Purpose. The aim of this study was to evaluate the role of serum tumor markers for the differential diagnosis of ACTH-dependent Cushing’s syndrome (ADCS). Methods. This study included 185 patients with ADCS, 153 with Cushing’s disease (CD) and 32 with ectopic ACTH syndrome (EAS) who were evaluated between 1991 and 2019 and had at least one tumor marker measured at the time of diagnosis. Results. At least one elevated tumor sample was verified in 33% of CD and in 72% of EAS patients. Two or more elevated tumor samples were found in 9% of CD and 44% of EAS. In CD, gastrin was the most common abnormality in 21% of cases. In EAS, urinary 24-h 5-hydroxy indol acetic acid was the most frequent alteration in 80%, followed by chromogranin in 67%. Higher concentrations and a higher percentage of patients with changes in the tumor markers gastrin, CEA and chromogranin were found in patients with EAS in relation to CD. Analyzing the best values of tumor markers to differentiate patients with EAS and CD, significant differences were found in gastrin, calcitonin, CEA and chromogranin but with an overlap between subgroups. A positive direct correlation between hormonal parameters and tumor marker data was commonly verified in patients as a whole group. Conclusion. Abnormalities in serum tumor markers at the time of diagnosis were more common in EAS than CD patients. However, due to significant overlap between the subgroups, no single tumor marker presented high applicability for the differential diagnosis of ADCS.

BACKGROUND: Solitary Fibrous Tumor is a mesenchymal neoplasm composed of CD34+ fibroblastic cells that can produce spontaneous hypoglycemia by the overproduction of IGF-2. It closely resembles the hypoglycemia characteristic of functioning islet cell tumors. CLINICAL CASE A 77-year-old male was found unconscious and taken to an emergency department with evidence of hypoglycemia and clinical improvement following intravenous glucose administration. He did not have a history of diabetes mellitus and was not taking any glucose lowering medications. He was discharged with nutritional orientation and for control of capillary glycaemia to prevent hypoglycemia. He had 3 episodes of capillary hypoglycemia (50, 45 and 38) at home, that was predominant in the fasting morning and during its occurrence he presented mild sweating, speech difficulty, staring and diplopia, with complete improvement of symptoms after oral glucose replacement. Months earlier, he sought an otolaryngologist for intermittent mild dyspnea; denied cough, hemoptysis, chest pain and unintentional weight loss. He performed chest X-ray with evidence of large right hemithorax mass. Physical examination revealed diminished breath sounds in the right middle and lower lung fields and dullness to percussion. Despite marked hypoglycemia (31 mg/dl), the serum insulin level was less than 0.6  μIU/mL (less than 3 μIU/mL), the C-peptide level was 0.24 nmol/L (less than 0,6 nmol/L), had negative ketonemia and a positive response after glucagon administration (glycaemia increased in 50 mg/dl). Anti-insulin antibodies were negative. Serum cortisol secretion and adrenocorticotropic hormone were normal. The serum level of growth hormone (GH) was 0,03 (less than 0,97ng/ml). The serum IGF-2 level was 227 ng/ml  (267 - 616 ng/ml), the IGF-I level was 72 ng/ml (37,1 - 172 ng/ml) and the IGF2/ IGF1 was 3,15 (equal or greater than 3). Computed tomographic (CT) scan revealed a large heterogeneous mass with dimensions of 17,4 × 15× 12.2 cm. It determines almost total atelectasis of the lower lobe on this side and maintains broad medial contact with the mediastinum, compressing the right atrium and the inferior pulmonary vein on this side. Preoperatively, was administered 40 mg oral prednisone with capillary glucose normalization. The tumor was completely resected and was a grayish-white solid, with dimensions of 17 x 16 x 12 cm. Immunohistochemical stains demonstrated positivity for CD34 and IGF2 expression. Postoperatively, serum glucose and insulin levels returned to normal, and episodes of hypoglycemia are resolved. CONCLUSION This case reinforce the importance of investigate IGF-2 tumor production as a cause of hypoinsulinemic hypoglycemia and reports the complete resolution of hypoglycemia after corticoid administration and/or tumor resection.