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Biomedical subjects

N F Taylor

Publications and source records attributed to N F Taylor.

At least 19 recordsLinked to original sources
PubMed2006

Progressive resistance exercise for people with multiple sclerosis.

PURPOSE: This study aimed to determine if participation in a progressive resistance exercise (PRE) programme can: (1) increase the ability to generate maximal muscle force, (2) increase muscle endurance, (3) increase functional activity, and (4) improve overall psychological function of people with multiple sclerosis (MS). METHODS: A pre-post single group research design with a 4-week baseline familiarisation phase was used. Nine people (mean age 45.6 years, SD 10.7) with MS attended a gymnasium three times over 4 weeks for familiarization. Participants then completed a twice-weekly 10-week PRE programme, with two sets of 10 - 12 repetitions of each exercise. Outcome measures of muscle strength (1RM for arms and legs), muscle endurance (repetitions at half 1RM), walking speed, the 2-min walk test (2MWT), a timed stairs test, and the impact of MS on physical and psychological function were taken at weeks 2, 4, and 14. RESULTS: Participants attended 94.3% (SD 8.2%) of the training sessions, with no adverse events. After accounting for baseline stability, significant improvements (P < 0.05) were found in arm strength (14.4%), leg endurance (170.9%), fast walking speed (6.1%), and there was a trend for increased distance in the 2MWT (P = 0.06). The perceived impact of MS on physical function was reduced (P = 0.02). CONCLUSIONS: Adults with MS benefited from a PRE programme by improving muscle performance and physical activities, without adverse events. These findings suggest that PRE may be a feasible and useful fitness alternative for people with mild to moderate disability due to MS.

Adult↗
PubMed2006

A qualitative analysis of a progressive resistance exercise programme for people with multiple sclerosis.

PURPOSE: This qualitative study explored the perceptions of adults with multiple sclerosis about the positive and negative effects of a progressive resistance strengthening programme; and identified factors that might facilitate or create barriers to participation. METHODS: Seven women and two men (mean age 45.6 years, SD 10.7) with multiple sclerosis participated in a 10-week gymnasium based progressive resistance strengthening programme held twice a week. Participants were interviewed at the end of the programme. The recorded interviews were transcribed and then independently coded by three researchers. From these codes, the main themes emerged. RESULTS: Reports about the programme were very positive with physical, psychological and social benefits noted. Most participants said that they had less fatigue as a result of the programme. Few negative outcomes were reported and these were minor such as aches and pains. Key extrinsic factors for programme completion were the leaders' encouragement and knowledge of exercise; and the group aspect of the programme. Key intrinsic factors were enjoyment, determination, seeing the signs of progress, and a previously held positive attitude about the benefits of exercise. CONCLUSIONS: The results of this study suggest that progressive resistance strength training is a feasible fitness option for some people with multiple sclerosis. Factors perceived to be important for programme completion suggest that choosing encouraging leaders with knowledge of exercise, and exercising in a group may contribute to programme success.

Adult↗
PubMed2006

A novel point mutation in P450c17 (CYP17) causing combined 17alpha-hydroxylase/17,20-lyase deficiency.

CONTEXT: Combined 17alpha-hydroxylase/17,20-lyase deficiency is a rare cause of congenital adrenal hyperplasia and hypogonadism. Novel single amino acid changes in P450c17 provide potentially important insights into key structural domains for enzyme function. OBJECTIVE, DESIGN, AND SETTING: We report a novel missense mutation in P450c17 in a 17-yr-old female presenting with a malignant mixed germ cell tumor with yolk sac elements who demonstrated clinical and biochemical features of combined 17alpha-hydroxylase/17,20-lyase deficiency. METHODS: Quantitative urinary steroid analysis was performed by high resolution gas chromatography. All eight coding exons of CYP17 were PCR amplified and sequenced. The position of arginine at codon 96 was modeled using the CYP17 structure 2c17 (www.rcsb.org). The CYP17 genes were subcloned into pcDNA3, expressed in HEK-293 cells, and chromatographed. PATIENT AND RESULTS: 17alpha-Hydroxylase deficiency was confirmed by marked reductions in urinary and serum cortisol, androgens, and estradiol. Mutational analysis revealed a novel homozygous R96Q missense mutation in P450c17, affecting an amino acid in a key substrate-binding region of the enzyme, leading to complete inactivity. CONCLUSION: The description of a second missense mutation at codon 96 (R96W and R96Q) in the substrate-binding region of P450c17 provides strong evidence for the key role of this amino acid in 17alpha-hydroxylase/17,20-lyase function. An association between a malignant germ cell tumor and 17alpha-hydroxylase deficiency has not been reported previously, although the presence of gonadoblastoma in the ovary of a patient with this condition has recently been described.

