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M Iihara

Publications and source records attributed to M Iihara.

14 recordsLinked to original sources
PubMed2000

Somatic mutations of the multiple endocrine neoplasia type 1 (MEN1) gene in patients with sporadic, nonfamilial primary hyperparathyroidism.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) is a syndrome with tumors of many endocrine tissues. Germline MEN1 gene mutations were found in most patients with familial or sporadic MEN 1. Recently, somatic MEN1 gene mutations were also detected in sporadic non-MEN 1 endocrine tumors. METHODS: We used direct sequence analysis to investigate MEN1 gene mutations in 30 parathyroid tumors obtained from 30 patients with sporadic, nonfamilial primary hyperparathyroidism. RESULTS: Four patients had somatic mutations of the MEN1 gene, comprising 1 small insertion (1091insAGC), one missense mutation (G42S), and 2 non-sense mutations (E388X, R460X). Identical missense and non-sense mutations were found in patients with familial and non-familial MEN 1. There were no differences between clinical features of patients with and without MEN1 gene mutations. CONCLUSIONS: The incidence of somatic MEN1 gene mutations (13.3%) in Japanese patients with sporadic, nonfamilial primary hyperparathyroidism is almost equal to those of such patients in the United States and Sweden. Occasionally, the MEN1 gene mutation sites in sporadic parathyroid tumors are identical to those reported in tumors from patients with familial or sporadic MEN 1.

DNA↗
PubMed1998

Efficacy of single-voided urine metanephrine and normetanephrine assay for diagnosing pheochromocytoma.

Urinary catecholamines (CAs) and their metabolites are usually measured during the process of diagnosing pheochromocytoma (pheo), but a 24-hour urine collection is not convenient for outpatients. Since 1987 we have utilized "spot" urine metanephrine (MN) and normetanephrine (NMN) assays for management of patients with pheo or adrenal incidentaloma. MN and NMN were measured by radioimmunoassay in 82 patients with surgically proved pheo and 15 patients with incidentaloma. In 10 patients with pheo, MN and NMN were measured with fractional every-3-hour urine samples, which were accumulated and then measured as a 24-hour urinary specimen. Fractions of 3-hour MN and NMN excretion were constant (MN 98.5 +/- 9.6%, NMN 97.6 +/- 10.8%; 24-hour MN and NMN 100%). The average levels of MN and NMN in patients with pheo were 6801 ng/mg creatinine (Cr) (range 93-88,248, median 1426) and 5627 ng/mg Cr (range 219-31,528, mean 3190), whereas the MN and NMN levels in patients with incidentaloma were 123 ng/mg Cr (range 36-246, mean 133) and 251 ng/mg Cr (range 84-472, mean 220), respectively. When we selected a cutoff value for MN + NMN of 1000 ng/mg Cr, the sensitivity was 97.6% and the specificity 100% for diagnosing pheo. When the standard was set as > 500 ng/mg Cr for either MN or NMN, both the sensitivity and specificity were 100%. The assay for MN and NMN is simple and effective, not only for screening but for diagnosing pheo and managing incidentaloma.

Adrenal Gland Neoplasms↗
PubMed1998

Genotype-phenotype correlation of patients with multiple endocrine neoplasia type 2 in Japan.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperparathyroidism. MEN 2 is caused predominantly by germ-line mutations of the RET proto-oncogene. This study aimed to clarify the genotype-phenotype correlation in MEN 2 patients in Japan in order to modify the clinical management according to the genotype. METHODS: Constitutive DNA of 64 MEN 2 patients (48 kindreds) were searched for mutations at exons 10, 11, 13, 14 and 16 of the RET proto-oncogene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing and restriction enzyme digestion. The clinical characteristics of the patients were obtained from a previous nationwide questionnaire survey. RESULTS: Overall, 62 (96.9%) out of 64 patients had a germ-line point mutation at the hot spots. MTC and pheochromocytoma occurred equally in every genotype except C630S. Specific genotype had a correlation between tumor size and age at the operation for MTC or extent of MTC, i.e. C618S developed late onset type of MTC as compared with that of C634R, C634Y and M918T. Small MTC in C634R may be less aggressive than those in C634Y and M918T. CONCLUSIONS: DNA testing has good clinical implications for the management of patients with MEN 2 and the timing and operative procedures of thyroidectomy can be modified according to the genotype.

