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Kenneth D Burman

Publications and source records attributed to Kenneth D Burman.

At least 19 recordsLinked to original sources
PubMed2006

Intravenous methimazole in the treatment of refractory hyperthyroidism.

BACKGROUND: Management of a hyperthyroid patient unable to take oral or rectal medication is a difficult clinical problem. The need for an alternative parenteral route of antithyroid medication administration in thyrotoxic patients occurs in certain rare cases, such as emergent gastrointestinal surgery, bowel ileus or obstruction, or severe vomiting and diarrhea. We report a simple and successful protocol for the preparation and use of intravenous methimazole (MMI) for treatment of hyperthyroidism in patients intolerant of orally and rectally administered thionamides. METHODS: Five hundred milligrams of methimazole USP powder was reconstituted with pH-neutral 0.9% sodium chloride solution to a final volume of 50 mL using aseptic technique, then filtered through a 0.22-microm filter. MMI injection was administered as a slow intravenous push over 2 minutes and followed by a saline flush. CASES: A 76-year-old man, intolerant of oral and rectal medications because of an ileus and intractable diarrhea, who developed worsening thyrotoxicosis after an emergent spinal cord decompression, and a 42-year-old man with chronic liver disease and hyperthyroidism, requiring emergent exploratory laparotomy and maintenance of complete bowel rest because of persistent gastrointestinal bleeding were rendered euthyroid using intravenous MMI. CONCLUSION: Two cases of hyperthyroidism successfully treated with a preparation of intravenous MMI are described.

Adult↗
PubMed2006

Overt and 'subclinical' hypothyroidism in women.

UNLABELLED: Thyroid disease in general, and hypothyroidism in particular, are very common in women. In the USA, the most common cause of primary thyroid deficiency is on an autoimmune basis due to lymphocytic (Hashimoto) thyroiditis. Because there are thyroid hormone receptors in virtually every tissue of the body, the manifestations of hypothyroidism are varied, but problems with abnormal menses, conception, fertility, and pregnancy can be especially troubling in young women. The single most important diagnostic test is measurement of serum thyrotropin (TSH). The overwhelming majority of patients with hypothyroidism are treated with a single daily dose of synthetic levothyroxine with the goal of therapy being restoration of a normal metabolic state with return of the TSH level down to the range of 0.5 to 1.5 mlU/L. "Subclinical" hypothyroidism refers to those patients with early or mild thyroid hypofunction manifested as slight elevations of thyrotropin (approximately 4-10 mlU/L) although serum thyroxine (T4) and triiodothyronine (T3) levels are within their reference ranges. The entity is somewhat controversial in regard to its consequences if left untreated, and whether or not we should be screening patients, at least susceptible populations, for the condition. Reports indicate an association between subclinical hypothyroidism and poor outcomes of pregnancy, as well as dyslipidemias, atherogenesis, and increased mortality in the long term. We believe these consequences are sufficiently compelling to warrant screening and treatment with levothyroxine when found to halt progression to overt hypothyroidism, and improve symptoms, pregnancy outcomes, lipid abnormalities, and cardiovascular function. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that hypothyroidism is a common disease in women, has many protean manifestations, and can be successfully diagnosed and treated; explain that the condition of subclinical hypothyroidism can be diagnosed and if treated can prevent many untoward complications; and state that there should be heightened awareness of the disease so that proper screening tests can be performed.

Female↗
PubMed2005

KiSS-1/G protein-coupled receptor 54 metastasis suppressor pathway increases myocyte-enriched calcineurin interacting protein 1 expression and chronically inhibits calcineurin activity.

