Should a stimulation test (STIM) or dexamethasone suppression test (DST) be performed in a patient with elevated adrenocorticotropic hormone (ACTH) levels and morning cortisol levels, presenting with difficulty losing weight, but no hypotension, electrolyte imbalance, or salt cravings?

From the Guidelines

A dexamethasone suppression test (DST) is the most appropriate next step in evaluating this patient's condition, given the provided ACTH and morning cortisol levels, and the presence of symptoms such as difficulty losing weight without signs of adrenal insufficiency. The patient's ACTH level of 12 and morning cortisol of 23.9, combined with symptoms of difficulty losing weight but absence of hypotension, electrolyte imbalances, or salt cravings, suggests possible hypercortisolism rather than adrenal insufficiency. According to the consensus guideline update on the diagnosis and management of Cushing's disease 1, if Cushing's disease (CD) is suspected, starting with either urinary free cortisol (UFC) and/or late-night salivary cortisol (LNSC) or DST could be an option. Given the patient's presentation, a DST would be more suitable to determine if there is appropriate suppression of cortisol with dexamethasone, which would help rule out Cushing's syndrome.

• Key points to consider:
  • The normal morning cortisol level is elevated at 23.9, while the ACTH is within normal limits.
  • Symptoms suggest possible hypercortisolism rather than adrenal insufficiency.
  • DST is useful in diagnosing Cushing's syndrome, especially when UFC or LNSC is not feasible or in specific patient populations like shift workers, as noted in the guideline update 1.
• The overnight 1mg dexamethasone suppression test involves taking 1mg of dexamethasone at 11 PM and measuring cortisol at 8 AM the following morning, with a normal response being suppression of cortisol to less than 1.8 μg/dL.
• An ACTH stimulation test would be more appropriate if adrenal insufficiency was suspected, which is not supported by the patient's normal ACTH level, normal-to-high cortisol, and absence of symptoms like hypotension or electrolyte abnormalities.

From the FDA Drug Label

1. 6 Interpretation of Plasma Cortisol Levels after Cosyntropin for Injection • Stimulated plasma cortisol levels of less than 18 mcg/dL at 30- or 60-minutes post cosyntropin for injection are suggestive of adrenocortical insufficiency.

The patient's AM cortisol level is 23.9, which is above the threshold for adrenocortical insufficiency. However, the ACTH level is 12, which may indicate a potential issue with adrenal function. Given the patient's difficulty losing weight and the absence of other symptoms such as hypotension, electrolyte imbalance, or salt cravings, a STIM test (e.g., Cosyntropin stimulation test) may be considered to further evaluate adrenal function 2. However, it is essential to note that the decision to perform a STIM or DST should be made on a case-by-case basis, taking into account the patient's overall clinical presentation and medical history. No conclusion can be drawn regarding the necessity of a DST (Dexamethasone Suppression Test) based on the provided information.

From the Research

Adrenal Insufficiency Diagnosis

The given ACTH level is 12 and am cortisol is 23.9. To determine if a STIM (cosyntropin stimulation test) or DST (dexamethasone suppression test) should be performed, we need to consider the following points:

• The patient's symptoms, such as difficulty losing weight, do not include hypotension, electrolyte imbalance, or salt cravings.
• The cosyntropin stimulation test is used to diagnose adrenal insufficiency, and its interpretation depends on the assay used to measure cortisol levels 3, 4.
• The normal cortisol response to cosyntropin stimulation is ≥18 μg/dL (500 nmol/L) using older serum cortisol assays, but newer specific cortisol assays may have lower thresholds for a normal response 3.
• A study using the Roche Elecsys II assay proposed lower thresholds of 14.6 μg/dL for a normal response 3, while another study using the Abbott Architect immunoassay proposed a threshold of 14.6 μg/dL at 60 minutes after stimulation 4.

Test Selection

Considering the patient's symptoms and the given ACTH and cortisol levels, the following points are relevant:

• The cosyntropin stimulation test is the initial endocrine evaluation of suspected primary or secondary adrenal insufficiency 5.
• The test performs well in patients with primary adrenal insufficiency, but its sensitivity is lower in patients with secondary adrenal insufficiency 5.
• The dexamethasone suppression test is used to diagnose hypercortisolism (Cushing's syndrome) and may be considered if clinical suspicion is high despite normal results on screening tests 6.
• Clinicians should be aware of the new cutoffs for the assays available to them when evaluating patients for adrenal insufficiency 3, 4.

Key Points to Consider

• The patient's clinical presentation and likelihood of adrenal insufficiency before testing should be taken into account when interpreting the results of the cosyntropin stimulation test 7.
• Technical aspects such as time of day, type of assay, and sample source used for cortisol measurement can affect the clinical value of the test 7.
• The use of assay-specific cutoffs is essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency 4.