[Our experience on follicular carcinoma of the thyroid].
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Adenocarcinoma, Follicular↗
Biomedical subjects
Shiro Noguchi
Publications and source records attributed to Shiro Noguchi.
Mutational analysis of the APC gene in cribriform-morula variant of papillary thyroid carcinoma.
INTRODUCTION: Familial adenomatous polyposis (FAP) is an inherited autosomal dominant syndrome caused by germline mutations in the adenomatous polyposis coli (APC) gene. Papillary thyroid cancer is one of the extracolonic manifestations of FAP. A characteristic histologic feature of this type of thyroid tumor is the cribriform-morula variant of papillary thyroid carcinoma (CMVPTC). METHODS: To investigate roles of the APC and beta-catenin genes in the development of CMVPTC, we examined germline and somatic mutations of these genes in a female patient with CMVPTC and FAP. The patient had undergone total colectomy at the age of 19 years and total thyroidectomy at age 25 years. RESULTS: Numerous tumors were disseminated in both lobes of the thyroid gland, and histopathologic examination revealed typical CMVPTC. DNA was extracted from peripheral blood leukocytes and 12 CMVPTC tumors, and exons 1-15 of the APC gene and exon 3 of the beta-catenin gene were examined. A germline mutation was detected in exon 13 of the APC gene, and this mutation generated a premature stop codon. Six somatic mutations (922delC, 1602delA, 1821delT, 1920delG, 2706del20, 2804insA) were found in the CMVPTC specimens. All mutations were truncating mutations in the N-terminus of the APC protein. Loss of heterozygosity was not observed in the remaining tumor tissues without somatic APC mutations. There were no mutations of the beta-catenin gene in peripheral blood leukocytes or 12 CMVPTC specimens. CONCLUSIONS: These results suggest that APC mutations play an important role in the development of CMVPTC and occur predominantly in the 5' side of the APC gene between codons 308 and 935.
Adenocarcinoma, Papillary↗
Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumour syndrome.
BACKGROUND: A subset of familial isolated primary hyperparathyroidism (FIHP) is a variant of hyperparathyroidism-jaw tumour syndrome (HPT-JT). AIM/PATIENTS AND METHODS: We investigated the involvement of the HRPT2, MEN1 and CASR genes in 11 provisional FIHP families and two HPT-JT families. RESULTS: Germline mutations of HRPT2 were found in two of the 11 FIHP families and one of the two HPT-JT families. One FIHP family with parathyroid carcinoma and atypical adenomas and another FIHP family with cystic parathyroid adenoma had novel frameshift mutations of 518-521del and 62-66del, respectively. In a patient with HPT-JT, a de novo germline mutation of 39delC was detected. Novel somatic HRPT2 mutations of 70-73del and 95-102del were found in two of five parathyroid tumours in a family with a 518-521del mutation. Biallelic inactivation of HRPT2 by a combination of germline and somatic mutation was confirmed in the parathyroid tumours. The finding that two families diagnosed with FIHP carried HRPT2 mutations suggests that they have occult HPT-JT. In the remaining 10 families, one family had a missense MEN1 mutation. No mutations of CASR were detected. CONCLUSION: Our results confirm the need to test for HRPT2 in FIHP families, especially those with parathyroid carcinomas, atypical adenomas or adenomas with cystic change.
Adenoma↗
Fibroblast growth factor-23 in patients with Graves' disease before and after antithyroid therapy: its important role in serum phosphate regulation.
