Learn more about the importance of referral for suspected hypercortisolism and the critical role of DCESs and primary care clinicians in the process.

The following content is made possible due to educational grant support from Corcept Therapeutics. Content was developed independently by ADCES. 

The Essential Role of Referral

Hypercortisolism is a complex condition that requires specialized expertise for definitive diagnosis and effective management. When an individual has a positive screening test, the most important next step is referral to an endocrinology practitioner, which is critical for further evaluation that may include additional biochemical testing, as well as imaging studies.

Diabetes Care and Education Specialists (DCESs) and primary care clinicians are central to this process, providing essential information and insights to facilitate the endocrinology practitioner’s work, guiding the individual with hypercortisolism to appropriate care and improved clinical outcomes. In this module, we will review the key steps DCESs and other clinicians can take to ensure appropriate referral, effective communication, and timely specialist evaluation for suspected hypercortisolism.

Starting With The Screening Test

As discussed in the preceding module, testing for hypercortisolism is a straightforward and meaningful next step to take once hypercortisolism is suspected. The priority is to identify people most likely to be at risk for hypercortisolism based on clinical features and comorbidities, including individuals with difficult-to-manage T2D.

When clinical suspicion is high, a screening test is warranted. The 1-mg overnight dexamethasone suppression test (DST) is simple and recommended for initial screening due to its high sensitivity (95% when using a post-DST serum cortisol cutoff of >1.8 μg/dL). For a step-by-step guide for providing DST testing, see the previous module.

Beyond the Screen: Ensuring Specialized Care

When a DST result is positive (post-DST serum cortisol >1.8 μg/dL), referral to an endocrinology practitioner is recommended for further evaluation, which may include additional biochemical tests and imaging studies. To facilitate further evaluation, the referring clinician should clearly communicate the individual’s relevant medical history, clinical findings, reasons that hypercortisolism is suspected, and results of screening tests so far.

By providing comprehensive and detailed information at the time of referral, DCESs and primary care clinicians can help to facilitate and expedite specialist care, which is essential for developing an individualized care plan, and ultimately, improving clinical outcomes.

The Endocrinology Practitioner's Playbook: Searching for the Source

Biochemical Testing

Further evaluation by an endocrinology practitioner may include additional biochemical testing as needed to determine the underlying cause. This additional testing accelerates the diagnostic process by determining the causes of elevated cortisol, which helps guide subsequent imaging decisions, and ultimately helps guide treatment decisions, as discussed in the next module in this guide.

Additional evaluation typically includes obtaining plasma adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEA-S) levels to determine the cause of cortisol excess:

• Low to low-normal ACTH and low DHEA-S levels point toward an ACTH-independent source of hypercortisolism (e.g., an adrenal tumor).
• A normal to high ACTH suggests an ACTH-dependent source, most commonly an ACTH-secreting benign pituitary tumor. Less commonly, the source is ectopic ACTH secretion from a non-pituitary tumor.

Imaging

Based on clinical findings and biochemical results, imaging may be performed. This might involve computed tomography (CT) to evaluate an adrenal mass, or magnetic resonance imaging (MRI) with contrast to evaluate the pituitary gland, depending on the biochemical test findings.

Putting it All Together

Once biochemical and imaging results are obtained, they need to be interpreted in the context of the individual’s medical history and current clinical presentation, including the presence of comorbidities such as T2D, hypertension, and obesity. This clinical assessment may include history of difficult-to-manage diabetes, difficult-to-manage hypertension, renal impairment, and obesity, including obesity that persists despite use of GLP-1 receptor agonist-based medications.

Key Takeaways

• By making informed referrals, DCESs and primary care clinicians can significantly impact patient health, reducing delays in diagnosis and serious health issues often associated with hypercortisolism.
• Referral to an endocrinology practitioner is warranted when screening test results are positive (e.g., post-DST serum cortisol >1.8 μg/dL).
• To facilitate further evaluation, the referring clinician should clearly communicate the patient’s relevant medical history, clinical findings, reasons that hypercortisolism is suspected, and results of screening tests.
• Providing comprehensive and detailed information at the time of referral facilitates and expedites specialist care that is essential for individualized care plans and improving clinical outcomes.

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