How well do questionnaires perform compared with physical examination in detecting flexural eczema? Findings from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two.

BACKGROUND: Questionnaires are widely used in epidemiological studies to measure eczema symptom prevalence, but there are concerns regarding their accuracy if used as a diagnostic tool. OBJECTIVES: To compare the performance of a validated eczema symptom questionnaire and a standardized skin examination protocol employed in the second phase of the International Study of Asthma and Allergies in Childhood (ISAAC). METHODS: A total of 30,358 schoolchildren aged 8-12 years from 18 countries were examined for flexural eczema. Parents also completed an eczema symptom questionnaire. We compared prevalence estimates at the population level based on the questionnaire vs. physical examination. We also compared the skin examination and the ISAAC questionnaire in making a diagnosis of flexural eczema. RESULTS: The point prevalences for flexural eczema at centre level based on a single examination were lower than the questionnaire-based 12-month period prevalences (mean centre prevalence 3.9% vs. 9.4%). Correlation between prevalences of both outcome measures was high (r = 0.77, P < 0.001). At the individual level, questionnaire-derived symptoms of 'persistent flexural eczema in the past 12 months' missed < 10% of cases of flexural eczema detected on physical examination. However, between 33% and 100% of questionnaire-based symptoms of 'persistent flexural eczema in the past 12 months' were not confirmed on examination. CONCLUSIONS: ISAAC questionnaire-derived symptom prevalences are sufficiently precise for comparisons between populations. Where diagnostic precision at the individual level is important, questionnaires should be validated and potentially modified in those populations beforehand, or a standardized skin examination protocol should be used.

Sexual precocity in a female infant due to feminizing adrenal carcinoma.

A 21-month-old female with virilizing and then feminizing sexual precocity due to an adrenal adenocarcinoma treated surgically at 21 months of age is reported. Urinary neutral 17-ketosteroids were 116 and 106 mg/24 h and correlated with high plasma levels (1408 microgram/dl) of dehyroepiandrosterone sulfate. Plasma estradiol (17 ng/dl) and urinary estradiol levels (6.3 and 7.1 mu/24 h) were elevated to adult levels and associated with breast development, clitoral enlargement, and an estrogenized vagina. Plasma cortisol was normal. The patient remains healthy over 10 yr later, although capsular invasion was present.

Plasma steroid concentrations in maternal and umbilical circulation after spontaneous onset of labor.

Blood samples were obtained from the maternal peripheral vein (n = 17) during the second stage of spontaneous labor and from the umbilical artery (UA) and vein (UVn) immediately after delivery. Four delta 4-and five delta 5-steroids as well as estradiol were measured by RIA. Additionally, cortisol was determined in maternal plasma. The maternal concentrations were compared with our control values obtained from samples (n = 30) collected at term but not in labor. All delta 5-steroids and F were significantly higher during labor than before labor. In the umbilical circulation, progesterone and 17-hydroxyprogesterone were significantly higher in the UVn than in UA (P < 0.05). Whereas androstenedione was significantly higher in the UA [1.01 +/- 0.12 ng/ml (mean +/- SEM)] than in the UVn (0.72 +/- 0.07 ng/ml), testosterone was almost identical in the two (UA, 0.33 +/- 0.03 ng/ml; UVn, 0.35 +/- 0.08 ng/ml). Four of the five delta 5-steroids (dehydroepiandrosterone, dehydroepiandrosterone sulfate, pregnenolone sulfate, and 17-hydroxypregnenolone) had significantly higher concentrations in the UA than in the UVn (P < 0.05). However, pregnenolone levels were not significantly different (UVn, 21.8 +/- 2.0 ng/ml; UA, 18.0 +/- 2.0 ng/ml). No significant correlations were observed between maternal and umbilical steroid concentrations.

Propranolol metabolism in normal subjects: association with sex steroid hormones.