Adrenal Gland Neoplasms↗
PubMed1997

A nationwide clinical survey of patients with multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma in Japan.

MEN (multiple endocrine neoplasia) type 2 syndrome is an inherited disease characterized by medullary thyroid carcinoma, pheochromocytoma, hyperparathyroidism and/or developmental anomalies. Germ-line mutations of the RET proto-oncogene have recently been identified as the underlying cause of the syndrome. Accordingly, several investigators have advocated prophylactic total thyroidectomy for medullary thyroid carcinoma at an early age in MEN 2 gene carriers identified by DNA analysis. Before applying this strategy in Japan, the biological behavior of each category of tumor in MEN 2 syndrome, and medullary thyroid carcinoma in particular, should be well understood. We conducted a nationwide questionnaire survey to clarify the clinicopathological features of MEN 2 in Japan, obtaining data for 230 patients diagnosed as having MEN 2. They included 84 males and 146 females, with a median age of 37.5 years (range 5-83). Patients were categorized as 179 with MEN 2A, 17 with MEN 2B, 12 with familial medullary thyroid carcinoma and 22 'other'. Medullary thyroid carcinoma, pheochromocytoma and parathyroid lesions occurred in 224 (97%), 132 (57%) and 25 (11%) patients respectively. Twelve patients (5.2%) died of medullary thyroid carcinoma and 11 patients died of other or unknown causes. Of 163 patients for whom follow-up data were obtained, 82 (50%) experienced recurrences of medullary thyroid carcinoma, including symptomatic recurrent tumors in 24 patients and elevated calcitonin levels alone in 54. In the era of RET mutational analysis for screening relatives of patients with MEN 2, these data provide useful information about surgical management for patients with MEN 2 in Japan.

Adolescent↗
PubMed1997

Measuring serum thyroglobulin in patients with follicular thyroid nodule: its diagnostic implications.

To determine the diagnostic implications of measuring the serum thyroglobulin level in patients with a solitary follicular thyroid tumor, a retrospective study was conducted on 122 consecutive patients with a solitary follicular thyroid nodule who underwent thyroidectomy. Data for eight variables were collected: the serum thyroglobulin (Tg) level (microgram/l), age, maximum diameter of the nodule, gender, histopathologic type, presence or absence of metastases, macroscopic characteristics of the cut surface of the resected tumor, and smoking habit. Multiple regression analyses were used to investigate the relationships between the serum Tg level and the seven other variables. The diagnostic value of serum Tg was examined by means of receiver operating characteristic (ROC) curves. There were significant correlations between the serum Tg level and the maximum diameter of the nodule, the macroscopic characteristics, and the smoking habit. The sensitivity and specificity of the serum Tg level with a cut-off value of 1,000 micrograms/l were 57% and 86%, respectively. The likelihood ratio favouring follicular carcinoma associated with the serum Tg > 1,000 micrograms/l was 4.41. Measuring the level of serum Tg may be useful in discriminating follicular carcinoma from follicular adenoma, but since there may be some biases in this retrospective study, the results are less definitive. Further research activities are mandatory to obtain valid evidence.

Adenocarcinoma, Follicular↗
PubMed1996

Pheochromocytomas: tendency to degenerate and cause paroxysmal hypertension.

Eighty-four patients with pheochromocytoma underwent surgery during the 13-year period from 1981 to 1994. These patients were divided into three groups according to the degree of parenchymal degeneration, which was estimated by preoperative dynamic computed tomography (CT) scans and resected specimens: solid group, cystic group, and highly cystic group. The relation between the degree of parenchymal degeneration and the clinical variety, size of the tumor, predominant plasma catecholamine, and type of blood pressure disturbance was analyzed. There were 39 cases of solid pheochromocytoma, 37 cases of cystic tumor, and 8 cases of highly cystic pheochromocytoma. The maximal mean diameters for each group were as follows: 5.1 +/- 2.3, 6.8 +/- 3.0, and 7.9 +/- 3.2 cm, respectively. Of the tumors < 3 cm in diameter, 84% were solid; when the tumors were >/= 6 cm in diameter, approximately 50% were cystic and 20% highly cystic. Of the adrenal pheochromocytomas, 60% were degenerated; 79% of the extraadrenal tumors were solid. Of the epinephrine-secreting tumors, 70% were degenerated, and 55% of the norepinephrine-secreting tumors were solid. The clinical pattern of hypertension was related to the degree of degeneration: In the paroxysmal hypertension group 87% of the tumors were degenerated, and in the sustained hypertension group 69% were solid. We therefore believe that parenchymal degeneration of pheochromocytoma is highly correlated with the tumor diameter, location of the tumor, secreted catecholamine, and clinical pattern of hypertension.

