First-degree relatives of persons with thyroid cancer are known to be at relatively high risk for the disease. To better understand the clinicopathologic characteristics of familial nonmedullary thyroid carcinoma (FNMTC), we carried out a retrospective study in which we identified individuals treated at our institution who had at least one first-degree relative with the disease. We used data obtained from our patient records to compare the features of 258 cases of the disease with the features of sporadic papillary or follicular thyroid carcinoma in another group of patients. The 258 patients represented 154 families and were selected from among 6458 patients with papillary or follicular thyroid carcinoma who underwent thyroidectomy between 1946 and 2000. Compared to the patients with sporadic disease, the FNMTC patients were more likely to have intraglandular dissemination (28.5% vs. 40.7%; p < 0.0001) and multiple benign nodules (29.8% vs. 41.5%; p <0.0001). There were no significant differences between the two types of patients in terms of gender, age, tumor diameter, adhesion to or invasion of the surrounding tissues, macroscopic metastasis observed at surgery, histology, presence of single benign nodules, presence of chronic thyroiditis, microscopic metastasis, or rate of lymph node metastasis. Recurrence was statistically frequent in the FNMTC patients compared with that in the sporadic disease patients (16.3% vs. 9.6%; p = 0.0005), and the disease-free survival rate was significantly poorer in the FNMTC patients (p = 0.0041 by the Wilcoxon test and p <0.0001 by the log-rank test). No significant difference in the overall survival rate was found between the two groups. Multivariate analysis by Cox's proportional hazards method showed FNMTC to be an independent predictor of shorter disease-free survival (risk ratio 1.88; confidence interval 1.35-2.54; p = 0.0003). Locoregional recurrence in the ipsilateral or contralateral lymph nodes and contralateral thyroid lobe was significantly more frequent in the FNMTC patients than in the sporadic disease patients, whereas no difference was found regarding distant metastases. We conclude that FNMTC is a clinically distinct entity with an aggressive nature. Because of the frequent presence of benign nodules, multifocality, and high rate of locoregional recurrence, total or near-total thyroidectomy with modified radical neck dissection in FNMTC patients is recommended.

The presence of extranodal invasion in patients with thyroid papillary carcinoma is an indicator of distant metastasis and poorer prognosis.

Background Papillary microcarcinoma (PMC) is increasing in incidence because of diagnosis by ultrasound-guided fine-needle aspiration cytology. Methods Between January 1966 and December 1995, we treated 6019 patients with papillary cancer; among them, 2070 patients with PMC were studied. Results PMC is essentially very similar to papillary cancer that is 11 mm or larger and has a very good prognosis. Smaller tumors and younger patients have a better prognosis. Among PMC, larger tumors (6-10 mm) recur in 14% at 35 years compared with 3.3% in patients with smaller tumors. Patients older than 55 years have recurrence in 40% at 30 years, with a worse prognosis than younger patients who have a recurrence rate of less than 10%. Extracapsular invasion by the primary tumor also has a higher recurrence rate. The majority of recurrences are in the neck. Therefore, annual ultrasound of the neck is effective for recurrence surveillance. Conclusion Papillary microcarcinoma is similar to larger papillary carcinomas with tumor characteristics and agebased recurrence rate that extends for many years, justifying long surveillance after surgery.

Seventy‐one cases of papillary adenocarcinoma of the thyroid were operated on from January 1967 to July 1968. in 14 cases, the diagnosis of carcinoma was established postoperatively, so that 57 patients underwent systematic lymph node excision. Among these 57 cases, 90% had evidence of metastasis. a majority of metastatic deposits were small, i.e., 57% of them were less than 3 mm in diameter. There was no relationship between the location of primary tumor and metastasis; the initial metastases were most commonly observed in the pre‐ and paratracheal nodes, and subsequently, metastases were noted in the deep inferior and lateral cervical nodes. in patients who had a small number of metastatic deposits, the metastases were concentrated in the following sequence: pre‐ and paratracheal nodes, deep lower and lateral, and deep upper submandibular nodes. in those who had extensive metastases, the sequence of concentration was as follows: pre‐ and paratracheal, paraglandular and deep upper cervical, deep lower and lateral, and submandibular. From these observations, it can be concluded that metastasis of papillary thyroid carcinoma occurs first in paratracheal nodes, regardless of the location of the primary tumor. in the early stages, metastases are more frequent in the lower part of the neck. in later stages, when lymphatic obstruction has occurred, metastases appear in upper and submandibular nodes.

