Cortisol function tests

Oral contraceptives have their most significant effect on endocrine parameters. Blood cortisol, thyroxine, protein-bound iodine, T3 uptake, and urinary free cortisol are elevated. Urinary 17,21-dihydroxy steroids, 17-ketosteroids, and estrogens are decreased. There is no effect on urinary catecholamines or VMA (Table 10) (LIO). The effect of thyroid functions tests is due to the administered hormone stimulating an increase in the production of thyroid-binding globulin which in turn binds 1-thyroxine. The lowering of free thyroxine stimulates the anterior pituitary to produce thyrotropin, which in turn stimulates the thyroid to produce more thyroxine. Since the additional thyroxine is bound to the extra protein, there is an equilibrium and the patient remains clinically euthyroid, but the protein-bound iodine and the thyroxine are elevated. 

The clinical biochemistry laboratory is commonly called upon to establish if there is excessive hormone secretion. Simple screening test.s to eliminate other diagnoses are followed by more complicated dynamic tests. If a pituitary tumour is suspected, it is important to establish the extent of damage to other pituitary functions. The combined anterior pituitary function test (Fig. 3) is used here. TRH. GnRH and insulin are given from separate. syringes. All hormones are measured at 0, 30 and 60 min, and cortisol and GH additionally at... 

There are functional tests in which ACTH or glucocorticoid measurements can be made following the administration of metyrapone, which inhibits adrenal llp-hydroxylase activity and causes a transient reduction in cortisol synthesis and increased secretion of 11-deoxycortisol (Orth et al. 1988), or dexamethasone suppression tests. However, these are not commonly employed in toxicological studies. 

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. 

The dexamethasone suppression test is the best way to evaluate the pituitary-adrenocortical axis function in horses. In normal horses, dexamethasone administration in the late afternoon, by intramuscular (i.m.) injection at a dose rate of 40 xg/kg (approximately 20 mg for a 450 kg horse), depresses cortisol production to less than lOng/ml (IfjLg/dl) by the following morning and cortisol levels will remain well below baseline for over 24 h. Cortisol levels are usually slightly depressed after dexamethasone administration to horses with ECD but the degree of suppression is less than in normal horses and plasma cortisol concentrations rebound more quickly. 

The lowered detection limits of the newer two-site immunoassays for the measurement of pituitary hormones now make it possible to distinguish an abnormally low value from the lower end of the normal reference interval. Although assessment of a particular aspect of pituitary function should also include clinical signs and symptoms of hormone deficiency and the measurement of hormones secreted by the pertinent endocrine gland (e.g., T4, cortisol, and testosterone), the newer, ultrasensitive assays for TSH, FSH, LH, and ACTH allow for an accurate distinction of a true low result from low normal. A scheme for testing of pituitary reserve is fisted in Box 50-6. 

Pituitary reserve is almost never compromised in patients with small pituitary tumors, so testing is usually limited to patients with large tumors or specific clinical indications, (see Box 50-6, A). For most patients with large pituitary tumors, in addition to history and physical examination, an adequate evaluation of endocrine function before surgery can be performed based on laboratory measurements of serum PRL, TSH, LH, FSH, sex steroids (testosterone in males and estradiol in females), serum sodium, and results of a morning serum cortisol or ACTH stimulation test. 

An understanding of the metabolism of cortisol is important in interpreting tests designed to evaluate alterations in cortisol production rates and disorders of adrenal function. Less than 2% of cortisol is excreted unchanged in the urine. As a result of its tight binding to CBG, cortisol is... 

A less risky indirect test of HPA axis function involves the administration of metyrapone, an inhibitor of the liP-hydroxylase enzyme that converts 11-deoxycortisol to cortisol. In normal individuals, the fall in the plasma cortisol concentration that accompanies the metyrapone-induced... 

Cushing s syndrome is an uncommon disorder but many of the usual signs and symptoms of this syndrome are seen in patients with normal adrenal function. The initial diagnosis of Cushing s syndrome, particularly in mild or early disease, rests on laboratory evidence of excessive and autonomous cortisol production. Two simple screening tests are... 

Fig. 2. Schematic representation of tests using exogenous ACTH, dbcAMP and pregnenolone (indicated by black horizontal arrows) of the functional integrity of teleost adrenocortical cells exposed to an adrenotoxicant (TOX). A lack of secretory response to ACTH (pattern A, black vertical arrow with X to show disrupted pathways) indicates a general dysfunction of the secretory pathways, possibly involving the ACTH receptor. No response to ACTH but a secretory response to dbcAMP, an analog of cAMP (pattern B), indicates that the steps downstream from cAMP are functional (white arrow bar) but steps upstream are disrupted by the toxicant. No response to ACTH or dbcAMP with a response to pregnenolone (pattern C) indicates that steps downstream from this precursor of cortisol are functional. Note that the concentrations of ACTH, dbcAMP and pregnenolone used in these functional in vitro tests should be physiological rather than pharmacological.

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