Adrenal steroids, Urinary

The synthesis of adrenal steroids is illustrated in Fig. 5.3.1. Cortisol, corticosterone, and aldosterone are formed by sequential hydroxylations and oxidoreductions from pregnenolone and progesterone. 17a-Hydroxypregnenolone (17HP) is a branchpoint constituent because it can be converted to cortisol or adrenal androgens. All of the components of this pathway can be quantified by MS/MS. The steroids around the periphery are urinary metabolites and these are measured by GC-MS following hydrolysis of conjugates and derivatization. 

The synthesis of adrenal steroids and major excreted metabolites is illustrated in Fig. 5.3.1. Little secreted steroid product is excreted unchanged and most of the catabolism takes place in the liver, although cortisol metabolism by the kidney is clinically important and microbial metabolism in the gut can be quantitatively significant. The major metabolic transformations of hormonal steroids and precursors are detailed by Makin [54] and summarized in Fig. 5.3.2. GC-MS steroid profiling is the technique of choice for measurement of important urinary constituents. 

Calcitonin (see below). When the hypercalcaemia is at least partly due to mobilisation from bone, calcitonin can be used to inhibit bone resorption, and it may enhance urinary excretion of calcium. The effect develops in a few hours, and responsiveness may be lost over a few days (but may sometimes be restored by an adrenal steroid). 

More recently, a similarity has been noted between urinary electrolyte changes after large doses of salicylate in man and those folio-wing stress or hydrocortisone administration . Further evidence, however, indicates that these findings may not reflect pituitary-adrenal stimulation . Perfusion of the dog adrenal with salicylate does not stimulate hydrocortisone secretion and there is no evidence to indicate that salicylates potentiate the thymolytic action of adrenal corticosteroids . Despite the confusing evidence, it seems doubtful that phenylbutazone influences the pituitary, and any stimulation of the adrenal cortex is probably slight and non-specific . There is, however, some indication that phenylbutazone in vitro inhibits the metabolic inactivation of adrenal steroids . 

Group Determination of Urinary Adrenal Steroids by Gas-Liquid Chromatograpny Ann. Clin. Biochem. 9(3) 88-90 (1972) CA 78 81660a... 

Cortisone Reductase DeGciency. In hirsutism and virilization in females, cortisone reductase deficiency has been described. Patients with this disorder convert all their cortisol into cortisone. This gives rise to an apparent cortisol deficiency. Adrenocorticotropic hormone increases and stimulates the adrenal steroid synthesis. The urinary steroid profile is characterized by a very high excretion of THE, cortolones, and adrenal androgens, and low excretion of THF and 5a-THF [33]. 

The answer is e. (Katzung, p 672. Hardman, pp 1477—1978.) Fludrocortisone is a synthetic steroid compound that exhibits profound mineralo-corticoid activity and some glucocorticoid activity Electrolyte and water metabolisms are affected by the administration of this compound. Fludrocortisone promotes the reabsorption of Na and the urinary excretion of K and hydrogen ions in the collecting duct of the nephron. The drug is indicated for mineralocorticoid replacement therapy in primary" adrenal insufficiency... 

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. 

Drug/Lab test interactions Naproxen use may result in increased urinary values for 17-ketogenic steroids. Temporarily discontinue naproxen therapy 72 hours before adrenal function tests are performed. 

After metyrapone administration, a patient with a disease of pituitary origin cannot achieve a compensatory increase in the urinary excretion of 17-hydroxycorti-costeroids or 11-deoxysteroids. Moreover, if pituitary corticotrophin is suppressed by an autonomously secreting adrenal carcinoma, there will be no increase in response to metyrapone. On the other hand, if pituitary corticotrophin secretion is maintained, as occurs in adrenal hyperplasia, the inhibition of corticoid synthesis produced by metyrapone will stimulate corticotrophin secretion and the release of metabohtes of precursor urinary steroids, which can be measured as 17-hydroxycortico-steroids. Metyrapone is now used less frequently in the differential diagnosis of Cushing s syndrome because of the ability to measure plasma corticotrophin directly. 

