Impact of total versus subtotal thyroidectomy on calcium metabolism and bone mineral density in premenopausal women.

OBJECTIVE: This study aimed to compare the impact of total versus subtotal thyroidectomy on calcium metabolism and bone mineral density in euthyroid, premenopausal women. SUBJECTS: The study included 24 premenopausal women who had undergone total (n = 10) or subtotal (n = 14) thyroidectomy and who were receiving nonsuppressive doses of thyroxine. The median post-operative period was four years. We determined, in all patients, the following parameters associated with calcium metabolism: total serum calcium, inorganic phosphate, intact parathormone, calcitonin and alkaline phosphatase. The bone mineral density of the spine and hip were measured using a Hologic QDR 4500C bone densitometer and were compared with controls matched for age and peak bone mineral density (using the t-test). RESULTS: The measured calcium metabolism parameters were normal in all patients, and none had osteoporosis. There was no significant difference in the bone mineral density measurements for the spine and hip, comparing patients who had undergone total versus subtotal thyroidectomy (using the t-test). CONCLUSION: The impact of total thyroidectomy on bone mineral metabolism is not significantly different from that of subtotal thyroidectomy, in premenopausal women with normal thyroid-stimulating hormone values.

Determination of remnant thyroid volume: comparison of ultrasonography, radioactive iodine uptake and serum thyroid-stimulating hormone level.

PURPOSE: We aimed to evaluate the accuracy of ultrasonography, radioactive iodine uptake and serum thyroid-stimulating hormone level in predicting the volume of remnant thyroid gland. METHODS: Sixty-six thyroidectomy patients were divided into two groups according to their functional status, i.e. those operated upon for nontoxic multinodular goitre (group one) and those operated upon for hyperthyroidism (group two). Ultrasonography, radioactive iodine uptake and thyroid-stimulating hormone assay were performed in all patients during the first post-operative month. The two groups were subdivided according to the amount of remnant thyroid volume detected on ultrasonography: <2 ml, 2-5 ml and >5 ml. RESULTS: The remnant thyroid volume was positively correlated with the radioactive iodine uptake (rs = 0.684, p = 0.0001). The increase in remnant thyroid tissue radioactive iodine uptake was significantly greater in the patients operated upon for hyperthyroidism compared with those operated upon for nontoxic multinodular goitre (p = 0.0001). There was a negative correlation between remnant thyroid volume and post-operative serum thyroid-stimulating hormone level (rs = -0.865, p = 0.0001) and between remnant thyroid tissue radioactive iodine uptake and post-operative serum thyroid-stimulating hormone level (rs = -0.682, p = 0.0001). CONCLUSION: Ultrasonography is a more accurate measure of remnant thyroid volume than radioactive iodine uptake in patients operated upon for hyperthyroidism, compared with those operated upon for nontoxic multinodular goitre.

The preoperative exclusion of thyroid carcinoma in multinodular goiter: Dynamic contrast-enhanced magnetic resonance imaging versus ultrasonography-guided fine-needle aspiration biopsy.

BACKGROUND: We compared the diagnostic values of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and ultrasonography (USG)-guided fine-needle aspiration biopsy (FNAB) in the detection of thyroid carcinoma associated with multinodular goiter. METHODS: USG-guided FNAB and DCE-MRI were performed consecutively on 26 patients who had multinodular goiter with dominant nodules and clinical suspicion of malignancy. DCE-MRI findings, cytodiagnosis, and final histopathologic results were correlated. We compared the sensitivity, specificity, diagnostic accuracy, and positive (PPV) and negative predictive values (NPV) of DCE-MRI and USG-guided FNAB. RESULTS: Of 57 nodules in 26 patients, 16, 37, and 4 nodules showed delayed, plateau, and rapid washout patterns, respectively. Thyroid carcinoma was found in 8 patients (31%). Delayed washout pattern in a nodule was correlated with the histologic diagnosis of thyroid carcinoma (P < .001). None of the nodules with thyroid carcinoma had a plateau or rapid washout pattern. The sensitivity and NPV of DCE-MRI to diagnose thyroid carcinoma were greater when compared with those in USG-guided FNAB (100 vs 71.4%, and 100 vs 91.7%, respectively; P < .001). CONCLUSION: When other diagnostic methods are inconclusive, DCE-MRI is superior to USG-guided FNAB to exclude thyroid carcinoma in patients with multinodular goiter.

