Overlapping Between Thymus Neuroendocrine Carcinoma as an Ectopic Cushing Syndrome and Exogenous Cushing’s Syndrome: A Case Report

ABSTRACT

Cushing’s syndrome results from an excess production of the hormone cortisol by the adrenal gland. It can be distinguished into ectopic and exogenous, also known as iatrogenic, depending on whether the cause exists inside or outside the body, respectively. The exogenous disease can occur due to the intake of corticosteroids medication. Thymic neuroendocrine carcinoma is one of the most common etiologies of ectopic Cushing’s syndrome. We report a case of overlapping condition between ectopic and exogenous Cushing’s syndromes and discussed the invasive characteristics of thymic low-grade neuroendocrine carcinoma and its capability to transform to a high-grade carcinoma. A 29-year-old male patient was presented with Cushing’s symptoms and hypokalemia. He had a history of repeated weekly dexamethasone injections during last year to treat generalized weakness, without physician's prescription. He reported relative improvement in his general condition with the use of corticosteroids. The case was managed as an iatrogenic Cushing’s syndrome because of excessive use of corticosteroids and low cortisol levels despite suppressed ACTH. He presented with weakness and hypercortisolism eight months after the discontinuation of dexamethasone with an ACTH >1.500 pg/mL; these features were in favor of ectopic Cushing's syndrome. Also, a thymus mass was detected on imaging. We performed thymus resection due to the early stage of the syndrome and there was no sign of metastasis to other organs. Pathology reported a thymic carcinoid tumor. Normal calcium, PTH, prolactin, and gastrin levels ruled out the involvement of MEN I. Tumor cells were immunoreactive for ACTH, and a whole body scan was performed. An 18-month delay in visiting the doctor and not undergoing whole body scan led to a severe relapse with full-blown Cushing’s syndrome, generalized bone pain, pulmonary metastatic nodules, hyperplasic adrenals, and widespread bone metastases as demonstrated by the whole body bone scan. Bilateral adrenalectomy was performed. Metastatic neuroendocrine carcinoma grade III was reported in the pathology. After consultation with an oncologist, palliative chemotherapy with octreotide was started. He died because of pulmonary metastases, severe opportunistic organism infections, and septic shock. This case represented one of endogenous hypercortisolism (ectopic Cushing’s syndrome) masked by the excess exogenous use of glucocorticoids, with unexpected relapse of localized and lowstage thymus neuroendocrine carcinoid tumor. Its conversion to invasive type within less than two years after thymus resection led to adrenals, lungs, and all bones metastases.