Abstract
PurposeNelson’s syndrome is a challenging condition that can develop following bilateral adrenalectomy for Cushing’s disease, with high circulating ACTH levels, pigmentation and an invasive pituitary tumor. There is no established medical therapy. The aim of the study was to assess the effects of pasireotide on plasma ACTH and tumor volume in Nelson’s syndrome.MethodsOpen labeled multicenter longitudinal trial in three steps: (1) a placebo-controlled acute response test; (2) 1 month pasireotide 300–600 μg s.c. twice-daily; (3) 6 months pasireotide long-acting-release (LAR) 40–60 mg monthly.ResultsSeven patients had s.c. treatment and 5 proceeded to LAR treatment. There was a significant reduction in morning plasma ACTH during treatment (mean ± SD; 1823 ± 1286 ng/l vs. 888.0 ± 812.8 ng/l during the s.c. phase vs. 829.0 ± 1171 ng/l during the LAR phase, p < 0.0001). Analysis of ACTH levels using a random intercept linear mixed-random effects longitudinal model showed that ACTH (before the morning dose of glucocorticoids) declined significantly by 26.1 ng/l per week during the 28-week of treatment (95% CI − 45.2 to − 7.1, p < 0.01). An acute response to a test dose predicted outcome in 4/5 patients. Overall, there was no significant change in tumor volumes (1.4 ± 0.9 vs. 1.3 ± 1.0, p = 0.86). Four patients withdrew during the study. Hyperglycemia occurred in 6 patients.ConclusionsPasireotide lowers plasma ACTH levels in patients with Nelson’s syndrome. A longer period of treatment may be needed to assess the effects of pasireotide on tumor volume.Trial registration: Clinical Trials.gov ID, NCT01617733
Highlights
Nelson’s syndrome is a very challenging condition that can develop following bilateral adrenalectomy (BLA) for Cushing’s disease (CD), and is due to the development of a progressive tumor of the corticotroph cells in the pituitary [1]
An acute response of plasma adrenocorticotropic hormone (ACTH) to pasireotide was assessed in a placebo-controlled randomized single-blinded crossover intervention where patients received either a test dose of 600 μg pasireotide s.c. or an equivalent volume of saline s.c. whilst omitting their glucocorticoid treatment to establish if an acute response predicts future efficacy
Patient 7 withdrew during the LAR phase due to significant hyperglycemia that persisted at the end of the study visit 2 months after stopping pasireotide but improved to baseline on longer follow-up after study completion
Summary
Nelson’s syndrome is a very challenging condition that can develop following bilateral adrenalectomy (BLA) for Cushing’s disease (CD), and is due to the development of a progressive tumor of the corticotroph cells in the pituitary [1]. Pituitary (2018) 21:247–255 undergoing bilateral adrenalectomy [2] progression of the size of a corticotroph tumor as assessed by MRI is more common and is detected in 50% of patients within 10 years of BLA for CD [3, 4]. The hallmarks of the syndrome are skin hyperpigmentation and high plasma adrenocorticotropic hormone (ACTH) levels that reflect the activity of the tumor and are used for monitoring [7]. In many patients with Nelson’s syndrome these conditions are not met; the levels of ACTH continue to rise, the symptoms persist and there are limited treatment options
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