Outcomes of Patients with Nelson’s Syndrome after Primary Treatment: A Multicenter Study from 13 UK Pituitary Centers

Abstract

Context Long-term outcomes of patients with Nelson’s syndrome (NS) have been poorly explored, especially in the modern era. Objective To elucidate tumor control rates, effectiveness of various treatments, and markers of prognostic relevance in patients with NS. Patients, design, and setting Retrospective cohort study of 68 patients from 13 UK pituitary centers with median imaging follow-up of 13 years (range 1–45) since NS diagnosis. Results Management of Cushing’s disease (CD) prior to NS diagnosis included surgery+adrenalectomy (n = 30; eight patients had 2 and one had 3 pituitary operations), surgery+radiotherapy+adrenalectomy (n = 17; two received >1 courses of irradiation, two had ≥2 pituitary surgeries), radiotherapy+adrenalectomy (n = 2), and adrenalectomy (n = 19). Primary management of NS mainly included surgery, radiotherapy, surgery+radiotherapy, and observation; 10-year tumor progression-free survival was 62% (surgery 80%, radiotherapy 52%, surgery+radiotherapy 81%, observation 51%). Sex, age at CD or NS diagnosis, size of adenoma (micro-/macroadenoma) at CD diagnosis, presence of pituitary tumor on imaging prior adrenalectomy, and mode of NS primary management were not predictors of tumor progression. Mode of management of CD before NS diagnosis was a significant factor predicting progression, with the group treated by surgery+radiotherapy+adrenalectomy for their CD showing the highest risk (hazard ratio 4.6; 95% confidence interval, 1.6–13.5). During follow-up, 3% of patients had malignant transformation with spinal metastases and 4% died of aggressively enlarging tumor. Conclusions At 10 years follow-up, 38% of the patients diagnosed with NS showed progression of their corticotroph tumor. Complexity of treatments for the CD prior to NS diagnosis, possibly reflecting corticotroph adenoma aggressiveness, predicts long-term tumor prognosis.

Hyperpigmentation and ACTH – an overview of literature

“…there is not general guideline as approach but radiotherapy, neurosurgery of the pituitary gland an and potential use of somatostatin analogues and/or dopamine agonists are the therapy lines (26,27). a study published in 2019 showed that 38% of the subjects with nelson's syndrome displayed some level of progression during a follow-up of 10 years (28). the risk of progression is higher if complex therapies are applied to Cushing's disease but this may also be correlated with a more severe form of disease (28).…”

“…a study published in 2019 showed that 38% of the subjects with nelson's syndrome displayed some level of progression during a follow-up of 10 years (28). the risk of progression is higher if complex therapies are applied to Cushing's disease but this may also be correlated with a more severe form of disease (28). nelson-Salassa syndrome has been revealed in half of the persons with Cushing's disease treated with bilateral adrenal removal associating a mild evolution (29).…”

Rapid response of Nelson’s syndrome to pasireotide in radiotherapy-naive patient

“…When feasible, surgical resection of the Nelson’s syndrome tumor is commonly recommended. Reported success rates of pituitary surgery varies widely from 10 to 70% [ 11 , 36 – 38 ]. Higher rates of remission have been associated with smaller tumors, adjuvant radiotherapy, and absence of tumor invasion into the dura mater [ 11 , 36 , 37 ].…”

“…Reported success rates of pituitary surgery varies widely from 10 to 70% [ 11 , 36 – 38 ]. Higher rates of remission have been associated with smaller tumors, adjuvant radiotherapy, and absence of tumor invasion into the dura mater [ 11 , 36 , 37 ]. The most common complications are hypopituitarism, cerebrospinal fluid leak, and meningitis occurring in up to 69%, 15%, and 8% of postoperative patients, respectively [ 38 – 40 ].…”

“…Medical therapy with a variety of drug classes have been studied with inconsistent effectiveness [ 9 – 11 ]. One potentially promising drug is pasireotide, a somatostatin analog with affinity for somatostatin-receptor subtypes 1, 2, 3, and 5 [ 12 ].…”