Biomedical subjects

R Azziz

Publications and source records attributed to R Azziz.

At least 91 records · Page 5Linked to original sources

PubMed1991

Magnetic resonance imaging of the adrenal gland in women with late-onset adrenal hyperplasia.

To determine the presence of structural abnormalities of the adrenal in late-onset adrenal hyperplasia, four consecutive patients were studied by MRI before beginning glucocorticoid replacement therapy. Three women were diagnosed as 21-hydroxylase deficient late-onset adrenal hyperplasia by a 17-OHP level greater than 1,000 ng/dL 30 minutes after acute adrenal stimulation, and one patient was diagnosed as 11-hydroxylase deficient late-onset adrenal hyperplasia when her 11-deoxycortisol level was threefold the upper 95th percentile of normal. Two patients with 21-hydroxylase deficient late-onset adrenal hyperplasia had normal adrenal glands on MRI. Another 21-hydroxylase deficient late-onset adrenal hyperplasia patient was noted to have a 2.5 x 3.3-cm left adrenal nodule, which had been documented some 4 years earlier on CT scan and had not changed in size during that interval. This patient was 40 years of age when the diagnosis of late-onset adrenal hyperplasia was established. The patient with 11-hydroxylase deficient late-onset adrenal hyperplasia demonstrated a diffuse enlargement of the left adrenal gland consistent with hyperplasia, with no focal lesions. In conclusion, although patients with late-onset adrenal hyperplasia may often demonstrate nodular or diffuse adrenocortical hyperplasia on MRI, not all patients with endocrinologically evident disease demonstrate such abnormalities, consistent with a lesser degree of ACTH stimulation compared with women with classical congenital adrenal hyperplasia.

Adrenal Glands↗

PubMed1991

The effects of prolonged hypertestosteronemia on adrenocortical biosynthesis in oophorectomized women.

Adrenal androgen production and adrenocortical biosynthesis are frequently abnormal in women with hyperandrogenism. It is possible that these abnormalities result from hypertestosteronemia of ovarian origin. We prospectively studied the effect of prolonged testosterone (T) administration on adrenocortical biosynthesis and basal hormone levels in seven oophorectomized euandrogenic volunteers, who received 20 mg T in oil (USP), im, three times weekly for 3 weeks. Blood was sampled before T administration (week 0), during therapy (weeks 1, 2, and 3), and 1 week after discontinuation of the medication (week 4). Acute adrenal stimulation using 250 micrograms ACTH-(1-24), iv, was performed on weeks 0, 2, and 3. Circulating T rose from an average of 1.53 nmol/L to 27.9 nmol/L by the end of week 3. Both LH and FSH decreased with T administration, while PRL rose slightly during the initial weeks of T therapy. Little change was observed in the basal levels of 17-hydroxyprogesterone, 11-deoxycortisol, 17-hydroxypregnenolone, estrone, and estradiol. Androstenedione (A) rose concurrent with T administration and normalized after therapy discontinuation. Dehydroepiandrosterone (DHA) decreased significantly with T administration, while DHA sulfate (DHS) increased, leading to an increased DHS/DHA ratio. Total cortisol (F) decreased during T therapy; however, corticosteroid-binding globulin levels also decreased, and the unbound F level remained unchanged. No significant change in adrenocortical response (measured by either the absolute poststimulation level or the net increment in steroid levels) for any steroid was noted after T administration. Although the absolute poststimulation level of A was higher during T administration, this change reflected the increased basal A levels, since the increment in A from 0-60 min was not different. In conclusion, raising endogenous T levels in oophorectomized healthy women 10- to 15-fold for a period of 3 weeks produced a decrease in circulating total F and corticosteroid-binding globulin levels, while maintaining normal levels of unbound F. Although the very high T levels produced in this study resulted in an increased DHS/DHA serum ratio, it remains to be proven that the lesser degree of hypertestosteronemia usually observed in hyperandrogenic patients is sufficient to alter DHS metabolism. With this exception, the adrenocortical biosynthetic abnormalities frequently noted in hyperandrogenism do not appear to result from the elevated circulating T levels.

