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Biomedical subjects

I D Hay

Publications and source records attributed to I D Hay.

At least 55 records · Page 3Linked to original sources
PubMed1994

Medullary thyroid carcinoma in multiple endocrine neoplasia types 2A and 2B.

BACKGROUND: Considerable emphasis has been placed on early diagnosis and surgery for multiple endocrine neoplasia (MEN)-related medullary thyroid carcinoma (MTC) during the past two decades. Genetic screening now promises earlier and more accurate diagnosis. We examine our experience with MTC in MEN 2A and MEN 2B and assess the benefits of biochemical screening during the past 20 years. PATIENTS AND METHODS: Seventy-seven patients undergoing 63 primary total thyroidectomies and 14 reoperative procedures for MEN-related invasive MTC and/or preinvasive C-cell hyperplasia are reported. Fifty-eight patients had MEN 2A and 19 had MEN 2B; 79% of patients had a family history of MTC; 27% had pheochromocytoma, and 25% had hyperparathyroidism. RESULTS: Patients with MEN 2B had more advanced disease than those with MEN 2A, in spite of presentation at a younger age (15 years versus 24 years). Every patient with MEN 2B had invasive carcinoma, whereas 14% of patients with MEN 2A had C-cell hyperplasia without invasive disease. Nodal metastases were found less frequently in MEN 2A (14%) than MEN 2B (38%), and biochemical cure was achieved in 56% of patients with MEN 2A compared with none in patients with MEN 2B. Among patients with MEN 2A the occurrence of invasive carcinoma increased with age (p = 0.0003); 40% of patients for less than 5 years had invasive MTC compared with 100% at more than 20 years. Cause-specific mortality among patients with MEN and invasive tumors at 6, 12, and 18 years was 2%, 4%, and 7%, respectively, lower than that of patients with sporadic MTC (12%, 17%, and 23%, respectively) treated during the same time period (p = 0.028). CONCLUSIONS: Intensive biochemical screening of MEN 2 kindreds for MTC can result in detection of early disease and a significant prospect of surgical cure. Genetic testing promises additional benefits through more reliable detection of preinvasive disease, allowing prophylactic thyroidectomy in infancy. In MEN 2B, MTC is considerably more aggressive than in MEN 2A. A policy of routine thyroidectomy in infants with MEN 2B, regardless of serum calcitonin levels, is justified.

Adolescent↗
PubMed1993

Role of thyrotropin measurements in the diagnosis and management of thyroid disease.

This article reviews the role of thyrotropin assays in clinical medicine and illustrates the advantages and limitations of assays that can measure subnormal concentrations. Analytic considerations that can significantly alter the performance of these assays are outlined. The concept of assay generations is defined, and the potential roles of third and fourth generation assays are postulated. In addition, a diagnostic strategy is presented for using TSH and other procedures in the diagnosis and management of thyroid disease.

Humans↗
PubMed1993

Thyroid cancer diagnosis and management.

This article provides an overview of the classification of thyroid carcinoma into well-differentiated forms (papillary and follicular) as well as the rare Hurthle cell, medullary, and anaplastic forms. The characteristics, relative frequency, and mortality rates of each form of thyroid cancer are summarized. The roles of history, physical examination, blood tests, such as thyroid function test, thyroglobulin (htg), calcitonin and CEA, radionuclide and ultrasound imaging, and fine-needle aspirates are outlined for the diagnosis and management of thyroid cancer. An algorithmic diagram of the monitoring procedures for long-term management of various forms of thyroid cancer is presented.

Humans↗
PubMed1993

Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989.

