What are the effects of Cushing's syndrome caused by exogenous steroid (corticosteroid) use?

From the Guidelines

Cushing's syndrome from exogenous steroid use should be managed by gradually tapering the steroid dose, rather than abrupt discontinuation, to prevent adrenal crisis, with a typical taper reducing prednisone by 2.5-5 mg every 1-2 weeks, and monitoring for symptoms of adrenal insufficiency 1.

Key Considerations

• The condition develops due to external steroids suppressing the hypothalamic-pituitary-adrenal axis, leading to characteristic symptoms including moon face, buffalo hump, central obesity, purple striae, thin skin, easy bruising, muscle weakness, hypertension, hyperglycemia, and mood disturbances.
• Prevention strategies include using the lowest effective steroid dose for the shortest duration possible, considering steroid-sparing agents when appropriate, and implementing alternate-day dosing when feasible.
• Recovery from HPA axis suppression may take months to years after steroid discontinuation, and some patients may require physiologic replacement doses of hydrocortisone (15-20 mg daily) during this recovery period.

Hypertension Management

• Hypertension is present in 70% to 90% of patients with Cushing’s syndrome, and the main mechanism is overstimulation of the nonselective mineralocorticoid receptor by cortisol 1.
• The most effective antihypertensive pharmacological agent in Cushing’s syndrome is a mineralocorticoid receptor antagonist (spironolactone or eplerenone) 1.
• Blocking the mineralo-corticoid actions of excess cortisol with agents such as spironolactone or eplerenone is likely a sensible strategy for managing hypertension in Cushing's syndrome 1.

Monitoring and Treatment

• Patients should be monitored for symptoms of adrenal insufficiency such as fatigue, weakness, nausea, and hypotension during tapering.
• Detailed guidelines on whom to screen, the diagnostic algorithm, and the treatment of patients with various forms of Cushing syndrome have been published, emphasizing the importance of aggressively treating hypertension to reduce the risk of CVD events 1.

From the FDA Drug Label

Cushing's syndrome from exogenous steroid use is mentioned in the following text from the drug label: "development of cushingoid state" This is found in the 2 drug label for prednisone (PO).

The development of Cushing's syndrome from exogenous steroid use is a possible adverse reaction of corticosteroids, including prednisone.

• Cushingoid state is a condition that can occur with long-term use of corticosteroids, characterized by symptoms such as weight gain, moon face, and buffalo hump.
• The risk of developing Cushing's syndrome or a cushingoid state can be minimized by using the smallest possible effective dosage and duration of corticosteroid therapy.
• Patients on long-term corticosteroid therapy should be monitored closely for signs of Cushing's syndrome or a cushingoid state.

From the Research

Cushing's Syndrome from Exogenous Steroid Use

• Cushing's syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology, with exogenous steroid use being the most frequent cause 3.
• The syndrome is associated with various symptoms, including hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders 3, 4.
• Evaluation of patients with possible Cushing's syndrome begins with ruling out exogenous steroid use, followed by screening for elevated cortisol levels using tests such as the 24-hour urinary free cortisol test or late-night salivary cortisol test 3.

Diagnosis and Treatment

• Diagnosis of Cushing's syndrome is often delayed due to its insidiously progressive course and diverse clinical presentation 4.
• First-line treatment for Cushing's syndrome due to endogenous overproduction of cortisol is surgery to remove the causative tumor, with medication and radiation therapy also being used in some cases 3, 4.
• Exogenous steroid use can cause Cushing's syndrome, and prolonged use of topical corticosteroids can lead to systemic adverse effects, including Cushing's syndrome and hypothalamic-pituitary-adrenal (HPA) axis suppression 5, 6.

Complications and Management

• Secondary adrenal insufficiency is a complication that can occur due to the interaction between ritonavir and exogenous steroid medications, and requires corticosteroid replacement therapy 5.
• Steroidogenesis inhibitors, such as osilodrostat, are effective in reducing hypercortisolism, but require close patient monitoring due to the risk of adverse effects, including adrenal insufficiency 7.
• Recovery from HPA axis suppression due to exogenous steroid use can take several months, and physiologic dose of hydrocortisone may be prescribed to prevent an adrenal crisis 6.