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Thyroid
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Thyroid OR22-1 Effects of Experimentally Induced Subclinical Hyperthyroidism on Quality of Life, Mood, and Cognition. Mary H Samuels*1, Kathryn G Schuff1, Phyllis Carello1, Jeri Janowsky1. 1Oregon Hlth & Sci Univ, Portland, OR. Many patients have subclinical hyperthyroidism (SCHyper - suppressed TSH, normal fT4 and T3 levels), due to endogenous thyroid autonomy or exogenous L-thyroxine (L-T4) therapy. The effects of SCHyper on quality of life, mood, and cognition are poorly understood. To address this, we recruited 25 healthy subjects (23 women, 2 men, ages 24-45) with primary hypothyroidism receiving L-T4 who had normal TSH levels. In random order they received 12 weeks of usual dose L-T4 (euthyroid arm), or a higher dose intended to achieve a low TSH with normal free T4 and T3 levels (SCHyper arm), in a double-blinded, placebo-controlled, cross-over design. At the end of each 12-week arm, subjects completed the Hyperthyroid Symptom Scale (HSS), the Short Form 36 (SF-36), to assess quality of life, Profile of Mood States (POMS), and measures of working memory (Digit Span Backwards, Subject Ordered Pointing, N-Back), long-term memory (Paragraph Recall, Complex Figure), and motor performance (Pursuit Rotor). The following biochemical changes were seen during the SCHyper arm: Mean L-T4 dose increased from 1.67 to 2.53 ug/kg/day. Mean free T4 levels increased from 1.41 to 1.72 ng/dL, and mean T3 levels increased from 120 to 139 ng/dL. Mean TSH levels decreased from 2.27 to 0.49 mU/L (p < .01 by paired t-tests for all comparisons). Nine subjects correctly guessed which arm was the SCHyper arm, 10 guessed incorrectly, and 6 could not tell any difference (NS). Ten subjects preferred the SCHyper arm, 6 preferred the euthyroid arm, and 9 had no preference (NS). Comparisons at the end of the euthyroid and SCHyper arms showed no changes in HSS scores but significant changes in the SF-36: General Health decreased from 85.9 to 81.7 (p = .03), while Mental Health increased from 79.8 to 85.3 (p = .03). Mood also changed as shown by lower scores on the POMS-tension scale (41.8 to 39.3, p = .05), and higher scores on the POMS-vigor scale (53.4 to 56.9, p = .04). There were no significant differences in measures of working or long-term memory, but Pursuit Rotor scores were faster in the SCHyper arm (p = .05 by RM-ANOVA). In summary, subjects with SCHyper perceive improved mental health and mood, without concomitant changes in short or long-term memory. However, SCHyper led to improvements in motor performance. These results suggest that brain systems for memory are not affected by mild hyperthyroid conditions, although mood and motor performance are. CLINICAL - Thyroid Disorders (1:00 PM - 2:30 PM) Presentation Date: 6/5/2005 Time: 1:00:00 PM Location: 20 B-C
Thyroid OR22-1 News Summary Mood and motor performance but not memory are affected in people with mild hyperthyroidism Mild hyperthyroidism — or an overactive thyroid — affects brain systems for mood and motor performance but not memory, according to a study being presented on Sunday, June 5, at The Endocrine Society’s 87th Annual Meeting in San Diego. Many people with thyroid problems have subclinical hyperthyroidism, a mild form of the disorder that involves a suppressed thyroid-stimulating hormone (TSH) level with normal free T4 and T3 levels, which are important hormones in the regulation of metabolism. This can be due to the underlying thyroid problem, or to slightly high doses of L-thyroxine (L-T4), the usual hormone given to replace low thyroid function. The effects of subclinical hyperthyroidism on quality of life, mood, and memory are poorly understood. In a 12-week study, Dr. Mary Samuels and colleagues at the Oregon Health and Science University in Portland, Ore., studied the effects of inducing subclinical hyperthyroidism (SCHyper) by giving various doses of L-T4 to 25 women and two men, ages 24–45, with hypothyroidism. In random order, they received 12 weeks of the usual dose of L-T4 — euthyroid, or normal thyroid function, part of the study — or a higher dose intended to achieve a low TSH with normal T4 and T3 levels — the SCHyper part of the study. They were then switched to the alternate dose for a second 12 weeks. At the end of each 12 weeks, they completed the Hyperthyroid Symptom Scale (HSS), the Short Form (SF-36) to assess quality of life, Profile of Mood States (POMS), and measures of short-term, long-term, and motor memory. The SCHyper part of the study led to the expected changes in thyroid hormone levels, with lowering of the TSH level and increases in fT4 and T3 levels within the normal range. Nine participants correctly guessed which part of the study was the SCHyper part, 10 guessed incorrectly, and six could not tell any difference. Ten participants preferred the SCHyper part of the study, six preferred the euthyroid part, and nine had no preference. None of these findings were significant. Comparisons at the end of the euthyroid and SCHyper parts of the study showed no changes in HSS scores but significant changes in the SF-36, with general health indicators decreasing while mental health indicators increased. Mood also changed, as shown by lower scores on the POMS-tension scale and higher scores on the POMS vigor scale. There were no differences between the two parts of the study in measures of short-term or long-term memory, but one measure of motor performance was better during the SCHyper part of the study. In summary, changes in TSH levels in people with hypothyroidism does not affect the brain system for memory but has an impact on mood and motor performance.
