Biomedical subjects

Norman F Taylor

Publications and source records attributed to Norman F Taylor.

8 recordsLinked to original sources

PubMed2006

Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome.

OBJECTIVE: The aim of this study was to obtain comprehensive information on basal hypothalamic-pituitary-adrenal (HPA) axis activity in chronic fatigue syndrome (CFS) patients who were not affected by medication or comorbid psychiatric disorder likely to influence the HPA axis. METHOD: Steroid analysis of urine collections from 0600 to 2100 h at 3-h intervals in CFS patients and in controls. RESULTS: Urinary free cortisol and cortisone concentrations showed a significant normal diurnal rhythm, but levels were lower across the cycle in CFS. In contrast, while urinary cortisol metabolites also showed a normal diurnal rhythm, levels were not significantly different between the CFS and controls at any time. Derived metabolite ratios were similar in both groups. CONCLUSION: This study provides further evidence for reduced basal HPA axis function in patients with CFS, based on lower free cortisol and cortisone levels, but this is not corroborated by cortisol metabolite data. The difference between these measures cannot be explained by an altered timing of the diurnal rhythm.

Adult↗

PubMed2006

Circadian rhythm of urinary steroid metabolites.

BACKGROUND: Samples submitted for urinary steroid profile analysis are often untimed, but influence of collection time on interpretation is unknown. We report circadian rhythms of the major steroid metabolites and derived ratios in urine collected at 3-h intervals over 24 h, after first establishing that disturbance of sleep associated with collection does not alter rhythms on the succeeding day. METHODS: Assay of steroid metabolites (gas chromatography) and creatinine in urine collections made by 10 men and 10 women every 3 h starting at 2,100 for 24 h. Data were subjected to cosinor analysis. RESULTS: Summed cortisol and androgen metabolites exhibited significant circadian rhythms, as expected, but with a surprisingly long time-lag (maxima at around 1,400). Amplitudes were different, so that the ratio cortisol/androgen metabolites also showed a significant rhythm. The ratios 5alpha/5beta tetrahydrocortisol and 20-hydroxy/20-oxo cortisol metabolites showed significant rhythms which were not in phase with total cortisol metabolites, while 11-hydroxy/11-oxo cortisol metabolites showed no rhythm. There were no gender differences in time of maxima. Previously established gender differences in metabolite levels were confirmed. Creatinine levels showed no circadian rhythm. CONCLUSION: Circadian variation should be considered when interpreting results from urine steroid analysis. Calculation of steroid/steroid or steroid/creatinine ratios is not informative in untimed collections.

Adult↗

PubMed2006

Urinary steroid profiling.

Urinary steroid profiling provides quantitative information on the steroid biosynthetic and catabolic pathways. It is essential for identification of inborn errors of steroid metabolism, and useful in other disorders with altered steroid secretion. A general method is detailed. Steroids, mostly in the form of glucuronide and sulphate conjugates, are extracted using solid-phase cartridges, followed by enzymatic hydrolysis, re-extraction of freed steroids, formation of methoxime trimethylsilyl derivatives and analysis by sas chromatography and gas chromatography-mass spectrometry. Newborns excrete large quantities of sulphates, so conjugate separation by liquid gel chromatography is used prior to hyrolysis. Normal ranges for adults and children are given, together with advice on chromatogram evaluation and a summary of the profile findings in steroid disorders.

Age Factors↗

PubMed2005

Assessment of subtle changes in glucocorticoid negative feedback using prednisolone: comparison of salivary free cortisol and urinary cortisol metabolites as endpoints.

