A unique case of ectopic Cushing's syndrome from a thymic neuroendocrine carcinoma

Abstract

Ectopic adrenocorticotropic hormone (ACTH) production leading to ectopic ACTH syndrome accounts for a small proportion of all Cushing's syndrome (CS) cases. Thymic neuroendocrine tumors are rare neoplasms that may secrete ACTH leading to rapid development of hypercortisolism causing electrolyte and metabolic abnormalities, uncontrolled hypertension and an increased risk for opportunistic infections. We present a unique case of a patient who presented with a mediastinal mass, revealed to be an ACTH-secreting thymic neuroendocrine tumor (NET) causing ectopic CS. As the diagnosis of CS from ectopic ACTH syndrome (EAS) remains challenging, we emphasize the necessity for high clinical suspicion in the appropriate setting, concordance between biochemical, imaging and pathology findings, along with continued vigilant monitoring for recurrence after definitive treatment. Learning points: Functional thymic neuroendocrine tumors are exceedingly rare. Ectopic Cushing's syndrome secondary to thymic neuroendocrine tumors secreting ACTH present with features of hypercortisolism including electrolyte and metabolic abnormalities, uncontrolled hypertension and hyperglycemia, and opportunistic infections. The ability to undergo surgery and completeness of resection are the strongest prognostic factors for improved overall survival; however, the recurrence rate remains high. A high degree of initial clinical suspicion followed by vigilant monitoring is required for patients with this challenging disease.

Keywords: 2019; ACTH; ACTH stimulation; Adrenal; Adult; Bicarbonate; Bilateral adrenal hyperplasia; Biopsy; Blood pressure; Buffalo hump; CT scan; Chest pain; Chest pain (pleuritic); Chromogranin A; Cortisol; Cortisol, free (24-hour urine); Creatine kinase; Cushing's syndrome; Dexamethasone; Dexamethasone suppression; Dyspnoea; Ectopic ACTH syndrome; Ectopic Cushing's syndrome; Facial fullness; Facial plethora; February; Glucocorticoids; Glucose (blood); Histopathology; Hypercortisolaemia; Hyperglycaemia; Hyperpigmentation; Hypertension; Hypokalaemia; Hypotension; Immunohistochemistry; Ketoconazole; Leukocytosis; Lymphadenitis; Lymphadenopathy; MRI; Male; Metabolic alkalosis; Myasthaenia; Neuroendocrine tumour; Obesity; PET scan; Photosensitivity; Pituitary; Potassium; Resection of tumour; Rhabdomyolysis; Steroids; Supraclavicular fat pads; Synaptophysin; Syncope; Thymus; Unique/unexpected symptoms or presentations of a disease; United Kingdom; Weight gain; White; White blood cell count; X-ray.

Figure 1

Chest CT with IV contrast. Axial (A), coronal (B) and sagittal (C) images of the chest demonstrate a bilobed mass (arrow) centered in the anterior mediastinum insinuating into the left paratracheal region displacing the aortic arch branch vessels, and extending in the thoracic inlet.

Figure 2

Whole-body 18F-FDG-PET/CT. 3D volume-rendered CT image (A) demonstrate central obesity and cushingoid facies. Fused coronal PET/CT image demonstrates moderate and heterogeneous FDG uptake by the mediastinal mass (arrow, B) and intense, symmetric uptake by the adrenal glands (arrows, C).

Figure 3

MRI pituitary with and without contrast. The pituitary gland (circled, A) is within normal limits of size and configuration without pituitary adenoma or suprasellar mass. Symmetric calcifications (arrows, B) within the caudate heads, and lentiform nucleus suggests dystrophic calcification.

Figure 4

(A) Low power showing a cellular highly vascularized neoplasm (H&E, 0.4×). (B) Solid nests of polygonal cells with round to slightly oval nuclei with finely granular chromatin, inconspicuous nucleoli and ample eosinophilic cytoplasm. No mitotic figures or necrosis are present (H&E, 25×).

Figure 5

Immunohistochemical markers confirm neuroendocrine immunophenotype of the tumor cells (A) synaptophysin, (B) chromogranin (10×).