Thyroid, Retinoid & Non-steroid Nuclear Receptors OR29-4 The Cholesterol-Raising Factor from Coffee Beans, Cafestol, as an Agonist Ligand for the Farnesoid and Pregnane x Receptors. Marie-Louise Ricketts*1, David D Moore1. 1Molec & Cell Biol, Baylor Coll of Med, Houston, TX. The coffee diterpene cafestol (CAF) is present in unfiltered coffee brews such as Scandanavian boiled, Turkish and cafetiere coffee. CAF is the most potent cholesterol-elevating compound known in the human diet. Several genes involved in cholesterol homoestasis have previously been shown to be targets of CAF, including cholesterol 7-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid biosynthesis. The aim of this study was to determine whether CAF exerts its effects via nuclear hormone receptors that control genes involved in cholesterol homeostasis, ie farnesoid x receptor (FXR) and/or pregnane x receptor (PXR). To answer this question both in vitro and in vivo studies were performed. CV-1 and HepG2 cells were used to investigate the effect of CAF on the full-length receptors. In addition, a range of Gal4 receptor ligand binding domain (LBD) constructs were used to determine the specificity of CAF. These studies revealed that CAF acts an an agonist ligand for both FXR and PXR, with no effect seen upon a range of other receptors tested, including CAR, LXR, RXR and RAR. Activation of FXR by CAF is comparable to the agonist chenodeoxycholic acid (CDCA) and requires the AF-2 transactivation function. CAF also activates both mouse and human PXR comparable to their respective ligands, 5- pregnen-3-ol-20-one-16-carbonitrile (PCN) and rifampicin (RIF), but not an AF-2 mutant. In a mammalian two-hybrid test of co-activator interaction, CAF is similar to CDCA in its ability to recruit a FXR-VP16 chimera to a Gal4-SRC-1 chimera. In addition, CAF is similar to PCN in its ability to recruit a PXR-VP16 chimera to a Gal4-SRC-1 chimera. In vivo studies were performed using both FXR and PXR knockout mice compared to wild type (C57/BL6) mice to further characterize the physiological effect of CAF. The mice were treated for 7 days and Northern analysis shows that the expression of several genes is altered by CAF treatment. Studies show that the expression of CYP7A1, CYP8B1 and NTCP are regulated via FXR, while CYP2A5 is regulated via PXR. In conclusion, CAF acts as a potential agonist ligand for both FXR and PXR and this may contribute to its effect on cholesterol homeostasis. BASIC - Novel Functions of Thyroid Hormone Receptor & Nonsteroidal Nuclear Receptors (1:00 PM - 2:30 PM) Presentation Date: 6/6/2005 Time: 1:45:00 PM Location: 29 C/D
Thyroid, Retinoid & Non-steroid Nuclear Receptors OR29-4 News Summary Compound in coffee beans can potentially raise cholesterol Researchers uncover, for the first time, how a compound in coffee beans — suspected in raising cholesterol — can affect genes that upset the cholesterol balance in the body, according to a new study being presented on Monday, June 6, at The Endocrine Society’s 87th Annual Meeting in San Diego. Elevated cholesterol is a serious health problem that affects millions of people around the world. According to the American Heart Association, one in five adults in the United States has high cholesterol. High blood cholesterol is a known contributor to the development of atherosclerotic lesions, subsequently leading to heart attacks. Individuals with elevated cholesterol need to be aware of any food products that can contribute to such elevated levels. Coffee beans contain a compound called cafestol, which has been shown to potently elevate cholesterol levels in people and in animals. Cafestol is present in unfiltered coffee brew types, such as Scandanavian boiled, Turkish, and Cafetière (or French-press) coffee. It is not present in filtered, instant, or decaffeinated coffee. Past research has found that several genes involved in cholesterol balance are affected by cafestol. Drs. Marie-Louise Ricketts and David Moore, of Baylor College of Medicine in Houston, wanted to determine how cafestol causes an elevation in cholesterol by looking at whether its effects are exerted via nuclear hormone receptors that control genes involved in cholesterol balance. The two important receptors involved in this regulation are the farnesoid x receptor (FXR) and the pregnane x receptor (PXR). To answer this question both in vitro and in vivo studies were performed. Kidney and liver cells were used to investigate the effect of cafestol on the full-length receptors. In addition, other nuclear receptors were tested to determine the specificity of cafestol. These studies revealed that