OBJECTIVE: Hyperthyroidism is a well-described cause of hyperphosphatemia. We aimed to clarify the physiological role of fibroblast growth factor (FGF)-23 in serum phosphate homeostasis in patients with Graves' disease during the course of treatment for hyperthyroidism. CONTEXT: The study group comprised 56 patients (45 for a cross-sectional study and 11 for a longitudinal study) with Graves' disease. For the cross-sectional study, patients were assigned, on the basis of their serum phosphate level, to a hypophosphatemia group (n = 14), a normophosphatemia group (n = 16), or a hyperphosphatemia group (n = 15). Serum FGF-23, calcium, phosphate, PTH, and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels were compared between the three groups. For the longitudinal study, we assessed changes in these biochemical indices before and after antithyroid treatment. RESULTS: In the cross-sectional study, the serum FGF-23 level was significantly higher (P < 0.05) in the hyperphosphatemia group than in the other groups (61 +/- 36 ng/liter vs. 31 +/- 22 ng/liter and 30 +/- 9 ng/liter). In the longitudinal study, serum levels of FGF-23 decreased significantly (P < 0.05) from a high of 54 +/- 12 ng/liter before treatment to 29 +/- 14 ng/liter after treatment. In contrast, the serum 1,25(OH)(2)D level increased significantly (P < 0.005) from 55 +/- 22 pmol/liter before treatment to 185 +/- 76 pmol/liter 3 months after treatment. Serum FGF-23 levels were positively correlated with serum phosphate levels (P < 0.0001) and negatively correlated with serum 1,25(OH)(2)D levels (P < 0.0001). CONCLUSIONS: The significant positive correlation between serum levels of phosphate and FGF-23 indicates that FGF-23 may play an important role in serum phosphate homeostasis by its up-regulation in the hyperphosphatemic condition.
Adult↗
Sequential changes in plasma intact and whole parathyroid hormone levels during parathyroidectomy for secondary hyperparathyroidism.
Most commercial assays for intact parathyroid hormone (iPTH) cross-react with non-PTH1-84 fragments (likely to be PTH7-84). We aimed to evaluate a whole PTH assay that measured only PTH1-84 by comparing it with an assay measuring iPTH levels during parathyroidectomy in secondary hyperparathyroidism (HPT). Twenty-eight patients with secondary HPT who underwent total parathyroidectomy with autotransplantation served as subjects. Blood samples for postoperative assay were drawn after anesthesia; immediately prior to excision of the last parathyroid gland; and at 5, 10, and 15 minutes after excision. The PTH7-84 level was calculated by subtracting the whole PTH value from the iPTH value. Plasma whole PTH decreased more rapidly than iPTH after parathyroidectomy (p < 0.0001). PTH levels that decreased by 50% or more from levels prior to excision to 10 minutes after excision were used to predict successful parathyroidectomy; decreases in whole PTH substantiated curative surgery for all patients without introducing false-positive and false-negative results. iPTH levels decreased by at least 50% in only 16 patients at 10 minutes after excision without false-positive results. Out of 11 cases in which iPTH decreased less than 50%, two were true-negatives and nine were false-negatives. Decreases in whole PTH levels more accurately reflect surgical outcome than do decreases in iPTH levels during parathyroidectomy in secondary HPT patients. Even though the quick iPTH assay is used infrequently during surgery for secondary HPT, our results suggest that a quick whole PTH assay may be more useful than the iPTH assay currently used in parathyroidectomy procedures for secondary HPT.
Female↗
Intraoperative parathyroid hormone assay in patients with Graves' disease for prediction of postoperative tetany.
We measured intraoperative parathyroid hormone (IOPTH) levels before and after thyroidectomy in a large group of patients to test whether changes in IOPTH can predict postoperative tetany. Subjects were 111 consecutive patients (94 females and 17 males) with Graves' disease undergoing subtotal thyroidectomy. Blood samples for IOPTH assay were obtained after anesthesia (basal) and following skin closure (postoperative). Data were compared between patients who developed tetany (n = 9) and those who did not (n = 102). There was no significant difference in sex, age, period of antithyroid drug administration, or the weight of the thyroid between the two groups. The preoperative serum calcium level was significantly lower (p < 0.05) and the basal IOPTH significantly higher (p < 0.05) in the tetany group than in the non-tetany group. The IOPTH level was significantly lower (p < 0.005) and the average percent decrease in IOPTH levels was higher (p < 0.001) in the tetany group than in the non-tetany group. A decrease in IOPTH of more than 70% was shown to be 78% sensitive, 94% specific, and 93% accurate, and it has 78% positive predictive value and 94% negative predictive value for the development of tetany. Our study shows that a postoperative decrease of IOPTH level is the most predictive of postoperative tetany of the clinical risk factors investigated. We recommend IOPTH measurement as an adjunct to postoperative management of patients with Graves' disease to assist in preventing hypocalcemia and determining the earliest time for safe discharge.