OBJECTIVE: Tumor metastasis is a critical determinant of death from cancer. Metastin, a product of the KiSS-1 gene, is an endogenously expressed metastasis suppressor that is the ligand for G protein-coupled receptor 54 (GPR54), a Gq/11-coupled receptor. In the present study, our goal was to define the basis of GPR54 action using thyroid cancer cells as a model. DESIGN AND RESULTS: We used GPR54-null thyroid cancer cells to create a stable GPR54 overexpression model. Cell growth and cell migration of the GPR54-expressing lines were inhibited by recombinant metastin, and metastin stimulated the protein kinase C, ERK, and phosphatidylinositol-3-kinase pathways. To identify metastin-regulated genes, we performed microarray analyses using RNA isolated from GPR54 stable transfectants before and after 1 and 24 h of metastin stimulation. Consistent increases in expression of the gene encoding myocyte-enriched calcineurin interacting protein 1 (MCIP-1), an inhibitor of calcineurin, were identified and confirmed using real-time RT-PCR and Western blot. Functionally, metastin treatment of GPR54-expressing cells initially increased calcineurin activity, followed by a prolonged reduction in calcineurin activity for 24 and 48 h, consistent with the pattern of MCIP-1 expression. In addition, treatment with cyclosporin A, a calcineurin inhibitor, blocked cell migration. Lymph node metastasis in papillary thyroid cancers demonstrated loss of MCIP-1 expression in comparison with primary tumors. CONCLUSIONS: These data suggest a role for MCIP-1 and calcineurin inhibition in GPR54-mediated metastasis suppression in human cancers.

Calcineurin Inhibitors↗
PubMed2005

Akt1 contains a functional leucine-rich nuclear export sequence.

Nuclear Akt1 expression and Akt activation are common in cancer invasion. However, the mechanisms for this association and its causal role in invasion are uncertain. In an effort to identify potential mechanisms for regulating Akt subcellular localization, we analyzed the Akt gene sequences and identified a highly conserved leucine-rich potential nuclear export sequence (NES). Initial experiments demonstrated that leptomycin B induced nuclear Akt1 localization. Transient expression experiments demonstrated that, in comparison to wild-type Akt1, NES-mutated (AKT/NES) Akt1 has reduced interactions with CRM-1 and persistent nuclear localization. Subsequent stable transfection experiments in Akt1-/- fibroblasts confirmed that expression of AKT/NES resulted in persistent nuclear localization and activation1. Finally, stable expression of AKT/NES in Akt1-/- fibroblasts was sufficient to enhance cell migration in vitro. Thus, Akt1 contains a functional NES and mutation of the NES results in nuclear-predominant Akt1 activation that is sufficient to induce migration.

Active Transport, Cell Nucleus↗
PubMed2005

Spontaneous normalization of thyrotropin concentrations in patients with subclinical hypothyroidism.

CONTEXT: Patients with subclinical hypothyroidism may revert to normal TSH values. OBJECTIVE: The objective of this study was to examine the time course of the normalization of TSH levels in subclinical hypothyroidism. DESIGN: This was a prospective, observational study with no intervention, with a duration of follow-up of 12-72 months. SETTING: Outpatients visited an endocrinology clinic of a general hospital. PATIENTS: Forty patients (32 women, mean age 62.8 +/- 8.2 yr) with spontaneous subclinical hypothyroidism (TSH > 5 mU/liter and normal free T(4)) participated in the study. Each patient normalized their TSH values without T(4) therapy throughout the follow-up. MEASUREMENTS: TSH and free T(4) levels were evaluated every 6 months. RESULTS: Normalization occurred at a median time of 18 months (range, 6-60 months). Fifteen patients normalized their TSH levels during the first year of follow-up and 27 during the first 2 yr. Ten patients normalized their TSH values at the fourth or fifth year. Only four patients reverted to TSH values less than 2 mU/liter. Final TSH levels achieved by the patients were significantly correlated with the time elapsed until normalizing these levels (r = 0.367; P = 0.020). CONCLUSIONS: There is no clear pattern of TSH normalization, although most patients normalize their TSH values early in the follow-up. The final TSH reached seems to be related to the time of normalization.

Aged↗
PubMed2005

Papillary and follicular variant of papillary carcinoma of the thyroid: Initial presentation and response to therapy.