cafestol acts as an activator for both FXR and PXR, with no effect seen upon the other receptors tested. In vivo studies were performed using mouse models — wild type and two others, one lacking FXR and the other lacking PXR to further characterize the physiological effect of cafestol. Two groups of mice were fed either a diet without cafestol or a diet supplemented with cafestol for seven days. Analysis of the liver and intestine showed that the expression of several genes is altered by cafestol treatment. For the first time, they were able to show that the expression of several genes involved in cholesterol balance are affected by cafestol and that they are regulated via FXR, while an enzyme involved in detoxification is regulated via PXR. Cafestol acts as a potential activator for both FXR and PXR, and this may contribute to its effect on cholesterol balance, say researchers. This research was funded by the National Institutes of Health and the U.S. Department of Agriculture.
Thyroid, Retinoid & Non-steroid Nuclear Receptors OR29-5 Defining the Molecular Actions of Linoleic Acid in Colon Cancer: Modulation of Peroxisome Proliferator-Activated Receptor Gamma. Clinton D Allred*1, Dominique R Talbert1, Michael W Kilgore1. 1Molec and Biomed Pharmacol, Univ of Kentucky Coll of Med, Lexington, KY. It has been hypothesized that specific types of dietary fat may influence colon cancer. Linoleic acid (LAA), an omega-6 fatty acid, has been shown to induce proliferation of several murine colon adenocarcinoma cell lines and rats fed diets high in LAA had enhanced colon cancer formation following tumor induction with azoxymethane. However, no molecular link has been identified to explain how LAA may elicit these effects. We hypothesize that LAA functions by acting as a ligand of the peroxisome proliferator-activated receptor gamma (PPAR) which is over expressed in colon cancer cells. In the presented studies, we tested whether LAA functioned directly through PPAR to activate a PPAR response element (PPRE)-mediated reporter construct in colon cancer (HT-29) cells. Also, we determined if LAA was itself a ligand of PPAR or if it must first be converted to a prostaglandin. We demonstrate that LAA activates the PPRE-reporter construct in HT-29 cells. Activation of the PPRE reporter is inhibited by co-treatment with GW 9662, a known PPAR antagonist. LAA also activated the PPRE-reporter in prostate cancer (22Rv1) cells that are PPAR negative when the cells were co-transfected with a PPAR expression plasmid. Together these data indicate that LAA directly binds PPAR and this action is both necessary and sufficient to activate the PPRE-reporter plasmid in colon cancer cells. LAA also transactivates PPAR in HT29 cells when co-treated with salicylic acid, an inhibitor of cyclooxygenase activity, suggesting that the metabolism of LAA to downstream prostaglandins is unnecessary. These are the first data that demonstrating LAA directly transactivates PPAR and begins to define a molecular link to the physiological actions of this fatty acid in colon cancer. This has practical applications for colon cancer patients in that this data is a first step toward dietary recommendations for consumption of certain fat sources for these patients. This work was supported by NIH grants CA95609-01 and NCRR-P20-RR15592 to MWK and by HD07436-09 (NIH) and W81XWH-04-1-0532 (US Army) to CDA. BASIC - Novel Functions of Thyroid Hormone Receptor & Nonsteroidal Nuclear Receptors (1:00 PM - 2:30 PM) Presentation Date: 6/6/2005 Time: 1:30:00 PM Location: 29 C/D
Thyroid, Retinoid & Non-steroid Nuclear Receptors OR29-5 News Summary Common fatty acid plays role in colon cancer growth Individual fatty acids play a role in colon cancer cell growth, according to first-time data being presented on Monday, June 6, at The Endocrine Society’s 87th Annual Meeting in San Diego. These findings are preliminary steps, say researchers, toward a better understanding of how to formulate dietary recommendations for people at risk of developing colon cancer as well as those who may be cancer survivors. Research has shown that the type of fat that people consume in their diet has the ability to influence colon cancer formation and growth. For example, people eating diets high in fats from fish have a much lower risk of developing colon cancer when compared to those who eat diets high in fats from other sources. Dr. Clinton Allred, of the University of Kentucky School of Medicine in Lexington, and colleagues undertook a study to determine how fats in the diet may help prevent colon cancer and slow colon tumor growth. Their research focused on