17-alpha-Hydroxypregnenolone↗

PubMed1991

Abnormalities of 21-hydroxylase gene ratio and adrenal steroidogenesis in hyperandrogenic women with an exaggerated 17-hydroxyprogesterone response to acute adrenal stimulation.

One to 2% of hyperandrogenic women demonstrate a 17-hydroxyprogesterone (17-HP) level greater than 36.3 nmol/L (1200 ng/dL) after acute ACTH-(1-24) adrenal stimulation, consistent with 21-hydroxylase (21-OH) deficient late-onset adrenal hyperplasia (LOAH). The following study was undertaken to endocrinologically and genetically define hyperandrogenic patients with an exaggerated 17-HP response to ACTH stimulation, and which do not represent LOAH. Of 265 consecutive patients suffering from hirsutism and/or hyperandrogenic oligomenorrhea, 23 (8.7%) demonstrated a 17-HP level 30 min post stimulation greater than 9.6 nmol/L or 316 ng/dL (the upper 95th percentile in 41 eumenorrheic nonhirsute healthy control women). Seven patients or five separate families (1.8% of total) demonstrated poststimulation 17-HP levels consistent with LOAH. Of the remaining 16 patients, the net increment in 17-HP (delta 17-HP0-30) was within normal limits in seven (2.6%) and these women were assumed to have a normal 17-HP adrenocortical response superimposed on an elevated basal level of nonadrenal (e.g. ovarian) origin. In the remaining nine hyperandrogenic patients (3.4%) various abnormalities of adrenal response were noted in all but one patient, consistent with adrenal hyper-responsiveness. One patient demonstrated an 11-deoxycortisol poststimulation level greater than 3-fold the upper 95th percentile of normal, consistent with 11-hydroxylase LOAH and was excluded from further study. Six of these women were available for further genetic characterization, all Caucasian and unrelated. Three were heterozygotes for HLA-B14, three for B40, and one for B35 antigen, HLA-types associated with the inheritance of 21-OH deficiencies. Although, normally there are two 21-OH genes (a pseudogene and a functional gene) present in a 1:1 ratio, we have previously reported a high frequency of 21-OH gene ratio abnormalities in LOAH. All but one of our patients demonstrated an abnormal 21-OH gene ratio. In conclusion, 3.4% of our hyperandrogenic population demonstrated an exaggerated 17-HP increment after ACTH stimulation, not consistent with LOAH or increased extraadrenal 17-HP production. The increased prevalence of HLA alleles known to be linked to inherited defects of 21-OH function and the increased frequency in 21-OH gene ratio abnormalities suggest that a majority of these individuals may be carriers for these genetic disorders. However, the adrenocortical abnormalities noted were more consistent with a generalized hyperreactivity of the adrenal to ACTH stimulation, than a specific enzyme deficiency, implying that carrier status for 21-OH deficiency may be incidental to the hyperandrogenism.

17-alpha-Hydroxyprogesterone↗

PubMed1991

Use of an oxidized, regenerated cellulose absorbable adhesion barrier at laparoscopy.

The use of an oxidized, regenerated cellulose absorbable adhesion barrier has been shown to significantly reduce the incidence, extent and severity of postoperative gynecologic adhesions in a multicenter, randomized, prospective trial. Since an increasing proportion of gynecologic surgery is being performed laparoscopically, a prospective, multicenter, open-label study was initiated to evaluate the feasibility of using the adhesion barrier laparoscopically and to establish techniques for applying the barrier during those procedures. Eighty patients were studied: 42 underwent lysis of adhesions; 35, removal of endometriosis implants; and 14, tuboplasty/fimbrioplasty. An average of two pieces were placed per patient, with an average piece size of 3 x 3 cm and an average time required per piece of 2 minutes, 40 seconds. Seventy-five percent of the cases required less than three pieces each for application. Eighteen percent of the pieces were difficult to place, generally because of problems unfolding the material, excessive size or nonadherence. For similar reasons, replacement was necessary for 27 of 157 pieces placed (17.2%). The barrier can be applied with relative ease during operative laparoscopy. The fabric can be placed through either the suprapubic or umbilical sleeve, depending on the size of the piece of barrier required.