The objective of this study was to determine the potential role of circulating testosterone and estradiol in regulation of the activity of the sex-dependent pathways of propranolol metabolism (i.e., alpha-naphthoxylactic acid and propranolol glucuronide). The pharmacokinetics of a single 80 mg oral dose of propranolol and the plasma levels of the sex steroid hormones were therefore determined in normal volunteers. In 33 young men there was a positive correlation between the testosterone levels and the propranolol clearances through both alpha-naphthoxylactic acid (p < 0.001) and propranolol glucuronide (p < 0.002), as well as the total clearance (p < 0.05), but not through aromatic ring hydroxylation. Testosterone cypionate administration led to an increased clearance of propranolol through alpha-naphthoxylactic acid in nine of the 11 men studied, further supporting a stimulatory effect of testosterone on propranolol metabolism. In 23 young women there was no significant association between the circulating levels of either estradiol or testosterone and any of the clearances of propranolol. These observations may be clinically relevant for propranolol therapy and may provide improved insight into the influence of gender and circulating gonadal hormones on drug metabolism in humans.

Diagnostic role of Mantoux test site biopsy in neurosarcoidosis.

We discuss a patient with sarcoidosis presenting with cranial neuropathy and a cerebral mass lesion evident on imaging. Also, we review from the literature six patients with sarcoidosis presenting with cerebral mass lesion. We emphasize the diagnostic role of Mantoux test site biopsy in patients with dominant or isolated neurologic presentation because the involved sites are not easily accessible and Kveim's test antigen is not commercially available.

Sex steroid hormones are altered in essential hypertension.

Little is known about the relationship between blood pressure and endogenous sex steroid hormones in patients with essential hypertension. Studies in hypertensive men have described decreased androgens. Men with cardiovascular disease may have estrogen levels which are increased or similar to healthy controls. We measured selected sex steroid hormones in 24 medication-free patients with uncomplicated essential hypertension (diastolic blood pressure less than or equal to 90 mmHg) and 24 normotensive subjects. The groups were equally divided by race, gender, age and weight. Hypertensive men had lower levels of both free and total testosterone and androstenedione than controls. The converse was true for hypertensive women. Androgen levels were similar in blacks and whites regardless of gender or blood pressure. Estradiol levels were higher in hypertensive men and women than controls and in blacks than whites. Levels of luteinizing hormone and sex hormone binding globulin were similar in all subjects. The clinical and pathophysiological significance of our findings merits further investigation.

Effect of hemodialysis on serum progesterone level in pregnant women.

The objective of this study is to evaluate the effect of chronic hemodialysis on serum progesterone level in pregnancy. Serum progesterone levels were measured predialysis and postdialysis using the radioimmunoassay technique in seven gravid women with renal failure requiring hemodialysis. Uterine contractions were measured before and after hemodialysis using home uterine activity monitoring (HUAM) in two patients. Thirty-three paired serum samples were obtained between 14 and 39 weeks' gestation. The mean change in serum progesterone level postdialysis throughout pregnancy ranged from -52.0% to +8.7% for each individual patient. The change in serum progesterone level was unrelated to gestational age. The woman experiencing the most significant decrease in serum progesterone level with dialysis continued her pregnancy to greater than 39 weeks. No significant increase in uterine contraction frequency was noted on HUAM postdialysis (P = 0.22), although both monitored patients experienced a small increase in serum progesterone levels. In conclusion, serum progesterone values showed a variable patient-specific response when measured predialysis and postdialysis in pregnancies complicated by renal failure. There was no significant increase in uterine activity noted postdialysis. Progesterone withdrawal does not appear to explain the increased frequency of preterm delivery in women after dialysis.

Vasoactive intestinal polypeptide stimulates nonovarian progesterone secretion in rabbits.

Recent experiments conducted in this laboratory have shown that intravenous infusions of vasoactive intestinal polypeptide (VIP) induced significant increases in plasma progesterone (P) in female rabbits. The purpose of this study was to determine the organ source of this P and to clarify the mechanisms by which it is induced. Intravenous infusions of VIP (37.5, 75, and 150 pmol/kg per min for 60 min) produced acute dose-dependent increases in plasma P in intact estrous rabbits. In ovariectomized (OVX) animals, VIP infusion (75 pmol/kg per min) produced a P increase of the same magnitude. In animals both OVX and adrenalectomized (ADX), this VIP effect was eliminated. The only significant change noted in luteotropic hormone (LH) or follicle stimulating hormone (FSH) was a decrease in FSH immediately following VIP infusion (150 pmol/kg). VIP infusion significantly increased plasma cortisol in intact and OVX animals, but not in OVX/ADX animals. It is concluded that VIP primarily stimulates the adrenal component of P secretion in the rabbit, via mechanisms independent of LH or FSH.