a receptor, peroxisome proliferator-activated receptor gamma (PPARg), that is found in several different cancer types, including colon cancer. Activation of this receptor by currently available drugs has been shown to inhibit the formation of colon cancer in animal models. Furthermore, drugs designed to bind this receptor can slow the growth and even kill the cells. Researchers found that several fatty acids are able to bind to the PPARg in colon cancer cells. Researchers also found that treating colon cancer cells with eicosapentaenoic acid (EPA) slows their growth. These findings demonstrate, for the first time, that EPA is capable of binding to a receptor within colon cancer cells. This study was funded by the National Institutes of Health and the U.S. Department of Defense.
Neoplasia of Endocrine Tissues (including Thyroid) OR53-6 “Aggressive Palliation” as a Treatment Strategy for Metastatic Differentiated Thyroid Carcinoma. Anne M Rosenberg*1, Julie E Hallanger Johnson1, Fusun Toruner1, Ian D Hay1, Bryan McIver1. 1Div of Endocrinol, Mayo Coll of Med, Rochester, MN. Distant metastatic spread is common in the Follicular (FTC) and Hurthle cell (HCC) subtypes of Follicular thyroid carcinoma. Treatment is limited to surgery for the primary tumor and radioactive iodine for metastases, while systemic chemotherapy has proven disappointingly ineffective. Unfortunately, a significant proportion of metastases fail adequately to concentrate I-131, making the disease incurable in many cases. Nevertheless, the mean life expectancy for Stage IV disease is close to 5 years for both FTC and HCC. During that time, growth of metastatic deposits may cause significant morbidity and can accelerate mortality, through impaired organ function. Methods: Review of the medical records of patients with metastatic FTC and HCC diagnosed between 1995 and 2000. Results: Thirty-four patients were diagnosed with metastatic disease from FTC (n=22) or HCC (n=12) during the 5-year study period, 18 (51%) at the time of diagnosis of the primary malignancy. Patient age at diagnosis was 58 ± 17 years, and 13 (34%) were female. There were a total of 6 metastatic sites in these patients, dominated by lung (23 patients) and bone (20 patients), and including brain (6 patients), liver (3 patients), adrenal (2 patients) and retroperitoneum (2 patients). All patients underwent near-total or total thyroidectomy and all were initially treated with high dose I-131, with failure of iodine concentration in the majority of metastatic sites. Fourteen patients underwent external beam irradiation to 18 metastatic sites (10 skeletal, 4 brain and 4 other), with effective palliation of symptoms in all patients. Twelve patients underwent 22 surgeries for removal of metastatic deposits (13 skeletal, 2 brain and 7 other sites), with effective palliation of symptoms. One patient has undergone a total of 10 surgeries for threatening or symptomatic metastases, and remains asymptomatic 5 years after diagnosis. Life expectancy was similar in the group of patients who underwent palliative treatment and those who did not. However, symptom control was achieved effectively in the palliated group. Conclusion: Aggressive palliation is a viable management strategy, while awaiting development of effective alternative systemic therapy for patients with metastatic Follicular and Hurthle cell carcinoma of thyroid in whom I-131 is no longer effective. CLINICAL - Neoplasia of Endocrine Tissues (11:15 AM - 12:45 PM) Presentation Date: 6/7/2005 Time: 12:30:00 PM Location: 32 A-B
Neoplasia of Endocrine Tissues (including Thyroid) OR53-6 News Summary Quality of life can be improved with terminal thyroid cancer patients Aggressive treatment of terminal thyroid cancer may not defeat the cancer but it can be useful to manage symptoms, according to a study being presented on Tuesday, June 7, at The Endocrine Society’s 87th Annual Meeting in San Diego. Researchers believe that this is the best course of action while more therapies are being developed for patients with certain types of metastatic thyroid cancers in which radioactive iodine is no longer effective. Cancer of the thyroid gland is a rare cancer that can affect people at any age. The initial treatment for all patients with thyroid cancer is surgery to remove the thyroid gland and the cancer. Because thyroid cells, including some thyroid cancers, can absorb and concentrate iodine, many patients also receive treatment with radioactive iodine to try to destroy any remaining thyroid cancer cells. For most patients, particularly those younger than 45 years old, this combination of treatments is very