Endocrine Abstracts

Introduction: Calcitonin is produced by parafollicular C cells of the thyroid, increased values being considered the hallmark for the medullary thyroid carcinoma (MTC). We discussed two challenging cases with high calcitonin, multinodular goitre and ACTH-dependent paraneoplastic Cushing syndrome.

Case 1: A 45-year-old female patient was admitted into our clinic due to severe fatigue, central obesity, proximal muscle atrophy, round face, buffalo hump, dorsal kyphosis due to osteoporotic vertebral fractures, high blood pressure. Laboratory evaluation revealed high morning and midnight serum cortisol, with no suppression on low-dose dexamethasone suppression test and high plasma ACTH (65.7 pg/ml), indicating an ACTH-dependent Cushing’ syndrome. Pituitary magnetic resonance imaging (MRI) didn’t reveal any pituitary adenoma. On thyroid ultrasound a mixed hypoechoic nodule of 6/6/8 mm in the right lobe was detected and increased calcitonin level (79.6 pg/ml). A MTC with ectopic paraneoplastic secretion of ACTH was suspected. The Calcitonin-stimulation test with Omeprazole was done, with no stimulation for Calcitonin. More extensive imaging exploration revealed a well-defined lung nodule of 10 mm. The tumor was removed and the pathology report confirmed a carcinoid tumor, stage pT1bN0M0, with Ki-67 index of 2%, and positive immunostaining for ACTH, calcitonin, chromogranin and synaptophysin. After surgery, ACTH, cortisol and calcitonin levels decreased significantly (5.4 pg/ml, 2.42 ng/dl and <2 pg/ml).

Case 2: A 44-year-old hypertensive women was admitted with typical Cushing’s syndrome features and amenorrhea for 5 years. Hypercortisolism was confirmed (increased basal and nocturnal serum cortisol, unsuppressed after 1 mg dexamethasone, high ACTH levels-253 pg/ml), increased chromogranin A (2980 ng/l, NR 27–94), hyperglycemia, severe hypokalemia. The imagistic investigations showed no pathological pituitary, pulmonary and abdominal lesions. Pelvic CT and MRI confirmed an ovarian tumoral mass of 15 cm. As the patient presented 2 highly suspicious left thyroid nodules and increased calcitonin (291 pg/ml), MTC with ectopic ACTH-secretion was considered, but the pathology revealed papillary thyroid cancer. After the removal of ovarian tumor, the values of ACTH, cortisol, calcitonin, and chromogranin A decreased significantly.

Discussions: In both cases, the absence of a clear ACTH source imposed the extensive hormonal and imagistic exploration. Calcitonin determination was included in the work-up flow due to the presence of thyroid nodules. The outcome of both cases underline that the high values for calcitonin don’t indicate a MTC, always.

Conclusion: When calcitonin level is elevated, but thyroid evaluation is not clear suggestive for a medullary thyroid carcinoma, an extrathyroidal neuroendocrine tumor should be taking into account for differential diagnosis.