Adrenal Function Testing

Introduction to Adrenal Function Testing

The American College of Emergency Medicine notes that etomidate can cause adrenal suppression, unlike valproate which has not been shown to have direct effects on cortisol synthesis 1

Valproate has been reported to have no significant effects on ACTH/cortisol circadian rhythmicity in humans, based on available studies 1
Etomidate can cause adrenal suppression by inhibiting 11β-hydroxylase 1

The Endocrine Society guidelines imply that there is no need to discontinue valproate therapy before performing the ACTH stimulation test, and standard interpretation criteria can be applied without adjustment 1
A normal response to the ACTH stimulation test is defined as a cortisol level >18 μg/dL at either 30 or 60 minutes after administration, with assay-specific cutoffs essential to avoid misclassification and overtreatment 2, 3
Measuring cortisol at both 30 and 60 minutes is important, as 54% of patients may reach peak cortisol levels at 60 minutes and 11% of patients who fail at 30 minutes may pass at 60 minutes 2
The high-dose (250 μg) ACTH test is preferred over the low-dose (1 μg) test due to similar diagnostic accuracy, ease of performance, and better standardization 2
A Cosyntropin stimulation test is the standard diagnostic test for adrenal insufficiency, requiring administration of 0.25 mg Cosyntropin intramuscularly or intravenously, followed by measurement of serum cortisol after 30 and/or 60 minutes 3

Alternative criteria for relative adrenal insufficiency include delta cortisol <9 μg/dL after ACTH administration or random cortisol <10 μg/dL, as recommended by the Society of Critical Care Medicine 2
In patients with altered binding proteins, such as those with cirrhosis or critical illness, alternative criteria for relative adrenal insufficiency include a delta total serum cortisol <250 nmol/L (9 μg/dL) after ACTH administration, or a random total cortisol <276 nmol/L (10 μg/dL) 4
Serum-free cortisol levels <50 nmol/L at baseline or <86 nmol/L after ACTH suggest RAI, and salivary cortisol (correlates with free cortisol): baseline <1.8 ng/ml or increment <3 ng/ml suggests RAI 4

In suspected acute adrenal crisis, treatment should never be delayed for diagnostic testing, and intravenous hydrocortisone should be administered immediately, with blood samples for cortisol and ACTH measurement obtained prior to treatment if possible 3, 1
For a patient with normal adrenal function, annual follow-up with assessment of health and well-being, measurement of weight, blood pressure, and serum electrolytes, and monitoring for development of autoimmune disorders, particularly hypothyroidism, is recommended 3
Attributing non-specific symptoms to adrenal dysfunction, overlooking other endocrine disorders, and premature treatment without clear diagnostic evidence should be avoided, as they can lead to unnecessary side effects and complications 3, 2

Weight status may affect timing of peak response, with overweight/obese individuals tend to peak at 30 minutes and normal/underweight individuals tend to peak at 60 minutes 2
The American College of Emergency Medicine recommends that treatment with intravenous hydrocortisone should never be delayed for diagnostic testing in cases of suspected acute adrenal crisis 1