Medullary Thyroid Carcinoma with Ectopic Adrenocorticotropic Hormone Syndrome
A 48-year-old male was referred to the endocrinology clinic complaining of generalized edema, increased blood pressure and blood glucose levels. The patient was on medication due to hypertension that was diagnosed 1 year ago. Recently, the blood pressure was not well-controlled, the blood glucose level was high and generalized edema developed.\nThe patient was diagnosed with MTC 14 years ago; total thyroidectomy with right cervical lymph node dissection was performed and I-131 metaiodobenzylguanidine (MIBG) 200 mCi was administered. He was treated with tumor resection for recurred MTC on a mediastinal lymph node 13 years ago. Nine years ago, MTC recurred on the left cervical and left parahilar lymph nodes and was treated with I-131 MIBG 200 mCi after surgery. Two years ago, MTC recurred thirdly on the cervical and mediastinal lymph nodes and lung and was treated with cervical and mediastinal lymph node dissection and the left upper lobe wedge resection of the lung. Since then, the patient has not shown any signs or symptoms of recurrence.\nThe patient's height was 172 cm and weight was 84 kg, 2 kg over his usual weight. His blood pressure was 185/110 mm Hg with a pulse rate of 90 beats per minute and a breathing rate of 18 breaths per minute. The patient's body temperature was 37℃. Moon face and facial flushing were observed. Buffalo hump and purple striae were absent. Mild pitting edema was observed on the anterior tibia and slight skin pigmentation was present.\nPeripheral blood examination showed a white blood cell count of 14,450 cells/µL, hemoglobin of 15.3 g/dL, and platelet count of 358,000 cells/µL. On serum biochemical examination, total cholesterol was 252 mg/dL with total protein of 6.5 g/dL, albumin of 4.1 g/dL, total bilirubin of 1.1 mg/dL, alkaline phosphatase of 101 U/L, aspartate aminotransferase of 17 U/L, alanine aminotransferase of 62 U/L, blood urea nitrogen of 10.3 mg/dL, and creatinine of 0.6 mg/dL. On serum electrolyte examination, sodium was 145 mmol/L with potassium of 2.8 mmol/L, chloride of 94 mmol/L, and bicarbonate of 40.4 mmol/L. Fasting plasma glucose level was 168 mg/dL with glycated hemoglobin of 8.6%. Hormone examination showed total T4 of 12.75 µg/dL (range, 5 to 13) and thyroid stimulating hormone of 0.07 µIU/mL (range, 0.15 to 5.0). Serum calcitonin was 127.86 pg/mL (<10.0) and carcinoembryonic antigen was 29.46 ng/mL (<5). Plasma ACTH concentration was measured with immunoradiometric assay (ELSA-ACTH kit, CisBio, Belford, MA, USA), and was 203.9 pg/mL (range, 6.0 to 60.0). Serum cortisol concentration was 36.0 µg/dL (range, 5 to 25.0) with a 24-hour urine cortisol of 2,237.1 µg/day (range, 20 to 90). On the low dose dexamethasone suppression test, inhibited serum cortisol was 32.50 µg/dL. The 24-hour urine examination results were as follows: metanephrine 14.46 µg/day (range, 52 to 341), normetanephrine 28.21 µg/day (range, 88 to 444), epinephrine 6.57 µg/day (<40), norepinephrine 26.43 µg/day (<80), and vanillylmandelic acid 3.51 mg/day (<8). To validate the RET gene mutation, peripheral blood was collected from the patient and white blood cells were separated by centrifugation to extract genomic DNA. For polymerase chain reaction, BIGDYE version 3.1 cycles sequencing kit (Applied Biosystems, Foster, CA, USA) reagent was utilized and 3,730 automated sequencer (Applied Biosystems) was used to analyze DNA sequence. The DNA sequencing showed no RET gene mutation.\nChest and abdomen computed tomography revealed recurred lesions on the mediastinal lymph nodes, lungs, and liver (), but no abnormal findings in adrenal glands (). Sellar magnetic resonance imaging showed no abnormality in the pituitary gland (). Gastroscopy, colonoscopy, and positron emission tomography did not identify suspicious primary lesions in other regions.\nCalcitonin and chromogranin A staining was positive on resected tissues on the third recurrence 2 years ago, which is indicative of MTC. ACTH immunohistochemistry staining was negative ().\nBecause curative resection of the MTC lesions was difficult on the fourth recurrence, close follow-up with further chemotherapy was considered. To control the ectopic ACTH syndrome, the patient was administered ketoconazole. The dosage was gradually increased over 3 months up to the maximum dosage (1,200 mg/day), but the serum cortisol concentration level did not decrease. Therefore, bilateral adrenalectomy was performed. After surgery, ACTH remained above 200 pg/mL, but plasma glucose and blood pressure levels were improved sufficiently and the oral antidiabetic agent and antihypertensive medication were discontinued. The patient has been living in good condition until 6 months after the surgery without any medication other than glucocorticoid and mineralocorticoid agents.