Carl R. Feind

Detection of circulating thyroid cells in peripheral blood

BACKGROUNDnDetection of circulating malignant thyroid cells may provide a method to identify postoperative patients at risk for metastatic thyroid cancer.nnnMETHODSnOn the basis of tissue specificity of thyroglobulin gene expression and the sensitivity of the reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, we performed RT-PCR using primers for thyroglobulin on blood samples from patients with thyroid disease to detect thyroglobulin RNA transcripts. Postoperative peripheral blood samples from 100 patients, including patients with known metastatic thyroid cancer (six papillary and three follicular), thyroid cancer and no evidence of current metastases (63 papillary, 10 follicular, and five patients with both papillary and follicular), benign thyroid disease (six nontoxic nodular goiters), and normal volunteers (seven).nnnRESULTSnThyroglobulin transcripts were detected in nine of nine patients with metastatic thyroid cancer, seven of 78 patients with thyroid cancer and no current metastases (although of these seven patients, five had a history of metastatic disease that had been previously treated by surgery, one had a coexisting parathyroid cancer, and one had both papillary and follicular thyroid cancers), zero of six patients with benign thyroid disease, and zero of seven normal volunteers. Identity of amplicons was confirmed by restriction enzyme digestion and by cloning and sequencing of RT-PCR amplified thyroglobulin fragment (the latter in a limited number of cases).nnnCONCLUSIONSnThese data indicate that RT-PCR can be used to detect thyroglobulin mRNA in peripheral blood. The presence of these transcripts correlates with the existence of extrathyroidal disease.

Parathyroid adenoma and nonmedullary thyroid carcinoma

The incidence of thyroid carcinoma in patients with hyperparathyroidism has been reported as higher than expected. We record our experience with 272 cases of primary hyperparathyroidism. Malignant thyroid lesions were found in 11.4%. We conclude that this is more than a fortuitous association.

Fine needle cytologic diagnosis of thyroid nodules: Review and report of 300 cases

Three hundred patients with thyroid nodules were evaluated with fine needle biopsy and cytologic evaluation. Nineteen of 23 cancers were diagnosed by fine needle biopsy alone, for a yield of 83 percent. Four of 300 diagnoses (1 percent) were false-positive, and the evidence of neoplasm at operation was 68 percent. We believe that fine needle biopsy will greatly decrease the number of unnecessary thyroid resections.

Serum clearance rates of immunologically reactive thyroglobulin

Serum thyroglobulin levels have been shown to have a role in detecting the presence of residual or recurrent disease in most patients who have undergone total thyroidectomy for thyroid cancer. It has not yet been determined at what interval postoperatively to begin following serum thyroglobulin levels in these patients to detect residual disease. Eight patients who underwent total thyroidectomy were studied to determine the clearance rate of this glyocoproteint. Serial samples were obtained pre‐ and postoperatively and clearance rate curves were plotted for each patient. The average half‐life of thyroglobulin was 14 hours, with a range of 8 to 22 hours. Based upon these results, it appears that 4 weeks is a sufficient period of time to allow for the clearance of the residual thyroglobulin in patients undergoing total thyroidectomy. Elevated levels of serum thyroglobulin after this time represent residual thyroid tissue or the presence of metastatic thyroid carcinoma.

Organ culture of human parathyroid glands: Effects of catecholamines☆

Normal and adenomatous human parathyroid glands were studied in organ culture to determine basal secretory rates of cyclic AMP and parathyroid hormone as well as sensitivity to β-adrenergic catecholamines. Basal cyclic AMP secretion was relatively constant over 4 weeks but parathyroid hormone secretion declined. Both normal and adenomatous tissue were stimulated to secrete cyclic AMP and parathyroid hormone in the presence of the β agonist, isoproterenol. Half-maximal stimulation for adenomas occurred at 1 μM. Propranolol, a β-adrenergic inhibitor, completely prevented the response, with half-maximal inhibition occurring at 0.1 μM. Under basal conditions, normal explants secreted significantly more cyclic AMP and parathyroid hormone than adenomas. The results indicate that both normal and adenomatous human parathyroid glands can be maintained in organ culture for up to 4 weeks and that β-adrenergic catecholamines can stimulate the secretion of cyclic AMP and parathyroid hormone.

Pancreatic polypeptide (PP) immunoreactivity in human parathyroid culture media.

Media from cultures of normal and abnormal human parathyroid fragments were assayed for parathyrin (PTH) and pancreatic polypeptide (PP) using sensitive radioimmunoassays. PP immunoreactivity was present in media (Day 6-7 in vitro) from cultures of 3/10 adenomas and 6/6 3 degrees hyperplastic glands (mean = 126. fmole/mg protein/day) (range = 6.-675.), and was not suppressed by 0 leads to 3 mM calcium challenge. PP was undetectable in media from cultures of one parathyroid carcinoma, one 1 degree hyperplasia, and one normal parathyroid. Medium C-terminal PTH levels were quite variable (26.-2,545,000. pg/mg protein/day). Presence of PP immunoreactivity in media from cultures of some hyperplastic parathyroids and some parathyroid adenomas suggests that PP may be released from these tissues in vitro. The significance of elevated PP levels in the MEA syndromes may be of special clinical relevance to this observation.