effective, and most young people who develop thyroid cancer live a normal life span. Follicular thyroid cancer and Hurthle cell cancer, which together make up about 10 percent to 15 percent of all thyroid cancers in the United States, tend to occur in somewhat older patients. Follicular cancer can metastasize, or spread, into blood vessels and then to distant areas, particularly the lungs and bones. Unfortunately, for those cancers that cannot absorb and retain radioactive iodine, no options currently exist for effective chemotherapy. Consequently, most such patients suffer the consequences of progressive tumor growth, invasion and spread, and ultimately die of their thyroid cancer. In a five-year study, Drs. Anne Rosenberg and collegues at Mayo College of Medicine in Rochester, Minn., reviewed the medical records of 34 patients with metastatic follicular (FTC) and HCC diagnosed between 1995 and 2000. The average age at diagnosis was 58 years. More than half the patients had metastatic disease at the time of diagnosis, while the remainder developed the metastases at a later date. The most common involved sites were the lungs and bones. In those sites, most of the tumors did not respond to radioactive iodine treatment. Fourteen patients were treated with external radiation therapy, with an effective decrease in symptoms in these patients. Twelve patients underwent a total of 22 surgeries for removal of metastatic disease. These surgeries improved symptoms in most cases. Life expectancy was similar in the group who underwent the more aggressive treatment with surgery and radiation when compared to the group who did not. However, symptom control was more effective in the aggressively treated group. The authors recommend an approach of “aggressive palliation,” managing the symptoms of the disease, while awaiting the development of more effective systemic treatments.
Thyroid P1-577 Weight Gain during the Treatment of Thyrotoxicosis. Manjusha S Rathi*1, Paul E Jennings1, Jeremy Miles2. 1Ctr for Diab & Endocrinol, York District Hosp, York, UK; 2Dept of Hlth Sci, Univ of York, York, UK. Patients often lose considerable weight prior to the diagnosis of thyrotoxicosis. Regaining weight with initial treatment of thyrotoxicosis until hormone levels normalise is expected. This study was to determine whether patients continued to put on weight once their biochemistry had returned to euthyroid levels. The records of 60 consecutive euthyroid patients were studied. All patients were continued to be treated with a dose titration regime of thyrostatic medication and had been rendered euthyroid. Patients on a block and replacement regime were excluded, as were patients with other diagnoses to cause weight gain, such as pregnancy. Any patients that had at any time become hypothyroid (TSH >4) were also excluded. Patient characteristics were as follows: This weight gain was not related to the patient’s age at presentation, gender, duration or dose of treatment required to initially achieve euthyroidism. However a diagnosis of Graves’ disease or non-smoking status independently predicted the weight gain. In conclusion patients gain weight for further six months on thyrostatic drugs when biochemically euthyroid. Preventing this weight gain by incorporating dietary advice or other interventions warrants further investigation. CLINICAL - Thyroid I (11:00 AM - 12:00 PM and 2:30 PM - 3:30 PM) Presentation Date: 6/4/2005 Time: 12:00:00 AM Location: Exhibit Hall
Thyroid P1-577 News Summary Weight gain is common in treatment of hyperthyroidism but stabilizes after treatment Weight gain is common in treatment of hyperthyroidism — an overactive thyroid — and patients with the condition should be advised that weight gain will occur even after normalizing thyroid function, according to a study to be presented Saturday, June 4, at The Endocrine Society’s 87th Annual Meeting in San Diego. However, six months later weight stabilizes, and many patients lose weight. Hyperthyroidism, also known as thyrotoxicosis, is a common disorder with annual incidence of one to two in 1000, and it is five to 10 times more common in females, with a prevalence of 2.7 percent in females. The condition is due to excessive production of thyroid hormone secreted by thyroid gland, which can be detected by a blood test. Thyroid hormone excess increases the body’s metabolic rate resulting in weight loss. There are three different treatment options. Usually the first-line treatment is thyrostatic medication, which reduces the production of thyroid hormone; second, there is radioiodine therapy, which slowly destroys the thyroid gland, often