Letter to the Editor. Upfront GKS for Cushing’s disease and acromegaly: is it suitable?

Abstract

The authors included 21 patients with Cushing's disease (CD) and 25 patients with acromegaly undergoing upfront Gamma Knife radiosurgery (GKS). After a median endocrine follow-up of 69.5 months, patients with CD achieved a faster and far better remission rate compared to patients with acromegaly. The authors suggest a possible differential radiosensitivity of two kinds, and then further recommend upfront GKS in CD rather than in acromegaly. We commend the efforts of the authors in carrying out this interesting study. Yet from the perspective of neurosurgeons, some conclusions are questionable.The biggest concern lies in the posttreatment remission criteria for CD that were used in this study. The authors defined remission as normalization of urinary free cortisol and morning serum cortisol levels, which is not recognized by most endocrinologists and neurosurgeons. According to the latest Endocrine Society Clinical Practice Guideline for CD, as well as other previous literature, remission is generally defined as morning serum cortisol values < 5 μg/dl, a stricter criterion than just normal range. 2,5,7 One meta-analysis suggests that patients with CD in whom subnormal cortisol levels are found after treatment have a clearly lower risk of long-term recurrence compared to those within the normal range. 8 The reduction of cortisol levels to the normal range after treatment does not necessarily represent the patient's cure, but rather a higher recurrence rate. 9 Regarding this condition as remission could give patients overly optimistic and misleading expectations, and may cause neglect of follow-up. Moreover, the use of different remission criteria hinders direct comparison of outcomes between this GKS study and other surgical treatment studies for CD.Nevertheless, although the authors have used more easily achievable remission criteria for CD, the remission criteria for acromegaly (i.e., growth hormone [GH] level < 1 ng/ml in response to a glucose challenge) are much stricter and in accordance with the latest guideline. 4 These varying degrees of rigor in criteria to assess CD and acromegaly may also make less convincing the conclusion that patients with CD achieve faster and better remission rates and that their disease is more sensitive to GKS than is the case in those with acromegaly.In addition, this study did not mention the impact of radiotherapy on the growth of younger patients, especially when the youngest patient with CD included in this study was 14 years old. A radiotherapy study in pediatric CD reported that the incidence of GH deficiency after radiation therapy was 36%-68%, and most patients failed to reach the target height. 1 In one study from the Mayo Clinic the investigators also believe that the risk of delayed hypopituitarism caused by radiotherapy is significant. 6 The risk of this hypopituitarism exists for a lifetime. 9 It is therefore recommended that this article add age factors when deriving the conclusion of efficacy for upfront GKS for CD and acromegaly treatment. Especially given the lac...