What are the symptoms and treatment options for elevated cortisol levels?

Symptoms and Treatment of Elevated Cortisol

Elevated cortisol levels cause Cushing syndrome, characterized by hypertension, hyperglycemia, hypokalemia, and muscle atrophy, requiring targeted treatment based on the underlying cause. 1

Symptoms of Elevated Cortisol (Cushing Syndrome)

Physical Symptoms

• Weight gain, particularly central obesity with thin extremities 1
• Muscle atrophy and weakness 1
• Purple/red striae (stretch marks) on abdomen, thighs, breasts, and arms 1
• Increased fat deposits in face (moon face) and upper back (buffalo hump) 1
• Thin, fragile skin that bruises easily 1

Metabolic Symptoms

• Hypertension (high blood pressure) 1
• Hyperglycemia (high blood sugar) which may progress to diabetes mellitus 1, 2
• Hypokalemia (low potassium levels) 1
• Increased susceptibility to infections 2

Psychological Symptoms

• Depression and anxiety 1, 2
• Cognitive impairment 1
• Mood swings 1
• Sleep disturbances 1

Other Symptoms

• Menstrual irregularities in women 1
• Decreased libido and erectile dysfunction in men 1
• Increased pigmentation (in ACTH-dependent cases) 1
• Osteoporosis and increased fracture risk 2

Treatment Options Based on Etiology

1. ACTH-Dependent Cushing Syndrome (Pituitary or Ectopic Source)

Pituitary Tumors (Cushing's Disease)

• First-line treatment: Transsphenoidal surgery to remove the pituitary adenoma 1
• For unsuccessful surgery or recurrence, medical therapy options include:
  • Pasireotide - particularly if visible tumor remains 1
  • Cabergoline - especially in young women planning pregnancy 1
  • Steroidogenesis inhibitors (see below) 1

Ectopic ACTH-Producing Tumors

• Surgical removal of the ectopic tumor (lung, thyroid, pancreas, or bowel) when possible 1
• If unresectable:
  • Bilateral laparoscopic adrenalectomy 1
  • Medical management with steroidogenesis inhibitors 1
  • Octreotide for Octreoscan-positive tumors 1

2. ACTH-Independent Cushing Syndrome

Adrenal Adenoma

• Laparoscopic adrenalectomy 1
• Postoperative corticosteroid supplementation until HPA axis recovery 1

Adrenal Carcinoma

• Open surgical resection with removal of adjacent lymph nodes 1
• Consider adjuvant radiation therapy for high-grade carcinoma 1
• Follow-up imaging and biomarkers every 3-6 months 1

Bilateral Adrenal Hyperplasia

• If cortisol production is asymmetric: Unilateral adrenalectomy of most active side 1
• If cortisol production is symmetric: Medical management 1

3. Medical Management Options

For Mild-to-Moderate Disease

• Ketoconazole (400-1200 mg/day) - most commonly used due to availability and tolerability 1
• Monitor liver function tests regularly 1

For Severe Disease (Rapid Control Needed)

• Osilodrostat or metyrapone - response within hours 1
• Ketoconazole - response within days 1
• Etomidate - for hospitalized patients unable to take oral medications 1
• Combination therapy for severe hypercortisolism not responsive to monotherapy 1

Common Medication Options

• Steroidogenesis inhibitors:
  • Ketoconazole (400-1200 mg/day) 1
  • Metyrapone 1
  • Osilodrostat (twice-daily dosing) 1
  • Mitotane (rarely used) 1
• Glucocorticoid receptor antagonist:
  • Mifepristone - improves hyperglycemia and weight gain but requires expert management 1

Monitoring Treatment Effectiveness

• Regular assessment of cortisol levels (24-hour urine cortisol, morning cortisol, late-night salivary cortisol) 1
• Monitor for symptom improvement (blood pressure, glucose levels, potassium, weight) 1
• Consider changing treatment if cortisol remains elevated after 2-3 months on maximum tolerated doses 1
• For adrenal-targeting agents, monitor ACTH levels and consider MRI if significant elevations occur 1

Non-Pharmacological Approaches

• Stress management interventions (particularly mindfulness, meditation, and relaxation techniques) may help reduce cortisol levels 3
• Regular physical activity as tolerated 1
• Cognitive behavioral therapy for associated depression and anxiety 1

Common Pitfalls and Caveats

• Avoid NSAIDs in patients with cortisol-induced hypertension as they increase fluid retention 1
• Be vigilant for adrenal insufficiency when treating with steroidogenesis inhibitors 1
• When using mifepristone, cortisol measurements are not reliable for monitoring 1
• Monitor for QTc prolongation with combination therapies 1
• For patients on ketoconazole, mild elevation of liver enzymes doesn't necessarily require discontinuation if stable 1
• Recognize that cortisol has a circadian rhythm, and single measurements may miss abnormal patterns 4