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Biomedical subjects

I D Hay

Publications and source records attributed to I D Hay.

At least 73 records · Page 4Linked to original sources
PubMed1990

Practical management of hyperthyroidism.

There are several causes of hyperthyroidism, and correct diagnosis is essential for management. Graves' disease is most commonly managed with radioactive iodine therapy (131I), antithyroid drugs or surgery. Toxic adenomas (single or multiple) may be treated with 131I or surgery. Most types of thyroiditis are managed expectantly. Pregnant women, children and the elderly deserve special consideration. Follow-up is vital to identify the later development of hypothyroidism.

Antithyroid Agents↗
PubMed1990

Prognostic significance of nondiploid DNA determined by flow cytometry in sporadic and familial medullary thyroid carcinoma.

To clarify the role of DNA measurements in predicting outcome after surgical treatment of medullary thyroid carcinoma (MTC), we performed flow cytometric analysis in nuclear suspensions of 119 MTC tumors. Of the 119 patients, 63 (53%) patients had sporadic tumors and 56 (47%) patients had familial tumors; survivors were followed for a mean of 13 years. DNA content was normal in 92 (77%) patients and abnormal (nondiploid) in 27 (23%) patients. Ten-year cause-specific mortality rates were 12%, 42%, and 49% with diploid, tetraploid/polyploid, or aneuploid tumors (p = 0.0009) and were greater with nondiploid tumors both in the sporadic (p = 0.012) and multiple endocrine neoplasia (familial) cases (p = 0.114). None of 27 patients with TNM stage I disease died of MTC. In patients with TNM stages II, III, and IV disease, DNA nondiploid tumors were associated with increased deaths from MTC. In a Cox proportional hazards model involving all 119 patients and adjusted for disease stage and inheritance pattern, nondiploid DNA was independently associated with increased deaths from MTC (p = 0.008). In an identical Cox model restricted to the 92 DNA diploid tumors, an S-phase fraction of 15.0% or more remained a significant variable (p = 0.034) after adjustment for stage and inheritance pattern. We therefore conclude that DNA measurements do have a role to play in predicting outcome after surgical treatment of MTC.

Adolescent↗
PubMed1990

Papillary thyroid carcinoma.

Multiple prognostic factors for outcome in papillary thyroid carcinoma are identified. For a cohort of 1500 consecutive patients followed an average of 16 years, survival rates for tumor recurrence and cause-specific mortality are described. Risk groups derived from novel prognostic scoring or staging systems and the role of DNA ploidy testing are discussed specifically. Lastly, controversies are reviewed regarding the extent of primary surgical resection and the efficacy of postoperative radioiodine remnant ablation in papillary thyroid cancer.

Adolescent↗
PubMed1989

Long-term follow-up of patients with benign thyroid fine-needle aspiration cytologic diagnoses.

Reliance on fine-needle aspiration (FNA) of the thyroid as the key determinant whether to observe only or proceed surgically is predicated on achieving a minimal false-negative error rate (the incidence of malignant disease in nodules diagnosed benign by means of FNA). To provide convincing data that malignant disease has not been overlooked requires extended follow-up on a large number of patients with cytologically benign lesions. The intent of our study was to assess the long-term accuracy of thyroid FNA-based diagnoses--particularly with respect to false-negative errors. From our total experience of more than 8000 patients, we reviewed the cases of 680 patients who underwent FNA in 1980, the first year we used it clinically. Follow-up information was obtained on 641 (94%) of the patients with a mean time since FNA of 6.1 years. Benign cytologic findings were reported on 439 (68%) of these patients, and only three (0.7%) had false-negative diagnoses. The false-positive rate was 0% for the 24 (4%) patients with positive aspirates. FNA is a safe, reliable, effective means of accurately discriminating benign from malignant thyroid lesions.

Biopsy, Needle↗
PubMed1988

Mortality from papillary thyroid carcinoma. A case-control study of 56 lethal cases.

