From the Guidelines
Elevated cortisol levels can be caused by various factors, including Cushing's syndrome, adrenal tumors, pituitary tumors, ectopic ACTH-producing tumors, and certain medications, as well as chronic stress, depression, and other conditions, and the most recent and highest quality study 1 recommends a comprehensive evaluation to determine the underlying cause.
Causes of Elevated Cortisol
Elevated cortisol levels can be caused by numerous factors, including:
- Cushing's syndrome
- Adrenal tumors
- Pituitary tumors
- Ectopic ACTH-producing tumors
- Certain medications like prednisone, hydrocortisone, or other glucocorticoids
- Chronic stress
- Depression
- Alcoholism
- Malnutrition
- Obesity
- Poorly controlled diabetes
- Pregnancy
- Intense physical exercise
- Acute illness
- Surgery
- Trauma
- Hyperthyroidism
Diagnosis and Evaluation
According to the most recent study 1, the diagnosis of Cushing's syndrome involves a comprehensive evaluation, including:
- 24-hour urine free cortisol test
- Late-night salivary cortisol test
- Dexamethasone suppression test
- Plasma ACTH measurement
- Pituitary MRI scan
- Bilateral inferior petrosal sinus sampling for ACTH
Treatment and Management
Treatment of elevated cortisol levels depends on the underlying cause, and may involve:
- Medication adjustments
- Lifestyle changes to reduce stress
- Surgery for tumors
- Medical management of hypercortisolism with adrenostatic agents, such as ketoconazole and mitotane, as recommended by 1
- Bilateral adrenalectomy in some cases, as recommended by 1 It is essential to identify the underlying cause of elevated cortisol levels to provide effective treatment and management, and to prevent potential complications, such as weight gain, high blood pressure, muscle weakness, mood changes, and impaired immune function, as highlighted by 1.
From the FDA Drug Label
Acting primarily through the hypothalamus a fall in free cortisol stimulates the pituitary gland to produce increasing amounts of corticotropin (ACTH) while a rise in free cortisol inhibits ACTH secretion. Normally the HPA system is characterized by diurnal (circadian) rhythm Serum levels of ACTH rise from a low point about 10 pm to a peak level about 6 am. Increasing levels of ACTH stimulate adrenocortical activity resulting in a rise in plasma cortisol with maximal levels occurring between 2 am and 8 am.
Elevated cortisol can be caused by:
- Stressful situations not directly related to the disease entity under treatment, which may require an increase in the dosage of prednisone for a period of time consistent with the patient's condition 2
- Corticosteroid therapy, which can suppress the production of cortisol by the adrenal cortex, but may also cause an increase in cortisol levels due to the exogenous administration of corticosteroids 2
- Cushing's disease, a syndrome of adrenocortical hyperfunction characterized by elevated cortisol levels 2
- Pharmacologic dose corticoid therapy, which can cause a disturbance in the diurnal cycle with maintenance of elevated corticoid values during the night 2
From the Research
Causes of Elevated Cortisol
- Exogenous steroid use is the most frequent cause of Cushing syndrome, which is characterized by elevated cortisol levels 3
- Endogenous overproduction of cortisol can be caused by a benign pituitary tumor, resulting in Cushing disease, which occurs in approximately 60% to 70% of patients with Cushing syndrome due to endogenous cortisol production 3
- Adrenal causes of hypercortisolism, such as adrenal tumors, can also lead to elevated cortisol levels 3, 4
- Chronic stress can disrupt cortisol regulation, leading to elevated cortisol levels and contributing to the progression of neurodegenerative diseases and psychological disorders 5
- Other factors, such as social hierarchies and chronic pain, can also impact cortisol regulation and contribute to elevated cortisol levels 5
Medical Conditions Associated with Elevated Cortisol
- Cushing syndrome: a condition characterized by prolonged increase in plasma cortisol levels that is not due to a physiological etiology 3
- Cushing disease: a condition caused by a benign pituitary tumor that produces excess corticotropin, leading to elevated cortisol levels 3, 6
- Adrenal tumors: can produce excess cortisol, leading to elevated cortisol levels 3, 4
- Neurodegenerative diseases, such as Alzheimer's and Parkinson's: chronic stress and cortisol dysregulation can contribute to the progression of these diseases 5
- Psychological disorders, such as major depressive disorder: cortisol dysregulation and HPA axis hyperactivity can contribute to the development and progression of these disorders 5