Adolescent↗
PubMed2006

Investigation into possible causes of interference in serum testosterone measurement in women.

BACKGROUND: Direct (non-extracted) testosterone immunoassays may give spuriously high results in women. The presumed interferents may be removed if testosterone is extracted into an organic phase before being measured. We aimed to clarify possible causes and effects of interference in testosterone measurement in women. METHODS: Women who had a blood sample referred to Hope Hospital Clinical Biochemistry laboratory for measurement of serum testosterone concentration over a six-month period were studied. Clinical and treatment data were recorded. A difference (direct-minus-extracted testosterone) of less than 1.0 nmol/L was used to define a group with low interference. A difference of 2.5 nmol/L or more was used to define a group with significant interference. RESULTS: The distribution of interference in 1271 serum samples from female patients was unimodal. There were no group differences in clinical presentation or treatment. The median degree of interference was 1.4 nmol/L. In 42 female patients with varying degrees of interference, identified on routine assay, regression analysis showed strong association between dehydroepiandrosterone sulphate (DHEA-S) and interference (direct-minus-extracted testosterone) (r = 0.77, P < 0.001). CONCLUSIONS: Given that DHEA-S is present in very variable amounts in blood, it is possible that even with a low cross reactivity, DHEA-S or one of its metabolites significantly interferes in the testosterone assay when at higher concentrations.

Adult↗
PubMed2005

A randomised clinical trial of activity-focussed physiotherapy on patients with distal radius fractures.

INTRODUCTION: Physiotherapy is considered by some authorities to be an important aspect of management in patients following distal radius fractures. There is evidence of improvement in impairment with physiotherapy; however, there is no evidence to support early return of functional activity. Traditional physiotherapy management has focussed on improving impairment; however, there are no trials with emphasis on skill acquisition via motor re-learning principles. MATERIALS AND METHODS: Forty-one participants with conservatively managed distal radius fractures were studied in a randomised, single-blinded, prospective trial. Two treatment options were compared: exercise and advice versus activity-focussed physiotherapy with measurement periods of 6 weeks after removal of cast and follow-up at 24 weeks. RESULTS: Participants allocated to the exercise and advice group consulted a physiotherapist an average of 0.9 (SD 0.4) times, while the participants allocated to the more intensive activity-focussed group consulted with physiotherapy a mean of 4.4 (SD 2.3) times. At both 6 and 24 weeks there were no significant differences between the groups for change in impairment (as measured by grip strength, range of motion of wrist flexion and extension and pain intensity), activity limitation and participation restriction, as measured by the Patient-Rated Wrist Evaluation (PRWE). Exercise and advice given by a physiotherapist were equally as effective as activity-focussed physiotherapy in recovery both at 6 and 24 weeks. CONCLUSION: The results suggest that after removal of cast from fracture of distal radius, patients may routinely require no more than a single session of advice and exercise provided by a physiotherapist.

Activities of Daily Living↗
PubMed2005

Diurnal patterns of salivary cortisol and cortisone output in chronic fatigue syndrome.

