Predictor of Steroid Replacement Duration after Removal of Cortisol-producing Adenoma.

The median duration of glucocorticoid replacement therapy after adrenalectomy for cortisol-producing adenoma was 12 months.

• Median duration was 12 months with an interquartile range of 5-24 months.
• The study included 124 patients who received hydrocortisone replacement therapy after adrenalectomy for CPA.
• The study was conducted at 10 referral centers as part of the ACPA-J study from January 2006 to December 2015.
• This was a multicenter retrospective observational study design.

Multiple pre-operative factors were significantly associated with glucocorticoid replacement therapy duration in single regression analysis.

• Sex was significantly associated with replacement therapy duration (p=0.04).
• Morning ACTH level was significantly associated with replacement therapy duration (p=0.02).
• Morning serum cortisol level was significantly associated with replacement therapy duration (p=0.003).
• Midnight serum cortisol level was significantly associated with replacement therapy duration (p<0.001).
• Serum cortisol level after a 1-mg dexamethasone suppression test was significantly associated with replacement therapy duration (p<0.001).
• Presence of lumbar compression fracture (p=0.015) and Cushingoid appearance (p<0.001) were also significantly associated.

In multiple regression analyses, midnight serum cortisol level and presence of lumbar compression fracture were independently correlated with glucocorticoid replacement therapy duration.

• These two factors remained significant after adjusting for other parameters in multiple regression analyses.
• Other factors significant in single regression analysis, including sex, morning ACTH, morning cortisol, post-dexamethasone cortisol, and Cushingoid appearance, did not remain independently significant in the multiple regression model.
• Midnight serum cortisol level is interpreted as reflecting persistent suppression of the hypothalamic-pituitary-adrenal (HPA) axis.
• Lumbar compression fracture is described as 'an important symptom that reflects the severity and persistence of cortisol secretion.'

High midnight serum cortisol levels were interpreted as contributing to delayed HPA axis recovery after adrenalectomy.

• The authors concluded that high midnight serum cortisol levels 'cause persistent suppression of the hypothalamic-pituitary-adrenal axis (HPA axis)' and 'contribute to a delay in HPA axis recovery.'
• Midnight cortisol was the strongest cortisol-related predictor in multivariable analysis among the several cortisol measures evaluated.
• Other cortisol measures assessed included morning serum cortisol and post-1-mg dexamethasone suppression test cortisol levels.

Lumbar compression fracture as a pre-operative clinical feature was identified as an independent predictor of longer glucocorticoid replacement therapy duration.

• Lumbar compression fracture was significant in both single regression (p=0.015) and multiple regression analyses.
• The authors interpret lumbar compression fracture as reflecting 'the severity and persistence of cortisol secretion.'
• This finding suggests that clinical manifestations of chronic cortisol excess are associated with more prolonged HPA axis suppression requiring longer replacement therapy.