Sequential occurrence of toxic nodular goiter followed by Graves' disease.

OBJECTIVE: To present the first case of Graves' disease occurring after toxic nodular goiter in a patient who had not received radioiodine therapy. METHODS: We describe the clinical, laboratory, and radiologic findings in a 65-year-old woman with toxic nodular goiter followed by Graves' disease and review related reports in the literature. RESULTS: Although isolated case reports have documented the sequential occurrence of toxic nodular goiter or toxic adenoma and Graves' disease, no definite connection currently exists between these two types of hyperthyroidism. In cases previously described, Graves' disease appeared after the use of radioiodine for the treatment of the toxic nodular goiter. In our current patient, toxic nodular goiter was treated surgically, followed by the occurrence of Graves' disease 3 years later. CONCLUSION: This is the first published case of sequential toxic nodular goiter and Graves' disease in which radioiodine was not used for treatment of the goiter and thus cannot be implicated as the inciting event for the subsequent development of Graves' disease.

Detection of circulating thyroid cells in peripheral blood.

BACKGROUND: Detection of circulating malignant thyroid cells may provide a method to identify postoperative patients at risk for metastatic thyroid cancer. METHODS: On 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). RESULTS: Thyroglobulin 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). CONCLUSIONS: These 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.

The intraoperative incidence of detectable bilateral and multicentric disease in papillary cancer of the thyroid.

This is a prospective study to determine the incidence of grossly detectable multicentric and bilateral cancer at operation in patients who, before surgery, were believed to have a unilateral lesion. The opposite lobe was inspected at the time of operation and the surgeon made a determination as to whether there was bilateral and/or multicentric disease present. A total thyroidectomy was then carried out and the accuracy of the surgeon's judgment was established by permanent-section pathologic examination. Fifteen of the 44 patients were assessed to have gross bilateral disease. Thirteen of these were confirmed by pathologic examination. One case of microscopic bilateral disease was not recognized by the surgeon. Seventeen patients were thought to have unilateral multicentric disease. Fifteen of these cases were confirmed by microscopy and an additional seven cases were documented to have secondary foci. It is obvious from this study that most disease that is called microscopic disease is actually palpable. A review of the literature confirms this. It was very unlikely for a patient who did not have unilateral multicentric disease to have a contralateral focus of carcinoma. The incidence of bilateral disease was 32%, and the incidence of multicentric disease was 50%; the surgeon was very accurate in assessing this. We believe that surgeons who advocate lobectomy as the primary treatment for thyroid cancer are recognizing grossly detectable disease in a significant number of patients and thus are doing total thyroidectomies in most patients with bilateral disease.

The incidence of carcinoma in encapsulated follicular thyroid lesions diagnosed by large needle biopsy.

During the period from 1975 to 1982, there were 132 patients who had encapsulated thyroid lesions diagnosed by Tru Cut needle biopsy. One hundred and nineteen patients have had operations and 20 had cancer. The 20 cancers occurred in a group of 86 lesions that were classified as microfollicular. No cancers were seen in lesions classified as macrofollicular. The incidence of cancer in the microfollicular group was 23%. This incidence of cancer was the same in Hürthle cell and non-Hürthle cell microfollicular lesions.

Immunotherapy of thyroid cancer by induction of autoimmune thyroiditis.

An animal model was used to investigate the most effective way to create autoimmune thyroiditis. Several modified forms of thyroglobulin (TG) with and without Freund adjuvant were tested. TG altered with the diazonium derivatives of arsanilic and sulfanilic acids was found to be the most effective immunizing agent for inducing autoimmunity. Human TG altered in the same manner was used to induce autoimmune thyroiditis in humans with untreatable metastatic thyroid cancer. There was minimal toxicity during the therapy and it was possible to create autoimmune thyroiditis in three of eight patients. Antibodies to TG were induced in five of eight patients. The clinical response to the immunotherapy was minimal, however, and it was not possible to demonstrate any significant measurable response to therapy.

Thyroglobulin in benign and malignant thyroid disease.

Thyroglobulin (TG) is a 19S glycoprotein produced by normal thyroids and almost all nonmedullary thyroid cancers. Radioimmunoassays measure serum levels of TG, and these levels are abnormally elevated in patients with metastatic thyroid cancer. Data from our study show that TG measurement is not effective in screening high-risk populations for thyroid cancer. Nevertheless, serum TG determinations are useful for assessing the presence and possibly the extent of residual or recurrent nonmedullary thyroid cancer in patients who have undergone total thyroidectomy.

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 glycoproteint. 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.

Serum thyroglobulin and recurrent thyroid cancer.

Many thyroid malignancies are sufficiently differentiated to produce thyroglobulin both in situ and in perpipheral blood. Since patients who have undergone total thyroidectomy for malegnancy should not have normally circulating thyroglobulin, their serum thyroglobulin may provide a simple and specific tumour marker for recurrent disease. Of 30 such athyroid patients who were studied, all of the 20 patients who were disease-free ten years after thyroidectomy had minimal (less than15 ng/ml) serum-thyroglobulin levels while all of 10 patients with recurrences had raised levels (greater than 90 ng/ml). Controls ranged from 0 to 60 ng/ml. This assay should prove valuable in following patients who have undergone total thyroidectomy for recurrent thyroid malignancy.

A simple technique for obtaining Pap smears of the esophagus.

A simple method for obtaining Papanicolaou smears of the esophagus is described. The procedure is easy to perform, does not require specialized equipment, and is a useful adjuvant to direct esophageal biospy.