A Case of Paraneoplastic Erythropoietin Secretion Secondary to Medullary Thyroid Cancer

Background: Paraneoplastic erythropoietin (EPO) secretion is a well-described phenomenon that is classically seen in renal cell carcinoma. It has also been described in parathyroid adenoma and in pheochromocytoma. Additionally, follicular thyroid cancer cells, papillary thyroid cancer cells, and anaplastic thyroid cancer cells have all been found to express EPO in vitro. To our knowledge, EPO expression by medullary thyroid cancer has not previously been studied. Here, we describe a case of suspected paraneoplastic EPO secretion in the setting of advanced medullary thyroid cancer. Clinical Case: A 46 year-old woman presented to our clinic with hoarseness and was proven to have a medullary thyroid cancer with enlarged lymph nodes on the right at levels IV, V and VI. Genetic testing was negative for a germline RET mutation. She underwent total thyroidectomy with bilateral lymph node dissection and was subsequently treated with external beam radiation therapy. Pathology confirmed the diagnosis of medullary thyroid cancer, with extension beyond the thyroid capsule and bilateral lymph node involvement. Rising calcitonin and CEA were noted over the following years. A MRI of the abdomen showed indeterminate subcentimetric liver lesions. A Gallium-68 Dotatate PET scan confirmed the suspicion of liver metastases. Five years after the initial surgery, the patient developed rising hemoglobin levels, despite a long-standing history of iron deficiency anemia. JAK2 testing was negative. EPO levels were elevated (43.45 mU/mL, reference range 2.59 - 18.5 mU/mL) suggesting secondary polycythemia. The patient had a negative smoking history and a pulse oximetry of 98%; there was no evidence of hypoxia that could cause an elevation in EPO. Other differential diagnoses including pheochromocytoma, Cushing’s syndrome from ectopic ACTH production, and renal and brain tumors were excluded. Biopsy of the liver lesions is not technically feasible at this time. Since discovery of the erythrocytosis, the patient has undergone repeated therapeutic phlebotomies, to maintain acceptable hematocrit levels. Conclusion: We believe that our patient’s case may be the first reported case of ectopic EPO production from medullary thyroid cancer causing polycythemia. We encourage other clinicians to report similar clinical cases in order to better understand this rare clinical entity.