To document the presentation, findings, therapy, and postoperative course of lethal papillary thyroid carcinoma (PTC), 56 fatal cases were studied in a retrospective case-matched control fashion. These patients and their controls were taken from a larger series receiving their primary treatment at one institution (Mayo Clinic; 1946-1970). Mean follow-up for the lethal cohort was 8.5 years and 16.6 years for controls. Age, sex, tumor size, histologic grade, extent of disease at presentation, European Organization for Research on Treatment of Cancer (EORTC) and AGES scores (patient's age, tumor grade, tumor extent, and tumor size), and DNA ploidy pattern were found to be significant prognostic factors. The immediate causes of death were most frequently either local airway obstruction or respiratory insufficiency from pulmonary metastases. The results suggest that it is possible, at the time of initial treatment, to assess an individual patient's risk of dying from PTC. Aggressive postoperative adjunctive therapy should be restricted to that minority of patients who are at highest risk of death from PTC.

Adolescent↗
PubMed1988

Sensitive thyrotropin assays: analytic and clinical performance criteria.

Thyrotropin (TSH) measurements in serum traditionally have been used for the diagnosis and management of hypothyroidism; the availability of highly sensitive TSH assays has expanded the utility of these measurements to include detection of hyperthyroidism, monitoring of thyroxine replacement therapy, and front-line assessment of thyroid function. The analytic advancement that has expanded TSH utility is the noncompetitive "sandwich" immunoassay, which is faster and more sensitive than traditional radioimmunoassays. All such assays, however, are not equivalent; therefore, we have developed analytic and clinical performance criteria for evaluating sensitive TSH assays. These criteria are as follows: (1) the overlap between the assay detection limit and the lower limit of normal should be less than 1%, (2) basal TSH measurements should predict the TSH response to thyrotropin releasing hormone stimulation at least 95% of the time, and (3) basal TSH measurements should be 95% sensitive and 95% specific for detecting hyperthyroidism. Three allegedly sensitive TSH assays were evaluated: (1) the Hybritech two-step Tandem-R method (assay A), (2) the semiautomated Boots-Celltech Sucrosep method (assay B), and (3) a modified Ciba Corning Magic Lite method (assay C). Both assay B and assay C fulfilled out criteria for a sensitive assay; assay B had slightly better performance, and assay C was easier to perform.

Humans↗
PubMed1988

Clinical utility of thyrotropin-receptor antibody assays: comparison of radioreceptor and bioassay methods.

Thyrotropin (thyroid-stimulating hormone or TSH)-receptor antibodies, important in the pathogenesis of Graves' disease, can be assayed by one of two methods: (1) bioassays that measure stimulation of thyroid cellular activity by patient immunoglobulins or (2) radioreceptor assays that measure inhibition of binding of labeled TSH to TSH receptors by the same substances. In this study, we report our experience with bioassay of thyroid-stimulating immunoglobulins (TSI) based on measurement of generation of cyclic adenosine monophosphate in a clone of the Fisher rat thyroid cell line (FRTL-5) in 279 patients, and we compare, in 163 consecutive samples, the results obtained by a radioreceptor assay for thyrotropin-binding inhibiting immunoglobulins (TBII). Among the untreated, hyperthyroid patients with Graves' disease, TSI were present in 95% (38 of 40), and TBII were present in 85% (17 of 20). In patients with euthyroid Graves' disease, TSI were found in 57% (16 of 28), and TBII were present in 41% (7 of 17). Of 49 nongoitrous and euthyroid controls, only 4% had TSI and 3% had TBII. Extremely high TSI indices were found in all patients who had pretibial dermopathy (N = 10) or severe Graves' ophthalmopathy (N = 19) requiring orbital decompression. We conclude that both assays are highly sensitive and specific in diagnosing Graves' disease. The TSI bioassay was more sensitive (P less than 0.001) than the TBII radioreceptor assay in detection of Graves' disease. In our experience, both assays have proved useful in the diagnosis of euthyroid Graves' disease with ophthalmopathy and atypical manifestations of hyperthyroid Graves' disease.

Antibodies↗
PubMed1988

US-guided biopsy of neck masses in postoperative management of patients with thyroid cancer.

