Bilateral Adrenal Masses, Extreme Catecholamine Excess, and Hypercalcitoninemia With Metastatic Neuroendocrine Neoplasia: A Diagnostic Dilemma

A 40-year-old man presented with back pain, urinary retention, mild unilateral weakness, weight loss, hypercalcemia, and newly recognized hypertension.During the early admission, blood pressure became markedly labile, reaching 225/106 mmHg.Contrast-enhanced computed tomography demonstrated approximately 10-cm bilateral heterogeneous adrenal masses and diffuse lytic skeletal metastases.Biochemical testing showed profound catecholamine excess, including urine metanephrine/creatinine 42,040 µg/g creatinine (reference range: 29-158 µg/g), normetanephrine/creatinine 6,079 µg/g creatinine (reference range: 53-659 µg/g), and vanillylmandelic acid/creatinine 212 mg/g creatinine (reference range: 1.1-4.1 mg/g).Serum calcitonin was 4,680 pg/mL (reference ≤8.4), with carcinoembryonic antigen (CEA) 239 ng/mL (reference <3.8 ng/mL for a non-smoker).Expert review of a bone biopsy showed a metastatic welldifferentiated neuroendocrine tumor, WHO grade 3 (2017), with Ki-67 approximately 40%.The tumor expressed chromogranin, synaptophysin, pancytokeratin, thyroid transcription factor 1 (TTF-1), CEA, paired box 8 (PAX8), and cytokeratin (CK) 7 but was negative for calcitonin, thyroglobulin, CK20, GATA3, and S100.Small polypoid lesions at the tip of the tongue, considered possible mucosal neuromas, together with thyroid calcifications raised concern for multiple endocrine neoplasia type 2B; however, thyroid fine-needle aspiration, RET testing, and functional imaging were not completed before rapid clinical deterioration.The patient received alpha-blockade, palliative spinal radiotherapy, and carboplatin/etoposide; his course was complicated by profound pancytopenia, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli bacteremia, respiratory and renal failure, gastrointestinal bleeding, intracranial hemorrhage, and death.The case illustrates clinicopathologic discordance: the biochemical phenotype strongly favored pheochromocytoma, whereas metastatic-site histology did not establish the primary site.