Adolescent↗
Significant clinical differences in primary hyperparathyroidism between patients with and those without concomitant thyroid disease.
PURPOSE: We evaluated the differences in diagnosis and treatment for primary hyperparathyroidism (pHPT) in patients with and those without concomitant thyroid disease. METHODS: One hundred and ten patients with pHPT underwent parathyroid localization and thyroid examination by ultrasonography (US) and sestamibi scintigraphy (MIBI). The clinical and biochemical findings, parathyroid localization, and operations performed were compared in 49 patients without thyroid disease and 61 patients with thyroid disease. RESULTS: Asymptomatic hypercalcemia was significantly more prevalent in patients with concomitant thyroid disease (88.5%) than in those without thyroid disease (49.0%) (P < 0.01). The mean serum calcium was significantly higher and the inorganic phosphate level was significantly lower in patients without concomitant thyroid disease than in those with concomitant thyroid disease (P < 0.05, P < 0.01, respectively). The pathologic parathyroid gland was identified significantly more often in patients without concomitant thyroid disease than in those with concomitant thyroid disease both by US and MIBI (P < 0.05). Unilateral exploration was performed more often in patients without thyroid disease than in those with thyroid disease (P < 0.01). CONCLUSION: Primary hyperparathyroidism was diagnosed at an earlier stage in patients with concomitant thyroid disease. Thyroid disease concomitant with pHPT influenced parathyroid localization as well as the indication for minimally invasive parathyroidectomy.
Adult↗
Reelevation of parathyroid hormone level after parathyroidectomy in patients with primary hyperparathyroidism: importance of decreased renal parathyroid hormone sensitivity.
BACKGROUND: We hypothesized that impaired peripheral sensitivity to parathyroid hormone (PTH) may play a role in reelevation of PTH after successful operation for primary hyperparathyroidism (pHPT). METHODS: Factors affecting reelevation of PTH were determined in 90 patients who underwent parathyroidectomy for pHPT. PTH/nephrogenous cyclic adenosine monophosphate ratio, as an index of renal resistance to PTH, was examined in relation to factors shown to influence reelevation of PTH. RESULTS: Serum PTH levels were elevated above the upper limit of normal in 23 patients (26%) at 1 week and in 39 patients (43%) at 1 month after parathyroidectomy. These 39 normocalcemic patients with elevated serum PTH at 1 month after parathyroidectomy had a higher preoperative serum level of PTH and lower serum phosphate and 25-hydroxyvitamin D (25OHD) concentrations than those with normal PTH (n = 59). Elevated PTH and low 25OHD were shown by multivariate analysis to be significant predictors of reelevation of PTH. Renal resistance to PTH was higher in patients with vitamin D deficiency or renal insufficiency than in patients with normal serum vitamin D concentrations or normal renal function, and it increased according to increases in levels of PTH. CONCLUSIONS: The mechanism of PTH reelevation in patients with pHPT after successful parathyroidectomy appears to be renal resistance to PTH.
Adenoma↗
Antithyroid drug-induced agranulocytosis: how has granulocyte colony-stimulating factor changed therapy?