BACKGROUND: Multivariate analyses in papillary thyroid carcinoma (PTC) have shown that age, tumor size, local invasion and distant metastasis are independent predictive variables. This study attempted to define a reliable prognostic scoring system for predicting PTC mortality rates with 15 candidate variables that included completeness of primary tumor resection but excluded histologic grade and DNA ploidy. METHODS: The study group comprised 1779 patients with PTC (followed up for > 26,000 patient-years), divided by treatment dates into 1940 to 1964 (n = 764) and 1965 to 1989 (n = 1015). Cox model analysis and stepwise variable selection led to a prognostic model initially derived from the training set (n = 764). The initial prognostic score was thereafter validated externally with the later (1965 to 1989) "test" data set. RESULTS: The final model included five variables abbreviated by metastasis, age, completeness of resection, invasion, and size (MACIS). The final prognostic score was defined as MACIS = 3.1 (if aged < or = 39 years) or 0.08 x age (if aged > or = 40 years), + 0.3 x tumor size (in centimeters), +1 (if incompletely resected), +1 (if locally invasive), +3 (if distant metastases present). Twenty-year cause-specific survival rates for patients with MACIS less than 6, 6 to 6.99, 7 to 7.99, and 8+ were 99%, 89%, 56%, and 24%, respectively (p < 0.0001). CONCLUSIONS: Because the five variables needed for MACIS scoring are readily available after primary operation, such a prognostic system could have widespread applicability in assessment of PTC.

Aged↗
PubMed1993

Linking medical needs and performance goals: clinical and laboratory perspectives on thyroid disease.

Diagnosis and management of thyroid disease benefit substantially from close interactions between clinicians and laboratorians. Clinicians desire reliable tests for diagnosis and management of both hypothyroidism and thyrotoxicosis. Traditionally, multitiered testing has been used, beginning with an index of free thyroxine concentration, which, if abnormal, has been followed by basal thyrotropin (TSH) measurements (for hypothyroidism) or thyrotropin-releasing hormone-stimulated TSH measurements (for thyrotoxicosis). Improvements in analytical methods for TSH have made it practical to use basal TSH measurements in serum as the first-line test for thyroid disease. However, performance guidelines are needed, because not all TSH assays work well in this role. The performance guidelines developed by the American Thyroid Association are reviewed to illustrate how they help to assure consistent analytical testing. Further improvements in TSH assays (third- and fourth-generation assays), which support measurements down to 0.01 mlU/L and 0.001 mIU/L, may provide additional advantages for classifying thyrotoxic patients and monitoring thyroxine-suppressive therapy in patients with thyroid cancer. The potential advantages of these newer assays are illustrated with case examples. Additional analytical performance monitors are proposed to help ensure that these next-generation TSH assays meet the expanded clinical needs.

Aged↗
PubMed1992

Medullary thyroid carcinoma: clinicopathologic features and long-term follow-up of 65 patients treated during 1946 through 1970.

We retrospectively reviewed the medical records of 65 consecutive patients with medullary thyroid carcinoma, who had had their primary surgical treatment at the Mayo Clinic during the years 1946 through 1970. Of these patients, 58 had sporadic and 7 had familial medullary thyroid carcinoma. Thyroid nodules were the most common initial manifestation. Near-total thyroidectomy was the most frequent initial operation. Survival was affected by the following factors: male sex, familial inheritance, size of the tumor, stage of the tumor (American Joint Committee on Cancer), and completeness of initial resection of the tumor. The mean duration of follow-up was 23.5 years, and the maximal follow-up was 36 years. Among 52 patients without initial distant metastatic involvement and with complete resection of the tumor, 20-year survival free of distant metastatic lesions was 81%. Overall 10- and 20-year survival rates were 63% and 44%, respectively. Because of the substantial morbidity and mortality associated with medullary thyroid carcinoma, early diagnosis and thorough initial resection of the tumor are important.

Adolescent↗
PubMed1992

Ret oncogene activation in human thyroid neoplasms is restricted to the papillary cancer subtype.

