calcitonin and Thyroid-Neoplasms

Medullary thyroid carcinoma (MTC) is a rare disease. Serum calcitonin levels and Tc-99m DMSA (V) scans are used in the follow-up of these patients after surgical resection. We present our experience in the follow-up of these patients at a tertiary institution.. A retrospective review of the medical records was performed. Patients with histologically-proven MTC, and who had serum calcitonin assays and DMSA (V) scans in their postoperative follow-up, were included.. There were 17 patients with 56 DMSA (V) scans. Four out of seven patients with elevated preoperative calcitonin measurements had calcitonin normalisation within six months of surgery, and have remained disease-free. Two patients had persistently elevated calcitonin levels after six months, which predated positive DMSA (V) scans. Results of DMSA (V) scans and serum calcitonin levels were concordant in 38 of 48 instances (79.2 percent) and discordant in 10 of 48 instances (20.8 percent). Sensitivity of DMSA (V) scans for detecting recurrence was 71.4 percent. There were no false-positive scans.. Serum calcitonin level is a sensitive and specific indicator of disease recurrence in postoperative follow-up of patients with MTC. Early (within six months) normalisation of calcitonin levels postsurgery may predict subsequent disease-free status. Discordant results between serum calcitonin levels and DMSA (V) scans may be due to undetectable lesions and follow-up scans or alternative radionuclide imaging may be required.

Topics: Adult; Aged; Calcitonin; Carcinoma, Medullary; Disease-Free Survival; Female; Humans; Male; Medical Oncology; Middle Aged; Radiopharmaceuticals; Technetium Tc 99m Dimercaptosuccinic Acid; Thyroid Neoplasms; Thyroidectomy; Treatment Outcome

Helodermin-like and salmon calcitonin (sCT)-like immunoreactivities co-existed in a subset of human calcitonin (hCT)-containing cells in normal human thyroid tissue and medullary thyroid carcinomas. Helodermin/sCT-immunoreactive cells were mostly different from calcitonin gene-related peptide (CGRP)-positive cells. Helodermin and sCT immunoreactivities were not identified in pulmonary and pancreatic hCT-positive neuroendocrine tumors, except for a few lung tumor cells showing positive staining with one of two sCT antisera used. Helodermin immunoreactivity demonstrated by rabbit antiserum R0086 was completely abolished in the presence of synthetic sCT, while sCT immunoreactivity was not absorbed by synthetic helodermin. The carboxyl terminal Arg30-Thr31 sequence (and Pro35 amide structure) of helodermin would be the epitopic site recognized by this antiserum, since a similar amino acid sequence is present in sCT molecules but absent from hCT and CGRP.

Topics: Amino Acid Sequence; Calcitonin; Calcitonin Gene-Related Peptide; Cells, Cultured; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Molecular Sequence Data; Peptides; Sequence Homology, Nucleic Acid; Thyroid Gland; Thyroid Neoplasms; Tumor Cells, Cultured; Venoms

We report the development and validation of three microbioassays for calcitonin based on calcitonin-induced inhibition of the activity of isolated osteoclasts. Having precisely quantified osteoclast motility, spreading and bone resorptive activity, we have applied stringent analytical procedures to define assay characteristics. We have found that the appropriately transformed responses significantly regress on log dose of the peptides. Furthermore, potency estimates obtained using calcitonins from three species (human, salmon and a synthetic analogue of eel calcitonin) have been found to be consistent with those obtained using conventional calcitonin bioassays. In addition, the assays are remarkably sensitive (detection limit 10(-15) M), highly specific and precise. We have determined plasma levels of bioactive calcitonin on samples from patients with medullary thyroid carcinoma; these are several-fold lower than those obtained using our routine calcitonin radioimmunoassay. Our study thus, forms the basis of an entirely new approach for the determination of 'biologically active' calcitonin, and we envisage that such target cell-specific assays could become useful microanalytical methods.

Topics: Animals; Animals, Newborn; Biological Assay; Bone Resorption; Calcitonin; Carcinoma; Cell Movement; Eels; Humans; Osteoclasts; Radioimmunoassay; Rats; Rats, Inbred Strains; Thyroid Neoplasms

Calcitonin-like peptides have been identified in the serum of normal subjects and of medullary thyroid carcinoma (MTC) patients. Using specific homologous radioimmunoassays (RIA) in combination with reversed-phase high performance liquid chromatography and gel permeation chromatography under denaturing conditions, we have recognized major components which coeluted with human calcitonin-(1-32), PDN-21, a carboxyl-terminal flanking peptide derived from the calcitonin mRNA sequence, and salmon calcitonin-(1-32). An additional 12000 molecular weight peak possibly represents a human calcitonin-PDN-21 polyprotein. In both the human calcitonin-(1-32) (normal value less than 0.043 ngEq/ml; MTC 140 +/- 80 ngEq/ml, mean value +/- SEM) and the PDN-21 (normal value less than 0.050 ngEq/ml; MTC 33.6 +/- 16.5 ngEq/ml) RIAs, serum levels were increased in MTC patients. Circulating levels of the salmon calcitonin-like peptide were indistinguishable between normal subjects (0.038 +/- 0.006 ngEq/ml) and MTC patients (0.037 +/- 0.011 ngEq/ml).

Topics: Calcitonin; Carcinoma; Chromatography, Gel; Chromatography, High Pressure Liquid; Humans; Peptides; Polydeoxyribonucleotides; Radioimmunoassay; Thyroid Neoplasms

A salmon calcitonin-like material indistinguishable from synthetic salmon calcitonin-(1-32) on high performance liquid chromatography (HPLC) has been recognized in thyroid extracts of normal subjects and of patients with medullary carcinoma. The same peptide was detected in extracts of the periventricular mesencephalic region which included the periventricular dorsal thalamus, the subthalamus and the hypothalamus. Human calcitonin-(1-32)- and carboxyl-terminal adjacent peptide (CCAP)-like components were also found. The content of immunoreactive salmon calcitonin of the periventricular mesencephalic region (n = 6) and of normal thyroid glands (n = 6) was comparable (mean +/- SE, 0.34 +/- 0.17 ngeq/g wet tissue and 0.39 +/- 0.22 ngeq/g, respectively); and the levels were slightly, but not significantly higher in medullary thyroid carcinoma extracts (1.95 +/- 0.69 ngeq/g) (P less than 0.1). Immunoreactive human calcitonin and CCAP occurred in roughly equimolar concentrations. They were lowest in the periventricular mesencephalic region (0.26 +/- 0.09 ngeq/g and 0.46 +/- 0.10 ngeq/g, respectively), followed by normal thyroid glands (146 +/- 26 ngeq/g and 94 +/- 19 ngeq/g, respectively), and they were highest in medullary thyroid carcinoma tissue (680 +/- 372 mu geq/g and 144 +/- 125 mu geq/g, respectively).

Topics: Brain; Calcitonin; Carcinoma; Diencephalon; Humans; Mesencephalon; Peptide Fragments; Thyroid Gland; Thyroid Neoplasms