This study examined whether granulocyte colony-stimulating factor (G-CSF) is beneficial for the treatment of antithyroid drug-induced agranulocytosis. From January 1975 to December 2001, 30,798 patients with Graves' disease were treated with antithyroid drugs at Noguchi Thyroid Clinic & Hospital Foundation. During this period, 109 patients (0.35%) were found to have agranulocytosis caused by antithyroid drugs. In the symptomatic group, the recovery time from agranulocytosis was significantly shorter after the introduction of G-CSF (5.5 +/- 3.5 days, n = 19) compared to the symptomatic group before its introduction (9.2 +/- 4.4 days, n = 37, p < 0.01). In the asymptomatic group, the recovery time from agranulocytosis was significantly shorter after the introduction of G-CSF (2.3 +/- 1.9 days, n = 15) compared to the asymptomatic group before the introduction of GCSF (5.4 +/- 4.3 days, n = 34, p < 0.05). However, G-CSF therapy was ineffective in severe cases with granulocyte count below 0.1 x 10(9)/L and symptoms. We recommend that G-CSF therapy should be applied only in asymptomatic patients and symptomatic patients with granulocyte count above 0.1 x 10(9)/L, and not for symptomatic patients with granulocyte count below 0.1 x 10(9)/L. In conclusion, G-CSF therapy shortens the period of recovery from antithyroid drug-induced agranulocytosis and benefits patients, except those with symptoms and a granulocyte count below 0.1 x 10(9)/L.
Agranulocytosis↗
Significance of an insular component in follicular thyroid carcinoma with distant metastasis at initial presentation.
Risk factors for distant metastasis were studied in 82 patients with follicular thyroid carcinoma (FTC). Metastases to either the lung or bone existing at the time of presentation were confirmed by I-131 radio-iodine uptake in 10 patients. FTC with an insular component was found in eight patients. Univariate analysis of 14 possible risk factors showed 7 to be statistically significant: insular component, poorly differentiated carcinoma, trabecular component, serum thyroglobulin level before surgery, patient age at the time of presentation, solid component, and vascular invasion (ranked by p values). After further analysis of the interrelation of the factors and of the logistic regression curves, we concluded that presence of an insular component and patient age were the only independent risk factors. Distant metastasis was not detected in any of the 27 patients < or = 49 yr old. Among the 55 older patients (> or = 50 yr old), 5 of the 49 (10%) without an insular component and 5 of the 6 (83%) with an insular component had distant metastasis. The remaining older patient with an insular component but without distant metastasis showed a gradual increase in thyroglobulin levels after total thyroidectomy.
Adenocarcinoma, Follicular↗
Thyroid evaluation in patients with primary hyperparathyroidism.
We evaluated the efficacy of preoperative high-resolution ultrasonography (US) for diagnosing possible concomitant thyroid disease which affects the surgical management in patients with primary hyperparathyroidism (pHPT). One hundred and nine patients with sporadic pHPT underwent US with or without ultrasound-guided fine-needle aspiration biopsy (US-FNAB). Diagnosis of concomitant thyroid nodules by US and US-FNAB were compared with the histopathological findings. Of the 109 patients, 19 (17.4%) had malignant thyroid nodules, 26 (23.9%) had benign thyroid nodules alone, and 12 (11.0%) had diffuse goiter. The sensitivity, specificity, and accuracy of diagnosing 72 thyroid nodules were 91.3%, 91.8%, and 91.7% for US, 57.9%, 94.3%, and 81.5% for US-FNAB, and 95.7%, 91.8%, and 93.1% for combined US and US-FNAB, respectively. True positive/false negative ratio of US-FNAB diagnosis was significantly lower in nodules of 5-9 mm than nodules of 10 mm or more. Four unexpected thyroid cancers existed at a different site in 3 of the 39 patients with palpable thyroid disease. Five thyroid cancers were histopathologically confirmed in 5 (7.1%) of 70 patients without palpable thyroid disease. Eight (88.9%) of the 9 non-palpable thyroid cancers were accurately diagnosed by combined US and US-FNAB. Preoperative US is useful for evaluation of possible concomitant thyroid disease, especially for prediction of malignancy.
Adenoma↗
Does lemon candy decrease salivary gland damage after radioiodine therapy for thyroid cancer?