BACKGROUND: Prednisolone is better than dexamethasone to probe subtle changes in HPA axis sensitivity but cortisol assay as an endpoint risks cross-reaction with prednisolone. We compared capillary gas chromatography, which distinguishes urinary cortisol and prednisolone metabolites, and salivary cortisol immunoassay. METHODS: Twenty adult volunteers (10 m) collected urine for consecutive 3 h periods and saliva at 3 h intervals from 2100 for 24 h, took prednisolone (5 mg) at midnight and continued collecting until 2100. RESULTS: Suppression of urine cortisol metabolites began at 0600 and ceased after 1800. The lowest CV was obtained for the period 0900-1800: mean suppression was 56 +/- 7% for males and 55 +/- 9% for females. Suppression of salivary cortisol was only consistently seen at 0900: mean suppression was 41 +/- 5% in males and 47 +/- 9% in females. Chromatography revealed significant cross reactivity of prednisolone in saliva at 0300 and 0600, but not by 0900. Suppression of salivary cortisol and urinary cortisol metabolites was not correlated for either gender. CONCLUSION: Both urinary cortisol metabolite and salivary cortisol assay following administration of 5 mg prednisolone have potential for investigation of changed HPA axis negative feedback, based on a convenient pre- and post-dose urinary collection between 0900 and 1800 and salivary sampling at 0900.

Adult↗

PubMed2004

Biochemical diagnosis of Antley-Bixler syndrome by steroid analysis.

Antley-Bixler syndrome (ABS, MIM 207410) is a skeletal abnormality syndrome primarily affecting head and limbs. Little is known of the origin of the condition but inactivating mutations in the fibroblast growth factor receptor (FGFR2) has been found in some patients. Genital ambiguity is seen occasionally in this condition, suggesting possible disordered steroidogenesis in early pregnancy. We report the steroid excretion of eight patients diagnosed with the syndrome and one with a related condition, a mild phenotype of the disorder since skeletal and genital abnormalities were not evident. The steroid excretion pattern was consistent and very distinctive in all nine patients. Metabolites of the two primary precursors of steroid hormones, pregnenolone and progesterone, were elevated as were the classical diagnostic metabolites for 17- and 21-hydroxylase deficiencies. Cortisol production was typically within the normal range but generally had blunted response to ACTH. Androgen metabolite excretion tends to be low in patients over 2 months of age, but may be elevated in the newborn period. The metabolome suggested attenuated steroid hydroxylation (including 17,20-lyase activity) although underlying cause is yet to be established. Mutations in CYP17 and CYP21 have not been found and currently the prime suspect is an abnormality in an essential redox partner (P450 oxidoreductase). This paper proposes use of the distinctive steroid metabolome as the primary biochemical parameter for diagnosis of ABS, at least the form not associated with FGFR2 mutations.

Abnormalities, Multiple↗

PubMed2004

Modulation of cortisol metabolism during treatment of acromegaly is independent of body composition and insulin sensitivity.

OBJECTIVES: The set point of cortisol-cortisone conversion is shifted in the direction of cortisone by the inhibition of the activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) during adult GH replacement and in active acromegaly. Additionally, both fat mass and insulin may modulate 11beta-HSD1 and are both influenced by changes in GH status. This study examined the relative direct contribution of GH/IGF1 in modulating cortisol metabolism. METHODS: Overall cortisol/cortisone conversion (ratio of urine 11-hydroxy-/11-oxo-cortisol metabolites; Fm/Em), insulin sensitivity (homeostatic model assessment; HOMA %S) and fat mass (DXA) were examined in parallel in 6 patients (mean age 53 years, range 42-76; 4 males, 2 females) with previously untreated active acromegaly during 6 months of therapy with Sandostatin LAR (20-30 mg i.m. 4 weekly). All but 1 patient had normal ACTH reserve. RESULTS: At baseline, Pearson correlation demonstrated an inverse relationship between serum GH (mean of a 5-point day curve) and Fm/Em (r = -0.83, p = 0.04) and a trend towards an inverse relationship between HOMA %S and Fm/Em (r = -0.79, p = 0.06) but no other patterns were evident. During the course of treatment, serum GH decreased from 9.9 +/- 6.4 (mean +/- SD) to 3.5 +/- 3.1 ng/ml (p < 0.01) and serum IGF-1 from 785 +/- 268 to 431 +/- 156 ng/ml (p < 0.005). Fm/Em increased from 0.52 +/- 0.1 to 0.75 +/- 0.08 (p < 0.03) consistent with increased 11beta-HSD1 activity. There were no significant changes in truncal fat percentage (33.0 +/- 9.0 vs. 33.0 +/- 8.2) or insulin sensitivity (HOMA %S: 37.1 +/- 8.6 vs. 52.8 +/- 33.7). CONCLUSIONS: Modulation of cortisol metabolism during treatment of active acromegaly is dependent on changes in GH/IGF-1 status and is not influenced by any individual change in body composition or insulin sensitivity.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