Cellulose, Oxidized↗

PubMed1991

No acute effect of physiological insulin increase on dehydroepiandrosterone sulfate in women with obesity and/or polycystic ovarian disease.

Conflicting information concerning the acute effect of hyperinsulinemia on circulating adrenal androgens, specifically DHEAS, is available. The effect of PCOD or obesity on this response is unclear. We prospectively examined the acute response of circulating DHEAS to the physiological rise in serum insulin after an OGTT in 10 women with PCOD (5 obese and 5 normal weight) and 10 ovulatory euandrogenic women (5 obese and 5 normal-weight). All underwent a standard 75-g 2-hour OGTT. Insulin and DHEAS were measured before and after OGTT. To control for the potential dilutional effects induced by hyperinsulinemia or hyperglycemia on intravascular tonicity, DHEAS levels were correlated to serum protein. As expected, the 2-hour insulin levels were significantly greater than baseline. No significant changes in circulating DHEAS or in the DHEAS to protein ratio was observed in any patient group 2 hours after glucose-induced hyperinsulinemia. The power of this study was greater than 89% for an alpha error of 0.05 and an expected change in DHEAS of 25%. In summary, it appears unlikely that acute increases in insulin within the physiological range are important in the regulation of circulating DHEAS in either PCOD or euandrogenic women, independent of obesity.

Administration, Oral↗

PubMed1991

Effect of obesity on the response to acute adrenocorticotropin stimulation in eumenorrheic women.

OBJECTIVE: Alterations in adrenocortical biosynthesis, as measured by the steroid response to acute adrenocorticotropic hormone (ACTH) stimulation, have frequently been reported in female hyperandrogenism. These patients are also commonly obese, which may account for some of these abnormalities. The object of this study was to test the hypothesis that obesity alters the adrenal response to acute adrenal stimulation. DESIGN: A prospective study of healthy premenopausal women of varying weights. SETTING: University-based clinical research center. PATIENTS: Fifty-seven healthy, eumenorrheic, nonhirsute female volunteers were studied, 30 weighing between 90% and 110% (normal-weight) and 27 weighing greater than 120% (obese) their ideal body weight. INTERVENTIONS: All subjects underwent a 60-minute acute intravenous ACTH-(1-24) stimulation test in the follicular phase (days 3 to 8) of the menstrual cycle. MAIN OUTCOME MEASURES: The basal levels of dehydroepiandrosterone sulfate (DHEAS), total and free testosterone (T), sex hormone-binding globulin (SHBG), estrone, estradiol, prolactin, and the luteinizing and follicle-stimulating hormone ratio were measured. Basal and poststimulation levels of androstenedione (A), dehydroepiandrosterone (DHEA), 17 alpha-hydroxyprogesterone (17 alpha-OHP), 17-hydroxypregnenolone (17-PREG), 11-deoxycortisol (S), and cortisol (F) were also obtained, and the net increments after stimulation were calculated. RESULTS: Normal-weight and obese women did not differ in age, height, or waist-hip ratio. Obese volunteers demonstrated lower circulating SHBG, 17-PREG, and S levels, and S/F ratio, but a higher free T and DHEAS/DHEA levels. No other differences were observed in either basal or adrenal response measures, with the exception of the net increment in A, which was almost twofold higher in obese volunteers (P less than 0.001). CONCLUSIONS: Obesity in eumenorrheic nonhirsute women is associated with lower circulating SHBG activity and higher free T and DHEAS/DHEA levels. No significant difference in adrenocortical response to acute ACTH-(1-24) stimulation was observed between obese and normal-weight women, with the exception of a higher net adrenal output of A. It does not appear that the abnormal adrenal stimulation results frequently observed in hyperandrogenic women are a consequence of their obesity.

Adult↗

PubMed1991

11 beta-hydroxylase deficiency in hyperandrogenism.