UNLABELLED: Salivary gland dysfunction is one of the common side effects of high-dose radioiodine therapy for thyroid cancer. The purpose of this study was to determine whether an early start of sucking lemon candy decreases salivary gland injury after radioiodine therapy. METHODS: The incidence of the side effects of radioiodine therapy on the salivary glands was prospectively and longitudinally investigated in 2 groups of patients with postsurgical differentiated thyroid cancer with varying regimens for sucking lemon candy. From August 1999 to October 2000, 116 consecutive patients were asked to suck 1 or 2 lemon candies every 2-3 h in the daytime of the first 5 d after radioiodine therapy (group A). Lemon candy sucking was started within 1 h after radioiodine ingestion. From November 2000 to June 2002, 139 consecutive patients (group B) were asked to suck lemon candies in a manner similar to that of group A. In the group B, lemon candies were withheld until 24 h after the ingestion of radioiodine. Patients with salivary gland disorders, diabetes, collagen tissue diseases, or a previous history of radioiodine therapy or external irradiation to the neck were excluded. Thus, 105 patients in group A and 125 patients in group B were available for analysis. There were no statistical differences in the mean age (55.2 y vs. 58.5 y), average levels of serum free thyroxine (l-3,5,3',5'-tetraiodothyronine) (0.40 ng/dL vs. 0.47 ng/dL), and the mean dose of (131)I administered (3.96 GBq vs. 3.87 GBq) between the 2 groups. The onset of salivary side effects was monitored during hospital admission and regular follow-up on the basis of interviews with patients, a visual analog scale, and salivary gland scintigraphy using (99m)Tc-pertechnetate. When a patient showed a persistent (>4 mo) dry mouth associated with a nonfunctioning pattern on salivary gland scintigraphy, a diagnosis of xerostomia was established. RESULTS: The incidences of sialoadenitis, hypogeusia or taste loss, and dry mouth with or without repeated sialadenitis in group A versus group B were 63.8% versus 36.8% (P < 0.001), 39.0% versus 25.6% (P < 0.01), and 23.8% versus 11.2% (P < 0.005), respectively. Permanent xerostomia occurred in 15 patients in group A (14.3%) and 7 patients in group B (5.6%) (P < 0.05). In both groups, bilateral involvement of the parotid gland was the most frequently seen and was followed by bilateral involvement of the submandibular gland. CONCLUSION: An early start of sucking lemon candy may induce a significant increase in salivary gland damage. Lemon candy should not be given until 24 h after radioiodine therapy.
Administration, Oral↗
[Necessity of registrar in medical institution].
In our hospital, we are routinely investigating and recording patients with familial thyroid disorders. We found that about 30% of patients with thyroid disease had some relatives with the same disease as a result of the investigation of more than 13,000 patients. Therefore, a registrar is working for research of familial thyroid disease as a specialist in our hospital. The study was conducted on 258 patients with familial nonmedullary thyroid carcinoma (FNMTC). In cooperation with the registrar, the clinical characteristics of FNMTC emerged. Moreover, 15 patients with nonmedullary thyroid carcinomas were newly found among 149 asymptomatic FNMTC relatives (10%) and underwent operation. In this paper, we report the role of the registrar and emphasize the necessity of a registrar.
Adult↗
[Recent advances in the diagnosis and treatment of primary hyperparathyroidism].
The incidence of hyperparathyroidism (pHPT) in Japan is lower than that in Western countries. The frequency of diagnosis, however, has increased due to the recent introduction of automated multichannel analysis of serum chemistry in routine screening and to the longevity of the Japanese population. The goal of surgical treatment for primary pHPT is restoration of calcium homeostasis by removal of hyperfunctioning parathyroid glands. Surgery is successful in over 95% of cases. The advent of the sestamibi scan in the early 1990s changed the management of pHPT. The trend has been toward less invasive procedures including endoscopic parathyroidectomy using sophisticated preoperative imaging tests, a hand-held gamma probe, and intraoperative rapid measurement of parathyroid hormone levels. We review recent advances in the diagnosis and treatment of pHPT.
Humans↗
[Fibroblast growth factor (FGF)-23 in patients with hypoparathyroidism].