High-frequency (10-MHz) sonography demonstrated a cervical mass or lymphadenopathy, or both, during postoperative follow-up of 52 patients who had undergone surgery for thyroid cancer. Percutaneous biopsy with ultrasonographic (US) guidance was performed in all 52 masses, 44 of which were nonpalpable. Malignant cells were obtained in 29 biopsies, and the results of 20 biopsies were negative, yielding benign lymphocytes only. Results in three biopsies were nondiagnostic due to hypocellular specimens. Therefore, 94% of biopsy results (49) of 52) were confidently assigned as either positive (56%) or negative (38%) for malignancy. There were no complications. High-frequency sonography can demonstrate clinically occult thyroid bed tumor recurrence and lymph node metastases. US-guided biopsy is an accurate and safe technique to confirm or exclude malignancy in patients at high risk of recurrence of thyroid cancer.

Adult↗
PubMed1988

The effects of transforming growth factor-beta on growth and differentiation of the continuous rat thyroid follicular cell line, FRTL-5.

Transforming growth factor-beta (TGF beta) has been shown to influence the growth and differentiation of many widely varied cell types in vitro, including some that are endocrinologically active. We have investigated the previously unknown effects of this unique growth factor in the differentiated rat thyroid follicular cell line FRTL-5. The cells demonstrated specific, high affinity binding of TGF beta, and as with other epithelial cells, the growth of these thyroid follicular cells was potently inhibited by addition of TGF beta to the culture medium. TGF beta caused a significant reduction in TSH-sensitive adenylate cyclase activity in the cells. The addition of (Bu)2cAMP along with the growth factor to cultures partially reversed the characteristic morphological changes seen with TGF beta, but did not reverse the growth inhibition. To further investigate the possible mechanisms of the effects of TGF beta on the cells, we measured the influence of the growth factor on [125I]TSH binding. TGF beta did not compete for specific TSH-binding sites; however, exposure of the cells to TGF beta for 12 or more h resulted in a dose-dependent down-regulation of TSH receptors that was fully reversible. While cellular proliferation was potently inhibited by TGF beta, differentiated function, as manifest by iodine-trapping ability, was stimulated by the growth factor. This stimulation of iodine uptake was independent of, and additive to, the stimulatory effects of TSH. Finally, FRTL-5 cells in serum-free medium and in response to TSH were shown to secrete TGF beta-like activity that competed for [125I]TGF beta in a RRA. These studies suggest that TGF beta may represent an autocrine mechanism of controlling the growth response to TSH in thyroid follicular cells, while allowing the continuance of differentiated function.

Adenylyl Cyclases↗
PubMed1988

Distant metastases in differentiated thyroid carcinoma: a multivariate analysis of prognostic variables.

From a cohort of 988 patients with differentiated thyroid carcinoma receiving primary surgical treatment between 1946 and 1970, we studied the 85 (9%) patients who had distant metastases diagnosed during life. Clinically detected metastases were found in 7% of the 859 patients with papillary cancers, 19% of the 100 patients with follicular cancers, and 34% of the 29 patients with Hürthle cell cancers. The total experience amounted to 607 patient-years of observation after the diagnosis of metastases, with a median follow-up in the 12 survivors of 23 yr (range, 13-32 yr). At the time of first diagnosis of metastases, the lungs only were involved in 53%, and bones only in 20%; 16% had multiple organ involvement. The overall mortality rates 5 and 10 yr after the diagnosis of metastases were 65% and 75%, respectively. Seventy-eight percent of all deaths were directly attributable to thyroid cancer; 82% of cancer deaths occurred within 5 yr. By univariate analysis, patient age, tumor extent, pattern of lung involvement, radioiodine uptake of the metastases, and radioiodine treatment were significant prognostic factors. By multivariate analysis, only age (as a continuous variable) at the time of first diagnosis of distant metastases (P less than 0.0001) and involvement of multiple organ sites (P = 0.0003) were independently associated with cancer mortality. The survival at 5 yr in 12 patients aged less than 40 yr with only a single organ involved was 92%. Older patients (aged greater than or equal to 40 yr) with a single metastasis (n = 59) had a lower survival (38% at 5 yr). The highest risk of cancer death (92% at 5 yr) was found in the 14 patients (any age) who at the time of first diagnosis of metastases had multiple organ involvement. The Cox regression model suggested that radioiodine therapy did not have a significant influence on survival, after adjusting for age and extent of metastatic involvement.

