Recovery of Adrenal Function after Pituitary Surgery in Patients with Cushing Disease: Persistent Remission or Recurrence?

Abstract

Background: Cushing disease (CD) represents the principal cause of endogenous hypercortisolism. The first-line therapy of CD is surgical removal of the ACTH-secreting pituitary adenoma, which is generally followed by adrenal insufficiency (AI). Objective: To analyze the recovery of AI in patients with CD after pituitary surgery in relation with recurrence and persistent remission of CD. Patients and Methods: We performed a retrospective analysis of patients with CD who met the following inclusion criteria: adult age, presence of AI 2 months after the surgical intervention, and a minimum follow-up of 3 years after the surgical intervention. Results: Sixty-one patients were followed for a median of 6 years. Ten (16.4%) patients recurred during follow-up. The patients who restored adrenal function did so after a median time of 19 months, with a significantly shorter time in the recurrence group (12.5 vs. 25 months, p = 0.008). All 10 patients who recurred recovered their adrenal function within 22 months. The recovery rate of AI in the persistent remission group was 37.3% (19/51) at 3 years and 55.8% (24/43) at 5 years. In all patients the duration of AI was negatively associated with disease recurrence. Conclusion: The duration of postsurgical AI in patients with recurrent CD is significantly shorter than that in patients with persistently remitted CD, and this parameter may be a useful predictor of recurrence. Patients showing a normal pituitary-adrenal axis within 2 years after surgery should be strictly monitored as they are at higher risk of disease relapse.

Recovery of hypothalamic‐pituitary‐adrenal axis in paediatric Cushing disease

“…Furthermore, the range of the reported median time to recovery varies between various cohorts (ranging from 6 months to more than 2 years). Of note, what has been more commonly reported is the association of early HPA axis recovery with higher risk for CD recurrence 5,7 . However, only one study, from our centre, has previously described the HPA axis recovery in paediatric patients, who may behave differently than adults due to varying sensitivity or maturation of the HPA axis, and this prior study because of its lower numbers did not allow for a meaningful statistical analysis of risk for recurrence 10 …”

“…Previous studies have shown increased risk for recurrence with earlier recovery in adult patients, but this has not been reported previously in the paediatric population. 5,25 In adults with recurrence, recovery of the [26][27][28] The most recent meta-analysis included 30 studies of patients with secondary AI and showed no statistical difference in the diagnostic accuracy of the two tests, although both test showed low sensitivity. 26 Given the technical difficulties in performance of a low-dose test, in our institute, we have been performing only standard-dose testing for our patients.…”

“…Previous studies, mostly in adults, tried to identify factors that may affect HPA axis recovery. Although it is tempting to hypothesize that the higher or longer the exposure to glucocorticoids, the more severe the suppression, studies have not consistently found that clinical or biochemical factors significantly contribute to the duration of HPA axis suppression 5‐9 . Furthermore, the range of the reported median time to recovery varies between various cohorts (ranging from 6 months to more than 2 years).…”

“…Although it is tempting to hypothesize that the higher or longer the exposure to glucocorticoids, the more severe the suppression, studies have not consistently found that clinical or biochemical factors significantly contribute to the duration of HPA axis suppression. [5][6][7][8][9] Furthermore, the range of the reported median time to recovery varies between various cohorts (ranging from 6 months to more than 2 years). Of note, what has been more commonly reported is the association of early HPA axis recovery with higher risk for CD recurrence.…”

“…Of note, what has been more commonly reported is the association of early HPA axis recovery with higher risk for CD recurrence. 5,7 However, only one study, from our centre, has previously described the HPA axis recovery in paediatric patients, who may behave differently than adults due to varying sensitivity or maturation of the HPA axis, and this prior study because of its lower numbers did not allow for a meaningful statistical analysis of risk for recurrence. 10 In the present study, we investigated the association of the time to recovery of HPA axis after successful treatment in a large cohort of paediatric patients with CD with the age of diagnosis and other relevant clinical and biochemical factors.…”