BACKGROUND: The aim of the present study was to obtain a naturalistic measure of diurnal hypothalamic-pituitary-adrenal (HPA) axis output in CFS patients unaffected by medication or comorbid psychiatric disorder likely to influence the axis. METHOD: Cortisol and cortisone levels were measured in saliva samples collected from 0600 h to 2100 h at 3-h intervals in CFS patients and healthy controls. RESULTS: Mean cortisol and cortisone concentrations were significantly lower in patients than controls across the whole day, as were levels at each individual time point except 2100 h. Cosinor analysis showed a significant diurnal rhythm of cortisol and cortisone that was not phase-shifted in CFS compared to controls. However, there was a lower rhythm-adjusted mean and a lower amplitude in CFS patients. The cortisol/cortisone ratio showed no diurnal rhythm and did not differ between CFS subjects and controls. LIMITATIONS: The sample size was relatively small, and drawn from specialist referral patients who had been ill for some time; generalisation of these results to other populations is therefore unwarranted. CONCLUSION: The main findings of this study are to provide further evidence for reduced basal HPA axis function in at least some patients with CFS and to show for the first time that salivary cortisone is also reduced in CFS and has a diurnal rhythm similar to that of cortisol. We have also demonstrated that the cortisol/cortisone ratio remains unchanged in CFS, suggesting that increased conversion of cortisol to cortisone cannot account for the observed lowering of salivary cortisol.

Adult↗
PubMed2004

Molecular basis for the apparent mineralocorticoid excess syndrome in the Oman population.

11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays a crucial role in converting hormonally active cortisol to inactive cortisone, thereby conferring specificity upon the mineralocorticoid receptor (MR). Mutations in the gene encoding 11beta-HSD2 (HSD11B2) account for an inherited form of hypertension, the syndrome of "Apparent Mineralocorticoid Excess" (AME) where cortisol induces hypertension and hypokalaemia. We report five different mutations in the HSD11B2 gene in four families from Oman with a total of 9 affected children suffering from AME. Sequence data demonstrate the previously described L114Delta6nt mutation in exon 2 and new mutations in exon 3 (A221V), exon 5 (V322ins9nt) and for the first time in exon 1 (R74G and P75Delta1nt) of the HSD11B2 gene. These additional mutations provide further insight into AME and the function of the 11beta-HSD2 enzyme. The prevalence of monogenic forms of hypertension such as AME remains uncertain. However, our data suggests AME may be a relevant cause of hypertension in certain ethnic groups, such as the Oman population.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2004

Effect of physiotherapy attendance on outcome after anterior cruciate ligament reconstruction: a pilot study.

BACKGROUND: In many centres patients are routinely referred for physiotherapy after anterior cruciate ligament (ACL) reconstruction. However, to date the role and amount of supervised physiotherapy required has not been clearly established. OBJECTIVE: To establish whether there was any difference in outcome between a group of patients who attended physiotherapy regularly after ACL reconstruction and a group who attended only infrequently. METHODS: Ten patients who had attended physiotherapy infrequently (mean 1.9 visits) during the first six months after ACL reconstructive surgery were matched for age, sex, graft type, and activity level and occupation before injury with 10 patients who had attended physiotherapy regularly (mean 26.5 visits). Outcome was assessed at 12 months using the Cincinnati knee rating system and the IKDC form. RESULTS: Compared with the regular physiotherapy group, patients in the minimal physiotherapy group had fewer symptoms (mean Cincinnati symptom score 46.2 v 43.4, p = 0.045). There was also a trend towards higher overall Cincinnati knee scores in the minimal physiotherapy group (mean 93.7 v 87.3, p = 0.06) but no difference in IKDC ratings. CONCLUSION: These preliminary results indicate that some patients who choose to attend physiotherapy on a very limited basis after ACL reconstruction can achieve satisfactory, if not better, outcomes than patients who attend physiotherapy regularly.

Adult↗
PubMed2003

The effects of growth hormone deficiency and replacement on glucocorticoid exposure in hypopituitary patients on cortisone acetate and hydrocortisone replacement.