We have recently reported the activation of a new oncogene in human papillary thyroid carcinomas. This oncogene, papillary thyroid carcinoma (PTC), is a novel rearranged version of the ret tyrosine-kinase protooncogene. Thyroid neoplasms include a broad spectrum of malignant tumors, ranging from well-differentiated tumors to undifferentiated anaplastic carcinomas. To determine the frequency of ret oncogene activation, we analyzed 286 cases of human thyroid tumors of diverse histologic types. We found the presence of an activated form of the ret oncogene in 33 (19%) of 177 papillary carcinomas. By contrast, none of the other 109 thyroid tumors, which included 37 follicular, 15 anaplastic, and 18 medullary carcinomas, and 34 benign lesions, showed ret activation.

Base Sequence↗
PubMed1992

Follicular thyroid carcinoma with capsular invasion alone: a nonthreatening malignancy.

BACKGROUND: The study was designed to determine whether invasion of the tumor capsule, in the absence of vascular invasion (VI), was significant in predicting cause-specific mortality in follicular thyroid carcinoma (FTC). METHODS: Seventy-two patients with FTC were treated by us during 1971 through 1985. In 65 cases the tumors could be classified as either showing capsular invasion (CI) alone (20) or VI, with or without CI, (45). Median follow-up of 45 survivors was 11 years; 12 patients died of FTC. RESULTS: The 10-year occurrence rates for cause-specific mortality and distant metastases were 28% and 19%, respectively, for patients with VI. Comparable rates for the patients with CI were 0% (p = 0.019) and 0% (p = 0.052), respectively. By univariate analysis, higher rates of cause-specific mortality were significantly associated with distant metastases at diagnosis (p < 0.0001), the presence of VI (p = 0.019), and moderate or marked microinvasion (p = 0.019). In stepwise multivariate analyses, only distant metastases at diagnosis had independent prognostic significance (p < 0.0001) in the prediction of cause-specific mortality. In a Cox model, adjusting for distant metastases at diagnosis, the presence of VI was of borderline significance (p = 0.06) in predicting cause-specific mortality. CONCLUSIONS: FTC, diagnosed on the basis of CI alone, did not result in either distant metastases or cancer-related death. The dominant determinant of cause-specific mortality was the presence of distant metastases at diagnosis.

Adenocarcinoma↗
PubMed1992

Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period.

BACKGROUND: The study aims were to characterize patients with papillary thyroid microcarcinoma and to provide data on outcome after surgical therapy. METHODS: Five hundred thirty-five patients with papillary microcarcinoma had initial treatment at Mayo Clinic from 1940 to 1989. Follow-up extended to 48 years. Median follow-up time for 400 survivors was 16 years. Recurrence and mortality details were derived from a computerized cancer database. RESULTS: Median tumor size was 8 mm. Ninety-nine percent of tumors were histologic grade 1; 98% were not locally invasive. Thirty-two percent of patients had nodal metastases at examination. TNM stages were I in 485 patients (91%), III in 49 patients (9%), and IV in one patient (0.2%). Ninety-one percent of patients underwent bilateral lobar resection. Tumor resection was incomplete in three cases (0.6%). Radioiodine remnant ablation was performed in 55 patients (10%). All-causes survival did not differ from expected; two patients (0.4%) died of papillary microcarcinoma. Twenty-year tumor recurrence rate was 6%. Higher recurrence rates were seen either with node-positive patients (p < 0.0001) or after unilateral lobectomy (p < 0.0001). Recurrence rates did not appear to be significantly altered by total thyroidectomy (p = 0.44) or radioiodine remnant ablation in node-positive patients (p = 0.99). CONCLUSIONS: These results reaffirm that papillary microcarcinoma has an excellent prognosis if managed initially by bilateral lobar resection. Routine radioiodine remnant ablation is not indicated.

Adolescent↗
PubMed1991

Loss of heterozygosity suggests multiple genetic alterations in pheochromocytomas and medullary thyroid carcinomas.

