What is exogenous steroid excess?

Exogenous Steroid Excess: Definition, Diagnosis, and Management

Exogenous steroid excess is a condition resulting from prolonged administration of synthetic glucocorticoids at supraphysiologic doses, leading to suppression of the hypothalamic-pituitary-adrenal axis and potentially causing adrenal insufficiency. 1

Definition and Characteristics

• Exogenous steroid excess occurs when synthetic glucocorticoids are administered at doses exceeding physiologic requirements for ≥1 month, causing suppression of the body's natural steroid production 2
• In the context of inflammatory bowel disease, steroid excess is specifically defined as two or more courses of steroid over 1 year 3
• Prolonged steroid use (continuous therapy for more than 3 months) is associated with numerous adverse effects including increased infection risk, osteoporosis, suppression of the hypothalamic-pituitary-adrenal axis, diabetes, weight gain, and cardiovascular disease 3

Pathophysiology

• Exogenous steroids suppress the hypothalamic-pituitary-adrenal (HPA) axis through negative feedback mechanisms 4
• This suppression leads to decreased production of endogenous cortisol, which can result in adrenal insufficiency when steroids are reduced or discontinued 1
• The timing of HPA axis recovery after cessation of glucocorticoids is variable, typically taking 6-12 months 4

Clinical Manifestations

• Patients with exogenous steroid excess may develop features resembling Cushing's syndrome during treatment 1
• When steroids are tapered, patients may experience glucocorticoid withdrawal syndrome, with symptoms that can overlap with those of the underlying disorder and adrenal insufficiency 1
• Symptoms of adrenal insufficiency include fatigue, weakness, anorexia, nausea, vomiting, abdominal pain, hypotension, and electrolyte abnormalities 5
• Hypercortisolemia induces a state of immunocompromise that predisposes patients to various bacterial, viral, fungal, and parasitic infections 6

Risk Factors for Developing Adrenal Insufficiency

• Duration of glucocorticoid therapy (longer duration increases risk) 1
• Mode of administration (systemic administration carries higher risk) 1
• Glucocorticoid dose and potency (higher doses and more potent steroids increase risk) 1
• Concomitant drugs that interfere with glucocorticoid metabolism 1
• Individual susceptibility factors 1

Diagnosis of Steroid-Induced Adrenal Insufficiency

• The standard diagnostic test is the 0.25 mg cosyntropin (ACTH) stimulation test with cortisol measurements at baseline and 30 minutes post-administration 5
• A peak cortisol value below 500 nmol/L is diagnostic of adrenal insufficiency 5
• Morning measurements of both cortisol and ACTH are essential for initial evaluation 5
• In secondary adrenal insufficiency (caused by exogenous steroids), the pattern shows low ACTH and low cortisol levels 5

Management Considerations

• Glucocorticoid therapy should not be completely stopped until recovery of adrenal function is achieved 1
• For patients on chronic steroid therapy, the use of alternate day therapy may help minimize suppression of the HPA axis 7
• When administering alternate day therapy, it is recommended to give the dose in the morning when adrenal cortical activity is naturally highest (between 2 am and 8 am) 7
• In patients with established glucocorticoid-induced adrenal insufficiency, treatment should follow the principles for central adrenal insufficiency 8

Prevention and Monitoring

• Patients on long-term steroids should have their bone mineral density assessed by bone densitometry, particularly those with high FRAX scores or receiving prolonged (more than 3 months) courses of oral corticosteroids 3
• Calcium and vitamin D supplementation is recommended for patients on long-term steroid therapy to reduce the risk of bone disease 3
• Regular monitoring for signs of adrenal insufficiency is essential during steroid tapering 1
• Patient education about the symptoms of adrenal insufficiency and the importance of not abruptly stopping steroid therapy is crucial 5

Special Considerations in Perioperative Management

• There is insufficient evidence supporting the routine administration of "push-dose" steroids perioperatively in patients on chronic steroid therapy 3
• Patients on steroids should remain on their usual regimen during surgical interventions, with awareness that there may be a higher rate of surgical complications 3
• In the event of unexplained hypotension during surgery that is unresponsive to fluids, adrenal insufficiency should be considered, and 100 mg IV hydrocortisone should be administered 3