OBJECTIVE: 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1) converts inactive cortisone to active cortisol. 11 beta HSD1 activity is increased in GH deficiency and inhibited by GH and IGF-I in acromegaly. However it is not known whether these changes in cortisol metabolism exert significant effects during hydrocortisone therapy, and the effect has not been studied in patients taking cortisone acetate. We have studied the effect of GH induced 11 beta HSD1 inhibition in hypopituitary adults with severe GH deficiency to determine whether this inhibition has a different magnitude of effect when patients are taking different forms of glucocorticoid replacement therapy. DESIGN, PATIENTS AND MEASUREMENTS: We have taken the ratio of 11-hydroxy/11-oxo cortisol metabolites (Fm/Em), an established measure of net 11 beta HSD activity to reflect the likely balance of cortisol to cortisone exposure in tissues expressing 11 beta HSD1, principally the liver and adipose tissue. We recruited 10 hypopituitary adults all on established glucocorticoid replacement therapy, but who were not receiving GH. Patients were treated with their standard hydrocortisone therapy for one week and an equivalent dose of cortisone acetate in its place for one week in random order. Serial serum cortisol assessments and urine steroid profiles were performed on each treatment. All patients were then established on GH therapy for at least three months before the two-week cycle was repeated. Fm/Em was also measured in a control population (20F, 20M). RESULTS: Prior to GH, the ratio Fm/Em was greater with hydrocortisone compared with cortisone acetate replacement (1.17 +/- 0.28 and 0.52 +/- 0.09 respectively, P < 0.001) or with normal subjects (normal males: 0.81 +/- 0.24, females 0.66 +/- 0.14). Following GH replacement Fm/Em fell in patients on hydrocortisone and cortisone acetate (Pre-GH: 0.84 +/- 0.40, Post-GH: 0.70 +/- 0.34, P < 0.05) confirming the inhibition of 11 beta HSD1 by GH/IGF-I. Conversely, the ratio of urinary free cortisol/cortisone did not change indicating unchanged 11 beta HSD2 activity. Mean circulating cortisol also fell in all subjects after GH. This effect was greater during cortisone acetate treatment (-18.7%, P < 0.0001), than during hydrocortisone replacement (-10.9%, P < 0.05). CONCLUSIONS: Our data suggest that tissue exposure to glucocorticoid is supra-physiological in hypopituitary patients with untreated GH deficiency taking hydrocortisone replacement therapy. This situation is ameliorated by GH replacement therapy. However, local and circulating cortisol concentrations are more vulnerable to the inhibitory effect of GH on 11 beta HSD1 in patients taking cortisone acetate, such that serum cortisol assessments should be made in patients taking cortisone acetate after GH therapy to ensure that glucocorticoid replacement remains adequate.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2001

Modulation of cortisol metabolism by the growth hormone receptor antagonist pegvisomant in patients with acromegaly.

Pegvisomant is a GH receptor antagonist and highly efficacious new treatment for acromegaly. The two isoenzymes of 11beta-hydroxysteroid dehydrogenase are responsible for the interconversion of cortisol and its inactive metabolite cortisone. We demonstrated previously that the type I isoform, which is principally responsible for conversion of cortisone to cortisol, is partially inhibited by GH. The net activity of the enzyme can be measured by analysis of the urinary ratio of 11-hydroxy/11-oxo cortisol metabolites or of the urinary ratio of tetrahydrocortisol/tetrahydrocortisone [(tetrahydrocortisol + 5alpha-tetrahydrocortisol)/tetrahydrocortisone]. We studied the influence of pegvisomant on cortisol metabolism in patients with active acromegaly. Seven patients (four women and three men; median age, 58 yr; range, 39-72) were studied at baseline and again after a mean of 46 weeks of treatment. The mean insulin-like growth factor I (IGF-I) level at baseline fell from 939.7 +/- 271.1 to 346.9 +/- 379.0 ng/mL on 20 mg/day pegvisomant. The 11-hydroxy/11-oxo ratio increased from a pretreatment mean value of 0.61 +/- 0.18 to 0.88 +/- 0.20 (P < 0.02) and when the six patients in whom serum IGF-I normalized were considered separately, the change was from 0.62 +/- 0.19 to 0.90 +/- 0.21 (P < 0.04). The tetrahydrocortisols/tetrahydrocortisone ratio increased from a pretreatment mean value of 0.64 +/- 0.21 to 0.98 +/- 0.26 (P < 0.02) and in the six patients in whom serum IGF-I normalized, the ratio rose from 0.66 +/- 0.23 to 1.01 +/- 0.26 (P < 0.04). These data 1) indicate that blockade of GH action with pegvisomant in patients with acromegaly is associated with reversal of the inhibition of 11beta-hydroxysteroid dehydrogenase and correction of cortisol metabolism, and 2) suggest that in active acromegaly, cortisol clearance is accelerated and that this is reversed by successful treatment. This is further evidence of the efficacy of pegvisomant in the management of acromegaly and has important implications for determining optimum glucocorticoid replacement.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2000

