Who should a patient with hypercortisolism be referred to?

Who to Refer for Elevated Cortisol

Patients with confirmed hypercortisolism should be referred to an endocrinologist for further evaluation and treatment. 1

When to Refer to an Endocrinologist

Refer immediately when screening tests are abnormal:

• If one or more initial screening tests (late-night salivary cortisol, 1-mg dexamethasone suppression test, or 24-hour urinary free cortisol) are abnormal 1
• When patients have normal screening results but high clinical suspicion of Cushing's syndrome persists 1
• If late-night salivary cortisol values are significantly elevated (e.g., 290 and 275 ng/dL), which strongly suggest loss of normal circadian rhythm 2

The Endocrine Society provides strong recommendations for endocrinology referral based on the rationale that subsequent diagnostic testing requires considerable expertise both clinically and in the laboratory, such that specialist referral is associated with better outcomes. 1

Why Endocrinology Referral is Critical

Diagnostic complexity requires specialized expertise:

• Determining ACTH dependency through morning plasma ACTH measurement (>5 ng/L suggests ACTH-dependent disease) 2
• Localizing the source using pituitary MRI, CRH stimulation testing, and bilateral inferior petrosal sinus sampling for ACTH-dependent disease 2
• Distinguishing between pituitary, ectopic, and adrenal sources requires sophisticated testing algorithms 2

Treatment decisions demand specialized knowledge:

• Transsphenoidal surgery for Cushing's disease should be performed at specialized Pituitary Tumor Centers of Excellence with experienced neurosurgeons 1
• Medical therapy options (ketoconazole, osilodrostat, metyrapone, mifepristone, cabergoline) require careful selection and monitoring by specialists 3
• Bilateral adrenalectomy decisions and lifelong hormone replacement management necessitate endocrine expertise 3

Additional Specialist Referrals

Refer to hypertension specialist or endocrinologist for primary aldosteronism:

• When screening is positive with elevated plasma aldosterone-to-renin ratio in patients with resistant hypertension, hypokalemia, adrenal mass, or family history of early-onset hypertension 1

Refer to neurosurgery at high-volume centers:

• Hospitals limiting TSS to specialized neurosurgeons show better outcomes, fewer complications, shorter stays, and lower costs 1
• Surgeons with >200 TSS procedures have the lowest complication rates 1
• Regionalized teams of 4-5 experts per 2.5-5 million inhabitants optimize outcomes 1

Urgent Referral Situations

Immediate endocrinology consultation for severe hypercortisolism:

• Life-threatening complications including severe opportunistic infections, particularly in patients with small cell lung cancer and ectopic ACTH syndrome 1
• Increased venous thromboembolism risk (2% without surgery, 4% after surgery) due to elevated clotting factors 1
• Severe metabolic decompensation with uncontrolled diabetes and hypertension 4

Hypercortisolism must be controlled before cancer chemotherapy or surgery to reduce therapy-induced complications and mortality. 1

Common Pitfalls to Avoid

Do not delay referral for "borderline" results:

• Even mild autonomous cortisol secretion (present in up to 2% of individuals >60 years, 10% with uncontrolled hypertension/diabetes) increases mortality risk 5
• Degree of cortisol suppression on dexamethasone testing correlates with cortisol-related consequences and mortality 5

Do not attempt complex diagnostic workup in primary care:

• False positives occur with severe obesity, alcoholism, depression, and disrupted sleep-wake cycles 2
• Cyclic Cushing's syndrome requires periodic repeated testing as cortisol fluctuates 2
• These nuances require endocrinology expertise to navigate 1, 2

Do not underestimate the urgency:

• Untreated hypercortisolism leads to cardiovascular disease, diabetes, osteoporosis, immunologic disorders, and increased mortality 2
• Early diagnosis and treatment prevent irreversible complications 6