OBJECTIVE: to determine the 11-deoxycortisol (S) response and incidence of 11 beta-hydroxylase deficiency in hyperandrogenism. DESIGN: Hyperandrogenic women prospectively and consecutively underwent acute adrenal stimulation studies. SETTING: Tertiary institution. PATIENTS: Two hundred sixty women complaining of hirsutism and/or hyperandrogenic oligomenorrhea were studied, excluding five unrelated families (1.9% of total) suffering from 21-hydroxylase deficient late-onset adrenal hyperplasia. Forty-one healthy premenopausal eumenorrheic women served as controls. MAIN OUTCOME MEASURES: Only two unrelated women (0.8%) had a poststimulation or net increment S level value greater than or equal to threefold the upper 95th percentile of controls and were presumed to suffer from 11 beta-hydroxylase deficient late-onset adrenal hyperplasia. One hundred nine (42%) of hyperandrogenic women had at least one S value above the 95th percentile of controls. These women also demonstrated higher basal (F0) and stimulated cortisol levels, but a similar increment compared with controls. RESULTS: Patients with high S measures had higher testosterone, dehydroepiandrosterone sulfate, and androstenedione levels, but similar luteinizing hormone/follicle-stimulating hormone ratios, than hyperandrogenic cohorts with no abnormal S measures. Basal values of S (S0), F0, or S0/F0 were not useful to predict an abnormal S response to stimulation. CONCLUSIONS: Although adrenocortical hyperactivity was present in 42% of our hyperandrogenic patients, only 0.8% were presumed to suffer from 11 beta-hydroxylase deficient late-onset adrenal hyperplasia. A systemic search for this deficiency in hyperandrogenism is probably unwarranted.

Adrenal Glands↗

PubMed1990

Pseudogene/functional gene ratio in late-onset 21-hydroxylase-deficient adrenal hyperplasia.

Late-onset adrenal hyperplasia caused by 21-hydroxylase deficiency leads to hyperandrogenic symptoms in 1% to 6% of hyperandrogenic women. Normally there are two 21-hydroxylase genes present in a 1:1 ratio. Gene CYP21A is a nonfunctional pseudogene, whereas CYP21B is an active gene. Abnormalities of the CYP21A/CYP21B gene ratio may serve as a marker for late-onset adrenal hyperplasia. Eight hyperandrogenic patients with late-onset adrenal hyperplasia and five control subjects were studied by evaluation of autoradiograms of Taq I and Kpn I digests by means of laser densitometry. Seven of eight (87%) patients with late-onset adrenal hyperplasia had an abnormal CYP21A/CYP21B gene ratio on laser densitometry, suggestive of CYP21A gene duplication, CYP21B gene deletion, or the conversion of a CYP21B gene to a CYP21A gene. One of the five control subjects had a heterozygous deletion of the CYP21A gene. The CYP21A/CYP21B gene ratio may serve as a useful genetic marker for late-onset adrenal hyperplasia in a non-high-risk population.

Adrenal Glands↗

PubMed1990

Late onset adrenal hyperplasia: mutation at codon 282 of the functional 21-hydroxylase gene is not ubiquitous.

Ten patients affected with 21-hydroxylase (21-OH) deficient late-onset adrenal hyperplasia were studied to determine the prevalence of a mutation at codon 281 of the functional 21-OH gene (CYP21B) that results in a valine to leucine amino acid shift. This mutation has been reported in eight unrelated late-onset adrenal hyperplasia patients of Ashkenazi Jewish descent possessing the human leukocyte antigen-B14,DR1 haplotype. Normally, there are two 21-OH genes; a pseudogene (CYP21A) and a functional gene (CYP21B). The aberrant codon 281 sequence is normally present only in CYP21A. In all of our late-onset adrenal hyperplasia patients, hybridization of an oligonucleotide probe specific for this mutation was demonstrated to CYP21A but not to CYP21B. The mutation at codon 281 of CYP21B does not appear to be a ubiquitous genetic marker for 21-OH deficient late-onset adrenal hyperplasia, suggesting that this disorder may demonstrate the same molecular heterogeneity as congenital adrenal hyperplasia.

Adrenal Glands↗

PubMed1990

On the origin of the elevated 17-hydroxyprogesterone levels after adrenal stimulation in hyperandrogenism.

