Rare Diseases Symptoms Automatic Extraction

Ectopic ACTH and CRH co-secreting tumors in children and adolescents causing Cushing syndrome: a diagnostic enigma and how to solve it.

[cushing syndrome]

Context: Ectopic ACTH/CRH syndrome is a rare cause of Cushing syndrome (CS), especially in children. The localization, work-up, and management of ACTH/CRH secreting tumors are discussed. Setting: A retrospective study was conducted of patients under 21 years of age evaluated at the National Institutes of Health (NIH) for CS and diagnosed with ectopic ACTH/CRH secreting tumors during the period 2009-2014. Patients: Seven patients with ectopic ACTH/CRH syndrome are included in this study, median age 13.6 years (range 1-21), 3 female. Measurements: Clinical, biochemical, radiological features, treatment and histological findings are described. Results: Seven patients were found to have ACTH/CRH secreting tumors with neuroendocrine features. The site of the primary lesion varied: pancreas (3), thymus (2), liver (1), right lower pulmonary lobe (1). Patients underwent biochemical evaluation for CS, including diurnal serum cortisol and ACTH levels, urinary free cortisol levels (UFC), and CRH stimulation tests. All patients underwent radiological investigations including MRI, CT and PET scan; imaging with octreotide and 68gallium DOTA-TATE scans were performed in individual cases. Five patients underwent inferior petrosal sinus sampling; 4 patients had sampling for ACTH levels from additional sites. Three patients underwent transsphenoidal surgery (TSS), and 3 patients required bilateral adrenalectomy. 3 patients (43%) died due to metastatic disease, demonstrating the high mortality rate. One of the unique findings in these seven patients is that in each case, their neuroendocrine tumors were ultimately proven to be co-secreting ACTH and CRH. This explains the enigmatic presentation, in which 3 patients initially thought to have Cushing's disease (CD) with corresponding pituitary hyperplasia underwent TSS prior to the correct localization of the causative tumor. Conclusions: Ectopic ACTH/CRH co-secreting tumors are extremely rare in children and adolescents. Its diagnosis is frequently missed and is sometimes confused with CD due to the effect of CRH on the pituitary.