Do Colles' fracture patients benefit from routine referral to physiotherapy following cast removal?

Colles' fracture patients who received physiotherapy immediately following cast removal were compared with patients who received no active therapy following cast removal in a prospective randomised study. Patients who attended physiotherapy achieved significantly greater increases in wrist extension and grip strength after 6 weeks compared to patients who received no active therapy.

Aged↗
PubMed2000

Central obesity, depression and the hypothalamo-pituitary-adrenal axis in men and postmenopausal women.

OBJECTIVE: We examined the relationship of adiposity to pituitary-adrenal responses to corticotrophin-releasing hormone (CRH) in men and postmenopausal women, controlling for the influence of depression. DESIGN: Studies of CRH responses, cortisol metabolite levels and depression scores in relation to adiposity in men and postmenopausal women. SUBJECTS: Thirteen men: age (median, interquartile range) 62 y (52-63), body mass index (BMI) 29.0 kg/m2 (26.3-33.1), waist circumference (waist) 105 cm (97-111), waist:hip ratio (WHR) 1.03 (0.98-1.07), subscapular to triceps skinfold thickness ratio (STR) 2.0 (1.2-2.4), total body fat (TBF) 25.4 kg (19.8-28.8); and eight women: age 54 y (53-62), BMI 30 kg/m2 (23-41), waist 86 cm (79-117), WHR 0.94 (0.87-1.10), STR 1.0 (0.85-1.07), TBF 35.0 kg (18.7-48.8). MEASUREMENTS: A standard CRH test was conducted with additional basal samples taken for leptin and interleukin 6 (IL-6). Total urine cortisol metabolites (TCM) and the ratio of urinary cortisol:cortisone (Fm/Em) metabolites were measured. Depression scores were measured by the General Health Questionnaire (GHQ-30) and Hospital Anxiety and Depression Scale (HAD) questionnaire. All subjects completed an overnight dexamethasone suppression test. RESULTS: The basal to peak percentage increments (%inc.) in adrenocorticotrophic hormone (ACTH) and cortisol in men correlated directly with STR (ACTH %inc. r=0.70, P<0.01; cortisol %inc. r=0.55, P=0.05); this relationship was independent of depression scores. In women, the ACTH area under incremental curve (AUIC) correlated negatively with STR (r=-0.81, P<0.05). In men, but not in women, there was a significant correlation between GHQ-30 score and ACTH AUIC (r=0.62, P<0.05) and cortisol AUIC (r=0.72, P<0.01). Depression scores were consistently and directly related to indices of obesity and central obesity. There were no significant relationships in either sex between urinary TCM or Fm/Em ratio and BMI, waist, WHR, TBF, STR or CRH responses. The urinary Fm/Em ratio was higher in men than in women (median 0.74 vs 0.66, P<0.05). In men, but not in women, GHQ-30 scores correlated positively with urinary TCM (r=0.57, P=0.05) and HAD-depression scores were inversely related to the urine Fm/Em ratio (r=-0.65, P<0.05). All subjects suppressed normally with dexamethasone. CONCLUSIONS: Cortisol metabolite levels were increased in depression in men, but were not related to adiposity in either sex. We demonstrate that central obesity in men, but not postmenopausal women, is associated with an enhanced pituitary-adrenal response to CRH and that this relationship is independent of depression score. International Journal of Obesity (2000) 24, 246-251

Adrenal Cortex Function Tests↗
PubMed2000

Increased response of cortisol and ACTH to corticotrophin releasing hormone in centrally obese men, but not in post-menopausal women.