Plasma androgens and sex hormone-binding globulin in the evaluation of hirsute females.

Hirsutism is usually associated with increased testosterone (T) production and metabolic clearance rates. Considerable overlap of plasma T occurs between hirsute and normal groups. Plasma levels of sex hormone-binding globulin (SHBG) and the factor T/SHBG might separate hirsute patients from normal subjects better than plasma T. A group of 39 hirsute females and 22 normal ovulatory control subjects were studied. Plasma T, androstenedione, and dehydroepiandrosterone were measured by radioimmunoassay; apparent free T (AFT) by equilibrium dialysis; and SHGBG by a method based on saturating the binding sites by labeled dihydrotestosterone. Mean levels of androgens and SHBG of the hirsute patients were significantly different from those of the normal subjects (P less than 0.01). Positive linear correlations were observed between T and AFT, T/SHBG and AFT, and T/SHBG and T; a negative correlation was observed between T/SHBG and SHBG, but no correlation was observed between SHBG and T or AFT. Thirty (77%) of the patients had elevated T/SHBG factors and 28 (72%) had suppressed SHBG levels. Only two patients (5%) had hirsutism associated with normal levels of androgens, SHBG, and T/SHBG. We conclude that SHBG and the factor T/SHBG separate the hirsute population better than any of the androgens studied.

Distinction between early and late ovarian hyperstimulation syndrome.

OBJECTIVE: To compare patient and cycle characteristics among three study groups: early ovarian hyperstimulation syndrome (OHSS), late OHSS, and non-OHSS. DESIGN: Prospective observational study. SETTING: University assisted conception service. PATIENT(S): Women undergoing in vitro fertilization, intracytoplasmic sperm injection or gamete intrafallopian transfer treatment at Bristol University In Vitro Fertilization Service between January 1, 1995, and December 31, 1998. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Patient age, prevalence of polycystic ovaries, gonadotropin requirement, peak serum estradiol (E(2)) concentration, number of oocytes retrieved, clinical pregnancy rate, number of gestation sacs, and severity of OHSS. RESULT(S): Women with early OHSS had significantly higher serum E(2) levels and lower gonadotropin requirements than did the other groups. Cycles with either early or late OHSS had significantly more oocytes collected than those without OHSS. Serum E(2) and oocyte numbers did not accurately predict the risk of developing late OHSS. Clinical pregnancies occurred in all cycles with late OHSS, and multiple pregnancies were significantly more frequent in the late OHSS group than in the other groups. Late OHSS was more likely than early OHSS to be severe. CONCLUSION(S): Early OHSS relates to "excessive" preovulatory response to stimulation, whereas late OHSS depends on the occurrence of pregnancy, is likelier to be severe, and is only poorly related to preovulatory events.

Female runners and secondary amenorrhea: correlation with age, parity, mileage, and plasma hormonal and sex-hormone-binding globulin concentrations.

Twenty-three white women, ages 18 to 42, with normal menses prior to running were studied. Miles per week varied from 10 to 70 for a period of 1 to more than 10 years. Of these, 6 were amenorrheic (AM), 14 had regular cycles (REG), and 3 with regular cycles became amenorrheic during the course of this study. The incidence of amenorrhea was higher in those less than 30 years of age (66.6%) than in the older group (9.0%); in those who ran 40 miles/week or less (37.5%) than in those who ran more (26.6%); and in the nulliparous (46.6%) than in the parous runners (25.0%). The age of menarche was significantly higher in the AM (13.8 +/- 0.5 years) than in the REG (12.2 +/- 0.3 years). Blood samples were collected between 12 and 24 hours after the last run for hormonal and sex-hormone-binding globulin (SHBG) measurements. Plasma estradiol (E2), SHBG, and LH were significantly lower in the AM than in the REG group. Furthermore, E2, LH, and prolactin were significantly lower in the AM group than in the control group. These results suggest that the incidence of secondary amenorrhea is higher in younger, nulliparous female runners and may be related to delayed onset of menarche.