Loss of heterozygosity (LOH) at specific loci may help localize tumor suppressor genes involved in the formation of various familial and sporadic tumors. In addition, the genetic loci for a number of familial tumor syndromes have been mapped by linkage analysis. To explore the possible role of tumor suppressor genes in endocrine tumors, we tested 41 pheochromocytomas (34 sporadic and 7 familial) and 11 medullary thyroid cancers (MTC) (10 sporadic and 1 familial) for LOH near a variety of potentially important genetic loci: (a) the multiple endocrine neoplasia type 2A (MEN 2A) locus on chromosome 10; (b) the von Hippel-Lindau locus on 3p; and (c) the p53 and neurofibromatosis 1 loci on 17. We also examined chromosomes 1p and 22q because previous studies in a small number of pheochromocytomas and MTCs suggested LOH in these regions. Background rates for LOH were assessed using several "random" probes. Finally, we examined a number of clinical and histologic characteristics of these tumors for possible correlations with specific genetic alterations. LOH in the region of the MEN 2A locus was uncommon (0% for MTCs, 5% for pheochromocytomas). However, we found significant allelic losses in pheochromocytomas on chromosomes 1p (42%), 3p (16%), 17p (24%), and 22q (31%). We also noted a correlation between LOH on 1p and urinary excretion of metanephrine by these patients (P = 0.02). LOH on 1p, 3p, and 17p also appeared to be associated with increased tumor volume. Analysis of the smaller number of MTCs demonstrated allelic losses on chromosomes 1p and 22q. Our results suggest that tumor formation and/or progression in pheochromocytomas and MTCs involves multiple genes, analogous with the model proposed for colon carcinoma.

Adolescent↗
PubMed1991

Cytogenetic and molecular genetic studies of follicular and papillary thyroid cancers.

Cytogenetic studies have shown frequent clonal abnormalities in papillary carcinoma (PTC) and follicular carcinoma (FTC). Loss of heterozygosity (LOH) may suggest the presence of tumor suppressor genes and has not been reported in these neoplasms. These studies were undertaken to determine if consistent chromosomal abnormalities are associated with thyroid cancer, to determine likely regions for molecular genetic investigations, and to determine if there is allelic loss in thyroid tumors. Cytogenetic analysis of 26 PTC and 5 FTC showed clonal abnormalities in 9 and included -Y, +5, or inv(10)(q11.2q21.2) in PTC, and -Y or near haploidy in FTC. Using DNA probes specific for chromosomes 1, 3, 10, 16, and 17, we carried out restriction fragment length polymorphism analysis on 6 FTC, 3 follicular adenomas (FA), and 12 PTC. LOH of all informative loci on chromosome 3p was observed in all 6 FTC, but not in FA or PTC. No LOH was observed for loci mapped to chromosome 10 in PTC. Our results suggest: cytogenetic abnormalities of chromosome 10q are associated with PTC; cytogenetic and molecular abnormalities of chromosome 3 are associated with FTC; and a tumor suppressor gene may be present on the short arm of chromosome 3 important for the development or progression of FTC.

Adenocarcinoma↗
PubMed1991

The association between Alzheimer's disease and thyroid disease in Rochester, Minnesota.

To determine whether an association exists between Alzheimer's disease (AD) and thyroid disease, we carried out two studies in the population of Rochester, Minnesota. We reviewed medical records of a cohort of 198 women with histologically confirmed Hashimoto's thyroiditis (1935 to 1974) for evidence of subsequent dementia, applying the criteria used for dementia in a previous determination of incidence and prevalence rates in this population. From a total of 4,197 person-years of follow-up, eight cases of AD were diagnosed, whereas the expected number was 5.8. The standardized morbidity ratio was 1.37, which failed to reach statistical significance. The second study was a retrospective case-control comparison that sought any relationship between AD and all thyroid disorders, using a previously identified (1960 to 1979) AD cohort (N = 646) and their age- and sex-matched controls. For myxedema there was a positive association for AD without significance, whereas in Graves' disease there was a significant negative association for AD.

Adolescent↗
PubMed1991

Prognostic significance of calcitonin immunoreactivity, amyloid staining, and flow cytometric DNA measurements in medullary thyroid carcinoma.

