The concept of a simultaneous dual analyte immunoassay based on two different metal ion labels is demonstrated. The model system consists of two proteins, human serum albumin (HSA) and immunoglobulin G (IgG). Bismuth and indium ions have been coupled to these proteins through the bifunctional chelating agent diethylenetriamine-pentaacetic acid (DTPA). A maximum molar labeling ratio of 6:1 and 10:1 was obtained for HSA and IgG, respectively. Following a competitive equilibrium between unlabeled and labeled protein for a limited amount of specific antibody immobilized on polystyrene, the bound metal ion labels were released by acidification and detected by differential pulse anodic stripping voltammetry (ASV). Limits of detection for HSA and IgG are 1.8 and 0.6 microgram/mL, respectively. Application of the dual immunoassay to human serum samples gave results that were comparable to those obtained by nephelometry.
Reports of concurrent thyrotoxicosis and thyroid cancer have appeared in the last three decades. While most of the tumours have been clinically inconsequential, it has been suggested that thyroid carcinomas arising in patients with Graves' disease tend to behave aggressively, while those associated with toxic nodular goitre follow a more benign course. We report a contrary clinical experience with four cases of thyrotoxicosis associated with metastatic thyroid cancer, two of which were fatal. All four patients had toxic nodular goitre. Thyroid eye signs were uniformly absent. Two patients had received 131I therapy; none had other history of irradiation to the head or neck. Antimicrosomal and antithyroglobulin antibodies were absent in all four patients. Thyroid-simulating immunoglobulin, which was measured in one patient, was also absent. Histopathological examination of the resected thyroid glands revealed two papillary cancers. one mixed anaplastic/papillary and one anaplastic cancer. All four patients had cervical node involvement and one had pulmonary metastases. Both patients with anaplastic carcinoma succumbed to their disease within 6 months: neither of the patients with papillary cancer had disease recurrence after 2 and 4 years, respectively. The experience reported here of aggressive thyroid cancer associated with toxic nodular goitre may represent coincidence or, alternatively, it may represent the early recognition of a change in the natural history of toxic nodular goitre.
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