Time-related changes in the plasma concentrations of prolactin, gonadotropins, sex hormone-binding globulin, and certain steroid hormones in female runners after a long-distance race.

Running is associated with an increase in plasma concentrations of certain anterior pituitary hormones and adrenal steroids. This study reports such increases after a marathon race. Six trained female runners, 26 to 42 years old, participated in a marathon race. Fasting (resting) blood samples were collected a few weeks before the race (baseline) and immediately (0 hour), 1 hour, and 4 hours after the run. The data were analyzed with the use of two-way analyses of variance (F-test), paired t-test, and Page's test. At 0 hour, compared with baseline, significant increases were observed in the plasma concentrations of testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), cortisol (F), free T index (T/SHBG), and prolactin (PRL). At 1 hour, levels of these steroid hormones and PRL declined, some significantly. At 4 hours, levels of all hormones except DHEA-S returned to baseline. No significant changes were observed in concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG), as evaluated by F-test. Running-associated changes in plasma hormonal concentrations revert to baseline in four hours, although DHEA-S may take a little longer.

Periovulatory human oocytes, cumulus cells, and ovarian leukocytes express type 1 but not type 2 11beta-hydroxysteroid dehydrogenase RNA.

OBJECTIVE: To further elucidate cortisol metabolism in the follicular microenvironment at the time of oocyte retrieval, the presence of 11beta-hydroxysteroid dehydrogenase (HSD) messenger (m)RNA transcripts in oocytes; cumulus cells; granulosa cells; and CD45(+), CD15(+) leukocytes was assessed semiquantitatively. DESIGN: Controlled study using semiquantitative assessment of 11beta-HSD mRNA. SETTING: University IVF center. PATIENT(S): Twenty-six patients undergoing controlled ovarian hyperstimulation for assisted conception. INTERVENTION(S): Metaphase II oocytes; cumulus cells; granulosa cells, and CD45(+), CD15(+) leukocytes from individual follicular fluid aspirates. MAIN OUTCOME MEASURES: Semiquantitative analysis of PCR products after total RNA extraction and complementary DNA synthesis. RESULT(S): Periovulatory human oocytes; cumulus cells; CD45(+), CD15(+) leukocytes; and granulosa cells consistently express type 1 but not type 2 11beta-HSD mRNA. Expression of mRNA is greatest in cumulus cells. Type 1 11beta-HSD mRNA expression varies considerably in all cell types and among individual follicles and patients. CONCLUSION(S): These studies of mRNA expression suggest that the enzymes present both in and around the periovulatory oocyte will favor a high-cortisol environment.

Plasma gonadotropins, prolactin, and steroid hormone concentrations in female runners immediately after a long-distance run.

Six normally menstruating women who regularly run participated in a 10-mile race. Blood samples were collected within 20 minutes after the completion of the race (group 1). Samples were analyzed, and the results were compared with plasma hormonal concentrations in the same runners in samples collected between 12 and 24 hours after a previous practice run (group 2) and with our nonathletic female controls. Plasma concentrations of the following hormones in group 1 were significantly elevated when compared with group 2: dehydroepiandrosterone (DHA), androstenedione (delta 4A), testosterone (T), cortisol (F), luteinizing hormone (LH), and prolactin (PRL). Levels of 17 beta-estradiol (E2), 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHAS), and follicle-stimulating hormone (FSH) were comparable in groups 1 and 2. However, DHAS in group 1 was elevated when compared with controls, as were HDA, delta 4A,T,F,LH, and PRL. In group 1, but not in group 2, a significant correlation (P less than 0.05) was observed between plasma LH and PRL concentrations but not between FSH an PRL. We conclude that the immediate effect of running is reflected in increased levels of the adrenal androgens, F, LH, and PRL. However, concentrations of these hormones revert back to baseline within 12 to 24 hours after the race.

Sex-hormone-binding globulin in clinically hyperandrogenic women: association of plasma concentrations with body weight.