Effects of thyroxine replacement on lipid profile and endothelial function after thyroidectomy.

BACKGROUND: Hypothyroidism is a risk factor for atherosclerotic cardiovascular disease. This study investigated the effects of L-thyroxine replacement therapy on lipid profile and endothelial function after thyroidectomy in patients with overt transient non-autoimmune hypothyroidism. METHODS: Twenty-two patients with non-toxic multinodular goitre treated by total or near-total thyroidectomy and 22 healthy individuals matched for age, sex and body mass index were studied. Lipid profile and endothelial function were determined in each patient at the euthyroid phase before thyroidectomy (stage 1), the hypothyroid phase 3 weeks after surgery (stage 2), and the euthyroid phase 3 months (stage 3) and 6 months (stage 4) after the start of thyroxine treatment. RESULTS: The lipid profile and endothelial function deteriorated between stage 1 and stages 2 and 3. Findings at stage 4 were similar to those at stage 1. There was a positive correlation between serum thyroid-stimulating hormone (TSH) and total cholesterol (r(s) = 0.588, P < 0.001), and a negative correlation between serum TSH and flow-mediated arterial dilatation (r(s) = 0.506, P < 0.001). Total cholesterol and TSH were independent determinants of endothelial function. CONCLUSION: A 3-week hypothyroid period after thyroidectomy led to a more atherogenic lipid profile and impaired endothelial function that persisted for at least 3 months.

Expression of bcl-2 in papillary thyroid cancers and its prognostic value.

PURPOSE: Papillary thyroid cancer has a good prognosis. This favourable prognosis may be attributed to the apoptotic tendency of the cancer cells. This study aims to evaluate the expression of bcl-2, which is an antidote of apoptosis, and aims to evaluate the value of bcl-2 as a prognostic marker in papillary thyroid cancer. MATERIAL-METHODS: Bcl-2 expression in the archival materials of 31 patients with papillary thyroid cancer was examined with immunohistochemical methods using bcl-2 and p-53 stains. The results were compared with 31 normal thyroid tissue specimens, which consisted of the contralateral lobes of these patients. The results were then analyzed in accordance with the clinical features of the patients. RESULTS: Thirty (96.7%) patients of the control group were positive for bcl-2 whilst one (3.3%) was negative. The staining for bcl-2 was positive in 12 (%75) patients with microcarcinomas (p < 0.05) and 13 (86.6%) with papillary cancers (p > 0.05). Two cases of the papillary cancer group were admitted to the hospital with local recurrence (6.4%) and both were positive for bcl-2 (p > 0.05). All cases (4/31), whose MACIS scores were higher than 7 were positive for bcl-2. Twenty-one of 27 cases whose MACIS scores were lower than 7 (77.7%) were positive for bcl-2 (p > 0.05). All tumours of this series were negative for p-53 immunstaining. CONCLUSION: The rate of bcl-2 expression in microcarcinomas of papillary thyroid cancer decreases when compared to normal thyroid tissue. This may be an early sign of oncogenesis, and a reason for the favourable prognosis in microcarcinomas. However, bcl-2 cannot be used as a prognostic marker.

What really affects the incidence of central venous catheter-related infections for short-term catheterization?

