Urinary free cortisol

The method measures cortisone (urinary free cortisone, UFE), cortisol (urinary free cortisol, UFF), 6/1-hydroxycortisol, and 18-OHF using deuterated internal standards [62]. Commercial tetradeuterocortisol was used as an internal standard for cortisol, and the remaining dideutero homologs prepared in the laboratory by deuteration of A1 analogues. UFF and UFE are considered better indicators of hormone availability and hypersecretion than the F and E (free plus conjugated) quantified in the comprehensive profile. Typically the values of total F and E are about three times that of... 

Initial screening tests to confirm the presence of hypercorti-solism and differentiate Cushing s syndrome from conditions with similar presentations include 24-hour urinary free cortisol determination and overnight low-dose dexam-ethasone suppression test (DST) (Table 42-9). 

Hour urinary Collect urine over 24 Urinary free cortisol greater Easy to perform but should not be used... 

Cyproheptadine can decrease ACTH secretion monitoring should include morning plasma cortisol and 24-hour urinary free cortisol concen-... 

Close monitoring of 24-hour urinary free cortisol levels and serum cortisol levels are essential to identify adrenal insufficiency in patients with Cushing s syndrome. Steroid secretion should be monitored with all drug therapy and corticosteroid replacement given if needed. 

Oral contraceptives have their most significant effect on endocrine parameters. Blood cortisol, thyroxine, protein-bound iodine, T3 uptake, and urinary free cortisol are elevated. Urinary 17,21-dihydroxy steroids, 17-ketosteroids, and estrogens are decreased. There is no effect on urinary catecholamines or VMA (Table 10) (LIO). The effect of thyroid functions tests is due to the administered hormone stimulating an increase in the production of thyroid-binding globulin which in turn binds 1-thyroxine. The lowering of free thyroxine stimulates the anterior pituitary to produce thyrotropin, which in turn stimulates the thyroid to produce more thyroxine. Since the additional thyroxine is bound to the extra protein, there is an equilibrium and the patient remains clinically euthyroid, but the protein-bound iodine and the thyroxine are elevated. 

Many centers have reported specific abnormalities on measures of hypo-thalamic-pituitary-adrenal axis activity in patients with psychotic depression. Patients with psychotic major depression (PMD) are among those with the highest rates of nonsuppression on the dexamethasone suppression test, and many of them have markedly elevated posttest levels (Carroll et al. 1976c, 1980 Coryell et al. 1982). Significant differences have been observed in 24-hour measures of urinary free cortisol between patients with psychotic and those with nonpsychotic major depression (NPMD) (R. F. Anton 1987). 

Ansseau M, Olie JP, Von Frencheil R, et al Controlled comparison of the efficacy and safety of 4 doses of suriclone, diazepam and placebo in generahsed anxiety disorder. Psychopharmacology 104 439-443, 1991 Anton RF Urinary free cortisol in psychotic depression. Biol Psychiatry 2 24-34, 1987... 

Table 5.3.2 The gas chromatography (GC)-MS urinary free cortisol (UFFj and metabolite panel internal standards, monitored ions, and normal excretions...

Turpeinen U, Stenman U-H (2003) Determination of urinary free cortisol by liquid chromatography-tandem mass spectrometry. Scand J Clin Lab Invest 63 143-150... 

The long-term effects of budesonide on adrenal function have been assessed in 63 asthmatic children using budesonide 400 micrograms/day, nedocromil 16 mg/day, or placebo over 3 years (74). There were no differences in serum cortisol concentrations after ACTH stimulation between the three treatment groups, regardless of the time after ACTH administration or months of follow-up. Cumulative inhaled glucocorticoid exposure did not affect the serum cortisol response to ACTH or urinary free cortisol excretion at 3 years. 

Fink RS, Pierre LN, Daley-Yates PT, Richards DH, Gibson A, Honour JW. Hypothalamic-pituitary-adrenal axis function after inhaled corticosteroids unreliability of urinary free cortisol estimation. J Clin Endocrinol Metab 2002 87(10) 4541-6. 

Urinary b-p-hydroxy-cortisol and free cortisol The following pharmacokinetic variables were derived from urine concentration data for 6-P-hydroxy-cortisol and free cortisol on Days 1 and 10 using SAS for Windows protocols amount excreted during each collection interval for 6- 3-hydroxy-cortisol and free... 

