A 71-year-old woman with shock and a high INR
7 am salivary cortisol measurement
The same principle applies to early morning salivary cortisol. Only extremely low values (< 2.65 ng/mL) may distinguish patients with adrenal insufficiency from healthy individuals, with 97.1% sensitivity and 93.3% specificity.25
Of note, early morning salivary cortisol is not routinely measured in most clinical practices for evaluation of adrenal function. Hence, morning serum and morning salivary cortisol are useful screening tools and have meaningful results when their values are in the extremes of the spectrum, but they are not reliable as a single test, as they may overlook patients with partial adrenal insufficiency.
Urinary cortisol measurement
Urinary cortisol measurement is not used to diagnose adrenal insufficiency, as values can be normal in patients with partial adrenal insufficiency.
The ACTH stimulation test
The ACTH stimulation test involves an intramuscular or intravenous injection of cosyntropin (a synthetic analogue of ACTH fragment 1–24 that has the full activity of native ACTH) and measuring total serum cortisol at baseline, 30 minutes, and 60 minutes to assess the response of the adrenal glands.
The test can be done using a high or low dose of cosyntropin. The Endocrine Society’s 2016 guidelines recommend the high dose (250 μg) for most patients.10 The standard high-dose stimulation test can be done at any time during the day.26 If the cosyntropin is injected intravenously, any value higher than 18 to 20 μg/dL indicates normal adrenal function and excludes adrenal insufficiency.27,28 If intramuscular injection is used, any value higher than 16 to 18 μg/dL at 30 minutes post-consyntropin excludes adrenal insufficiency.29
The ACTH stimulation test may not exclude acute secondary or tertiary adrenal insufficiency.
Insulin tolerance testing
Insulin tolerance testing remains the gold standard for diagnosing adrenal insufficiency and assessing the integrity of the pituitary-adrenal axis. However, given its difficulty to perform, safety concerns, and the availability of other reliable tests, its use in clinical practice is limited. It is nonetheless useful in assessing patients with recent onset of ACTH deficiency.30,31
CASE RESUMED: PATIENT DISCHARGED, LOST TO FOLLOW-UP
Abdominal CT without contrast is done and demonstrates bilateral adrenal hemorrhage. Thus, the patient is diagnosed with primary acute adrenal insufficiency due to adrenal necrosis.
She is started on oral hydrocortisone and fludrocortisone after intravenous hydrocortisone is discontinued. She is counseled about adhering to medications, wearing a medical alert bracelet, giving herself emergency cortisol injections, taking higher doses of hydrocortisone if she is ill, and monitoring her INR. She is discharged home after her symptoms resolve.
The patient does not keep her scheduled appointment and is lost to follow-up. She returns 2 years later complaining of fatigue and feeling unwell. She admits that she stopped taking hydrocortisone 1 year ago after reading an online article about corticosteroid side effects. She has continued to take fludrocortisone.
MINERALOCORTICOID VS CORTICOSTEROID DEFICIENCY
4. Which of the following is least likely to be present in this patient at this time?
- Intravascular volume depletion
- Hyponatremia
- Skin hyperpigmentation
- Normokalemia
- Elevated serum ACTH level
Intravascular volume depletion
Intravascular volume depletion is the least likely to be present. This is because intravascular volume depletion is mainly secondary to mineralocorticoid deficiency rather than corticosteroid deficiency, which is not present in this patient, as she is compliant with her mineralocorticoid replacement therapy.32,33 However, even with sufficient mineralocorticoid replacement, mild hypotension may be present in this patient due to corticosteroid deficiency-induced loss of vascular tone.
Hyponatremia
Hyponatremia in adrenal insufficiency is not due only to mineralocorticoid deficiency. Patients with secondary or tertiary adrenal insufficiency may also exhibit hyponatremia.34 ACTH deficiency in such patients is not expected to cause mineralocorticoid deficiency, as ACTH has only a minor role in aldosterone production.
It has been proposed that hyponatremia in secondary adrenal insufficiency is due to cortisol deficiency resulting in an increase of antidiuretic hormone secretion.35,36 The mechanisms for increased antidiuretic hormone include cortisol deficiency resulting in an increased corticotropin-releasing hormone level, which acts as an antidiuretic hormone secretagogue,37,38 and cortisol directly suppressing antidiuretic hormone secretion.39
In our patient, volume expansion and hyponatremia are expected due to increased antidiuretic hormone secretion as a result of corticosteroid insufficiency.