Hyperandrogenic women appear to demonstrate an exaggerated 17-hydroxyprogesterone (17-HP) response to adrenal stimulation which is not due to the marked 21-hydroxylase deficiency of late-onset adrenal hyperplasia (LOAH). Furthermore, in hyperandrogenism the ovary also appears to secrete excessive amounts of 17-HP. It is not clear to what extent the elevated 17-HP levels after ACTH stimulation are due to extraadrenal production of the steroid. This investigation was undertaken to assess the adrenal contribution to the elevated 17-HP levels after ACTH stimulation observed in non-LOAH hyperandrogenism. One hundred and sixty consecutive unselected women with hirsutism and/or hyperandrogenic oligomenorrhea formed the clinical population. Excluded were 4 women with LOAH and all patients with hyperprolactinemia. For the purpose of investigating the relationship between adrenal response and clinical symptoms, hyperandrogenic patients were divided into 3 subgroups: hirsute only (n = 23), hirsute oligomenorrheic (n = 84), and oligomenorrheic only (n = 24). Subclassification for an additional 29 patients (18%) with hyperandrogenemia was not possible, since their symptomatology was not clearly stated in the record. However, these individuals were included in the patient group as a whole. Controls consisted of 21 healthy, regularly menstruating, nonhirsute female volunteers. Both patients and controls underwent acute adrenal stimulation with 1 mg ACTH-(1-24), and serum was obtained before and 30 min after ACTH administration. Hyperandrogenic patients had higher mean basal total testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHS), 17-HP, and LH/FSH levels, but not cortisol (F), compared to normal subjects (P less than 0.02). Oligomenorrheic only women had higher mean A and progesterone (P) levels than other hyperandrogenic patients (P less than 0.02). No correlation was noted between body mass index (BMI) and the levels of DHS, P, or A, while a weak positive association was noted between the BMI and the mean T (r = 0.31; P less than 0.002) and a weak negative correlation between the mean F and BMI (r = -0.21; P less than 0.05). The mean 17-HP level 30 min after ACTH administration (17-HP30) was significantly higher in hyperandrogenic women than in normal subjects whether analyzed in separate subgroups or together and was due to the higher basal 17-HP levels. Basal 17-HP correlated with the circulating levels of T, A, and P, steroids largely of ovarian origin. Alternatively, the net increment in 17-HP from 0-30 min after ACTH (delta 17-HP30) was not significantly higher in hyperandrogenic women than normal subjects and did not correlate with the basal levels of T, A, and P. Neither the basal level of 17-HP nor its response to ACTH correlated with circulating DHS levels.(ABSTRACT TRUNCATED AT 400 WORDS)

17-alpha-Hydroxyprogesterone↗

PubMed1990

Acute adrenocorticotropin-(1-24) (ACTH) adrenal stimulation in eumenorrheic women: reproducibility and effect of ACTH dose, subject weight, and sampling time.

