Can long-term use of bilateral hip steroid injections cause secondary adrenal insufficiency in patients, particularly those with a history of hip pain or osteoarthritis, who have received high doses or frequent injections?

Can Long-Term Bilateral Hip Steroid Injections Cause Secondary Adrenal Insufficiency?

Yes, long-term use of bilateral hip steroid injections can absolutely cause secondary adrenal insufficiency, and this risk increases substantially with repeated injections, higher cumulative doses, and bilateral administration. 1

Evidence for HPA Axis Suppression from Intra-Articular Steroids

The evidence clearly demonstrates that intra-articular steroid injections suppress the hypothalamic-pituitary-adrenal (HPA) axis across all routes of administration, including joint injections:

• Glucocorticoid therapy across all routes of administration (oral, inhaled, topical, intranasal, and intra-articular) can cause suppression of the HPA axis, sometimes referred to as tertiary adrenal insufficiency. 1

• In a controlled study of bilateral knee injections with 80 mg methylprednisolone acetate per knee (160 mg total), 60% of patients developed secondary adrenal insufficiency within one week, and 10% still had evidence of adrenal insufficiency 8 weeks after the injection. 2

• Case reports document that even single intra-articular steroid injections can cause secondary adrenal insufficiency with clinically significant symptoms requiring temporary glucocorticoid replacement therapy. 3

Duration and Severity of HPA Suppression

The duration of adrenal suppression varies by steroid type and dose:

• With 80 mg methylprednisolone (the depot form most frequently used for chronic pain), secondary adrenal insufficiency can last up to 4 weeks, and in a small proportion of patients, up to 2 months. 1

• Long-term epidural steroid injections over 6 months or longer resulted in an 11.8% incidence of confirmed adrenal insufficiency in one study, with no clear predictors for which patients would develop this complication. 4

• The risk is particularly concerning with bilateral injections, as the cumulative steroid dose is doubled compared to unilateral injection. 2

Clinical Implications and Risk Assessment

For patients receiving repeated bilateral hip injections:

• All steroid-dependent patients are at risk of adrenal crisis, which can be life-threatening if not rapidly recognized and treated. 1

• The threshold to test for adrenal insufficiency should be low in clinical practice, especially for patients with nonspecific symptoms (fatigue, nausea, hypotension, weight loss) after steroid injections. 3

• Patients who receive steroids have the potential for secondary adrenal insufficiency and an altered immune response, along with several other adverse effects including myopathy and osteoporosis. 1

Diagnostic Approach

If secondary adrenal insufficiency is suspected:

• The standard 0.25 mg cosyntropin stimulation test with cortisol measurements at baseline and 30 minutes post-administration is medically necessary to rule out adrenal insufficiency. 5

• A peak cortisol <500 nmol/L (<18 mcg/dL) at 30 or 60 minutes is diagnostic of adrenal insufficiency. 5

• Morning cortisol and ACTH measurements can provide initial screening, with low cortisol and low-normal ACTH suggesting secondary adrenal insufficiency. 5

Critical Management Considerations

• Treatment of suspected acute adrenal insufficiency should never be delayed for diagnostic procedures—if the patient is clinically unstable with unexplained hypotension, give 100 mg IV hydrocortisone immediately plus 0.9% saline infusion. 1, 5

• Once diagnosed, temporary treatment with glucocorticoid replacement may be required until HPA axis recovery occurs, which can take weeks to months. 3

• Regular monitoring of adrenal function in patients who have received long-term steroid injections may be prudent, as an unexpected adrenal crisis could be life-threatening. 4

Important Caveats

• The absence of hyperkalemia cannot rule out adrenal insufficiency, as it is present in only about 50% of cases—hyponatremia is much more common, occurring in 90% of newly diagnosed cases. 5

• Secondary adrenal insufficiency from intra-articular steroids did not significantly correlate with any demographic, clinical, or laboratory parameter in research studies, making it difficult to predict which patients will be affected. 2

• Patients receiving bilateral injections with high cumulative doses (such as 80 mg per hip) are at particularly high risk and warrant closer monitoring. 2