Adolescent↗
PubMed1996

Bilateral adrenalectomy with autotransplantation of adrenocortical tissue or unilateral adrenalectomy: treatment options for pheochromocytomas in multiple endocrine neoplasia type 2A.

Surgical strategies for pheochromocytomas in patients with multiple endocrine neoplasia (MEN) type 2 syndrome have been controversial. The purpose of this study is to review the current status of patients with MEN 2 who underwent adrenalectomy with or without adrenal autotransplantation. We studied 15 patients with MEN 2A who underwent adrenal surgery between 1981 and 1992. The follow-up survey included physical examination and biochemical determinations. The median period from initial surgery to follow-up was 54 months (range, 0-145 months). Initial bilateral total adrenalectomy was performed on seven patients, and subtotal adrenalectomy was carried out on two. Among six patients who initially underwent unilateral adrenalectomy, four had remained normotensive (median follow-up, 61 months), whereas the other two patients had to undergo reoperation on the contralateral side because of recurrent symptoms. Two patients were suspected of having had a relapse of the disease after total adrenalectomy. Seven patients underwent adrenal autotransplantation; however, none of them were able to discontinue glucocorticoid replacement therapy. In MEN 2A patients having large pheochromocytomas on only one side, unilateral adrenalectomy can be a suitable alternative to bilateral adrenalectomy in terms of blood pressure control and preservation of adrenocortical function. The attempt to preserve adrenocortical function by autotransplantation is discouraged.

Adolescent↗
PubMed1993

[Seven patients with hyperparathyroid crisis: emphasis on prompt parathyroidectomy].

Although hyperparathyroid crisis is rare, the management of this disease remains controversial. We analyzed the clinicopathological features and treatment outcome of this disease to evaluate the significance of prompt parathyroidectomy. Seven patients with an episode of hyperparathyroid crisis who consisted of 2.3% of all surgical patients of primary hyperparathyroidism were treated from 1981 to 1992 at the Department of Endocrine Surgery, Tokyo Women's Medical College. They all showed grave hypercalcemia greater than 15mg/dl, renal dysfunction and gastrointestinal toxicity. Their ages ranged between 33 and 75 years (mean age 49.7 years); two patients were men and five were women. Six patients had an adenoma, and only one had a carcinoma. The weights of the parathyroid tumors ranged between 3.5g and 11g, and ultrasonography disclosed an enlarged parathyroid gland in all patients. All of the seven patients underwent prolonged medical treatment (mean of durations 52 days), but four of them remained with hypercalcemia greater than 15mg/dl. On the other hand, the serum calcium levels of all patients returned to normal within five days after their operations without any surgical complication. Therefore, we recommend prompt parathyroidectomy for hyperparathyroid crisis, since medical treatment requires a prolonged clinical course and sometimes fails to control grave hypercalcemia.

Adenoma↗
PubMed1993

[Characteristics and clinical course of patients with subacute thyroiditis without typical signs and symptoms].

To determine the characteristics and clinical course of patients with subacute thyroiditis (SAT) without typical signs and symptoms, clinical and pathologic records of the patients were reviewed and compared with those of patients with typical SAT. During the past 10 years, 11 of 105 patients with SAT did not have enough typical features for a diagnosis of SAT (atypical SAT). They included one male and 10 females with the average age of 50 years. The incidence of neck pain as the initial symptom in the patients with atypical SAT was low (18%) compared with that in the patients with typical SAT (69%). Of the patients with atypical SAT, 42% had elevated thyroid hormone levels and 46% had suppressed TSH levels, whereas the percentages in the patients with typical SAT were 76% and 85% respectively. Nine of 11 patients were misdiagnosed as having papillary carcinoma by physical examination, and 4 by ultrasonography. However, aspiration cytology could make a precise diagnosis of SAT in 4 patients at the time of clinical diagnosis and 3 other patients after reevaluation. Eight patients were admitted to the hospital under the diagnosis of thyroid cancer and 4 underwent surgical resection. Differential diagnosis between atypical SAT and papillary carcinoma is important, and aspiration cytology could be a conclusive diagnostic tool to avoid unnecessary treatment.