Adolescent↗
PubMed1988

The effects of synthetic alpha-subunit peptides on thyroid-stimulating immunoglobulin activity.

Synthetic peptides, representing specific portions of the alpha-subunit of the human glycoprotein hormones, can inhibit both the binding of labeled TSH to thyroid membranes and adenylate cyclase stimulation by TSH in vitro. The same synthetic peptides (alpha 26-46 and alpha 31-45) significantly (P less than 0.05) inhibited the adenylate cyclase-stimulating activity of thyroid-stimulating immunoglobulins (TSI) from 10 patients with hyperthyroid Graves' disease. Peptide alpha 26-46 was the most potent, resulting in 79.1 +/- 8.8% (+/- SE) inhibition at 133 micrograms/mL, while peptide alpha 31-45 inhibited TSI activity by 36.3 +/- 5.2%. Peptides alpha 61-75 and alpha 81-92, that had only minimal ability to inhibit TSH-mediated cAMP generation, did not significantly inhibit TSI activity. The inhibitory action of alpha 26-46 was dose dependent, and a significant negative correlation was found between the maximum TSI activity of the serum sample and the inhibition achieved by the synthetic peptide, suggesting that differences in TSI affinity and/or titer may account for the variable inhibitory activity of the peptides. These results suggest that TSI interact with the TSH receptor at the site that recognizes the portion of the TSH alpha-subunit represented by the synthetic peptide alpha 26-46 and, thus, support the concept that the TSH-binding site of the TSH receptor is the site of antigen binding between TSI and the thyroid cell.

Cyclic AMP↗
PubMed1988

Thyroid dysfunction.

This article reviews currently available thyroid function tests and considers the utility of these tests in the investigation of suspected thyroid dysfunction. Potential thyroid screening tests as well as those secondary tests useful in establishing or excluding thyroid dysfunction are evaluated. Current controversies regarding free thyroid hormone and sensitive TSH assays are considered, and algorithms are provided for diagnosing both hypothyroidism and thyrotoxicosis.

Humans↗
PubMed1988

Papillary thyroid carcinoma in children and adults: long-term follow-up of 1039 patients conservatively treated at one institution during three decades.

Fifty-eight children (18 boys, 40 girls) less than 17 years of age, undergoing initial surgery because of papillary thyroid carcinoma (PTC) at Mayo Clinic from 1946 through 1975 and followed up for a median time of 27.6 years were compared with 981 adults (323 men, 658 women) treated during the same period and followed up for a median period of 19.5 years. At initial evaluation, mean tumor size (+/- SD) was greater in children (3.1 +/- 1.7 cm) than in adults (2.1 +/- 1.7 cm) (p less than 0.001); tumor DNA content was nondiploid in 10% of 39 children and in 25% of 110 adults (p = 0.047). Neck node metastases at diagnosis were detected in more children (89.7%) than adults (34.7%) (p less than 0.0001), but extrathyroidal invasion was not significantly more frequent in children (24.1%) than adults (15.8%) (p = 0.095). Distant metastases at diagnosis were detected in more children (6.9%) than adults (2.1%) (p = 0.022). Postoperatively, neck node metastases recurred more frequently in children (30%) than in adults (7%) (p less than 0.001), but local neck recurrences were not significantly more frequent in children (12%) than in adults (5%) (p = 0.083). Postoperative distant metastases occurred with similar frequency in children (6%) and adults (5%) (p = 0.98). Survival (all causes of death) for both adults and children up to 30 years after the initial surgery was no different from expected survival rates. Only adults aged more than 40 years had a significantly higher mortality from PTC than did children (p less than 0.0001). Fourteen percent of children had died of PTC by 15 years after diagnosis of distant metastases, whereas 68% of similarly affected adults were dead at 15 years (p = 0.014). PTC was more often metastatic to neck nodes and lungs before initial surgery and more often recurrent in neck lymph nodes postoperatively. However, PTC tended to be less fatal in children, and this may be related to the infrequency of nondiploid DNA content in the childhood PTC tumors.

Adolescent↗