Use of Endoscopy in the Diagnosis of a Patient With an ACTH-producing Pancreatic Tumor

Case Report

A 66-year-old man was suspected of having acute Cushing syndrome based upon the following symptoms: hyperglycemia; hypokalemic alkalosis; an elevated serum total cortisol level of 41.0 μg/dL (normal, 2.9–19.4 μg/dL), which did not respond to corticotrophin-releasing hormone stimulation; and adrenocorticotropic hormone (ACTH) levels of 121–146 pg/mL (normal, 20–80 pg/mL), which were not suppressed by either low- or high-dose dexamethasone. Magnetic resonance imaging of the patient's pituitary was negative; however, computed tomography (CT) imaging of the chest, abdomen, and pelvis suggested a vague 1.7-cm × 2.4-cm mass-like abnormality in the uncinate process and bilateral adrenal thickening (Figures 1).

Figure 1.

Coronal computed tomography image of the chest, abdomen, and pelvis. The arrow reveals a 1.7-cm × 2.4-cm mass at the uncinate process.

The patient was referred for endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) evaluation of the pancreas. A linear EUS examination clearly revealed a 2.4-cm × 2.4-cm hypoechoic heterogenic uncinate mass with regular borders and without cystic features (Figures 2), which was consistent with a T2N0MX neuroendocrine tumor based upon EUS criteria. Tissue evaluation was performed using 2 passes each of 25- and 22-gauge FNA needles as well as a core biopsy. Pathologic evaluation of both the fine-needle aspirates and the core biopsies demonstrated uniform neoplastic cells, small to medium in size, with scant cytoplasm, oval nuclei with coarse chromatin, and a solid nesting pattern (Figures 3). Immunoperoxidase stains showed strong cytoplasmic staining within the tumor cells for antibodies directed against ACTH (Figures 4).

Figure 2.

Linear endoscopic ultrasound of a 2.4-cm × 2.4-cm hypoechoic heterogenic uncinate mass.

Figure 3.

Uniform neoplastic cells, small to medium in size, with scant cytoplasm, oval nuclei with coarse chromatin, and a solid nesting pattern (hematoxylin & eosin stain, 40×).

Figure 4.

Strong cytoplasmic staining within the tumor cells for antibodies directed against adrenocorticotropic hormone (immunohistochemical stain, 40×).

The patient underwent a successful pancreaticoduo-denectomy. Postoperatively, his ACTH level decreased from 121 pg/mL to 21 pg/mL, confirming the diagnosis of an ectopic ACTH-secreting tumor (Cushing syndrome).

Discussion

Approximately two thirds of patients with symptoms consistent with Cushing syndrome actually have Cushing disease, an ACTH-secreting pituitary tumor.¹ Cushing syndrome secondary to ectopic ACTH production is a relatively uncommon clinical condition that accounts for up to 16% of patients with ACTH-dependent hypercorti-solism.^1,2 These patients have elevated cortisol and ACTH levels and frequently have CT scans that show bilateral adrenal enlargement.³ The most common ectopic ACTH-secreting tumors are bronchial and thymic carcinoids, with pancreatic islet cell tumors being responsible for less than 1% of all causes of Cushing syndrome.¹

Although the chronic syndrome is often clinically indistinguishable from pituitary-dependent hypercorti-solism presenting with plethora, truncal obesity, buffalo hump, and red striae, the typical Cushing habitus is absent in many acute cases.⁴ Acute Cushing syndrome, which is how our patient presented, is more often associated with the rapid onset of hypertension, weakness, edema, hypokalemia, glucose intolerance, anorexia, and weight loss.⁴

Dynamic testing based upon differential sensitivity to glucocorticoid feedback or ACTH stimulation in response to corticotropin-releasing hormone or cortisol reduction is a reliable way to discern between an ectopic versus a pituitary source of excess ACTH.⁵ High-dose dexamethasone suppresses morning serum cortisol levels in approximately 80% of pituitary ACTH-producing adenomas, though it fails to suppress ACTH in approximately 90% of ectopic cases. However, bronchial and other carcinoids are well-documented exceptions to these general guidelines, as these ectopic sources of ACTH may exhibit feedback regulation indistinguishable from pituitary adenomas.⁵

Although approximately 90% of patients with ectopic ACTH-producing tumors can be cured by surgical resection, pancreatic tumors are virulent neoplasms associated with a rapidly progressive clinical course.¹ In a retrospective analysis of patients with pancreatic islet cell tumors associated with Cushing syndrome, 60% of patients died within 2 years, and the 5-year survival rate was reported to be 16%.⁶ Patients with ectopic ACTH secretion may be at risk of death from metastasis and infections caused by the immunosuppressive effects of excess adrenocortical steroid.⁶ Therefore, functioning pancreatic tumors should be operated early on in the course of the disease to provide a cure.⁷ The optimal treatment for patients with ectopic ACTH production is localization and surgical excision of the source of the ACTH secretion.¹ Successful surgical excision depends upon the ability to identify the site of the tumor and the resectability and metastatic capacity of the neoplasm before operation.¹