A 71-year-old woman with shock and a high INR

Other possible steps

Abdominal CT should be done in our patient to address the possibility of bilateral adrenal hemorrhage. However, it is preferable to wait until the patient is stabilized.

Echocardiography. Our patient is likely to have an element of cardiac failure, given her hypertension and cardiomegaly. However, decompensated heart failure is probably not the cause of her presentation. Thus, the first priority is to treat her adrenal crisis, and echocardiography should be deferred.

Increasing the norepinephrine infusion is unlikely to improve her blood pressure very much, as she is significantly volume-depleted. Further, low cortisol decreases the vascular response to norepinephrine.¹⁵

Mineralocorticoids such as fludrocortisone are used to treat primary adrenal insufficiency. However, they are not required during acute management of adrenal crisis, as 40 mg of hydrocortisone offers mineralocorticoid activity equivalent to 100 µg of fludrocortisone. Thus, the high doses of hydrocortisone used to treat adrenal crisis provide adequate mineralocorticoid therapy.^10,18

If dexamethasone is used, its effect along with normal saline supplementation would be sufficient to replete the intravenous space and bring the sodium level back up to normal in the acute setting.

CASE RESUMED: IMPROVEMENT WITH HYDROCORTISONE

The patient’s blood is drawn for serum cortisol and plasma ACTH measurements. A 100-mg intravenous bolus of hydrocortisone is given, followed by a 50-mg bolus every 6 hours until the patient stabilizes.

Twenty-four hours later, the patient states that she has more energy, and her appetite has improved. The norepinephrine infusion is stopped 48 hours after presentation, at which time her blood pressure is 120/70 mm Hg, heart rate 85 beats per minute and irregular, and temperature 36.7°C (98.1°F). Her current laboratory values include the following:

• Serum sodium 137 mmolL
• Serum potassium 4.3 mmol/L
• Hemoglobin 9.3 g/dL
• Serum cortisol (random) 7.2 μg/dL
• Plasma ACTH 752 pg/mL (10–60 pg/mL).

ESTABLISHING THE DIAGNOSIS OF ADRENAL INSUFFICIENCY

3. Which of the following is the most appropriate test to establish the diagnosis of adrenal insufficiency?

• 7 am total serum cortisol measurement
• Random serum cortisol measurement
• 7 am salivary cortisol measurement
• 24-hour urinary free cortisol measurement
• ACTH stimulation test for cortisol
• Insulin tolerance test for cortisol

These tests also help determine the type of adrenal insufficiency (primary, secondary, or tertiary) and guide further management. Secondary adrenal insufficiency is caused by inadequate pituitary ACTH secretion and subsequent inadequate cortisol production, whereas tertiary adrenal insufficiency is caused by inadequate hypothalamic corticotropin-releasing hormone secretion and subsequent inadequate ACTH and cortisol production. The diagnosis of adrenal insufficiency relies first on demonstrating inappropriately low total serum cortisol production. Subsequently, serum ACTH helps to differentiate between primary (high ACTH) and secondary or tertiary (low or inappropriately normal ACTH) adrenal insufficiency.

Each test listed above may demonstrate a low cortisol level. However, in a nonacute setting, safety concerns (especially regarding insulin tolerance testing), poor diagnostic value, feasibility (ie, the difficulty of 24-hour tests), and poor sensitivity of 7 am cortisol make the ACTH stimulation test the most appropriate test in clinical practice to establish the diagnosis of adrenal insufficiency.

7 am serum cortisol measurement

Measuring the serum cortisol level early in the morning in the nonacute setting could be of diagnostic value, as an extremely low value (< 3–5 μg/dL) is almost 100% specific for adrenal insufficiency in the absence of concurrent exogenous steroid intake. However, the very low cutoff for this test causes poor sensitivity (about 33%), as many patients have partial adrenal insufficiency and hence have higher serum cortisol levels that may even be in the normal physiologic range.^19–22

Random serum cortisol measurements

Random serum cortisol measurements are not very useful in a nonacute setting, since cortisol levels are affected by factors such as stress and hydration status. Moreover, they fluctuate during the day in a circadian rhythm.

On the other hand, random serum cortisol is a very good test to evaluate for adrenal insufficiency in the acute setting. A random value higher than 15 to 18 μg/dL is almost always associated with adequate adrenal function and generally rules out adrenal insufficiency.^11,23,24