The relationship of sex-hormone-binding globulin (SHBG) with actual body weight (ABW), ideal body weight (IBW), ABW as percentage of the IBW (% IBW), Quetelet index (weight/height2) and plasma concentrations of various androgens and 17 beta-estradiol (E2) were studied in 9 normal and 57 hirsute patients (group 1). In hirsute patients, plasma levels (ng/dl, mean +/- standard error of the mean [SEM]) of testosterone (T; 77 +/- 4), dihydrotestosterone (DHT; 26 +/- 2), androstenedione (delta 4A; 184 +/- 16), and SHBG (0.91 +/- 0.05 micrograms DHT/dl) but not of dehydroepiandrosterone (DHA; 608 +/- 55) and E2 (6.1 +/- 0.1) were significantly different from those in controls. A negative correlation was observed between SHBG and ABW, both in controls (P less than 0.05) and hirsute patients (P less than 0.01). The hirsute patient population was subdivided into two groups: nonobese (group 2; 60 +/- 1 kg; n = 35) and obese (group 3; 96 +/- 2 kg; n = 22). Plasma androgens, T/SHBG (an index of free T) and E2 in groups 2 and 3 (T: 75 +/- 4, 81 +/- 7; DHT: 24 +/- 2, 28 +/- 3; T/SHBG: 85 +/- 7, 105 +/- 11; delta 4A: 203 +/- 13, 155 +/- 16; DHA: 663 +/- 83, 521 +/- 49; E2: 6.1 +/- 1.0, 5.8 +/- 0.9) were similar; yet SHBG in group 3 (0.75 +/- 0.04) was significantly lower than in group 2 (1.0 +/- 0.01). Inverse correlations between SHBG and ABW, % IBW, and ABW/H2 were observed in group 2 but not in group 3. We conclude that a negative relationship exists between SHBG and the body size in nonobese women and that in hirsute patients, obesity leads to a further lowering of SHBG through mechanism(s) probably independent of androgens.

Plasma androgens, 17 beta-estradiol, and sex hormone-binding globulin in patients with hirsutism and/or clitoromegaly.

Plasma androgen, 17 beta-estradiol, and sex hormone-binding globulin (SHBG) levels were measured in 11 normal subjects (group 1), 18 hirsute patients with no clitoromegaly (group 2), 13 hirsute patients with clitoromegaly (group 3), and 8 patients with clitoromegaly but no hirsutism (group 4). Significantly elevated levels of testosterone (T) and dihydrotestosterone (DHT) were found in groups 2 and 3 but not in group 4 when compared with group 1. In contrast, levels of dehydroepiandrosterone (DHEA) in groups 1 and 2 were comparable but significantly lower than those in group 3 and 4; the levels in the latter two groups were not significantly different from each other. In groups 2, 3, and 4, levels of androstenedione (delta 4A) and the factor T/SHBG were significantly elevated whereas SHBG levels were significantly suppressed when compared with those of group 1. The clitoral index correlated (P less than 0.01) with DHEA levels in group 3. It is concluded that clitoromegaly without hirsutism is associated with increased plasma levels of DHEA and delta 4A. In contrast, hirsutism without clitoromegaly is associated with elevated levels of T, DHT, and delta 4A but normal DHEA levels.

Androstenedione increases thromboxane A2 receptors in human erythroleukemia cells.

Previous studies have demonstrated an increased thromboxane A2 (TXA2) receptor expression in human erythroleukemia (HEL) cells and rat aortic smooth muscle (RASM) cells in response to testosterone treatment. HEL cells have served as a model for megakaryocytes, the progenitor cell for platelets. Platelets have previously been shown to convert androstenedione to testosterone. This study investigated the effects of androstenedione on the TXA2 receptor density in HEL and cultured RASM cells. Both cell lines were incubated with vehicle, 150 nM testosterone or 250, 500 or 750nM androstenedione for 48 hours. Co-incubation with testosterone or androstenedione significantly (p<0.05) increased the maximum number of TXA2 binding sites (Bmax) in HEL cells compared to controls. There was no significant change in Kd values. In a separate series of experiments, HEL cells were incubated with the androgen receptor antagonist hydroxyflutamide (2.5mM). Treatment with androstenedione (500nM) significantly (p<0.05) increased the Bmax value by 35% compared to control and hydroxyflutamide completely antagonized this effect of androstenedione. Incubation with hydroxyflutamide alone had no effect on the Bmax values compared to control. RASM cells also showed an increase in Bmax values by 25% and 23% over control (95+/-6.6, 118+/-7.2 and 117+/-5.1 fmoles/mg protein, control, testosterone and androstenedione, n=3). Both cell lines converted androstenedione to testosterone. The results raise the possibility that the adrenal androgen, androstenedione can regulate the expression of TXA2 receptors either on its own or via conversion to testosterone and through an androgen receptor.