Central venous catheterization is one of the important sepsis reasons in surgical patients. In this randomized controlled study, the effect of the frequency and type of catheter site care, as well as age, coexisting malignancy or diabetes mellitus, total parenteral nutrition administration and antibiotics use, on central venous catheter infection was investigated. Seventy-two single-lumen polyurethane catheters were included. In group I (n: 33), a transparent occlusive dressing was applied to the insertion site and not removed for 7 days unless there were signs of local infection. In group II (n: 39), daily site care was done with povidone-iodine 10% solution and a new sterile gauze was applied. Chi-square, linear correlation and multiple regression tests were used for statistical analysis. Mean duration of catheters was 8 +/- 4 days. There was no catheter-related sepsis. Ten (13.9%) patients had positive catheter tip cultures of whom three had site infection as well. The incidence of site and tip infections were not significantly different in group I and II (p > 0.05). Site infection and age younger than 60 years significantly increased the rate of tip infection (p: 0.004 and p: 0.02 respectively). Total parenteral nutrition administration was associated with higher rate of tip infection (p: 0.06). Coexisting malignancy or diabetes mellitus, duration of catheter and antibiotics use did not have any significant effect on the rate of central venous catheter infections (p > 0.05). In conclusion, we observed that the frequency of insertion site care and the type of dressing applied to the site had no significant effect on the rate of CVC infection. Insertion site infection was the most significant factor increasing the incidence of catheter tip infection. The use of the CVC for total parenteral nutrition facilitated tip infection as well.

The value of DNA content in predicting the prognosis of thyroid carcinoma in an endemic iodine deficiency region.

DNA content of tumour was found to correlate with various prognostic factors and survival, especially in well differentiated thyroid carcinoma. The aim of this investigation was to evaluate the correlation between the DNA ploidy and the prognosis as well as the survival in thyroid carcinoma in our country, being an endemic iodine deficiency region. DNA flowcytometry was performed on paraffin embedded archival tissue blocs of 74 patients with thyroid carcinoma (70 well differentiated, 3 anaplastic and Hurthle cell carcinoma) and 12 patients with multinodular goitre. DNA ploidy was defined as diploidy or aneuploidy. Aneuploidy was detected in 5 (6.8%) patients with thyroid carcinoma (3 anaplastic, 1 papillary and 1 Hurthle cell carcinoma). Aneuploidy was significantly more frequent in patients with anaplastic carcinoma (n: 3/3, 100%) compared to well differentiated thyroid carcinoma (n: 1/70, 1.4%) (p < 0.0001). Aneuploid DNA content significantly correlated with advanced age (p < 0.01), large tumour size (p < 0.001), and low survival (p < 0.01). Mean survival period of patients with anaplastic carcinoma in whom aneuploidy was frequently encountered, was shorter compared to patients with diploid well differentiated tumours (p < 0.01). In conclusion, although anaplastic and follicular carcinoma are more frequently diagnosed in endemic areas, the rate on aneuploidy was found to be lower in thyroid carcinoma in our country compared to data reported to nonendemic areas. As the prognostic predictive value of DNA ploidy is reliable in well differentiated thyroid carcinoma, DNA measurement of FNA biopsy may influence the extent of surgery. Thyroid carcinoma, other than well differentiated types, require radical operations independent of the DNA content. However, adjunctive treatment methods may be used earlier postoperatively according to quantitative DNA measurement.

Gastroesophageal reflux and a comparison of the different antireflux procedures following esophagomyotomy: an experimental study in rabbits.

The surgical options for achalasia remain controversial regarding the surgical access route, whether it be transthoracic or transabdominal, the need of, and the type of an added antireflux procedure following an esophagomyotomy. These questions were investigated in an experimental study that used 30 albino rabbits divided into six groups, as follows: transabdominal Heller's esophagomyotomy (TAHE), transthoracic Heller's esophagomyotomy (TTHE), TAHE and Nissen total fundoplication (NF), TAHE and partial fundoplication (PF), TAHE and modified fundoplication (MF), and a control group. Esophageal transit time (ETT) and gastroesophageal reflux (GER) were evaluated by scintigraphy on the seventh postoperative day. When an esophagomyotomy was performed either with a transabdominal or transthoracic approach, a significantly increased GER rate was found in comparison to the controls. All types of antireflux procedures performed prevented GER effectively. Although NF and PF groups showed a significant delay in ETT when compared to the control group (P < 0.001), no such finding was observed in the MF group. In conclusion, an antireflux procedure following an esophagomyotomy is recommended. A modified fundoplication was thus found to be as effective as the other techniques in preventing GER, and was even a safer method when obstructive findings following a total or partial fundoplication were considered.