Assessment of adrenal reserve and the diagnosis of adrenal insufficiency by acute adrenocortical stimulation with ACTH-(1-24) has been well established. Alternatively, estimation of adrenocortical enzymatic activities by this method for the detection of inherited or acquired biosynthetic abnormalities has been less well characterized. Some of the discrepancies between studies estimating adrenocortical enzymatic activities in different pathological conditions (e.g. hyperandrogenism) may result from the different stimulation protocols used. The objective of this prospective study was to establish the inherent variability of the adrenal response to acute ACTH-(1-24) stimulation and to determine the effect of sampling time, stimulation dose, and subject weight on the same. Forty-one normal female volunteers were recruited (mean age, 29.1 yr), 30 within 90-110% ideal body weight and 11 weighing more than 120% ideal body weight. Three protocols were designed to study 1) the effects of sampling time, ACTH-(1-24) dose, and subject weight on adrenal response; 2) the effect of time of the day on the variability of basal steroid levels and the adrenal response to stimulation; and 3) the long term reproducibility of the adrenal response to ACTH-(1-24). Androstenedione, 17-hydroxyprogesterone, 11-deoxycortisol, dehydroepiandrosterone, and cortisol were measured in serum under basal and stimulated conditions. All subjects had normal basal levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, and PRL. The acute iv administration of 0.10, 0.25, and 1.0 mg ACTH-(1-24) elicited similar and maximal steroid responses, with all steroid levels reaching a plateau 60-90 min poststimulation regardless of subject weight. Sampling of basal steroid levels every 5 min in the morning (AM; beginning 0700-0900 h) or evening (PM; 1500-1700 h) did not reveal any difference in steroid variability. Only the mean basal cortisol level was higher in AM than PM testing (P less than 0.03). Although the mean levels of dehydroepiandrosterone and 17-hydroxyprogesterone 60 min after stimulation were significantly higher in AM than PM studies, these differences were minimal. Ten volunteers underwent an average of four (range, 2-6) adrenal stimulation studies using 1.0 mg ACTH-(1-24) over a 1-yr period. The long term coefficient of variation (CV) for basal steroid levels ranged from 15-28%. Calculations of net adrenal response (delta steroid O-T and area delta steroid O-T) were less reproducible (CV, 0-82%) than measures of absolute response (steroid T, area steroid T, and %steroid T; CV, 7-32%). This difference in CV between the measures of net and absolute adrenal responses was significant for all steroids except androstenedione.(ABSTRACT TRUNCATED AT 400 WORDS)

17-alpha-Hydroxyprogesterone↗

PubMed1990

Dexamethasone receptor levels in palatal and lung fibroblasts of adult A/J and C57BL/6J mice: relationship to glucocorticoid-induced cleft palate.

Glucocorticoid-induced cleft palate (CP) has been used as an animal model for hormonal teratogenesis. In mice, the susceptibility to glucocorticoid-induced CP varies with the strain, A/J being very sensitive and C57/BL6J relatively resistant. Studies in adult and embryonic murine tissues have attempted to correlate the number of glucocorticoid receptors and CP susceptibility, with conflicting results. The relative quantities of dexamethasone receptors were now studied in established palatal and lung fibroblast cell cultures obtained from adult C57 and A/J mice. A rapidly saturable, stable binding system was demonstrated. Scatchard plots were linear indicating a single class of high affinity receptors. The glucocorticoid receptor number ranged from 6.2 x 10(-16) mole/microgram prot to 8.6 x 10(-16) mole/microgram prot, while the KD varied from 1.0 x 10(-8) M to 2.8 x 10(-8) M. The differences in receptor characteristics between murine strains were not significant (p greater than 0.05). The absence of a difference in receptor number between the two strains may reflect the limitation of fibroblast cell culture in assessing glucocorticoid binding in vivo. Alternatively, if a difference in palatal dexamethasone receptor levels between mice strains exists, it may occur only in the embryo.

Animals↗

PubMed1989

Postoperative recuperation: relation to the extent of endoscopic surgery.

Ninety patients undergoing a total of 92 endoscopic procedures were assessed regarding their subjective recovery times, their delays in returning to their places of employment, the duration of analgesic use, and their inhospital stays. A significant association (P less than 0.05) between recuperation parameters and the extent of the intra-abdominal surgery at laparoscopy was observed. A weak association also was noted between the number of incisions performed, the duration of surgery, and postoperative recuperation. Nonetheless, even the most radical endoscopic procedures required considerably less recuperation time when compared with laparotomies. With the out-of-work period reduced 5- to 6-fold, obese individuals appeared to tolerate these procedures as well as their thin counterparts.

Abdomen↗

PubMed1989

Reproductive endocrinologic alterations in female asymptomatic obesity.