The proven power of DNA ploidy to predict mortality risk in medullary thyroid carcinoma (MTC) may be weakened when analyzed in conjunction with calcitonin immunoreactivity (CI) and amyloid staining (AS) of tumors. In this study 12 prognostic variables, including DNA ploidy, CI, and AS, were studied in 65 patients with MTC (57 sporadic; mean age 51 years) treated during 1946 through 1970. Cause-specific mortality rates at 10 and 15 years were 15% and 26%, respectively. By univariate analysis, TNM stages III or IV (p less than 0.0001), tumor unresectability (p less than 0.0001), male sex (p = 0.019), negative AS (p = 0.032), and low CI (p = 0.033) were significant predictors of increased mortality rates. DNA ploidy (p = 0.058) and inheritance pattern (p = 0.25) were nonsignificant. By multivariate analysis, only TNM stage, tumor resectability, and AS were independently significant (p less than 0.005). A prognostic model was created, based on presence or absence of these independent risk factors, and four risk groups were defined, capable of predictably defining mortality rates in MTC (p less than 0.0001). The model requires validation in larger series and independent verification by others. However, we believe that a risk-group scheme for MTC based on AS, disease stage, and completeness of tumor resection may have wide applicability and prove relevant to clinicians treating this disease.

Adolescent↗
PubMed1990

Frequent occurrence of cytogenetic abnormalities in sporadic nonmedullary thyroid carcinoma.

Cytogenetic studies may provide important clues to the molecular pathogenesis of thyroid neoplasia. Thus, the authors attempted cytogenetic studies on 12 thyroid carcinomas: seven papillary, three follicular, and two anaplastic. Successful cytogenetic results were obtained on all 12 tumors; nine (75%) had one or more chromosomally abnormal clones. Four of the papillary carcinomas had a simple clonal karyotype, and three had no apparent chromosome abnormality. All four abnormal papillary tumors contained an anomaly of a chromosome 10q arm. In one instance, an inv(10)(q11.2q21.2) was observed in a Grade 2 papillary carcinoma as the sole acquired abnormality. In another case, an inversion or insertion involving 10q21.2 was found in a Grade 1 papillary tumor. The karyotype of a third tumor, a Grade 1 papillary carcinoma, was 46,XX,der(5)t(5;10)(p15.3;q11),der(9)t(9;?)(q11;?). A fourth abnormal papillary carcinoma, a Grade 1 tumor, had a t(6;10)(q21;q26.1) as the sole abnormality. Each of the five follicular or anaplastic carcinomas had a complex clonal karyotype. The three follicular carcinomas contained an abnormality of 3p25-p21, along with several other chromosome abnormalities.

Adenocarcinoma↗
PubMed1990

Long-term course of patients with persistent hypercalcitoninemia after apparent curative primary surgery for medullary thyroid carcinoma.

Thirty-one patients with persistent hypercalcitoninemia after seemingly adequate primary operation for medullary thyroid carcinoma (MTC) were followed for a mean period of 11.9 years after operation. Ten patients had sporadic MTC and the remaining patients were members of families with multiple endocrine neoplasia (MEN)--either MEN 2A (15 patients) or MEN 2B (six patients). Overall 5- and 10-year survival rates were 90% and 86%, respectively. Only four patients died at the completion of the study: two of MTC and two of unrelated causes. Eleven patients (35.5%) underwent surgical re-exploration after demonstration of recurrent disease clinically or radiologically. In no patient did the calcitonin level return to normal after re-exploration. The presence of more than three metastatic nodes at the time of initial operation was a statistically significant (p = 0.003) predictor for disease recurrence. Factors approaching statistical significance were patients younger than age 35 (p = 0.06) and the percentage of cells in the S phase of cell division (0.07). This data supports a conservative surgical philosophy in the management of the patient with persistent hypercalcitoninemia after resection of MTC.

Adolescent↗