Signs, symptoms and biochemistry in recurrent Cushing disease: a prospective pilot study

Abstract

Cushing disease (CD) is a rare endocrine disorder caused by ACTH secretion leading to cortisol excess [1]. Reported recurrence rates are quite high throughout most of the studies [2, 3]. Usually, close surveillance after first successful therapy is recommended [4–6], including both clinical and biochemical assessment. The Endocrine Society Clinical Practice Guideline on the treatment of CS recommends to screen patients for recurrence after recovery of the HPA axis and after that, annually or if the patient has clinical symptoms [5]. Low-dose dexamethasone suppression test, late-night salivary cortisol and cortisol in a 24-h collection are part of the standard screening approach. Of these tests, midnight salivary cortisol is the first parameter to become abnormal in patients with recurrence [7–9]. Currently, there is a level of uncertainty in the diagnosis of recurrence as on one side, a cyclic biochemical pattern is not uncommon in recurrent CS [10], which makes it challenging to confirm suspected recurrence by biochemical screening. On the other side, physiological forms of hypercortisolism may also occur in patients who are actually in remission [11]. Based on this background, we analyzed prospectively the clinical and biochemical course of patients with recurrent CD to answer the question, in which sequence clinical and biochemical parameters recur. Using a historic retrospective cohort for comparison, we wanted to answer whether annual follow-up identifies recurrence earlier.