Excess body fat has been clearly associated with an increased risk of oligo-ovulation and endometrial/breast carcinoma. The connection has been assumed to lie within derangements of the metabolic/endocrine compartments, particularly of estrogens and androgens. To differentiate the effect of obesity from its related disease process, an attempt has been made to define the reproductive-endocrinologic alterations encountered in otherwise asymptomatic obese women. Androgen metabolism is accelerated in obesity. It is not clear whether the increased clearance precedes or follows the accelerated production of androgens. A servocontrol mechanism appears to be operative in these asymptomatic individuals, maintaining plasma steroid levels normal. The unbound fraction of T may be somewhat increased in overweight women with predominantly upper body fat deposition. The increased clearance of androgen may arise from an obesity-related depression in SHBG concentration (e.g., for T, E2, delta 5-diol, etc.). Adipose tissue, by virtue of the lipid solubility of most of these steroids, concentrates androgens, estrogens, and progesterone. This steroid sequestration not only contributes to the obesity-related increase in androgen clearance but also leads to an extremely enlarged total body steroid pool. Fat tissue sequestration also increases the concentration of androgens in the vicinity of adipose stromal cells, possibly encouraging their aromatization. Adipose tissue also has a moderate degree of 17-hydroxysteroid dehydrogenase activity, which appears to stimulate the conversion of A to T. Finally, alterations in peripheral and hepatic conjugation and an accelerated urinary excretion may contribute to the elevated clearance of androgens. The accelerated PR of androgens may simply result as compensation for the elevated MCR in obesity. Nonetheless, evidence of alteration(s) in adrenocortical steroidogenesis has been presented suggesting a selective obesity-related enhancement in adrenal androgen secretion. These remain to be confirmed. Nonetheless, adrenocortical abnormalities may arise secondary to the influence of other circulating and intra-adrenal factors, including insulin, prolactin, estrogens, and androgens. It is not known whether the accelerated androgen metabolism or the aberrant adrenal steroidogenesis improve with weight reduction. Excess body fat increases androgen aromatization which, together with an obesity-related decrease in SHBG, is associated with mildly elevated levels of E1 and free E2 in postmenopausal women. Although premenopausal obese individuals have the same tendency, the far greater ovarian estrogen secretion overshadows any differences. The bulk of aromatization activity in fat lies in the stromal comportment. The major substrate for peripheral estrogen production is A. Testosterone also contributes to the estrogen pool via its conversion to E2.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1989

21-Hydroxylase deficiency in female hyperandrogenism: screening and diagnosis.

21-Hydroxylase-deficient late-onset adrenal hyperplasia (LOAH) appears to affect 1-6% of hyperandrogenic women. Screening and diagnostic criteria for LOAH have not been well established, as these patients are clinically indistinguishable from other hyperandrogenic women. The following prospective study was undertaken to 1) determine the predictive value of screening hyperandrogenic women for LOAH with a morning follicular phase basal 17-hydroxyprogesterone (17-HP) level and 2) compare the various in vivo estimates of 21-hydroxylase activity after adrenal stimulation for the diagnosis of LOAH. Twenty-one euandrogenic control women (physically normal, without hirsutism, with regular menses, and a negative family history) were studied. The clinical population consisted of 164 consecutive unselected patients seen at the Division of Reproductive Endocrinology and Infertility of Johns Hopkins University School of Medicine between 1983 and 1987 demonstrating hirsutism and/or hyperandrogenic oligomenorrhea. Controls and patients underwent acute adrenal stimulation with 1 mg ACTH-(1-24), administered in the morning to fasting patients in the follicular phase of their menstrual cycle. Blood was sampled before and 30 min after ACTH-(1-24) administration. Steroid RIA determinations were performed for 17-HP, progesterone, testosterone, dehydroepiandrosterone sulfate, androstenedione, FSH, LH, and PRL. Three estimates of 21-hydroxylase activity were studied: the 17-HP level 30 min post-ACTH (17-HP30), the change in 17-HP (delta 17-HP0-30) and the summed rate of change in 17-HP and progesterone ([delta 17-HP0-30) + delta P0-30]/30 min). The upper 95th percentiles for these estimates of 21-hydroxylase activity in control women were 9.6 nmol/L (316 ng/dL), 8.8 nmol/L (292 ng/dL), and 0.39 nmol/L.min (13 ng/dL.min), respectively. Thirteen of 164 (7.9%) hyperandrogenic women had at least 1 abnormal 21-hydroxylase measurement. Four of these women (2.4%) had 17-HP measurements 3- to 20-fold above the upper normal 95th percentile (17-HP30 greater than 36.3 nmol/L or 1200 ng/dL) and were considered as suffering from LOAH. In our population the 3 measures of 21-hydroxylase studied clearly differentiated the LOAH women from all others, although a single 17-HP level 30 min post-ACTH was the simplest and most cost effective. Nine other hyperandrogenic women (5.5%) had at least 1 abnormal 21-hydroxylase measurement less than 3-fold the upper normal 95th percentile value and were designated as having mild 21-hydroxylase deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