PubMed2002

The diagnosis of congenital adrenal hyperplasia in the newborn by gas chromatography/mass spectrometry analysis of random urine specimens.

Definitive neonatal diagnosis of congenital adrenal hyperplasia (CAH) is frequently complicated by normal 17-hydroxyprogesterone levels in 21-hydroxylase-deficient patients, residual maternal steroids, and other interfering substances in neonatal blood. In an effort to improve the diagnosis, we developed a gas chromatography/mass spectrometry method for simultaneous measurement of 15 urinary steroid metabolites as early as the first day of life. Furthermore, we developed 11 precursor/product ratios that diagnose and clearly differentiate the four enzymatic deficiencies that cause CAH. Random urine samples from 31 neonatal 21-hydroxylase-deficient patients and 59 age-matched normal newborns were used in the development. Additionally, samples from two 11 beta-hydroxylase-deficient patients and one patient each for 17 alpha-hydroxylase and 3 beta-hydroxysteroid dehydrogenase deficiencies were used. The throughput for one bench-top gas chromatography/mass spectrometry instrument is 20 samples per day. Thus, this method affords an accurate, rapid, noninvasive means for the differential diagnosis of CAH in the newborn period without the need for invasive testing and ACTH stimulation.

17-alpha-Hydroxyprogesterone↗

PubMedDate not supplied

Urinary cortisol and cortisol metabolite excretion in chronic fatigue syndrome.

OBJECTIVES: Reduced basal hypothalamic-pituitary-adrenal (HPA) axis output in chronic fatigue syndrome (CFS) has been inferred from low cortisol levels in blood, saliva, and urine in some studies. Because > 95% of cortisol is metabolized before excretion, we assessed cortisol output by assay of both cortisol metabolites and free cortisol in 24-hour urine collections and also investigated sex differences in these between CFS and control groups. METHOD: We calculated total urinary cortisol metabolites (TCM) and cortisol metabolite ratios from individual steroid data in 40 patients (20 males and 20 females) with CFS who were free of medication or comorbid psychiatric disorder likely to influence the HPA axis. Results were compared with those of 40 healthy volunteers (20 males and 20 females) well matched for age and body mass index. Data for free cortisol was obtained on 28 of the patients and 27 of the controls. RESULTS: The mean of TCM and cortisol metabolite ratios was not significantly different between patients and controls for either sex (p > .05 for all parameters). Previously established sex differences were confirmed in our controls and were found to be similar in CFS for TCM and the ratios 11OH/11OXO, 5alpha/5beta THF, and 20OH/20OXO (see text) (p < .005, p < .05, p < .05, and p < .005, respectively). Urinary free cortisol values were numerically (but not statistically) lower in patients with CFS than controls, and correlated inversely with fatigue levels in patients. CONCLUSION: The finding of normal urinary cortisol metabolite excretion in patients with CFS is at variance with earlier reports that CFS is a hypocortisolemic state. If serum and saliva cortisol levels are lower in CFS, this would suggest that metabolic clearance of cortisol is faster in patients with CFS than controls. This study also demonstrates that sex differences must be taken into account when interpreting results in patients with CFS.

11-beta-Hydroxysteroid Dehydrogenases↗