Corticotroph tumor progression after bilateral adrenalectomy (Nelson’s syndrome): systematic review and expert consensus recommendations

Abstract

BACKGROUND: Corticotroph tumor progression (CTP) leading to Nelson’s syndrome (NS) is a severe and difficult-to-treat complication subsequent to bilateral adrenalectomy (BADX) for Cushing’s disease. Its characteristics are not well described, and consensus recommendations for diagnosis and treatment are missing. METHODS: A systematic literature search was performed focusing on clinical studies and case series (≥5 patients). Definition, incidence, treatment and long-term outcomes of CTP/NS after BADX were analyzed using descriptive statistics. The results were presented and discussed at an interdisciplinary consensus workshop attended by international pituitary experts in Munich on October 28th, 2018. RESULTS: Data covered definition and incidence (34 studies, 1275 patients), surgical outcome (12 studies, 187 patients), outcome of radiation therapy (21 studies, 273 patients), and medical therapy (15 studies, 72 patients). CONCLUSIONS: We endorse the definition of CTP-BADX/NS as radiological progression or new detection of a pituitary tumor on thin-section MRI. We recommend surveillance by MRI after 3 months and every 12 months for the first 3 years after BADX. Subsequently, we suggest clinical evaluation every 12 months and MRI at increasing intervals every 2-4 years (depending on ACTH and clinical parameters). We recommend pituitary surgery as first-line therapy in patients with CTP-BADX/NS. Surgery should be performed before extrasellar expansion of the tumor to obtain complete and long-term remission. Conventional radiotherapy or stereotactic radiosurgery should be utilized as second-line treatment for remnant tumor tissue showing extrasellar extension.

Prevalence of Nelson’s syndrome after bilateral adrenalectomy in patients with cushing’s disease: a systematic review and meta-analysis

“…Three of these studies found that high ACTH concentrations one year after BA [49,52,53] were associated with pituitary tumor progression. Thus, these findings support the suggestion that ACTH should be monitored following BA in patients with CD [54,55].…”

“…*additional data. Abbreviations: Surgery, pituitary surgery prior to bilateral adrenalectomy [55]. Furthermore, the authors recommend active surveillance with MRI three months after BA, and every 12 months for the first 3 years, and every 2-4 years thereafter, based on clinical findings.…”

The Role of Glucocorticoid Receptor in the Pathophysiology of Pituitary Corticotroph Adenomas

“…Corticotroph tumor progression (CTP) leading to Nelson’s syndrome (NS) is characterized by hyperpigmentation and an increase in tumor size in patients with refractory CD submitted to bilateral adrenalectomy (BA); tumor growth can be dramatic with severe complications including death [ 62 ]. To date, no effective predictive factors are available to a priori identify patients at high risk of developing NS, and the only option is the close post-operative monitoring of all patients [ 62 ].…”

Glucocorticoid Withdrawal Syndrome following treatment of endogenous Cushing Syndrome

“…Pituitary radiotherapy is an additional treatment option for CD but can take months to years to lower cortisol production. Bilateral adrenalectomy (BLA) provides immediate, reliable correction of hypercortisolism but mandates life-long corticosteroid replacement therapy, and, in patients with CD, may be complicated by corticotroph tumor progression syndrome in 25–40% of patients[ 14 ].…”