fluid from 73 women obtained at the time of laparoscopy was examined for the presence of IL-6 using an IL-6 specific sandwich enzyme-linked immunosorbent assay. Thirty-nine patients had pelvic endometriosis, 17 had nonendometriotic pelvic adhesive disease, and 17 subjects undergoing tubal sterilization without evidence of pelvic pathology served as controls. RESULTS: Immunoreactive IL-6 was observed in the PF of all 73 subjects (range 0.26 to 11.16 ng/mL). The mean concentration of IL-6 was higher in women with nonendometriotic pelvic adhesions as compared with control subjects (1.28 +/- 0.16 versus 0.80 +/- 0.06 ng/mL, P less than 0.03). There was no difference in the mean peritoneal concentrations of IL-6 between women with endometriosis (1.16 +/- 0.28 ng/mL) and controls, P = 0.38. Twenty-seven of 73 patients (37%) demonstrated elevated levels (greater than 1.0 ng/mL) of IL-6. Patients with pelvic adhesions were significantly more likely to have elevated concentrations of IL-6 than controls (10/17 [59%] versus 3/17 [18%], P less than 0.02). Alternatively, the percentage of patients with elevated IL-6 concentrations did not differ between patients with endometriosis or controls (14/39 [36%] versus 3/17 [18%], P greater than 0.10). CONCLUSIONS: These findings demonstrate that IL-6 is a normal constituent of PF and that elevated levels are found in many patients with pelvic adhesions.

Adult↗