Glucocorticoid, Mineralocorticoid, and Androgenic Function Assessment
Glucocorticoid Function
A single determination of cortisol or ACTH in blood is of little use, as their levels vary throughout the day (peak episodic secretion, circadian changes, influence of stress, etc.).
If the sample is drawn in the morning at 8:00 AM without stress, plasma cortisol concentration is 10-25 µg/dL, while at night (11:00 PM) it is usually less than 6 µg/dL. The determination of ACTH in both petrosal sinuses may help lateralize the location of an ACTH-secreting pituitary adenoma.
Urinary free cortisol excretion over two or three days indicates the integrated secretion of this hormone. In the absence of stress, persistently abnormal figures suggest adrenal dysfunction.
Cortisol secretion can also be evaluated by blood sampling throughout the day to see if cortisol levels vary according to the circadian rhythm (loss of circadian rhythm is characteristic of hypercortisolism).
Determinations of 11-deoxycortisol and 17-hydroxyprogesterone are useful for detecting disturbances in the function of the enzymes 11-hydroxylase and 21-hydroxylase, respectively. When these enzymes are deficient, their metabolites accumulate in the blood.
The determination of 17-hydroxycorticoids (Porter-Silber chromogens) in 24-hour urine is an index of adrenal activity, as it measures cortisol metabolites and several related compounds. The levels rise in hypercortisolism and fall in adrenal insufficiency. However, when there is a disturbance in the function of 11-hydroxylase, 17-hydroxycorticoids rise at the expense of 11-deoxycortisol, even though the patient has hypocortisolism.
Stimulation Tests
Stimulation tests are useful in assessing possible glucocorticoid hypofunction. An intravenous bolus of Synacthen (the first 24 amino acids of ACTH) raises plasma cortisol in healthy individuals, but in adrenal insufficiency, this response does not occur.
The administration of metyrapone inhibits 11-hydroxylase and induces a decrease in plasma cortisol, as it blocks the conversion of 11-deoxycortisol to cortisol. This decrease in cortisol increases ACTH, which stimulates the adrenal glands. However, the adrenals may only produce 11-deoxycortisol, which increases in blood and urine. If the response is low, it indicates insufficient axis function but does not identify the location of the lesion.
Hypoglycemia induced by insulin, vasopressin, and CRH are other stimuli that release ACTH, which under normal conditions causes an increase in plasma cortisol.
Adrenal antienzyme antibodies are positive in primary adrenal insufficiency of autoimmune origin.
Suppression Tests
Suppression tests are used to assess possible glucocorticoid hyperfunction. The Nugent test involves administering 1 mg of dexamethasone orally at 11:00 PM and taking a blood sample for cortisol at 8:00 AM the following day. Normally, dexamethasone at this dose inhibits the secretion of ACTH and therefore cortisol, which decreases to levels below 5 µg/dL. In hypercortisolism, this decline is not seen.
Dexamethasone may also be administered in doses of 0.5 mg every 6 hours to assess if cortisol levels fall in urine (if they do not drop, it suggests hypercortisolism).
If dexamethasone is given, it is expected that, in addition to lower cortisol levels, sex hormones will also diminish.
Mineralocorticoid Function
Mineralocorticoid function can be assessed by measuring aldosterone in plasma or urine and its regulatory hormone, angiotensin II, or plasma renin activity. Angiotensin I is generated from the action of circulating renin on angiotensinogen.
The normal levels of these hormones vary depending on the amount of salt in the diet, the position of the patient (walking or supine), and the time of day (circadian rhythm).
If aldosterone and angiotensin are persistently high, it may be due to secondary hyperaldosteronism, whereas if aldosterone is raised but angiotensin is suppressed, it suggests primary hyperaldosteronism.
Ambulation, alone or in combination with a diuretic such as furosemide, reduces circulating volume and increases the concentration of aldosterone and angiotensin in healthy individuals. However, in primary hyperaldosteronism, the renin-angiotensin system is not elevated.
Saline infusion (2 L in 4 hours) normally suppresses aldosterone secretion, except in primary hyperaldosteronism.
Androgenic Function
The determination of 17-ketosteroids in 24-hour urine is a somewhat specific measure of adrenal androgen production, as these are also produced by the gonads. To assess adrenal androgen secretion, dehydroepiandrosterone sulfate can be measured in blood.
Adrenal androgen reserve can also be assessed by measuring the response of androstenedione and dehydroepiandrosterone to Synacthen.
Anatomical Exploration
Ultrasound, CT, and MRI are valuable for assessing the anatomy of the adrenal glands. Scintigraphy with radioiodine-labeled cholesterol provides a picture of the functional anatomy of the adrenal cortex, as it is selectively taken up by this tissue.
For example, in hypercortisolism due to ACTH excess, diffuse uptake is seen in both adrenal glands, whereas in hypercortisolism due to a hyperfunctioning adenoma, uptake is seen localized in the adenoma, while the rest of the affected adrenal and the contralateral adrenal do not show uptake, as they are atrophied due to the lack of ACTH.