Adrenal cortex measurement

Historically the only melanocortin peptide to be used clinically is the parent hormone from which all these peptides are derived from namely ACTH (see above). It has also been used in the treatment infantile spasms for epilepsy, where it is administered as an intramuscular injection only over a 2-12 weeks period. Obvious side effects include weight gain, puffy face, high blood pressure and an increased risk of infection and should never be administered to patients with diabetics, renal or heart failure. ACTH is also used as a stimulation test to measure adrenal cortex activity, i.e. production of cortisol and is used to ascertain whether someone has Addison s disease. 

Metyrapone is commonly used in tests of adrenal function. The blood levels of 11-deoxycortisol and the urinary excretion of 17-hydroxycorticoids are measured before and after administration of the compound. Normally, there is a twofold or greater increase in the urinary 17-hydroxycorticoid excretion. A dose of 300-500 mg every 4 hours for six doses is often used, and urine collections are made on the day before and the day after treatment. In patients with Cushing s syndrome, a normal response to metyrapone indicates that the cortisol excess is not the result of a cortisol-secreting adrenal carcinoma or adenoma, since secretion by such tumors produces suppression of ACTH and atrophy of normal adrenal cortex. 

Since the organs and tissues are not destroyed during a QWB A study (in contrast to the homogenisation of the organs and tissues for LSC-measurements), substructures can be distinguished clearly (e.g. adrenal medulla and adrenal cortex often show very different concentrations of radioactivity). 

Diagnostic use as a test of the capacity of the adrenal cortex to produce cortisol with the short test, the plasma cortisol (hydrocortisone) concentration is measured before and after an i.m. injection of tetracosactride (Synacthen) a normal response is a rise of more than 200 nanomol/1 in the plasma concentration of hydrocortisone. Longer variants of the test in cases of difficulty involve use of the depot (sustained-release) formulation i.m. For example, 1 mg of the depot is injected daily for 3 days at 9.00 am, with a short tetracosactride test performed on day 3. 

It is felt, however, that true adrenocortical exhaustion is a very uncommon condition (C3) and low plasma values imresponsive to ACTH are found in only a minority of very ill people (M6). The adrenal cortex usually responds to prolonged stress by hypertrophy and measurements of cortisol after prolonged stress show that they are frequently high (C12). True adrenal exhaustion or insufficiency can be diagnosed only when the plasma cortisol levels are constantly low and do not respond to ACTH stimulation. 

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). 

Cortisol secretion fluctuates widely throughout the day, and single. serum measurements are of little value in clinical practice. There is a marked diurnal rhythm. Dynamic tests of cortisol production involving stimulation of the adrenal cortex by synthetic ACTH. or of stimulation or suppression of the whole HPA axis, form an important part of investigations of adrenocortical hyper- or hypofunction and are discussed on the following pages. 

An octopeptide hormone which is produced as a result of the action of a peptidase on angiotensin I. Its two main actions are the stimulation of aldosterone production from the adrenal cortex, and an action on the blood vessel walls causing vasoconstriction. It can be measured by radioimmunoassay. 

An androgenic steroid synthesized in the ovaries, testes and adrenals. It is an intermediate in the synthesis oif testosterone. Together with androstenedione, it constitutes one of the main androgens secreted by the adrenal cortex. It is one of the 17-oxosteroids which can be measured by the Zimmermann reaction. 

In order to determine the site of action of these two differing effects of peripherally administered catecholamines, the corticotropin releasing activity (as measured by the increase in adrenal corticosterone) of a crude acid extract of rat median eminence (MEE) was compared in rats in which the endogenous secretion of CRF was effectively Inhibited by a single subcutaneous injection of prednisolone (2.5 mg/lOO hours earlier) with animals given phentolamine only, steroid plus phentolamine, or normal saline only (see Table 3) Phentolamine injected 3-l/2 hours after the steroid and 30 minutes before use of the animals was without effect in preventing the stress of ether and intravenous saline and the response of the pituitary to MEE, nor did it affect the sensitivity of the adrenal cortex to injected ACTH. 

In order for the heme to combine with such ligands as oxygen and carbon monoxide, one electron must be introduced to form the ferrous state (Peterson et a/., 1977). The oxidation-reduction step has been measured for the purified cytochrome P450 from adrenal cortex mitochondria and from P auaomorm putida. In each case large negative values have been obtained and correlated with the reductive titration of cytochrome P450 in rat liver microsomes (Cooper et a/., 1977). 

Naturally there are obvious objections to this hypothesis for instance, Hechter (1951), in measuring the output of cortical hormones from the perfused adrenals of cows, was unable to find that the presence or absence of ascorbic acid in the perfusion fluid made any difference in the output. He would probably agree, however, that the conditions of his experiment were not precisely physiological, and the results cannot be taken as an indication of what ascorbic acid might be doing within the surviving cells of the cortex. 

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