Hypoparathyroidism is a well-described cause of hyperphosphatemia. We aimed to clarify the physiological role of FGF-23 in serum phosphate homeostasis in hypoparathyroidism after thyroidectomy. Increased serum FGF-23 levels were found in patients with hyperphosphatemia and hypocalcemia, caused by hypoparathyroidism after thyroidectomy. After the recovery of parathyroid function, the serum level of calcium, phosphate, and FGF-23 was normalized. Serum FGF-23 levels were significantly higher in patients with permanent hypoparathyroidism than in healthy controls. These results indicate that FGF-23 may play an important role in serum phosphate homeostasis by its up-regulation in the hyperphosphatemic condition.
Female↗
[High prevalence of secondary hyperparathyroidism due to vitamin D insufficiency in Graves' disease].
We studied concentrations of serum calcium, intact parathyroid hormone (iPTH), and 25 hydroxyvitamin D (25 [OH] D) in 343 patients with Graves' disease (273 women, 70 men) during one year period. The serum 25 (OH) D levels were 37+/-19 nmol/L and vitamin D deficiency (defined as a serum 25 (OH) D value below 25 nmol/L) was found in 35% of the patients. There was a significant seasonal variation in the 25 (OH) D concentrations, with high values of 51+/-21 nmol/L during the summer term (July-September), and with low values of 26+/-17 nmol/L during the winter term (January-March). The average serum iPTH level was 48+/-26 pg/mL, with 26% (89/343) having values above the normal range. Our results showed high prevalence of secondary hyperparathyroidism in patients with Graves' disease during antithyroid drug therapy and vitamin D and/or calcium supplements are recommended for patients with vitamin D deficiency.
Adult↗
Modified radical neck dissection for differentiated thyroid cancer: operative technique.
Our standard surgical approach to patients with papillary thyroid cancer is subtotal thyroidectomy with modified radical neck dissection (MRND) on the affected side. MRND preserves the jugular vein, the sternocleidomastoid muscle, and the accessory nerve, effectively conserving function and cosmesis. Knowledge of the anatomy of the neck, precise staging, prognostic evaluation, and experience are needed for a surgeon to perform MRND. Radical neck dissection should not be performed unless the tumor invades the jugular vein and sternocleidomastoid muscle. Berry picking is not indicated for patients with thyroid cancer. The skin incision used is an extended collar incision. If lymph node metastasis is present at the upper bifurcation of the carotid artery, a modified MacFee incision is used. Taping of the carotid artery or sternocleidomastoid muscle is avoided unless the tumor invades these tissues. MRND is a safe procedure when performed by skilled, experienced surgeons.
Humans↗
Diagnostic applicability of dipeptidyl aminopeptidase IV activity in cytological samples for differentiating follicular thyroid carcinoma from follicular adenoma.
HYPOTHESIS: Dipeptidyl aminopeptidase IV (DPP IV) activity in cytological samples from a follicular thyroid tumor is the most sensitive and specific indicator for the detection of follicular carcinoma of the thyroid gland. Dipeptidyl aminopeptidase IV activity is independent of cytological characteristics and superior to other clinical findings. DESIGN AND PATIENT SELECTION: Among the patients surgically treated for follicular thyroid tumors, we recruited approximately equal numbers of those with true-positive (n = 19), true-negative (n = 26), false-negative (n = 16), and false-positive (n = 18) cytological characteristics. MAIN OUTCOME MEASURES: We examined DPP IV activity using cytological specimens obtained from 35 patients with follicular thyroid carcinomas and 44 patients with follicular adenomas. Tumor size, patient age, serum thyroglobulin level, and ultrasonographic findings were also analyzed. RESULTS: The positive rate of DPP IV activity was 97% in 35 patients with follicular thyroid carcinomas and 5% in 44 patients with follicular adenomas, resulting in a sensitivity of 97%, a specificity of 95%, and an overall accuracy of 96%. This discriminating ability of DPP IV activity was far higher than that of tumor size, patient age, serum thyroglobulin level, or ultrasonographic findings. CONCLUSIONS: Positive DPP IV activity in cytological samples is the best discriminatory marker between follicular thyroid carcinoma and follicular adenoma. Its application could alter the clinical management of patients with follicular thyroid tumors.
Adenocarcinoma, Follicular↗