Establishment of a highly differentiated thyroid cancer cell line of Hürthle cell origin.

Hürthle cell carcinomas (HCC) of the thyroid are a variant of follicular thyroid tumors. In contrast to follicular thyroid carcinoma, HCC rarely take up radioiodine and frequently metastasize to the lymph nodes. Histologically they are indistinguishable from Hürthle cell adenomas except for evidence of invasion and metastasis. How these carcinomas develop and why they behave differently than other follicular tumors is not known. Although some differentiated thyroid cancer cell lines exist, none are from Hürthle cell tumors. We have established a well-differentiated thyroid cancer cell line from a metastasis of a HCC, designated XTC.UC1. In vitro, XTC cells display epitheloid morphology, grow with a population doubling time of 4.3 +/- 0.3 days, migrate, and invade through reconstituted basement membranes. The cells are immunoreactive for and release thyroglobulin, respond to thyrotropin (TSH) with increase of intracellular cyclic adenosine monophosphate (cAMP), proliferation, and invasion of reconstituted basement membrane, thus exhibiting characteristics of well-differentiated thyroid carcinoma. In vivo, xenografted XTC cells grow with a doubling time of 9.8 +/- 0.8 days. Tumors spontaneously metastasize to the lymph nodes and less frequently to the lungs and the liver. The cells retained their differentiated function in vivo as assessed by human thyroglobulin (hTG) secretion and immunohistochemistry. This is a first report of the establishment of a unique, highly differentiated thyroid carcinoma cell line derived from an HCC. Based on the ability to invade through reconstituted basement membrane in vitro and the potential to metastasize in vivo, this cell line may provide a unique model to study invasion and metastazation of well-differentiated thyroid cancer.

Heterologous desensitization in neoplastic thyroid cells: influence of the phospholipase C signal transduction system on the thyrotropin-adenylate cyclase signal transduction system.

Desensitization is defined as a decreased functional response after continuous or repetitive stimulation of a receptor with its agonist. Thyrotropin (TSH) increases cAMP levels in normal and neoplastic thyroid tissue. The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) activates protein kinase C (PKC). The aim was to determine whether TPA induces heterologous desensitization of the TSH-adenylate cyclase (AC) signal transduction system. Three human thyroid neoplasms in culture for 6 months or longer (one papillary carcinoma, one Hurthle cell carcinoma, one follicular adenoma) were incubated with TSH (10 mU/ml) and TPA (1.6 x 10(-8) M) separately and together for various time periods (from 10 minutes to 24 hours). The mixture was subsequently incubated for 30 minutes with TSH. TPA alone had no effect on cAMP levels, but co-incubation of TPA and TSH caused a significant reduction in cAMP response when compared to the cAMP response that resulted after stimulation with only TSH (p < 0.001). cAMP levels in response to TSH decreased by 31%, 44%, and 57% after preincubation with TSH for 10 minutes, 4 hours, and 24 hours, respectively (p < 0.01; ANOVA). Co-incubation of cells with TPA and staurosporine (10 ng/ml), a PKC inhibitor, prevented the effect of TPA on desensitization at 10 minutes and blunted the effect at 4 hours. This is the first demonstration in human neoplastic thyroid cells that TPA induced heterologous desensitization of the cAMP response to TSH. This TPA-induced effect appears to involve PKC activation, as it can be blocked by staurosporine.

Great cervical vein invasion of thyroid carcinoma.

