Examination of the total 24 hour excretion of steroids
eliminates the fluctuations seen in serum samples as a function
of time of day, episodic bursts of corticotropin (ACTH) and steroid
secretion, and transient stress (eg, clinic visit, difficult venipuncture).
Two consecutive 24 hour collections should be obtained,
and each should be assayed for creatinine to monitor the completeness
of the collection. Because of the diurnal and episodic nature of
steroid secretion, one cannot obtain 8 or 12 hour
collections and infer the 24 hour excretory rate from partial
collections.
The analytic procedures for urinary steroid analysis typically
rely on a chromatographic procedure for separating steroids followed
by a colorimetric, immunologic, or other assay. Urinary 17 hydroxycorticosteroids
(17OHCS) measure the major urinary metabolites of cortisol, cortisone,
and 11 deoxycortisol, which will be increased in 11 hydroxylase
deficiency or after treatment with metyrapone, a commonly used diagnostic
agent. Urinary 17OHCS secretion is increased in obesity, hyperthyroidism,
and anorexia nervosa; it is decreased in starvation, hypothyroidism,
renal failure, liver disease, and pregnancy. Drugs that induce hepatic
enzymes, such as phenobarbital, can give low urinary 17OHCS values
by stimulating hepatic metabolism of circulating steroids to other
compounds. Phenothiazines, spironolactone, hydroxyzine, and some
antibiotics can give falsely elevated values. In most centers, measurement
of 17OHCS has been replaced by measurement of urinary free cortisol,
which avoids problems of nonspecificity and drug interference inherent
in 17OHCS measurement. Free cortisol is extracted from the urine
and measured by immunoassay or high-performance liquid chromatography
(HPLC), providing specificity. Excretion of urinary free cortisol
and of total cortisol metabolites is closely correlated with age,
body surface area, and adiposity, but are typically 11 ± 5 μg/m2/day.6,7 Values
vary substantially among different reference laboratories, reflecting
variations in assay technologies; thus, it is essential to use a
laboratory with good data for normal children. It remains important
to measure urinary creatinine to monitor the completeness of the
collection. Other urinary steroid tests, such as 17 ketosteroids
(17KS), which measures metabolites of dehydroepiandrosterone (DHEA)
and dehydroepiandrosterone sulfate (DHEAS) and thus correlates with
adrenal androgen production, may be helpful; however, measurements
of 17-ketogenic steroids, a crude measure of glucocorticoids, are outmoded,
unreliable, and should not be used.