resulting in hypothyroidism, or an underactive thyroid; and the third option is surgery, in which part or all of the thyroid gland is removed. This, too, can lead to hypothyroidism, and patients gain weight. During treatment of hyperthyroidism, it is expected that patients will regain the weight they have lost prior to diagnosis and treatment. However, during the treatment, many patients are concerned about the weight gain which, on occasion, may result in non-compliance to treatment, exposing them to the risks associated with excess thyroid hormone, such as heart failure and osteoporosis. Dr. Manjusha S. Rathi, of York Hospital in York, United Kingdom, and other colleagues in York examined 60 patients whose thyroid hormone level was maintained within normal range for at least six months with medication alone. They monitored their weight at three months, six months, and nine months while they worked toward euthyroidism, or normal thyroid function. The study group excluded patients who received surgery or radioiodine as well as any patients with other condition that can affect weight, such as pregnancy and steroid therapy. The study team found that patients gain weight from start of treatment until their thyroid hormone level is brought within normal reference range. As researchers expected, the average weight gain was 4 kg, or 8.8 pounds. They also noticed that patients continued to gain weight for another six months after becoming euthyroid, after which, however, their weight plateaued and often began to decrease. The additional weight gain was 2 kg, or 4.4 pounds. They found that the weight gain was not related to patient’s age, gender, or duration of treatment. Patients who smoked gained less weight. Researchers advise that patients should be informed that the weight gain is likely the result of normalizing thyroid function and is not due to them becoming hypothyroid. This advice may improve compliance with treatment.
Thyroid P1-591 Grave’s Hyperthyroidism Is Radio-Resistant in African American (AA) Women Compared to Anglosaxon Women (W). Amanda Cunningham*1, Edward Staab1, Jorge Calles-Escandon1. 1Intern Med; 2Nuclear Med; 3Endocrinol and Metab, Wake Forest Univ Hlth Scis, Winston Salem, NC. Graves’ disease is the most common cause of hyperthyroidism and affects predominantly women. The most popular approach to treatment in the USA is radioablation (RAI) of the thyroid gland, a procedure with a 80-90% cure rate with a single dose of radioactive iodine. However, no information exists in the literature if the same degree of therapeutic success can be achieved amongst different racial groups. PURPOSE METHODS RESULTS CONCLUSIONS CLINICAL - Thyroid I (11:00 AM - 12:00 PM and 2:30 PM - 3:30 PM) Presentation Date: 6/4/2005 Time: 12:00:00 AM Location: Exhibit Hall
Thyroid P1-591 News Summary African-American women may need higher dose of treatment to fare as well as Caucasian in hyperthyroidism African American women do not fare as well as Caucasian women when it comes to treatment for Graves’ Disease, according to a new study being presented on Saturday, June 4, at The Endocrine Society’s 87th Annual Meeting in San Diego. Graves’ Disease is an autoimmune disorder of the thyroid gland resulting in clinical hyperthyroidism, or an over-active thyroid. Autoantibodies attack the thyroid gland leading to an excess of thyroid hormone. In the United States, ablation of the thyroid gland with radioactive iodine (RAI) is the primary treatment of choice. Current literature supports approximately a 10 percent to 20 percent failure rate with RAI in Graves’ Disease. Currently, there is no reported literature on racial differences in response to RAI in Graves’ Disease. Therefore, Dr. Amanda Cunningham, of Wake Forest University Health Sciences in Winston Salem, NC, and colleagues conducted a retrospective analysis of patients with the diagnosis of Graves’ hyperthyroidism and who had treatment with RAI. Fifty-five patients, including 34 Caucasian and 21 African Americans, were studied. Participants in the study had to be female, older than 18, diagnosis of Graves’ disease, treatment with RAI, and undergo follow up at one year. Patients were evaluated for the dose of RAI, success or failure of treatment, and time to success. The researchers found that African-American women have a higher rate of failure to RAI compared to Caucasion women. In addition, African-American women with therapeutically successful RAI received a higher dose. The findings, say researchers, could potentially affect the dosing of RAI to treat Graves’ Disease, with aim of preventing failures to the initial dose of RAI.