Intraluminal tumor thrombus in great cervical veins as a result of thyroid carcinoma is extremely rare. Three patients (2 Hürthle cell, 1 papillary carcinoma) were surgically treated for thyroid carcinoma associated with tumor thrombus in the great cervical veins. Tumor thrombus in the internal jugular vein due to extension of thyroid carcinoma was found in these 3 patients. Segmental resection of the internal jugular vein was performed in all cases and a tumor thrombectomy from subclavian vein was accomplished in 1 patient. Histological examination verified intraluminal tumor thrombus resulting from invasion of thyroid carcinoma in all patients. The postoperative follow-up period ranged from 1 to 2 years. Of 2 patients undergoing completion thyroidectomy, 1 died of distant metastasis, the other underwent reoperation for local recurrence. The patient who had a definitive primary surgical procedure is free of recurrence. Appropriate initial surgical procedure in rare cases of thyroid carcinoma associated with intraluminal tumor thrombus in great cervical veins seems to improve the clinical outcome of the disease.

The effect of prostaglandin E1 on experimental colitis in the rat.

Prostaglandin E1 (PGE1) is known to have a strong vasodilator effect and to block coagulation and inflammation in high concentrations. The aim of this study has been to investigate whether PGE1 has an inhibitory effect on inflammation in experimental colitis. Experimental colitis was produced by rectal instillation of 10% acetic acid in 60 rats. These were divided into prostaglandin (PG) (n = 30) and control groups (n = 30). Twelve hours later, an intraperitoneal injection of 2 micrograms PGE1 in 1 ml saline was given to the PG group and 1 ml saline to the control group. This was repeated daily and the animals were sacrificed in groups of 10 on the 3rd, 7th and 10th day. Histopathological examination and hydroxyproline determination for assessment of collagen synthesis were performed. PGE1 significantly decreased inflammation on third day with the hydroxyproline level significantly higher in the PG group compared with the control group (p < 0.05). This difference was however not significant at the 7th and 10th day. The present study supports a beneficial role for prostaglandin E1 in reducing the severity of colonic inflammation following chemically induced colitis but only in the early stages of development.

Desensitization of cyclic adenosine 3,5'-monophosphate response to thyrotropin in normal and primary or metastatic papillary thyroid cancer cells in vitro.

BACKGROUND: Desensitization is an important physiologic process resulting in a decreased functional response after continuous or repeated stimulation. Prior exposure of normal human thyroid tissue to thyrotropin either in vivo or in vitro causes desensitization of adenylate cyclase. Little is known, however, about whether the thyrotropin-adenylate cyclase-cyclic adenosine 3,5'-monophosphate (cAMP) signal transduction system desensitizes in human thyroid carcinomas. Failure to desensitize could result in increased growth or metastases. METHODS: Cell cultures from Chinese hamster ovary (CHO) cells transfected with normal human thyrotropin receptor (hTSHr) and thyroid neoplasms including one papillary carcinoma and one papillary lymph node metastases were evaluated for desensitization. CHO cells were stably transfected with plasmid DNA containing hTSHr. Cells were incubated with thyrotropin (10 mU/ml) for different periods (1 to 24 hours). A second incubation (30 minutes) was done with and without thyrotropin in medium including 3-isobutyl-1-methylxanthine (1 mmol/L). Intracellular cAMP accumulation was determined by means of radioimmunoassay. RESULTS: Maximal stimulation and desensitization to thyrotropin were observed at 30 minutes and 4 hours, respectively. The cAMP response to a second incubation with thyrotropin was 52% and 48% lower than the initial response to thyrotropin in CHO-hTSHr and papillary thyroid cancer cells, respectively (p < 0.001). A papillary carcinoma lymph node metastases had an increased basal cAMP level and also an increased cAMP level in response to thyrotropin stimulation (227%) but failed to desensitize (p < 0.001). CONCLUSIONS: Desensitization of the cAMP response to thyrotropin occurred in a papillary thyroid cancer but not in a metastatic thyroid cancer. Failure to desensitize might play a role in tumor progression.

