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From the Journals

New Guidelines Tackle Adrenal Insufficiency in GC Tapering

“'Clinicians must maintain a high index of suspicion' for adrenal insufficiency in patients tapering glucocorticoids, according to new guidelines."

Conexiant

Newly published guidelines provided recommendations for managing glucocorticoid-induced adrenal insufficiency during glucocorticoid tapering in patients with inflammatory rheumatic diseases.

Published in RMD Open by the European Society of Endocrinology (ESE) and the Endocrine Society (ES), the guidelines aimed to improve patient outcomes and reduce risks associated with prolonged glucocorticoids (GC) therapy, particularly for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polymyalgia rheumatica, and giant cell arteritis.

The guidelines stressed that GC-induced adrenal insufficiency (GIAI) risk becomes significant when GC therapy exceeds 3 to 4 weeks at doses higher than physiological levels (15 to 25 mg/day hydrocortisone or 4 to 6 mg/day prednisone). Prolonged GC use suppresses the hypothalamic-pituitary-adrenal (HPA) axis, potentially leading to adrenal atrophy and clinical outcomes like adrenal crises.

For tapering, the guidelines recommended transitioning from long-acting GCs, such as dexamethasone or betamethasone, to short-acting agents like prednisone or hydrocortisone. Two approaches were proposed for monitoring adrenal insufficiency during dose reduction:

  • Gradual tapering with clinical monitoring for adrenal insufficiency symptoms
  • Measuring morning serum cortisol levels at least 24 hours after the last GC dose.

"No studies have demonstrated the superiority of one method over the other, leaving the choice to clinical judgment," noted lead study author Paul Ornetti, of the Department of Rheumatology & INSERM U1093 at the Centre Hospitalier Universitaire Dijon & Université Bourgogne Europe in Dijon, France, and his colleagues.

Studies cited in the guidelines highlighted the prevalence of GIAI among long-term GC users. For instance:

  • 43% of patients treated with long-term GCs for rheumatic diseases exhibited evidence of GIAI.
  • 13% of the patients with SLE receiving < 5 mg/day or who had discontinued prednisolone showed signs of adrenal insufficiency.
  • 20% of the patients with rheumatic diseases experienced overt adrenal insufficiency during GC tapering, particularly in cases of disease relapse.

Incomplete HPA axis recovery can result in severe clinical outcomes, including increased mortality. The STAR study indicated that tapering prednisone by 1 mg/day per month or replacing prednisone with hydrocortisone yielded comparable success rates for GC withdrawal at 1 year in patients with RA.

Meanwhile, the diagnosis of GIAI remains complex as a result of variability in HPA axis recovery. Risk factors included GC potency, route of administration, treatment duration, dose, age, and individual genetics. Clinicians must maintain a high index of suspicion and educate patients on recognizing adrenal insufficiency symptoms, particularly during physiological stress or surgery.

The guidelines emphasized the importance of educating patients on "sick-day rules," which involve temporarily increasing GC doses during illness, surgery, or other stress-inducing events to prevent adrenal crises.

While the guidelines consolidated expert recommendations, further research is needed to establish evidence-based protocols for tapering GCs and monitoring adrenal function.

Full disclosures can be found in the study.