INTRODUCTION: The 2 most common histologic variants of papillary carcinoma are pure papillary carcinoma (PTC) and follicular variant of papillary thyroid carcinoma (FVPTC). The purpose of this study is to compare the presentation and short-term response to therapy of these variants and to determine if FVPTC is a more aggressive form of thyroid cancer that warrants intensive therapy. METHODS: A retrospective chart review of patients treated for PTC and FVPTC between 1996 and 1999 was performed. Clinical variables were compared with the Wilcoxon Rank-Sum test or the Fischer's Exact Test. RESULTS: Of 160 patients with papillary thyroid carcinoma included, 114 (71%) had PTC and 46 (29%) had FVPTC. Mean follow-up was 38.6 months. FVPTC presented with larger tumors (median 1.5 cm vs 1.0 cm, P = 0.007) and higher tumor stage than PTC. PTC patients were more likely to present with local invasion and to have local recurrence (9.65% vs 0% for both variables). There were no significant differences in patient age, gender, vascular invasion, lymph node or distant metastases, surgical treatment, radioactive iodine therapy, remission, or mortality. CONCLUSION: FVPTC presented with larger original tumor size and higher tumor stage but a lower local invasion rate and recurrence rate than patients with PTC despite similar therapies. These data suggest that FVPTC and PTC carry similar prognoses in early stages and that FVPTC may have a reduced predilection for local invasion. Although further studies with longer follow-up are required, these results do not suggest that FVPTC warrants more aggressive therapy than PTC.

Adult↗
PubMed2005

Radioiodine therapy for thyroid cancer and hyperthyroidism in patients with end-stage renal disease on hemodialysis.

Treatment with radioactive iodine ((131)I) may be necessary for thyroid cancer or for hyperthyroidism in patients with end-stage renal disease who require hemodialysis. Because (131)I is cleared mainly by the kidneys in patients with normal renal function, many issues arise in patients who require (131)I treatment but who are on hemodialysis. This paper presents a case report of a patient on dialysis who required treatment with (131)I for thyroid cancer. We describe a mathematical model, which suggests that the treatment dose of (131)I for a patient with thyroid cancer on hemodialysis would be approximately 13%-28% of a typical empiric dose of (131)I for a patient with normal renal function. Also, we present a comprehensive review and discussion of the literature on patients who are receiving hemodialysis who were treated with (131)I for either thyroid cancer or hyperthyroidism. Using a multidisciplinary approach and special precautions, (131)I therapy can be administered safely and effectively for patients with thyroid cancer or hyperthyroidism who are receiving hemodialysis.

Adult↗
PubMed2005

Volume changes in intra- and extraorbital compartments in patients with Graves' ophthalmopathy: effect of smoking.

The objective of this study was to demonstrate the effect of smoking history on soft tissue expansion in specific orbital compartments in patients with Graves' ophthalmopathy. The volumes of the rectus muscles, intra and extraorbital connective, and soft tissues were measured in 110 orbits of 35 patients and 20 control subjects. Data sets from current smokers, ex-smokers, and non-smokers were compared. The total number of cigarettes smoked was calculated, and it was used as an estimate for the severity of smoking (cumulative smoking). The volume measurements were performed on T1-weighted contiguous transversal magnetic resonance images of the orbits. Connective tissue volumes were influenced by smoking history, while muscle volumes were not affected. Ex-smokers had larger amount of extraorbital connective tissue than current smokers (p = 0.012), and this volume showed a good correlation with the number of cigarettes smoked (r = 0.539, p < 0.05). In current smokers, the amount of intraorbital connective tissue correlated well with the cumulative smoking (r = 0.635, p < 0.001). We conclude that connective tissue volumes in certain orbital compartments correlate well with cumulative smoking. Extraocular muscle volumes are not influenced by smoking in patients with Graves' ophthalmopathy.

Adult↗
PubMed2005

Transient Graves' hyperthyroidism during pregnancy in a patient with Hashimoto's hypothyroidism.