Immunocytochemical detection of p53 in human thyroid carcinomas is associated with mutation and immortalization of cell lines.

Mutations in the tumor suppressor gene p53 are the most-common mutations found in human cancers. In thyroid cancers, p53 mutations generally are found only in poorly differentiated and undifferentiated tumors and in cell lines. To determine the prevalence of p53 mutations in thyroid neoplasms and thyroid cell lines, we screened 58 thyroid tissues and 3 thyroid cell lines, p53 primers bracketing exons 4, 5/6, 7, and 8 were used to amplify genomic DNA using the PCR. Mutations were screened by denaturing gradient gel electrophoresis and confirmed by sequencing. The two papillary thyroid cancer cell lines and the follicular thyroid carcinoma cell line (positive control) had transitions (CGT->CAT) in exon 8, codon 273, resulting in the replacement of arginine with histidine. No normal thyroid tissues or primary tumors from which the cell lines were derived demonstrated exon 8 mutations, using this technique. p53 immunocytochemistry demonstrated a progression of p53 immunopositivity between synchronous and metachronous neoplasms, paralleling the neoplastic progression from a benign adenoma to primary carcinoma, regional, and distant metastasis and ultimately, the cell lines, where intense immunopositivity is noted. In addition, fluorescence in situ hybridization, using probes specific for the p53 locus, revealed the presence of 3 homologues of p53 in the follicular cell line and 2 homologues in the papillary and Hürthle cell lines. These results suggest that a point mutation present in a small number of original tumor cells and amplification of the mutant allele may be responsible for immortalizing well-differentiated thyroid cancer cells into cell lines.

Endoscopic retroperitoneal adrenalectomy.

BACKGROUND: The anterior transabdominal approach for adrenalectomy is associated with a longer postoperative recovery period than a posterior extraperitoneal adrenalectomy. The posterior approach is useful for patients requiring bilateral adrenalectomy or in those undergoing unilateral adrenalectomy for benign adenomas smaller than 5 cm. Recently transabdominal laparoscopic adrenalectomy has been used in patients with adrenal tumors. Endoscopic retroperitoneal adrenalectomy (ERA) is an alternative method that provides excellent exposure and should be associated with less postoperative morbidity. METHODS: Between 1993 and 1994 11 ERAs were performed in eight patients in the Department of Surgery, Istanbul Faculty of Medicine. The patients were placed in the prone semijackknife position on the operating table. After the retroperitoneal space was expanded with a balloon trochar, four 10 mm trochars were placed to perform the procedure. RESULTS: Among the eight female patients 23 to 65 years of age (mean, 42 +/- 12.4 years), three had bilateral adrenal hyperplasia caused by Cushing's disease, three patients had functioning adenoma, one patient had nonfunctioning adenoma (three on right and one on left adrenal), and one patient had right adrenal cyst. The mean operation time was 150 minutes (range, 90 to 300 minutes). No changes in PCO2 values have been found during intraoperative blood gas analyses. No intraoperative or postoperative complications occurred. All patients were discharged on the third postoperative day. CONCLUSIONS: ERA is a new and safe method of adrenalectomy. It is less invasive than the posterior approach. Patients treated by ERA seem to experience less postoperative pain and discomfort and have a shorter postoperative hospitalization and recovery period.

Persistent or recurrent hyperparathyroidism in patients with double adenomas.

