Endocrine Abstracts

Introduction: Cushing’s syndrome (CS) is a rare disease with incidence estimated 2-4 cases per million inhabitants per year. ACTH-dependent forms comprise up to 80% of all cases, of which 80% are central and 20% are ectopic, paraneoplastic forms of ACTH-dependent CS. Thymic neuroendocrine tumors (NET) are accounting for 0,4 - 3% of all NET’s with incidence of 0.02/100 000 inhabitants/year. Up to one third of them are hormonally active (secrete adrenocorticotropic hormone - ACTH, antidiuretic hormone, growth hormone releasing hormone and other hormones).

Clinical case report: A 39-year-old man presented with a rapid development of CS. CS was only partially expressed due to its relatively short history - discrete Cushingoid facies, hyperpigmentation, hypertension, sleep disorders, decreased libido, depression and also complaints of intermittent retrosternal pressure and mild cough. Examination proved highly active ACTH-dependent paraneoplastic hypercortisolism (ACTH 247 ng/l, free urinary cortisol 3220 nmol/day, unsuppressed cortisol in 1mg dexamethasone test: 1110 nmol/l) with hypokalemia and glucose intolerance. CT showed an anterior mediastinum tumor 69x47x64mm. Tumor was resected. Histopathology revealed a thymic atypical carcinoid - neuroendocrine tumor grade 2, however, a resection margin was positive for tumor cells. Postoperatively, the symptoms of hypercortisolism vanished and a central hypocortisolism was proved. As a postoperative OctreoScan examination was negative, no adjuvant therapy was started. Thirteen months after the surgery, laboratory markers suggested recurrence of hypercortisolism. Two tumor masses close to the pulmonary veins found on imaging were considered inoperable. Therefore, cyber knife irradiation was applied, and lanreotide and everolimus were initiated. The effect was insufficient and new metastases appeared in spine, lymphatic nodes, myocard and lungs. Palliative chemotherapy was started - using dacarbazine, subsequently capecitabine and oxaliplatin. What is more, hypercortisolism was not sufficiently suppressed by pharmacotherapy (ketoconazole, metyrapone), which necessitated palliative bilateral adrenalectomy. Later, due to metastatic disease, the patient suffered from malignant pericardial and pleural effusions, both of which required repetitive drainage (in spite of application of cisplatin for pericardial one), and obstructive jaundice caused by tumorous infiltration of gall bladder and pancreas. He died 42 months after the first surgery.

Conclusion: Thymic neuroendocrine tumors are very rare. One third of them manifests itself by paraneoplastic secretion of hormones. Finding the origin of hormone production in ectopic CS can be very challenging but is pivotal for the causal resection of the tumor. The other therapy options include somatostatin analogues, everolimus or chemotherapy.