The effect of estrogen treatment on plasma concentrations of steroid hormones, gonadotropins, prolactin and sex hormone-binding globulin in post-menopausal women.

Twenty-one post-menopausal women on no other medication were treated with a low dose (0.625 mg/day) of conjugated equine estrogen (CEE) for a mean (+/- SEM) period of 2.6 +/- 0.2 mth (range 1.75-4.75). Blood samples were collected before and at the completion of therapy, and alterations in the levels of prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG) and certain steroid hormones, including the free testosterone (T) index (T/SHBG) were studied. Following treatment, a significant increase in SHBG levels produced a significant decrease in the free T index (P less than 0.005). As expected, no changes were observed in the levels of PRL and steroid hormones other than estrone (E1) and estradiol-17-beta (E2). Our observations indicate that treatment of post-menopausal women with low-dose estrogen lowers the unbound T.

Effect of adrenalectomy on rat epididymidis.

AIM: To investigate the effect of adrenalectomy (ADX) on the epididymidis of Sprague-Dawley rats. METHODS: The histological, biochemical (cholesterol protein, zinc, copper, alkaline and acid phosphatase aryl sulphatase, lactic dehydrogenase and leucine amino peptidase) and hormonal (FSH, LH and testosterone) changes of caput and cauda epididymis in ADX rats were observed. RESULTS: Organ wet weight, histological studies and morphometric measurements indicated a cellular degeneration in caput and cauda epididymis of ADX rats. Serum testosterone level was significantly lower in ADX than in sham-operated rats, while the serum FSH and LH were below the detection limit of 1 mIU/mL. The enzymatic activity was higher in ADX than in sham-operated rats. Epididymal zinc level increased whereas copper level decreased in ADX rats compared to the sham-operated. CONCLUSION: Adrenalectomy leads to degeneration of caput and cauda epididymidis epithelial cells as a result of decreased supply of testosterone.

Effect of adrenalectomy and hydrocortisone on ventral prostate of rats.

AIM: To study the effects of adrenalectomy and hydrocortisone on the ventral prostate of SD rats. METHODS: In adrenalectomised (ADX) and ADX + hydrocortisone (1, 2, or 4 mg) treated rats, the prostatic histology and the cholesterol, protein, zinc, and copper levels and the enzymic profile (acid phosphatase, alkaline phosphatase, aryl sulphatase, lactic dehydrogenase, and leucine aminopeptidase) in the prostatic tissue were determined; the serum hormonal profile (testosterone, FSH and LH) was also assayed. RESULTS: Adrenalectomy caused a progressive degeneration in prostatic structure that was not reversed by hydrocortisone treatment. The serum testosterone were significantly lower in ADX than in sham operated rats and lower in ADX + hydrocortisone than in ADX-C rats (P < 0. 01). The serum FSH and LH were below the detection limit of 1 mIU/mL. The enzymatic activity was higher in ADX than in sham operated rats and higher in ADX + hydrocortisone than in ADX-C rats (P < 0.05-0.01). The prostatic zinc levels were significantly higher in sham operated than in ADX, and higher in ADX-C than in ADX + hydrocortisone rats (P < 0.05-0.01). The prostatic copper level was significantly lower in sham operated than in ADX, and lower in ADX-C than in the ADX + hydrocortisone rats (P < 0.01). CONCLUSION: In rats, adrenalectomy leads to pathological and functional changes of the prostate. Hydrocortisone treatment at the doses employed did not reverse these changes.