BACKGROUND: Are double parathyroid adenomas a discrete clinical entity or are all hyperplastic parathyroid glands of varying size? This investigation was done to determine whether patients with persistent or recurrent hyperparathyroidism and double adenomas (DA) differ in clinical profile or in response to treatment from patients with hyperplasia. METHODS: From 1982 to 1993, 37 unselected patients with persistent (11) or recurrent hyperparathyroidism (26) were treated. Twenty-one had DA and 16 had hyperplasia. DAs were defined as two abnormal and two normal parathyroid glands. RESULTS: Patients with persistent or recurrent hyperparathyroidism caused by DA were older and had more muscle weakness, neuropsychiatric disorders, constipation, and weight loss (p < 0.001) than patients with persistent or recurrent hyperparathyroidism caused by hyperplasia. Nephrolithiasis was more common in patients with recurrent hyperparathyroidism caused by hyperplasia than in patients with recurrent hyperparathyroidism caused by DA (p < 0.001). Serum Ca2+ levels before operation were similar in these groups with variable parathyroid hormone levels. No recurrences occurred in either group (DA [mean, 6 yr]; hyperplasia [mean, 5 yr]). Postoperative levels of serum Ca2+ and parathyroid hormone were normal in both groups. CONCLUSIONS: Patients with persistent or recurrent hyperparathyroidism caused by DA are older, have different clinical manifestations, and are cured by resection of the second adenoma. These findings support the concept that DA and hyperplasia are distinct entities.

Comparison of preoperative imaging techniques (thallium technetium scan and ultrasonography) and intraoperative staining (with methylene blue) in localizing the parathyroid glands.

We carried out a prospective study to compare the predictive value of preoperative thallium technetium scan, ultrasound (US) and intraoperative staining of the parathyroid glands (with methylene blue) in patients with parathyroid adenoma, parathyroid hyperplasia, thyroid carcinoma and thyrotoxicosis, in the Istanbul School of Medicine, Department of General Surgery. Methylene blue was given at a dose of 5 mg/kg/body weight in a 500 ml 5% Dextrose +0.9% saline solution 1 hour before surgery. All adenomas (10 patients), hyperplastic parathyroid glands (12 patients) and 45 of 52 suppressed glands (82%) were stained. In patients with thyroid carcinoma (7) and thyrotoxicosis (5), 42 of 48 normal parathyroid glands (87%) were stained. There were no maneuver-related complications. Thallium technetium scan (TT) accurately identified 10 of 10 (100%) parathyroid adenomas and 13 of 26 (50%) hyperplastic parathyroid glands. US successfully localized 10 of 10 (100%) adenomas and 18 of 26 (66%) hyperplastic glands. Neither technique was successful in identifying normal glands. The intraoperative identification of the parathyroid glands with methylene blue was found to be an effective, safe and cost-effective technique which helps the surgeon in the dissection and shows abnormal parathyroid glands more accurately than preoperative imaging techniques.

Immunoprecipitation isolates multiple TSH receptor forms from human thyroid tissue.

Attempts to purify the thyroid-stimulating hormone receptor (TSHR) have been complicated by its susceptibility to proteolysis and its low level of expression in thyrocytes and many transfected cells. Controversy exists over its size and structure. Multiple, single-polypeptide forms of the TSHR (230, 187, and 95-100 kDa) have been recently identified in immunoblots of crude plasma membranes prepared from COS-7 cells transfected with rat or human cDNA, but the relationship of these receptor species to the TSHR in human thyroid tissue has been heretofore unknown. We have developed a technique for immunoprecipitation of the TSHR which employed IgG purified from a polyclonal rabbit antiserum to TSHR residues 352-366. We have used immunoprecipitation to isolate the previously characterized 95-100 kDa TSH-holoreceptor, 187 kDa intermediate, and 230 kDa precursor forms of the TSHR from plasma membrane prepared from transfected COS-7 cells and human thyroid tissue. The presence of all three forms was not altered by the addition of reducing agent to the sample buffer, demonstrating the single polypeptide structure of the TSHR. This is, to our knowledge, the first report of the purification from transfected COS-7 cells of these TSHR species identified previously only in immunoblots of crude plasma membrane, and the first report of the identification by any means of these TSHR forms in human thyroid tissue. The isolation of TSHR from human thyroid tissue requires confirmation by direct means, but promises to make the receptor available in a soluble form for studies of its structure and function.