There is evidence for enhanced hypothalamo-pituitary-adrenal axis (HPAA) activity in centrally obese premenopausal women. This has led to the hypothesis that increased cortisol production rates may be an aetiological factor in the genesis of central obesity. However, the relationship of obesity and body fat distribution to HPAA activity in men and postmenopausal women has not been established. We carried out CRH tests in 13 men and 8 post-menopausal women. We measured 24 h urine cortisol metabolites prior to the CRH test in each subject, as an indication of cortisol production rate. There was a significant direct relationship between central obesity as measured by the ratio of subscapular:triceps skinfold thickness (STR)--and the ACTH/cortisol response to CRH in men, but not in postmenopausal women. There was no relationship between obesity or body fat distribution and 24h urine cortisol metabolites. This study provides evidence for hyperactivity of the HPAA in centrally obese men, but not in postmenopausal women.

Adrenocorticotropic Hormone↗
PubMed2000

Sexual dimorphism of cortisol metabolism is maintained in elderly subjects and is not oestrogen dependent.

OBJECTIVE: The net interconversion of inactive cortisone to active cortisol by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) may determine hepatic and adipose tissue exposure to glucocorticoid action. Cortisol metabolism exhibits a sexual dimorphism with an apparently lower activity of 11betaHSD1 in females that, in an animal model, has been attributed to the effects of oestrogen. The aim of this study is to determine whether the sexual dimorphism of cortisol metabolism persists between post-menopausal, oestrogen-deficient women and elderly men. PATIENTS: Fifteen healthy men, aged 60.8-82.0 years, and 7 healthy women, aged 62.4-87.5 years, were studied. None of the subjects was receiving steroid medication at the time of the study. All the women were post-menopausal and none was receiving sex steroid replacement therapy. MEASUREMENTS: 24-h urine collections were taken from each patient and assayed for steroid metabolites by gas chromatography. Body composition was determined by dual energy X-ray absorptiometry. Blood was drawn, after an overnight fast, for the determination of serum IGF-I and IGFBP1 levels. RESULTS: The ratio of 11-hydroxy cortisol metabolites to 11-oxo cortisol metabolites (Fm/Em) was significantly higher in men than in women, 0.80 (0.55-1.86) vs. 0.67 (0.46-0.98) (P < 0.02), as was the ratio of allo-tetrahydrocortisol (5alpha-THF) + tetrahydrocortisol (THF)/tetrahydrocortisone (THE), 0.74 (0.37-2.08) vs. 0.40 (0.22-1.10) (P < 0.047). In the group as a whole there was a negative correlation between Fm/Em and percent body fat, r = - 0. 43 (P < 0.05), and the negative relationship between cortisol and cortisone metabolite (Fm/Em) and total fat mass approached significance, r = - 0.39 (P = 0.07). These relationships were not apparent in the women when considered alone. Among the men there were negative relationships between Fm/Em and total fat mass, r = - 0.48, and Fm/Em and trunk fat mass, r = - 0.48 which approached significance (both P = 0.07). Serum IGFBP-1 levels were not significantly different between the two sexes. There was a significant correlation between IGFBP-1 and Fm/Em in the men, r = 0. 84 (P < 0.0001) which persisted when total body fat mass, r = 0.85 (P < 0.0001) and trunk fat mass, r = 0.83 (P < 0.0001), were controlled for. This relationship was not evident among the women. CONCLUSION: This study demonstrates that the previously described sexual dimorphism in cortisol metabolism is not dependent on oestrogen, although the possibility that oestrogen exerts a permanent modifying effect on 11beta-HSD1 gene expression during the pre-menopausal period cannot be excluded. The findings confirm the primary importance of body fat as a determinant of cortisol-cortisone conversion.

Aged↗
PubMed2000

Endogenous inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 do not explain abnormal cortisol metabolism in polycystic ovary syndrome.

