Urinary 17-ketosteroids

Although a number of studies have pointed to substantial variation in the 24-hr-urinary 17-ketosteroid excretion of men and women, the most definitive work dealing with inter-individual differences is that of Dobriner and co-workers23 which was referred to earlier (p. 99). In this study samples were collected from individuals over long periods of time and analyzed separately by exhaustive research methods involving the use of chromatography and infrared spectrometry in addition to the more usual techniques. 

Cephalosporins may falsely elevate urinary 17-ketosteroid values. 

The catabolism of plasma testosterone and other androgens occurs primarily in the liver (Fig. 63.3), where they are conjugated into water-soluble compounds that are excreted by the kidney as the urinary 17-ketosteroids. 

E) A sharp drop in urinary 17-ketosteroid levels 2. Which of the following is mostly likely to be found... 

C. In adolescent males, testicular testosterone production dramatically rises from prepuberal levels and then declines into adulthood. However, with advancing adulthood there is a drop in the metabolic clearance rate of testosterone, increasing the length of time that testosterone remains in the serum. Evidence of a relatively constant level of serum testosterone is seen in the relative constant levels of urinary 17-ketosteroids, a metabolite of testosterone, from the second to the fifth decade of life. 

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... 

The composition of the excreted urinary 17-ketosleroids also reveals a close similarity between the hormones of different origin the testis accounts for 30% while the adrenal cortex contributes the remaining 70% of the total urinary 17-ketosteroids [383]. Androsterone, ep a-androsterone, and 5/8-androsterone (etiocholanolone) are the main urinary metabolities of testosterone, and dehydroepiandrosterone is the major urinary 17-ketosteroid derived from the adrenal cortex. 

Llerena O, Pearson OH. Interference of nalidixic acid in urinary 17-ketosteroid determinations. N Engl J Med 1968 279(18) 983. ... 

The adrenal cortex, the zona reticularis in particular, daily secretes substantial amounts of DHEA and DHEAS, equaling or exceeding the amount of cortisol. Table 32-1 shows approximate blood levels of the important corticosteroids. Most of the DHEA and all of the DHEAS come from the adrenals. Negligible amounts of testosterone, dihydrotestosterone (DHT), and estradiol are secreted by the cortex however, DHEA and, to a lesser extent, DHEAS undergo conversion to estradiol in skeletal muscle and adipose tissue they also can be converted to testosterone. The adrenal cortex accounts for about two-thirds of the urinary 17-ketosteroids, which are a measure of androgen production. This steroidogenic versatility makes the adrenal cortex an important factor in certain disease states (see below). 

Admittedly only the axial and epimeric pairs can be reasonably easily separated from each other further subdivision is difficult and more is said about this in connection with the urinary 17-ketosteroids. Even the 3j5,6a-isomer (epiandrosterone) cannot be separated from the important J ,3iS-compound (dehydroepiandrosterone) using normal TLC. As mentioned in the preceding section, complex formation on silver nitrate-containing layers helps in this instance. Many synthetic Cig -steroids contain a 17a-alkyl as well as the 17j8-hydroxyl group the former reduces the polarity in the order — CH3, — CgHg, — CH=CH2 equals — CsCH, — C3H7. 

Routine Gas-Liquid Chromatographic Method for Simultaneous Assay of Major Urinary 17-Ketosteroids, and Pregnanediol and Pregnanetriol... 

Individual Urinary 17-Ketosteroids. Critical Evaluation Acta Endocrinol. (Copenhagen) 68(2) 311-333 (1971) CA 75 148340e... 

Quantitative Determination of Individual C19O2 and C19O Urinary 17-Ketosteroids by Gas Chromatography Anal. Chem. 35 1231-1238 (1963) CA 59 9033f... 

Woods, R. A., and Lantz, C. D. AClinical Gas Chromatographic Analysis of Urinary 17-Ketosteroids... 

The chemical assay of urinary 17-ketosteroids has become a widely used tool for the evaluation of gonadal function and some phases of adrenal cortical and pituitary function, as well as more obscure aspects of endocrine imbalance. Its principal value lies in the fact that gross hyper-and hypofunction of these endocrine glands may be detected rather readily. In addition, the assay may be used as a guide in adjusting dose levels of those steroids which give rise to 17-ketosteroids in the urine, as well as agents such as ACTH which exert a more indirect effect upon ketosteroid excretion. 

The occurrence of urinary 17-ketosteroids possessing functional groups characteristically found in adrenal cortical steroids provides further proof that this gland is an important source of urinary steroids. Such compounds are etiocholane-3a-ol-ll,17-dione (VI), etiocholane-3 ,ll 8-diol-17-one (VII), and their analogues in the androstane series (VIII, IX). The dio-lones may also be found as unsaturated monohydroxy-monoketones (see Section III,4). 

This chapter will be concerned with the assay of urinary 17-ketosteroids, from the collection of the specimen to the final analytical procedures. In addition, a brief survey will be given of methods whidi have been employed for the further fractionation of this complex mixture into its principal components. 

In summary, the hydrolysis of urinary 17-ketosteroid conjugates may be achieved under a variety of conditions of acid concentration, temperature, and time. Using the criterion of total yields of 17-ketOBteroids, those methods which employ refluxing of the urine, made approximately 1.6 N in acid, for 10 to 30 minutes can be considered satisfactory. 

Transformation products of the urinary 17-ketosteroids which are introduced during such acid hydrolysis will be discussed below in Section III,4. 

A polarographic method for the estimation of urinary 17-ketosteroids was introduced by Wolfe et al. (132) and extended by Morris and his as-... 

This type of chromatographic separation has been modified for application to small quantities of ketosteroids such as are obtained in a single 24-hour specimen. Dingemanse et al. (34) and others (7,13,103,108,129,138) have described methods with which one may obtain an elution pattern upon relatively small quantities of urinary extracts. Thus, fractionations may be achieved and some information may be gained as to the qualitative composition of the 17-ketosteroid complex. Silica gel has also been employed in an adsorption chromatogram for urinary 17-ketosteroids (110). However, the resolution does not appear to be as good as in the alumina chromatogram. 

These compoimds are believed to be metabolites of cortical hormones which have a 17-hydroxyl group. The administration of compound A (XXVII), which does not possess a 17-hydroxyl function, produced no increase in urinary 17-ketosteroids in human beings. 

As noted above, CoA is required for Golgi function, involved in protein transport. Pantothenate deficiency can therefore cause reductions in the amounts of some secreted proteins. Other metabolic responses to deficiency include a reduction in urinary 17-ketosteroids, a reduction in serum cholesterol, a reduction in drug acetylation, a general reduction in immvme response, and an increase in upper respiratory tract infection. 

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