Recognizing the role of hypercortisolism in managing patients with difficult-to-control type 2 diabetes

Patients with difficult-to-control type 2 diabetes (T2D) are on multiple medications to lower blood glucose and/or blood pressure but still have an HbA1c greater than 7.5%. More than 25% of patients with type 2 diabetes fall into this category.1 Recent research has shown the prevalence of hypercortisolism in patients with difficult-to-control T2D can be as high as 24%.¹

In this article:

Clinical challenge | Why it matters | Ordering recommendations | Interpreting test results | Next steps | Supporting resources

Clinical challenge: Hypercortisolism is often overlooked as a driver of hyperglycemia 

Hypercortisolism is a condition of high cortisol levels that can negatively impact overall health in several ways, from metabolic complications to increased risk of cardiovascular events.²

Chronically elevated cortisol levels cause insulin resistance, hyperinsulinemia, and glucose intolerance, and disrupt the hypothalamic-pituitary-adrenal (HPA) axis—which can lead to psychiatric, metabolic, and immune disorders.³

While severe cases may present as Cushing syndrome, many patients lack classic symptoms and/or present nonspecific symptoms. This leads to frequent under-recognition and delayed evaluation of hypercortisolism.^4,5

Potential symptoms of high cortisol⁶

• Weight gain, particularly around the face (moon face) and abdomen
• Acne
• Thinning skin
• Susceptibility to bruising
• Flushed face
• Slow healing
• Muscle weakness
• Severe fatigue
• Irritability
• Difficulty concentrating
• High blood pressure
• Headache

Why it matters: Hypercortisolism is associated with significant morbidity and mortality risk¹⁰

Chronic elevated cortisol levels can impact nearly every organ system in the body, including cardiovascular, infectious, metabolic, reproductive, dermatologic, neuropsychiatric, and bariatric comorbidities.¹⁰

Hypercortisolism is independently associated with cardiovascular disease and the increased mortality seen in individuals with T2D.⁵

The significant morbidity and mortality risk associated with hypercortisolism¹⁰ reinforces the importance of cortisol level screening in primary care settings.

Hypercortisolism may affect a significant subset of T2D patients

Ordering recommendations: Hypercortisolism screening in primary care settings may be appropriate for certain T2D patients

Quest Diagnostics offers several tests for initial evaluation of hypercortisolism.

In primary care, screening for hypercortisolism may be appropriate for patients presenting with these clinical features:

• Persistent hyperglycemia despite intensified therapy
• Worsening hypertension or metabolic syndrome
• Progressive weight gain or central obesity

Clinical guidelines focus on screening for chronic high cortisol levels and Cushing syndrome with high-sensitivity tests including the dexamethasone suppression test (DST), dexamethasone levels, morning cortisol (Cortisol AM), and total cortisol.¹⁰

Recommended tests: Dexamethasone, cortisol testing for hypercortisolism

Dexamethasone Suppression Test (DST), 1 specimen

• Test code: 6921
• CPT® code: 82533

Clinical use: Diagnosing hypercortisolism

Dexamethasone

• Test code: 29391
• CPT® code: 80299*

Clinical use: Aiding the interpretation of DST (test code 6921)

Cortisol, AM

• Test code: 4212
• CPT® code: 82533

Clinical use: Evaluating for hypercortisolism

Cortisol, Total

• Test code: 367
• CPT® code: 82533

Clinical use: Evaluating for hypercortisolism

* CPT code is subject to a Medicare Limited Coverage Policy and may require a signed ABN when ordering.

Note: The CPT codes provided are based on American Medical Association guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Interpreting test results: Using cortisol test findings to guide further diagnostics and other recommendations

Cortisol, AM

Typically, cortisol levels are highest early in the morning and lowest at night. The normal morning serum cortisol (6:00-8:00 AM) range is 10-20 mcg/dL.¹² Elevated levels greater than 20 mcg/dL suggest possible hypercortisolism but alone are nonspecific, as they can be markers of stress or pseudo-Cushing states. Diurnal rhythm loss (elevated late-night cortisol) is more diagnostic.⁷

Cortisol, Total

Total serum cortisol measures both free and bound forms, with AM reference range 10-20 mcg/dL and PM reference range 3-10 mcg/dL.12 For hypercortisolism screening, total cortisol is used in conjunction with other tests. Isolated elevations are common in physiologic states and require confirmation with DST or urinary free cortisol.¹⁰

Next steps: Referral for further diagnostic evaluation and hypercortisolism management

Patients with suspected hypercortisolism should be referred to an endocrinologist for additional evaluation, etiologic determination, and condition management. Treatments do exist to lower cortisol levels and can significantly improve patient outcomes. Additional specialist referrals may be indicated depending on the underlying cause(s) of high cortisol levels.¹⁰

Supporting resources