In the study described the time-dependence and reversibility of the enzyme induction was not studied. Also the enzyme substrate used as a marker for the CYP 1A2 activity was caffeine, which although frequently encountered in the target population and commonly used as a marker for CYP 1A2 activity, is not a drug with a narrow therapeutic index used by the target population. The enzyme substrate used as a marker for the CYP 3A4 activity, urinary 6- 3-hydroxy-cortisol and free cortisol, although readily amenable to inclusion in studies, is not a drug and is also known to be a relatively insensitive marker for CYP 3A4 induction. Also urinary 6- 3-hydroxy-cortisol and free cortisol does not differentiate between intestinal and liver CYP 3A4 activities. 

The free component of plasma cortisol is biologically active and is filtered and excreted in the urine, where it can be measured. It would appear that urinary free cortisol estimations may give a more accurate picture of glucocorticoid activity at a tissue level than most other measurements. 

Espiner found that the 24-hour urinary free cortisol excretion ranged from 20 to 320 jag (E6). Four out of fourteen patients had levels in excess of patients with medical stress and comparable to levels found in patients with florid Cushing s syndrome. Similar observations have been recorded in other preoperative patients (F3). It is suggested that these levels are due to anxiety about impending surgery even though... 

The different methods of assessing hypothalamic-pituitary-adrenal axis activity in patients using inhaled glucocorticoids have been compared (35). The AUC of serum cortisol concentrations was the most reliable method. There were significant positive correlations between AUC and the 8 a.m. serum and salivary cortisol concentrations. The authors favored the non-invasive method of salivary concentration measurement. However, 24-hour urine collection is not recommended, as it correlated only moderately well. This finding is consistent with the results of other studies. Urinary free-cortisol estimation based on immunoassay after inhaled glucocorticoids may be an unreliable surrogate marker of... 

Strenuous exercise for 10 minutes increases plasma renin activity by 400%. Cortisol secretion is stimulated and the normal diurnal variation may be abolished. Urinary free cortisol excretion and the plasma concentrations of cortisol, aldosterone, growth hormone, somatotropin, and prolactin are also increased by exercise. Plasma insulin concentration is decreased by exercise. Strenuous exercise increases both the plasma and urinary concentrations of catecholamines. The changes in hormone concentrations are probably responsible for the increase in leukocyte count to about 25,000 cells/juL that has been observed following strenuous exercise. 

Plasma growth hormone concentration may rise by as much as 15 times at the start of a fast but may return to normal after 3 days. Reduced energy expenditure is associated with decreased concentrations of thyroid hormones. Free and total triiodothyronine decrease by up to 50% witliin 3 days of the start of a fast. Free thyroxine concentration is also affected, but to a lesser extent total thyroxine is little changed. Urinary free cortisol is decreased by fasting, and the plasma cortisol concentration (free and total) shows a slight increase together with loss of the normal diurnal variation. 

Urinary free cortisol obtained from a 24-hour urine collection is an integrated measure of plasma free cortisol and eliminates the circadian influence on cortisol secretion. Urine free cortisol measurements are therefore considered to be the best screening test for hyperadrenocorticism. The urinary free cortisol excretion rate in normal subjects falls between 20 and 80[lg/day (Figure 51-9), The measurement of urinary 17-hydroxycorticosteroid excretion rates for determining adrenocortical hyperfunction is no longer recommended because of problems with method sensitivity and specificity. 

Figure 5 -9 Urinary free cortisol excretion in normal individuals with Cushing s syndrome. (From Bur/ce CW, Beardwell CG. Cushing s syndrome. An evaluation of the clinical usefulness of urinary free cortisol measurements in screening for Cushing s syndrome. QJ Med I973 42 l 175.)...

Procedure ACTH gel, 80U/day, is injected for 3 days. This is followed by a standard 8-hour infusion of ACTH (250 p.g of Synacthen over 8 hours). Urinary free cortisol and serum cortisol are measured daily. 

Rationale Normal subjects show lowering of serum and urinary free cortisol concentrations under the conditions of low-dose dexamethasone suppression. Patients with excess cortisol production regardless of etiology usually show persistent elevation of cortisol under these conditions. 

Interpretation Normal subjects have suppressed serum and urinary free cortisol concentrations on day 4 to <50% of baseline values serum cortisol at 2000 hours on day 1 should be one third of the value at 0800 hours. Patients with Cushing s syndrome usually do not show diurnal rhythmicity and do not show suppression with low-dose dexamethasone. Those patients taking phenytoin or phenobarbital, or both, metabolize dexamethasone more rapidly than do normal subjects and may not show suppression. 

Interpretation Patients with Cushing s syndrome caused by an ACTH-secreting pituitary adenoma usually show (1) suppression of urinary free cortisol and 17-hydroxycorticosteroid excretion >50% of baseline by day 4 ... 

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