Clinical Significance Of The Investigations Of Adrenal Cortical Disorders
Investigations Of Adrenal Cortical Disorders
These investigations involve urinary cortisol, metabolites of sex hormones, metyrapone test, 17 ketogenic steroids (17-KGS) and many more.
Measurement of adrenal steroids- 11-hydroxycorticosteroid: Levels of this hormone in plasma, urine or adrenal tissue can be estimated.
Urinary cortisol: Level of free cortisol excreted in urine depends on the plasma level of unbound cortisol. Normal range is 30-40 micromol (100- 150 ug) in 24 hours.
Urinary 17-hydroxycorticoids (17-OHCS): These are excretory products of cortisol and 30% of the total output appears in urine as the glucuronides. The steroid can be liberated by enzyme glucuronidase. The free steroids can be estimated as 17 OHCS. Normal range is below 1.3 mg/Kg body weight in 24 hours.
Aldosterone and its derivatives: Normal plasma concentration estimated by RIA is 10 ng/dl, and the urinary excretion is 10 ug/day.
Metabolites of sex hormones [17- Ketosteroids (17 KS)]: These are androsterone and etiocholonalone which are derived mainly from androgens and their precursors. These appear in urine. Part of the urinary 17-KS is derived from cortisol. In males, testicular androgens contribute one third of the urinary 17 KS, the rest being derived from adrenal androgens. In women, the whole of the 17 KS is derived from adrenal hormones. Normal range is 5- 25mg/ 24 hours in males and 3- 20 mg/24 hours in females.
17 Ketogenic steroids (17-KGS): These are derived from cortisol, cortisone and pregnanetriol. Oxidising agents like sodium bismuthate convert KGS into ketosteroids. Estimation of urinary 17 KGS is less specific diagnostically since it is derived from a wide range of precursors. Normal daily excretion varies from 5- 22mg in men and 5- 15mg in women.
Secretory activity of the adrenal cortex: Cortisol secretory rate can be determined isotopically. Normal value is 250- 840 micromols/ 24 hours. Other hormones can also be estimated by RIA. The plasma levels of cortical hormones and urinary values generally correlate, but this relationship is disrupted in pregnancy, hyperthyroidism, hypothyroidism and hepatic insufficiency.
Hypothalamic- Pituitary- Adrenal Axis
The Pituitary- Adrenal System
Test For Pituitary- Adrenal Interaction
These tests are designed to evaluate
- The reserve of the adrenal cortex
- ACTH secreting capacity and
- Normal pituitary adrenal feed back control
Adrenal Reserve: The estimation of plasma and/or urinary steroids before and during ACTH administration reveals the responsiveness of the adrenal cortex to ACTH (ACTH is infused intravenously for 8 hours at the rate of 5 U/hour and plasma levels of cortisol are estimated prior to and during the infusion). Irrespective of the initial values normal subjects show an elevation of 10- 25 ug/dl in the first hour and 15- 40 ug/dl in the eight hour of the infusion. Urinary 17 OHS is estimated in 24 hours collections of urine done before and just after commencement of the ACTH infusion. Normally, urine contains 3- 7mg of 17 OHS/g of creatinine. With the infusion of ACTH urinary 17 OHS rises to 1.5 to 2.5 times the normal range.
Metyrapone test: This test detects disorders in the mechanism of control of cortisol production by ACTH and corticotrophin releasing factor (CRF). Metyrapone inhibits 11- beta-hydroxylase which is one of the enzymes required for cortisol biosynthesis. Reduction in plasma cortisol stimulates CRF production by the hypothalamus and ACTH secretion by the pituitary. These hormones stimulate the adrenal cortex to produce glucocorticoids. Since metyrapone blocks 1-beta-hydroxylase which is required for cortisol secretion, the alternate product 11- deoxycortisol is formed instead. Rise in the production of 11- deoxycortisol is reflected as a rise in urinary 17- hydroxycorticoids.
Metyrapone is given in a dose of 10 mg/Kg of ideal body weight every 4 hours for 24 hours (6 doses). Normal subjects show a two fold increase in urinary 17- OHS the same day or on the next day. When the test is negative, it may be due to disorders of the hypothalamus, pituitary or adrenal cortex or failure of metyrapone to suppress the enzyme. A positive response to exogenous ACTH suggests that the adrenal is not at fault and that the lesion is in the controlling mechanisms.
Dexamethasone Suppression test: Exogenous or endogenous glucorcoticoids normally suppress ACTH secretion. This feed back inhibition is lost in Cushing’s syndrome. Dexamethasone is given in a dose of 0.5mg 6 hourly for 2 days. Urinary 17 OHCS comes down below 2.5 mg/day and plasma cortisol falls below 2 mg/dl on the second day of the test. In the modified dexamethasone suppression test, 2 mg dexamethasone is given 6 hourly.
Normal subjects show prompt suppression even when small doses of dexamethasone are administered. In adrenal hyperplasia, suppression can be achieved only with the higher dose. In the case of adenoma, carcinoma and actopic sources of ACTH, cortisol production is not suppressed even by higher doses of dexamethason.
Demonstration of Lesion
Adrenals can be visualized radiologically, especially if they are calcified. In many cases, the rumours are 4 to 6 cm in diameter by the time they show endocrine abnormalities. Alteration in renal outline seen in intravenous pyelography should suggest adrenal neoplasms. Adrenal arteriography helps in visualizing the tumour. Contrast radiography after presacral air insufflations was employed to delineate tumours before the advent of CT and ultrasonography. These noninvasice methods have made demonstration of adrenal tumours easier. Selective catheterization of adrenal vein gives information about the secretion of the gland.
© 2014 Funom Theophilus Makama