medwireNews: The prevalence of glucocorticoid (GC)-induced adrenal insufficiency (GIAI) after planned cessation of prednisolone therapy may be lower than previously reported, suggests a multicenter Danish study, although the data point to a steroid withdrawal syndrome that may evade biochemical testing.
The cross-sectional study of 267 patients aged 50 years or older with polymyalgia rheumatica (n=90), giant cell arteritis (n=18), or both (n=21) found that 1.9% of patients developed GIAI a median of 39 days after stopping prednisolone. GIAI was defined as a stimulated plasma cortisol level less than 420 nmol/L in response to a short synacthen test (SST).
This prevalence is “much lower” than previously reported rates of “4% to 52% depending on GC dose, route, duration of treatment, and time since cessation, as well as analysis method,” observe the researchers. They say that it “speaks against routine screening, which should be restricted to patients with overt symptoms.”
The study participants (median age 73 years, 54.3% women) had received prednisolone for a median of 13 months and were treated in accordance with European guidelines, at a prednisolone dose of 12.5–25.0 mg if they had polymyalgia rheumatica and 40.0–60.0 mg if they had giant cell arteritis. Tapering was conducted over 44 to 53 weeks and once prednisolone 5 mg/day was reached, the dose was reduced by 1.25 mg every 5 weeks until cessation.
Despite the low GIAI prevalence based on biochemical testing, the investigators found that 34% of patients had GC withdrawal symptoms compatible with adrenal insufficiency, as evidenced by an Addison disease-specific quality of life questionnaire (AddiQoL-30) score of 85 points or below out of a possible 120 points. This group of 75 symptomatic patients included four out of the five people who had biochemical GIAI.
Simon Bøggild Hansen (Aarhus Universitetshospital, Denmark) and colleagues report in JAMA Network Open that the total AddiQoL-30 score for these symptomatic patients was a mean 78 points versus 94 points in the remaining asymptomatic patients. The symptomatic patients scored significantly worse on all four dimensions of the AddiQoL-30 questionnaire than the asymptomatic patients – particularly for fatigue (18 vs 24 points) and musculoskeletal symptoms (26 vs 31 points).
The symptomatic group also had significantly worse scores on the 12-item CushingQoL questionnaire, at a mean of 51 points, compared with 76 points for the asymptomatic patients. The questionnaire rates the mental and physical adverse effects of GC excess out of a possible 100 points, with lower scores indicating poor QoL.
Additionally, sleep quality measured over the previous 7 nights, using the 10-point Single Item Sleep Quality Scale, was significantly impaired for the symptomatic group, with a mean score of 4.7 points, compared with 6.7 points in the asymptomatic group.
Hansen and team note that patients with a low AddiQoL-30 score had lower basal cortisol levels than those with higher scores (mean 263 vs 309 nmol/L), and levels of 250 nmol/L or below significantly increased the likelihood of a low score by 2.17-fold.
This finding “could suggest a subtle suppression of adrenocortical function not captured by the SST, which provides a supraphysiological stimulus,” the researchers propose.
Linear regression showed a significant correlation whereby a 50 nmol/L increase in basal cortisol was associated with a 1.4-point improvement in AddiQoL-30 score, and this association remained significant after taking into account sex, age, handgrip strength, and body fat percentage.
The team notes that stimulated cortisol levels did not significantly differ between patients with low or high AddiQoL-30 scores.
Other factors significantly associated with low AddiQoL-30 scores included being female, having a high body fat percentage, a low maximum handgrip strength, a short duration of prednisolone cessation (2–8 weeks), and a score of 9 points or less on the Short Physical Performance Battery, where a score of 0 points indicates the best performance and a score of 12 the worst performance.
The study authors comment that their study suggests there is “an unmet need for additional diagnostic and therapeutic tools to aid health care professionals involved in the management of patients receiving glucocorticoid treatment including the glucocorticoid withdrawal syndrome.”
They conclude that “is evident that [this syndrome] is negatively associated with patient-perceived QoL and may lead to prolonged prednisolone treatment and adverse effects.”
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