Cortisol excretion

Table 1 Summary of data from studies of 24-h urinary cortisol excretion in adults with PTSD...

Yehuda R, Southwick SM, Nussbaum G, Wahby V, GUler EL, Mason JW (1990) Low urinary cortisol excretion in patients with posttraumatic stress disorder. J Nerv Ment Dis 178 366-369... 

Yehuda R, Boisoneau D, Mason JW, Giller EL (1993a) Glucocorticoid receptor number and cortisol excretion in mood, anxiety, and psychotic disorders. Biol Psychiatry 34 18-25... 

Yehuda R, Kahana B, Binder-Brynes K, Southwick S, Mason JW, Giller EL (1995b) Low urinary cortisol excretion in Holocaust survivors with posttraumatic stress disorder. Am J Psychiatry 152 982-986... 

Yehuda R, Halligan S, Grossman R (2001) Childhood trauma and risk for PTSD relationship to intergenerational effects of traiuna, parental PTSD and cortisol excretion. Stress Dev 13 731-751... 

A limited number of studies have evaluated the consequences of early-life stress in adults (Table 9.1). Although there is evidence for increased 24-hour urinary cortisol excretion in abused women with PTSD (Lem-ieux and Coe, 1995), findings on basal plasma or salivary cortisol levels in women with a history of childhood abuse are conflicting, likely because of methodological differences (Heim and Nemeroff, 2001). There is evidence for increased HPA feedback sensitivity in abused women with PTSD (Stein et al., 1997a). Given the preclinical evidence for a sensitization of the... 

The effect of inhaled ciclesonide on adrenal function has been analysed in 164 asthmatic adults in a double-blind, randomized, placebo-controlled study (40). The patients used ciclesonide 320 micrograms once daily, ciclesonide 320 micrograms twice daily, or fluticasone propionate 440 micrograms twice daily for 12 weeks. Adrenal function was significantly suppressed by fluticasone propionate but not by ciclesonide. Oral candidiasis was reported in 2.4% of patients on ciclesonide versus 22% of patients on fluticasone propionate. Even high daily doses of ciclesonide up to 1280 micrograms did not suppress adrenal function, as measured by 24-hour urinary cortisol excretion (41). This is in accordance with other studies in asthmatic subjects, in which serum or 24-hour urinary cortisol concentrations were unchanged by ciclesonide (42-48). 

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. 

Agertoft L, Pedersen S. Short-term lower-leg growth rate and urine cortisol excretion in children treated with cicle-sonide. J Allergy Clin Immunol 2005 115 940-5. 

Because of its effects on the pituitary/adrenal system, ketoconazole has been used in the long-term control of hypercortisolism of either pituitary or adrenal origin (SED-12, 677). In seven patients with Cushing s disease and one with an adrenal adenoma, ketoconazole 600-800 mg/day for 3-13 months produced rapid persistent clinical improvement (585). Plasma dehydroepiandrosterone sulfate concentrations and urinary 17-ketosteroid and cortisol excretion fell soon after the start of treatment, and remained normal or nearly so throughout treatment. Urinary tetrahydro-ll-deoxycortisol excretion rose... 

Table 14 Mean (SD) ratio of urinary 6- 3-hydroxy-cortisol/free cortisol excreted by treatment.

The ratio of 6-f-)-hydroxy-cortisol/frcc cortisol excretion was about 11 for all treatments on both day 1 and 10 suggesting that there was no noticeable effect on CYP 3A4 activity. 

No abnormalities were found in Brian s urine and his blood cell count was normal. However, his blood glucose was 8.1 mmol l-1 (normal value 3.5-6.7 mmol l-1) and a glucose tolerance test later indicated impaired glucose tolerance. Tests for plasma insulin and thyroid hormones (T3, T4 and TSH) showed normal levels. Two further tests were then performed. A 24-hour urine sample was collected and Brian s free cortisol excretion was found to be considerably higher than normal. A second test, the dexamethasone suppression test, was also carried out. In this test, the patient is given a dose of dexamethasone at 11 -12 p.m. and plasma cortisol is measured early next morning. 

Q9 Why is a 24-hour urine collection, rather than a single sample, necessary when estimating a patient s cortisol excretion ... 

Kelly C J et al 2001 Raised cortisol excretion rate in urine and contamination by topical steroids. British Medical Journal 322 594. 

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 metabolic effects of exogenous cortisone are similar to the sequence of events following injury. A close correlation was found between urinary cortisol excretion and nitrogen losses in surreal patients (MIO). For these reasons it was considered that the adrenocortical hormones initiated and controlled the metabolic response to injury. There are serious objections, however, to this hypothesis, as the complete interdependence of the responses has been demonstrated in man and animals. 

E6. Espiner, E. A., Urinary cortisol excretion in stress situations and in patients with Cushing s syndrome. J. Endocrinol. 35, 29-44 (1966). 

Beclomethasone dipropionate and budesonide Modulite formulations have been compared with equivalent chlorofluorocarbon products in small groups of healthy volunteers and asthmatic patients (18) there was no significant difference in morning serum cortisol or urinary cortisol excretion, suggesting that the systemic availability of the inhaled corticosteroids with different propellants is similar. Moreover, plasma profiles of beclomethasone dipropionate and B17MP were similar after inhalation of beclomethasone dipropionate Modulite and beclomethasone dipropionate-chlorofluorocarbon, suggesting that pulmonary delivery to the lung is comparable with the two propellants (18). 

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. 

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.)...

The following are representative values for free cortisol excreted per 24 hours in urine ... 

Fig. 3 The dexamethasone suppression test. Palicnl A showed a >75% fall in urin ary cortisol excretion on the low dose. This is a normal response. Patienl B showed stnite suppression of cortisol secretion on the high dose. This is typical of pituitary-dependent (. ushing s syndrome.

Ohnaus, E. E., and B. K. Park. 1979. Measurement of urinary 6-p-hydroxy cortisol excretion as an in vivo parameter in the chnical assessment of the microsomal enzyme-inducing capacity of antipyrine, phenoharhitone and rifampicin. European Journal of Clinical Pharmacology 15 139-145. 

Kronfol, Z. et al. (1986). Depression, urinary free cortisol excretion and lymphocyte function. British Journal of Psychiatry 148 70-3. 

Sixteen healthy subjeets were given a single 1-mg inhaled dose of budesonide after taking ketoeonazole 200 mg daily for 2 days. Plasma cortisol levels and urinary cortisol excretion were used as a measure of how much budesonide was absorbed systemically, and ketoconazole was found to cause a 37% decrease in the AUC0.24 of cortisol. ... 

Seeman, T E., McEwen, B. S., Singer, B. H., Albert, M. S., Rowe, J. W. (1997). Increase in urinary cortisol excretion and memory declines. MacArthur studies of successful aging. 7o wa/ of Clincal Endocrinology and Metabolism, 82, 2458-2465. 

The environmental stress brings to lower 24h mean cortisol excretion and to partial inhibition of feedback mechanisms. 

In conclusion, only obesity and hypertension are consistent findings. Among the clinical findings, the most reliable seems to be that of free cortisol excreted in the urine. The results of the administration of dexa-methasone (which suppresses urinary 17-ketogenetic steroid excretion) may be suggestive, but not always conclusive. Measurements of 17-ketosteroid excretion or of 11-hydroxycorticosteroid excretion are of little or limited value. 

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