Nelson's syndrome

Abstract

Nelson's syndrome is a potentially life-threatening condition that does not infrequently develop following total bilateral adrenalectomy (TBA) for the treatment of Cushing's disease. In this review article, we discuss some controversial aspects of Nelson's syndrome including diagnosis, predictive factors, aetiology, pathology and management based on data from the existing literature and the experience of our own tertiary centre. Definitive diagnostic criteria for Nelson's syndrome are lacking. We argue in favour of a new set of criteria. We propose that Nelson's syndrome should be diagnosed in any patient with prior TBA for the treatment of Cushing's disease and with at least one of the following criteria: i) an expanding pituitary mass lesion compared with pre-TBA images; ii) an elevated 0800 h plasma level of ACTH (O500 ng/l) in addition to progressive elevations of ACTH (a rise of O30%) on at least three consecutive occasions. Regarding predictive factors for the development of Nelson's syndrome post TBA, current evidence favours the presence of residual pituitary tumour on magnetic resonance imaging (MRI) post transsphenoidal surgery (TSS); an aggressive subtype of corticotrophinoma (based on MRI growth rapidity and histology of TSS samples); lack of prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels in year 1 post TBA. Finally, more studies are needed to assess the efficacy of therapeutic strategies in Nelson's syndrome, including the alkylating agent, temozolomide, which holds promise as a novel and effective therapeutic agent in the treatment of associated aggressive corticotroph tumours. It is timely to review these controversies and to suggest guidelines for future audit.

Tan Without the Sun: A Case of Nelson’s Syndrome

“…These potentially useful predictors include: (1) a rapid increase in plasma ACTH concentration in the year after adrenalectomy, (2) residual pituitary tumor after transphenoidal surgery, (3) aggresive subtype of corticotrophinoma of Cushing's Disease (CD), and (4) lack of prophylactic neoadjuvant pituitary radiotherapy after bilateral adrenalectomy. 3,4,8,14 After bilateral adrenalectomy, it is necessary to maintain lifelong glucocorticoid replacement with oral hydrocortisone (15 to 20 mg upon awakening and 5 to 10 mg in the early afternoon) and mineralocorticoid (fludrocortisone 0.05 to 0.2 mg/day). 10 No written data regarding the last maintenance dose of prednisone was available upon review of the patient's records.…”

“…The benefit of giving prophylactic pituitary radiotherapy after bilateral adrenalectomy to prevent or delay the development of NS is still controversial. 4,14 Pituitary surgery, commonly through the transsphenoidal approach, is the treatment of choice in NS, especially if there is evidence of compression of the optic apparatus. 4,15 The complications of this procedure include panhypopituitarism, cranial nerve palsy, leakage of cerebrospinal fluid and meningitis.…”

“…4,14 Pituitary surgery, commonly through the transsphenoidal approach, is the treatment of choice in NS, especially if there is evidence of compression of the optic apparatus. 4,15 The complications of this procedure include panhypopituitarism, cranial nerve palsy, leakage of cerebrospinal fluid and meningitis. 4,8,15 Radiotherapy is a treatment option when surgery is unsuccessful or cannot be performed.…”

“…1 Although the prevalence of NS after bilateral adrenalectomy varies between 8 to 29%, the procedure is not frequently performed. [2][3][4] In the United States, the annual rate of bilateral adrenalectomy for Cushing's syndrome (CS) was reported to be 0.32 per 100,000 hospital discharges in 2000. 5 Cushing's Syndrome is the clinical manifestation of chronic exposure to excessive glucocorticoids, either from an exogenous or an endogenous source.…”

Budget impact of pasireotide for the treatment of Cushing’s disease, a rare endocrine disorder associated with considerable comorbidities

“…Costs for stroke, endometrial thickening, meningitis, cerebrospinal fluid (CSF) leak, Nelson's syndrome 46 , thrombolytic events, and hepatotoxicity are assumed to be one-time costs and are based on sources from the literature. Costs of each complication/AE and their corresponding prevalence rates can be found in Supplementary Table 7.…”