The course and severity of autoimmune thyroid disease are altered during pregnancy and in the postpartum period. The thyroidal response to a fluctuating immune status, combined with changes in thyroid economy during pregnancy, may result in a need to adjust the treatment regimen for thyroid disease during pregnancy. Patients with Hashimoto's hypothyroidism on thyroid hormone replacement are frequently observed to have an increased requirement for levothyroxine early in pregnancy, although this is not a universal finding. Hashimoto's hypothyroidism does not typically remit during pregnancy, although further progression of thyroiditis may be seen in the postpartum period. Graves' disease usually improves during pregnancy and flares after delivery, again necessitating monitoring of thyroid status and possible adjustments in thionamide therapy. However, spontaneous transformation from Hashimoto's hypothyroidism to Graves' disease during pregnancy is rare. We report a case of transient Graves' hyperthyroidism during the late second trimester in a patient on levothyroxine replacement for Hashimoto's hypothyroidism. This resulted in a need to discontinue the patient's thyroid hormone entirely to avoid exacerbation of her hyperthyroidism. This interesting case is presented, along with a discussion of how the expression of autoimmune thyroid disease may be altered during pregnancy.

Adult↗
PubMed2004

Subclinical thyroid disease: scientific review and guidelines for diagnosis and management.

CONTEXT: Patients with serum thyroid-stimulating hormone (TSH) levels outside the reference range and levels of free thyroxine (FT4) and triiodothyronine (T3) within the reference range are common in clinical practice. The necessity for further evaluation, possible treatment, and the urgency of treatment have not been clearly established. OBJECTIVES: To define subclinical thyroid disease, review its epidemiology, recommend an appropriate evaluation, explore the risks and benefits of treatment and consequences of nontreatment, and determine whether population-based screening is warranted. DATA SOURCES: MEDLINE, EMBASE, Biosis, the Agency for Healthcare Research and Quality, National Guideline Clearing House, the Cochrane Database of Systematic Reviews and Controlled Trials Register, and several National Health Services (UK) databases were searched for articles on subclinical thyroid disease published between 1995 and 2002. Articles published before 1995 were recommended by expert consultants. STUDY SELECTION AND DATA EXTRACTION: A total of 195 English-language or translated papers were reviewed. Editorials, individual case studies, studies enrolling fewer than 10 patients, and nonsystematic reviews were excluded. Information related to authorship, year of publication, number of subjects, study design, and results were extracted and formed the basis for an evidence report, consisting of tables and summaries of each subject area. DATA SYNTHESIS: The strength of the evidence that untreated subclinical thyroid disease is associated with clinical symptoms and adverse clinical outcomes was assessed and recommendations for clinical practice developed. Data relating the progression of subclinical to overt hypothyroidism were rated as good, but data relating treatment to prevention of progression were inadequate to determine a treatment benefit. Data relating a serum TSH level higher than 10 mIU/L to elevations in serum cholesterol were rated as fair but data relating to benefits of treatment were rated as insufficient. All other associations of symptoms and benefit of treatment were rated as insufficient or absent. Data relating a serum TSH concentration lower than 0.1 mIU/L to the presence of atrial fibrillation and progression to overt hyperthyroidism were rated as good, but no data supported treatment to prevent these outcomes. Data relating restoration of the TSH level to within the reference range with improvements in bone mineral density were rated as fair. Data addressing all other associations of subclinical hyperthyroid disease and adverse clinical outcomes or treatment benefits were rated as insufficient or absent. Subclinical hypothyroid disease in pregnancy is a special case and aggressive case finding and treatment in pregnant women can be justified. CONCLUSIONS: Data supporting associations of subclinical thyroid disease with symptoms or adverse clinical outcomes or benefits of treatment are few. The consequences of subclinical thyroid disease (serum TSH 0.1-0.45 mIU/L or 4.5-10.0 mIU/L) are minimal and we recommend against routine treatment of patients with TSH levels in these ranges. There is insufficient evidence to support population-based screening. Aggressive case finding is appropriate in pregnant women, women older than 60 years, and others at high risk for thyroid dysfunction.

Humans↗
PubMed2004

Chronic expression of RET/PTC 3 enhances basal and insulin-stimulated PI3 kinase/AKT signaling and increases IRS-2 expression in FRTL-5 thyroid cells.