OBJECTIVE: The aetiology of enhanced adrenal androgen secretion in polycystic ovary syndrome is poorly understood. Previous reports suggest that enhanced peripheral metabolism of cortisol results in decreased negative feedback suppression of ACTH secretion, either by enhanced inactivation of cortisol by 5alpha-reductase or impaired reactivation of cortisol by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). Endogenous inhibitors of hepatic 11beta-HSD1 can be extracted from urine. We have tested the hypothesis that these are increased in patients with polycystic ovary syndrome. DESIGN: A case-control study. PATIENTS: 57 patients with polycystic ovary syndrome and 27 healthy control women. MEASUREMENTS: Aliquots from 24 h urine samples were extracted with Sep-Paks and incubated with rat liver microsomes in which 11beta-HSD1 activity was quantified by conversion of 3H-corticosterone to 3H-11-dehydrocorticosterone. RESULTS: Inhibition of 11beta-HSD1 activity was not different in extracts from patients compared with controls (40.8 +/- 18.9 arbitrary units in patients vs. 42.7 +/- 16.6 in controls, mean (+/- SEM, P > 0.60) and did not correlate with ratios of cortisol metabolites in urine or with body mass index. CONCLUSIONS: The altered cortisol metabolism in polycystic ovarian syndrome, which is consistent with impaired 11beta-HSD1 activity, cannot be accounted for by increased production of measurable endogenous inhibitors of this enzyme.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2000

Modulation of cortisol metabolism by low-dose growth hormone replacement in elderly hypopituitary patients.

11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) functions as a net reductase converting cortisone to cortisol. GH inhibits 11beta-HSD1, resulting in a shift in cortisol metabolism favoring cortisone, an observation that may have significance in patients with ACTH deficiency who are unable to compensate for such changes. We have studied the effect of three doses of GH replacement (0.17, 0.33, and 0.5 mg each given for 12 weeks in ascending order) on cortisol metabolism in nine patients, aged 62-70 yr, with hypopituitarism who were receiving fixed doses of oral hydrocortisone. Serum insulin-like growth factor I levels rose in a dose-dependent manner over the course of the study. Fat mass decreased significantly at 24 weeks (P = 0.02), a change that was maintained at 36 weeks. Fasting serum insulin levels did not change significantly over the course of the study. The ratio of urine cortisol to cortisone metabolites (Fm/Em) fell significantly at 12 weeks (GH dose, 0.17 mg/day) from 1.32 (0.91-2.20) at baseline to 1.08 (0.89-2.11) (P < 0.05). Although it did not fall further as the dose of GH was increased, the reduction in the Fm/Em ratio persisted at 24 weeks (GH dose, 0.33 mg/day), 1.09 (0.8-2.11) (P < 0.05 vs. baseline), and 36 weeks (GH dose, 0.5 mg/day), 1.19 (0.82-2.31) (P < 0.05 vs. baseline). The Fm/Em ratio did not correlate with serum insulin-like growth factor I, fat mass, or fasting insulin levels at any time during the study. This study confirms the inhibitory effect of GH on 11beta-HSD1 but has shown that the effect occurs maximally at very low GH doses and is not mediated indirectly by change in circulating insulin. Patients with partial or total ACTH deficiency, in whom cortisol replacement is suboptimal, may be at risk of the clinical manifestations of cortisol deficiency when they are commenced on GH therapy.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Analysis of Chinese herbal creams prescribed for dermatological conditions.

OBJECTIVE: To determine whether Chinese herbal creams used for the treatment of dermatological conditions contain steroids. DESIGN: 11 herbal creams obtained from patients attending general and paediatric dermatology outpatient clinics were analysed with high resolution gas chromatography and mass spectrometry. SETTING: Departments of dermatology and clinical biochemistry. MAIN OUTCOME MEASURE: Presence of steroid. RESULTS: Eight creams contained dexamethasone at a mean concentration of 456 micrograms/g (range 64 to 1500 micrograms/g). All were applied to areas of sensitive skin such as face and flexures. CONCLUSION: Greater regulation needs to be imposed on Chinese herbalists to prevent illegal and inappropriate prescribing of potent steroids.

Administration, Topical↗