Adult↗
PubMed1993

[Relative lymphopenia in Cushing's syndrome].

The differential white blood cell (WBC) count often reveals relative lymphopenia in Cushing's syndrome and may be a clue to the discovery of the ailment. However, the incidence of this finding has rarely been reported in the literature. We conducted a study on 40 patients with Cushing's syndrome due to adrenocortical adenoma to evaluate the diagnostic implications of relative lymphopenia. Total WBC count, differential WBC count, basal level of plasma cortisol, urinary excretion of free cortisol and thyroid function were evaluated preoperatively. We also investigated the differential WBC count in 40 patients with thyroid tumors matched for age and sex with the Cushing's syndrome patients. The proportion of lymphocytes among WBCs was also compared between the two groups. The proportion of lymphocytes among WBCs was significantly lower in the patients with Cushing's syndrome (19.4 +/- 10.8%) than in those with thyroid tumors (42.3 +/- 9.5%, mean +/- SD, p < 0.05). The incidence of relative lymphopenia was high (82.5%) as well as that of increased urinary excretion of free cortisol (85.3%) in Cushing's syndrome patients. The low T3 syndrome was frequently seen (73.9%), whereas the incidences of leukocytosis and an increased level of basal plasma cortisol were relatively low (42.5% and 47.5%, respectively). Relative lymphopenia provides useful information for diagnosing Cushing's syndrome since it has high sensitivity although it should be kept in mind that its specificity is low.

Adenoma↗
PubMed1993

[Unfavorable characteristics in patients with early postoperative recurrence of Graves' disease after subtotal thyroidectomy].

Unfavorable characteristics of early postoperative recurrence of hyperthyroidism were studied in patients with Graves' disease after subtotal thyroidectomy. We examined 338 patients who underwent subtotal thyroidectomy during a 9-year period from 1981 to 1989. Thyroid functional status was determined biochemically and the following variables were collected and divided into two categories for each patient: sex, age at operation, indication for surgery, serum titer of antimicrosomal hemagglutination antibody, weight of resected thyroid tissue and size of remnant thyroid tissue relative to body surface area. Early postoperative recurrence was defined as relapse of the disease within one year after surgery, necessitating medication or radioiodine therapy. Logistic regression analysis disclosed that the most important characteristics were age < 20 yr, relatively large thyroid remnant and weight of resected thyroid tissue > or = 100g, the odds ratios for these variables being 20.6, 16.7 and 3.4, respectively (p < 0.05). Although candidates for surgical treatment of Graves' disease are likely to be younger and to have a large goiter, these characteristics are unfavorable, since they predict the early recurrence of hyperthyroidism. One alternative is to leave a smaller than usual thyroid remnant thyroid in these patients, even if the risk of postoperative hypothyroidism is high.

Adult↗
PubMedDate not supplied

Functioning parathyroid carcinoma: clinicopathologic features and rational treatment.

Parathyroid carcinoma is a rare, reported to be less than 1% of patients with primary hyperparathyroidism. Recently, cell cycle regulators such as the retinoblastoma gene and p53 have been implicated in the pathogenesis of parathyroid carcinoma. Yet definite diagnosis remains difficult not only clinically but also pathologically. However, the clinical presentation, biochemical and hormonal findings, and appearance at the operation may possibly raise suspicion regarding the diagnosis. A radical en bloc resection at the primary operation is most important. Even after a successful initial operation parathyroid carcinoma carries an increased risk of recurrence. There is wide diversity in the interval between the initial operation and the manifestation of metastasis. Histopathology and DNA ploidy are valuable predictors of the clinical outcome. Because the severe hypercalcemia it engenders has catastrophic consequences, proper management of the recurrent hypercalcemia is also mandatory. The lung is the most common site of distant metastasis. Selected patients with pulmonary metastasis of parathyroid carcinoma can obtain significant benefit from aggressive surgical resection even when they have multiple or recurrent lesions. When hypercalcemia is refractory to surgical resection, medical treatment with bisphosphonate has a beneficial effect.

Carcinoma↗