The RET/PTC3 oncogene is a genetically rearranged and constitutively activated tyrosine kinase receptor that is common in papillary thyroid cancer. Because RET/PTC3 is chronically overexpressed in these thyroid cancer cells, and RET/PTC3-expressing tumors are associated with overactivity of tyrosine kinase signaling pathways and a more aggressive clinical course, we questioned whether chronic RET/PTC3 expression enhances cellular responses to thyroid mitogens in vitro. We stably transfected FRTL-5 cells with the RET/PTC3 gene; transfected and control cell lines were cultured without insulin, TSH, or serum. Thymidine incorporation into DNA was enhanced in the RET/PTC3 cells, but transformation was not observed. RET/PTC3 cells demonstrated higher basal and insulin-stimulated levels of activated Akt, both of which were reduced by LY294002, a PI3 kinase inhibitor, but not PD98059, a MEK inhibitor. By contrast, mitogen activated protein kinase (MAP kinase) was only minimally activated in RET/PTC3 cells before and after stimulation. Consistent with preferential activation of PI3 kinase, increased levels of total and phosphorylated IRS2 protein, relative activation of PDK-1, and enhanced IRS2-p85 interactions were identified in RET/PTC3-expressing cells. RET/PTC3 cells were also sensitized to insulin-induced thymidine incorporation; this effect was blocked by PI3 kinase (LY294002) rather than MEK 1/2 (PD98059) inhibitors. In summary, we have demonstrated that RET/PTC3 expression enhances basal and insulin-stimulated DNA synthesis through PI3 kinase, cooperatively activates Akt with insulin via PI3 kinase, and preferentially activates the Akt rather than MAP kinase pathway in FRTL-5 cells.

Animals↗
PubMed2004

17-Allylamino-17-demethoxygeldanamycin activity against thyroid cancer cell lines correlates with heat shock protein 90 levels.

Heat shock protein 90 (Hsp90) is a molecular chaperone that stabilizes growth factor receptors and signaling molecules. Disruption of this action inhibits the MAPK and phosphatidylinositol-3 kinase cascades and can induce cancer cell death. The goal of this study was to determine whether thyroid cancer cells are sensitive to the cytotoxic effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG), an Hsp90 inhibitor in clinical trials, and to determine predictors of this response. Papillary (NPA), follicular (WRO), and anaplastic (ARO) thyroid cancers were incubated with 17-AAG in vitro. Surprisingly, the ARO cells were most sensitive to the cytotoxic effects of this agent. Conversely, all cell lines displayed similar responses to specific blockers of phosphatidylinositol-3 kinase and MAPK kinase (LY294002 and U0126, respectively). Western blot demonstrated that the NPA cells that were most resistant to 17AAG-induced cytotoxicity had the lowest levels of Hsp90 and were the only cells with persistent levels of Akt protein. Interestingly, even the WRO and ARO cell lines that were sensitive to 17-AAG-induced cell death did not undergo apoptosis. These data suggest that sensitivity of thyroid cancer cells to 17-AAG-induced cytotoxicity relates to Hsp90 levels rather than histological subtype and that thyroid cancer cells have a reduced apoptotic response to 17-AAG.

Apoptosis↗
PubMed2003

The EUROPA trial.

Explore the source record for details and available documents.

Age Factors↗
PubMed2002

Subclinical hyperthyroidism: controversies in management.

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. The thyroid-stimulating hormone value is typically measured in a third-generation assay capable of detecting approximately 0.01 microU per mL (0.01 mU per L). Subclinical hyperthyroidism may be a distinct clinical entity, related only in part to Graves' disease or multinodular goiter. Persons with subclinical hyperthyroidism usually do not present with the specific signs or symptoms associated with overt hyperthyroidism. A detailed clinical history should be obtained, a physical examination performed and thyroid function tests conducted as part of an assessment of patients for subclinical hyperthyroidism and to evaluate the possible deleterious effects of excess thyroid hormone on end organs (e.g., heart, bone). A reasonable treatment option for many patients is a therapeutic trial of low-dose antithyroid agents for approximately six to 12 months in an effort to induce a remission. Further research regarding the etiology, natural history, pathophysiology, and treatment of subclinical hyperthyroidism is warranted.

Algorithms↗