17-alpha-Hydroxyprogesterone↗

PubMed1989

Adenomyosis: current perspectives.

Adenomyosis frequently involves gravid and nongravid uteri, remaining asymptomatic in up to one half of all cases. The symptoms of adenomyosis, particularly menorrhagia and dysmenorrhea, correlated with the depth of myometrial involvement, and consequently with the patient's age. Adenomyosis is most frequent in parous women in their middle to late forties. There is a high frequency of associated pathology, including leiomyomas, endometriosis, endometrial hyperplasia, and carcinoma. This relationship may suggest a common underlying disorder, such as hyperestrogenemia. Adenomyosis is a frequent finding in pregnancy, and obstetric or surgical complications are rare. Approximately 30 to 50 per cent of adenomyotic foci respond to progesterone, particularly to the high serum levels in pregnancy. The preoperative diagnosis of adenomyosis remains poor. Radiologic procedures and serum levels of CA-125 are of limited diagnostic value. Only a high degree of clinical suspicion will aid in the diagnosis of this histopathologic entity. Hysterectomy remains the mainstay of treatment and diagnosis.

Endometriosis↗

PubMed1988

Acute myometritis and chorioamnionitis during cesarean section of asymptomatic women.

Postoperative endomyometritis develops in as many as 85% of women undergoing cesarean section, which is 10- to 30-fold higher than after vaginal delivery. The timing and mechanism by which the infecting organisms gain access to the uterine cavity are unclear. One possibility is that the infection may occur postpartum by ascending colonization of the wound. Alternatively, myometritis may be already present at the time the cesarean section is performed in asymptomatic patients. With tissue necrosis, the stage is then set for puerperal endomyometritis. To study this second alternative mechanism, myometrial and placental biopsy specimens were obtained in 91 asymptomatic patients at the time of cesarean section. Histologic evidence of chorioamnionitis was identified in 10% (9/91) of patients. Acute myometritis was present in 11% (10/91) of the myometrial biopsy specimens. Seven of the nine women (77%) with subclinical acute chorioamnionitis demonstrated extension of the inflammation into the myometrium. Thirty-two percent (8/25) of women in labor and 31% (5/16) of those with rupture of membranes for greater than 6 hours had acute chorioamnionitis or myometritis, which is significantly higher (p less than 0.01) than in women without these risk factors. These findings suggest that approximately one third of asymptomatic women with rupture of the membranes for more than 6 hours or who are in labor at the time of cesarean section demonstrate histologic evidence of subclinical chorioamnionitis. In most of these patients the myometrium is also involved. The uterine incision is then performed through infected myometrium, possibly setting the stage for puerperal endomyometritis.

Acute Disease↗

PubMed1988

The development and use of a standard symphysial-fundal height growth curve in the prediction of small for gestational age neonates.

The symphysial-fundal height (SF) measurement has been routinely used in obstetrics, although its value in the prediction of small-for-gestational-age (SGA) infants remains controversial. A retrospective study was performed in order to assess the sensitivity and specificity of the SF distance and establish guidelines for its use. Local neonatal birthweight distribution and SF growth curves were developed. Eighty-six percent of 28 SGA infants demonstrated one measurement under--1 S.D. of the mean SF growth curve as did 36% of appropriate for gestational age (AGA) neonates. Seventy-five percent of SGA infants subsequently demonstrated a second measurement below--1 S.D. of the mean curve, 90% prior to 36 weeks. Only 16% of AGA exhibited such a SF growth pattern. A protocol for maximizing the use of this inexpensive and easily obtained parameter is proposed.

Adult↗