Normal Perioperative Serum Calcitonin Levels in Patients with Advanced Medullary Thyroid Carcinoma: Case Report and Review of the Literature. José Miguel ...
THYROID Volume 18, Number 8, 2008 ª Mary Ann Liebert, Inc. DOI: 10.1089=thy.2007.0231
Normal Perioperative Serum Calcitonin Levels in Patients with Advanced Medullary Thyroid Carcinoma: Case Report and Review of the Literature Jose´ Miguel Dora, Maria Heloisa Busi da Silva Canalli, Clarissa Capp, Ma´rcia Khaled Pun˜ales, Jose´ Gilberto H. Vieira, and Ana Luiza Maia
Context: Medullary thyroid carcinoma (MTC), a tumor of the parafollicular C cells of the gland, comprises 3–5% of all malignant thyroid neoplasms. Calcitonin, a polypeptidic hormone secreted by the neoplastic cells, is considered a very sensitive and specific MTC tumor marker. Patients with MTC usually present elevated serum calcitonin levels, which correlate with tumor burden and prognosis. Objectives: To describe a case of advanced MTC with normal serum calcitonin and review the literature on this subject. Design: A case study was performed. Intervention: There were no interventions. Patients: A case of advanced MTC with normal serum calcitonin was studied. Results: Serum calcitonin was measured by two distinct assays, a chemiluminescent immunometric and an in-house two-site monoclonal antibody–based immunofluorometric assay. To rule out a ‘‘hook effect,’’ or posttranslational modifications of calcitonin molecule, serum dilutions and tumor immunohistochemistry for calcitonin with the same antibodies used for serum calcitonin measurements were performed. Serum calcitonin levels were within the normal range in both assays, whereas the tumor stained strongly positive for calcitonin. These findings suggest that the tumor was able to produce but not to secrete the calcitonin protein. Five other cases of advanced MTC with normal serum calcitonin levels had been previously reported. Conclusions: We present an unusual case of advanced MTC with normal serum calcitonin levels. Awareness of MTC cases presenting with normal serum calcitonin levels is important in clinical practice and is particularly relevant to centers that use this test for screening.
Introduction
M
edullary thyroid carcinoma (MTC), a malignant tumor of the parafollicular C cells of the thyroid, may occur sporadically or in hereditary forms. Hereditary MTC is associated with germline mutations in the RET protooncogene, and occurs either as isolated familial MTC or as part of the multiple endocrine neoplasia type 2 (MEN 2) (1). MTC is a relatively uncommon disease, accounting for 3–5% of all malignant thyroid neoplasms. A distinguishing feature of this tumor is the ability to synthesize and secrete the 32aminoacid polypeptidic hormone calcitonin, which is considered a very sensitive and specific tumor marker. Patients with MTC present elevated serum calcitonin, and routine
calcitonin measurement has been suggested for MTC screening in patients with nodular thyroid disease (2–7). Moreover, serum calcitonin levels are usually proportional to tumor size and are predictive of metastatic disease (8–10). Based on these figures, we were surprised by a case of a male patient with metastatic MTC who, despite extensive disease in the neck, presented normal serum calcitonin levels. Here, we report this case and review the literature on this uncommon feature of advanced MTC presentation. Case Report A 43-year-old male patient presented at the Hospital Universita´rio, Universidade Federal de Santa Catarina,
Thyroid Section, Endocrine Division, Hospital de Clı´nicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
895
896 (Florianopo´lis, SC, Brazil), for evaluation of a thyroid nodule detected on ultrasonography (US). He had Hashimoto’s thyroiditis and hypothyroidism treated with 100 mcg=day of levothyroxine. His family history was positive for hypothyroidism and negative for other thyroid diseases, hyperparathyroidism, or pheochromocytoma. Physical examination was unremarkable. Thyroid US showed a 22.5 mL heterogeneous gland with several hypoechoic solid nodules, the largest in the left lower lobe measuring 2.01.81.5 cm. Fine-needle aspiration cytology (FNAC) of this nodule was positive for atypias, and the cellular pattern suggested malignancy. The patient underwent total thyroidectomy. Frozen-section analysis at surgery was suspicious for MTC, and transoperative levels of serum calcitonin and carcinoembryonic antigen (CEA) were requested. Calcitonin 4 ng=L (Immulite 2000, Diagnostic Products Corporation, Gwynedd, UK; reference range < 12 ng=L) and CEA 0.78 mg=L (reference range