Biphasic effects of thyrotropin on invasion and growth of papillary and follicular thyroid cancer in vitro.

The rationale for TSH suppression in the treatment of follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC) is to inhibit tumor growth, prevent recurrent disease, and eventually prolong survival. We analyzed the effects of TSH on invasion and growth of 3 FTC cell lines from 1 patient (FTC133, primary; FTC236, lymph node; FTC238, lung metastasis) and 2 PTC cell lines (PTC-UC1, PTC-UC3). Cell growth and invasion through an 8-micron pore polycarbonate membrane coated with Matrigel were measured using the MTT assay. The dose-response to TSH was biphasic, stimulating invasion and growth of FTC and PTC at low concentrations (0.1-10 mU/mL), and inhibiting them at high concentrations (100 mU/mL). Interestingly, the metastatic FTC cell lines had higher basal invasion, but were less responsive to TSH than the primary tumor. TSH (1 mU/mL) stimulated invasion of FTC133 by 21%, FTC236 by 8%, and FTC238 by 8% (p < 0.01). At 100 mU/mL, TSH inhibited invasion of FTC133 by 21%, compared to 11% in FTC236 and 12% in FTC238. Also, TSH dose-dependently influenced proliferation of follicular thyroid cancer cells. At low concentrations it stimulated growth of FTC133 (20%) and inhibited it at high concentrations (23%; p < 0.01). Again, the amplitude of TSH effects was significantly smaller in the cell lines from metastatic tumors. TSH affected invasion and growth of PTC-UC1 and PTC-UC3 also biphasically. These results show that TSH may act as a mitogenic and antimitogenic growth factor for invasion and proliferation of well-differentiated thyroid cancer cells in vitro.

Primary hyperparathyroidism in patients who have received radiation therapy and in patients who have not received radiation therapy.

BACKGROUND: Primary hyperparathyroidism (HPT) occurs more frequently in persons who have been exposed to low-dose therapeutic radiation. Little information is available concerning whether or not the clinical, metabolic, and pathologic manifestations, as well as outcome, differ in these patients when compared with patients with sporadic HPT. STUDY DESIGN: Records from 438 unselected patients with primary HPT, who were treated from 1982 to 1993 were retrospectively analyzed. All patients prospectively received a standard questionnaire preoperatively and postoperatively concerning clinical manifestations and a history of radiation exposure. Forty-nine patients had a history of radiation exposure (rHPT), whereas 389 did not have sporadic HPT (sHPT). RESULTS: There was no difference in gender (36 women and 13 men versus 289 women and 100 men) or age (mean of 52 +/- 12 versus 57 +/- 16 years) in patients with rHPT or sHPT. Fatigue, neuropsychiatric disorders, memory loss, nocturia, and polyurea were more common in patients with sHPT (p < 0.05), whereas pain in joints was more common in patients with rHPT (63 versus 52 percent; p < 0.001). Serum calcium levels were similar (11.1 +/- 0.8 versus 11.2 +/- 0.8 mg per dL), but serum parathyroid hormone levels were higher in rHPT (448 +/- 14 percent of upper limit of normal versus 371 +/- 12 percent upper limit of normal). The parathyroid pathology was similar in the two groups (single adenoma 74 versus 72 percent, hyperplasia 14 versus 16 percent, and double adenoma 12 versus 12 percent in rHPT versus sHPT, respectively). Thyroid pathology was more common in the rHPT group (multinodular goiter 27 versus 7 percent and papillary thyroid carcinoma 14 versus 0.3 percent). Seven (1.8 percent) of patients not receiving radiation therapy treated by us had persistent HPT, but no patients receiving or not receiving radiation therapy had recurrent HPT during the follow-up period (six years). CONCLUSIONS: Patients who have HPT after radiation treatment have more thyroid neoplasms but are otherwise quite similar to other patients with primary hyperparathyroidism.