We found normal levels of conventional urinary steroids in this disorder, but these patients can show blunted response to ACTH, and adrenal hyperplasia is often noted post-mortem in nonsurviving newborns. Many distinctive metabolites have been found in urine from patients with the disorder, major examples being 5/3-prcgn-... 

Shackleton CH (1976) Congenital adrenal hyperplasia caused by defect in steroid 21-hydroxylase. Establishment of definitive urinary steroid excretion pattern during first weeks of life. Clin Chim Acta 67 287-298... 

Haack D, Engel R, Vecsei P (1978) The effect of chronic ACTH treatment on blood pressure and urinary excretion of steroids in the rat. Klin-Wochenschr 56(Suppl 1) 183—186 Harvey PW, Everett DJ (2003) The adrenal cortex and steroidogenesis as cellular and molecular targets for toxicity criti-... 

The most striking aspect of the endocrine response involves the adrenal cortex. Albright was among the first to observe a raised output of urinary steroids in injured patients and to note the similarity between the postoperative response and the changes of Cushing s syndrome (A2). 

The 17-KSs are metabolites of precursors secreted by the adrenal glands, the testes, and to some extent the ovaries. In men, approximately one third of the total urinary 17-KSs represent metabolites of testosterone secreted by the testes, whereas most of the remaining two thirds are derived from the steroids produced by the adrenal glands. In women, who normally excrete smaller quantities than men, the total 17-KS concentrations are derived almost exclusively from the adrenal glands. 

The bulk of the urinary 17-KSs consists of andro-sterone, epiandrosterone, etiocholanolone, DHEA, 11-keto-and lip-hydroxyandrosterone, and 11-keto- and 11(3-hydroxyetiocholanolone. DHEA and 11-oxygenated 17-KSs are produced only by the adrenal glands, whereas the others also arise from precursors (androstenedione and testosterone) elaborated by the gonads. Thus the main purpose of measuring these steroid metabolites is to assess adrenal androgen production. 

Elevated urinary free cortisol concentrations are highly suggestive of Cushing s syndrome. Normal reference values for urinary free cortisol are 20 to 90 meg per 24-hour period. It is not unusual to detect a twofold or threefold increase in urine cortisol in the patient with hyperfunction of the adrenal gland. Starvation, topical steroid application, hydration from water loading, and acute stress aU are capable of elevating the urine cortisol concentrations. Because other pathologic conditions can increase the amount of free cortisol, additional... 

Mitotane appears to be the drug of choice in inoperable functional and nonfunctional adrenal carcinoma. Tumor regression is seen in approximately 35% to 50% of patients, with most regression occurring between the second and fourth month of therapy. Seventy-five percent of patients will exhibit a 30% fall in urinary steroids, with 50% of patients showing an improved clinical response after 5 months of... 

Striking anatomical changes take place in the adrenal glands of the human infant during the first few days and weeks of life (B9, M6, S26, S31) while they are adapting from the type of steroid production necessary in utero to that required for independent life, and during this period considerable qualitative and quantitative changes occur in the urinary steroid output. 

Early studies with the group assays of urinary and blood steroids indicated that the newborn infant may go through a period of adrenal... 

Evidence that the A steroids are of adrenal origin has been supplied by Reynolds (R2), who showed that the urinary excretions of 16a-OH-DHA and 16-oxo-androstenediol were 0.3-1.4 mg/24 hours in a newborn female with the C-21 hydroxylase deficiency type of congenital adrenal hyperplasia. These fell to undetectable amounts with dexamethasone suppression therapy. A very low excretion of three 3y8-hydroxy-A steroids was found by the authors in the case of a baby shown subsequently at autopsy to have little adrenal tissue (see Section 11). Further circumstantial evidence is given when abnormalities are considered in Section 11 and also the effect of corticotropin in Section 12. 

M5. Mattox, V. R., Hayles, A. B., Salassa, R. M., and Dion, F. R., Urinary Steroid patterns and loss of salt in congenital adrenal hyperplasia. J. Clin. Endocrinol. 

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