Thyroid, Retinoid & Non-steroid Nuclear Receptors P3-334 Topical Thyroid Hormone Accelerates Wound Healing in Mice. Joshua D Safer*1, Tara M Crawford1, Michael F Holick1. 1Sect of Endocrinol/Dept of Med, Boston Univ Sch of Med, Boston, MA. Although the physiologic role of thyroid hormone in skin is not well understood, mounting evidence suggests that triiodothyronine (T3) plays an important role in epidermal proliferation. The goal of this project was to evaluate whether the topical application of supra-physiologic doses of T3 could accelerate wound healing. We evaluated mice treated with topical T3 versus mice receiving vehicle alone (Novasome A). Ten mm diameter (79 mm2) dorsal skin wounds were established on all animals and wounds were re-measured 4 days following injury. Daily topical application of 150 ng T3 accelerated wound healing by 72% relative to wounds on animals receiving vehicle alone (p<0.005). Further, we determined that wound healing associated keratin 6 protein expression in hair follicle keratinocytes increased in a dose dependent manner in vivo during topical T3 treatment. When the topical T3 was not placed directly on the wounds, no healing acceleration was seen. Also, when T3 was injected into the mice, healing was not accelerated relative to control mouse healing. The data support our previous hypothesis that T3 is necessary for optimal wound healing. Now, we further suggest that topical thyroid hormone may be an inexpensive agent to hasten healing of certain wounds. BASIC - Thyroid Hormone Receptor, Retinoids & Nonsteroid Nuclear Receptors (11:00 AM - 12:00 PM and 2:30 PM - 3:30 PM) Presentation Date: 6/6/2005 Time: 12:00:00 AM Location: Exhibit Hall
Thyroid, Retinoid & Non-steroid Nuclear Receptors P3-334 News Summary Topical thyroid hormone may be potent, inexpensive wound healer The thyroid hormone, triiodothyronine, or T3, is a powerful, inexpensive wound healer when applied directly to wounds, according to a study of mice being presented on Monday, June 6, at The Endocrine Society’s 87th Annual Meeting in San Diego. The researchers emphasize that the study represents the first demonstration that topical thyroid hormone may prove to be a useful wound-healing agent, which may have future treatment potential for the growing number of diabetics, in whom wound healing is compromised because of the disease. The thyroid is a walnut-size organ that sits in the neck and controls how the body uses energy. The thyroid exerts its control by means of thyroid hormone, a chemical that is released into the bloodstream to travel throughout the body directing cells in their energy use and growth patterns. Physicians have long known that thyroid disease causes striking changes in skin and that thyroid hormone must be important for normal skin cell growth. However, the specific action of thyroid hormone on skin has not been studied in detail. In addition, poor wound healing is a major problem in general and is one of the most debilitating aspects of the rampant diabetes epidemic. However, current topical wound healing agents are expensive and underused. Dr. Joshua D. Safer, of Boston University School of Medicine in Boston, and colleagues have previously found that topical thyroid hormone stimulates the growth of skin and hair in mice. For these reasons, the researchers evaluated mice treated with topical T3 cream and mice treated with the same cream without T3. Standard skin wounds were established on all animals and wounds were re-measured four days following injury. Daily topical application of T3 cream accelerated wound healing by 72 percent compared to wounds on animals receiving cream without T3. When the topical T3 was not placed directly on the wounds or when it was injected into the mice, no healing acceleration was seen. These findings show that topically applied T3 dramatically accelerates wound healing in mice. As for its potential use in people, researchers note that thyroid hormone is not only one of the most potent stimulators of cell growth but also inexpensive. This study was supported by Abbott Pharmaceuticals–sponsored Thyroid Research Advisory Council and the Evans Foundation at Boston University School of Medicine.
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