Ectopic ACTH by Carcinoid Tumor Mimicking Nelson Syndrome in a Patient with Bilateral Adrenalectomy

ABSTRACT

Introduction: Nelson syndrome has been reported in up to 25% of adults after bilateral adrenalectomy (BLA) for Cushing’s disease (CD). It usually manifests as an expanding pituitary mass, rising adrenocorticotropic (ACTH) hormone levels and, in many patients, the development of hyperpigmentation. We review the clinical course of a patient with rising ACTH levels after BLA for presumed CD. Although the diagnosis of Nelson syndrome was considered, he was found 9 years after BLA to have an ectopic ACTH secreting bronchial carcinoid tumor as a cause for the elevated ACTH levels. Case Description A 35 year old male was evaluated at another institution in 2010 after he presented with weight gain, new onset hypertension, muscle weakness with multiple falls, depression, irritability and emotional lability. He was diagnosed with CD and was referred to a university center where he underwent trans-sphenoidal pituitary surgery in May 2011. An adenoma was seen on frozen section but not on the final pathology. He developed transient symptoms of adrenal insufficiency on the second post-operative day. Because of persistent hypercortisolism he underwent BLA in November 2011. We started following him in 2012 and signs of hypercortisolism gradually resolved. He appeared euadrenal on hydrocortisone 10 mg am, 5 mg 12 noon and 5 mg 6 pm and fludrocortisone 0.05 mg daily. ACTH levels increased from 54 pg/ml (6-50) in 2012 to 1024 pg/ml in 2019. He had no hyperpigmentation and MRI of the pituitary from 2014-20 did not show a pituitary mass. During an evaluation for COVID-19 infection in May 2020, a chest x ray revealed a right lower lobe lung mass measuring 3.3 x 2.0 cm. He underwent right lower lobe lung lobectomy in July 2020 and pathology revealed a carcinoid tumor-spindle cell pattern which stained strongly positive for ACTH and weakly positive for chromogranin. ACTH levels after the surgery decreased to 16.3 pg/ml. Discussion: Some authors have suggested that Nelson syndrome be considered in patients with BLA who have one of the following an expanding pituitary mass or ACTH levels >500 p/ml at 3 different time points after surgery. This case highlights the need to consider ectopic ACTH syndrome as another cause for rising ACTH levels after BLA for CD especially in those patients who are not found to have a discreet adenoma after pituitary surgery.