Purpose: Assessment of the proliferative ability of cancer cells is necessary not only for the biologic characterization of tumors, but also for the selection of treatment and evaluation of prognosis. Recently, there have been several studies examining the proliferative activity of various malignant tumors using immunohistochemical methods. PCNA is a nuclear protein related to the cell cycle and found with high expression in proliferative tissues, including cancers. Methods: In our study, to evaluate whether PCNA expression was useful as a prognostic factor in patients with pa-pillary thyroid carcinoma, we quantitated the immunohisto-chemical expression of PCNA in the formalin-fixed paraffin embedded tissue from 55 patients with papillary thyroid car-cinoma and correlated the results with established clinico-pathologic parameters. Results: The results were as follows. 1) PCNA expression in papillary thyroid carcinoma did not correlate with the age, sex or metastatic L/N activity of the patient, nor with the size, invasion, or recurrence of the tumor. 2) There was a close relationship between the expression rate of PCNA in thyroid tumor cells and that in metastatic L/N cells (p=0.056, in p0.1). 3) The expression of PCNA in the metastatic L/N (+) group was higher than in the metastatic L/N (-) group (p=0.045). Conclusion: It is suggested that PCNA expression is not an appropriate prognostic factor in papillary thyroid carcino-ma. (Korean J Endocrine Surg 2001;1:61-66)

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Objective: We aimed to determine the serum level of fibroblast growth factor-23 (FGF-23) in patients with primary hyperparathyroidism (pHPT) to understand its physiological role in the disorder. Patients and methods: Ninety-eight patients with pHPT who underwent parathyroidectomy formed the study group. We also measured serum FGF-23 in 11 of these patients on postoperative day 6. Results: Serum FGF-23 levels was significantly higher in pHPT patients than in healthy controls (35.6^17.8 ng/l vs 28.9^11.2 ng/l (mean^S.D.); P , 0.001 (Pearson's correlation coefficient)), but there was no significant difference in the serum FGF-23 level between pHPT patients with normal renal function (creatinine clearance (Ccr) of $70 ml/min) and healthy controls. Serum FGF-23 correlated positively with serum calcium (P , 0.0001) and intact parathyroid hormone (PTH) (P , 0.01), and negatively with Ccr (P , 0.001), serum phosphate (P , 0.05), and serum 1,25-dihydroxyvitamin D (1,25(OH) 2 D) (P , 0.05). Multiple linear regression analysis of factors potentially determining serum FGF-23 levels in pHPT patients showed serum calcium (P , 0.01) and Ccr (P , 0.001) to be significant predictors. The serum levels of FGF-23 did not change after parathyroidectomy despite the normalization of serum calcium values. Multiple linear regression analysis revealed that serum FGF-23 was not a significant predictor of serum phosphate or 1,25(OH) 2 D in pHPT patients. Conclusions: FGF-23 may not play a significant role in regulating phosphate or 1,25(OH) 2 D in pHPT patients, especially in those with normal renal function. Further studies are warranted to determine the role of FGF-23 in renal insufficiency or failure.European Journal of Endocrinology 151 55-60

This retrospective study was aimed at revealing the incidence of normal white blood cell (WBC) count agranulocytosis in patients treated with antithyroid drugs (ATDs). From January 1975 to December 2001, 109 patients (0.35%) presented with ATD-induced agranulocytosis at our clinic. In 18 patients (16.5%), the WBC count exceeded 3.0 x 10(9)/L at the onset of agranulocytosis. Ten showed a downward trend in WBC count (3.0-3.9 x 10(9)/L) after the initiation of ATDs. Four had symptoms of infection. In the remaining 4 patients, routine WBC and granulocyte count monitoring detected an agranulocytosis. During the first 3 months of ATD treatment, 3347 patients (10.9%) had WBC count 3.0-3.9 x 10(9)/L even once with no symptom and normal granulocyte count and 26672 patients had WBC count >or= 4.0 x 10(9)/L with no symptom and normal granulocyte count. When agranulocytosis was found, twelve patients with normal WBC count agranulocytosis (0.36%) had WBC count 3.0-3.9 x 10(9)/L with no symptom, whereas only 2 patients with agranulocytosis (0.008%) had WBC count >or= 4.0 x 10(9)/L with no symptom. In conclusion, clinicians should take normal WBC count agranulocytosis into consideration at least during the first 3 months of antithyroid drug therapy, especially when WBC count is 3.0-3.9 x 10(9)/L.