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Purpose: Binge eating disorder (BED) is a prevalent eating disorder. Many individuals with BED do not receive evidence-based care due to many barriers. This preliminary study evaluated the feasibility, acceptability, and potential efficacy of a manualized guided self-help (GSH) intervention with support in the form of a culturally adapted manual for a French-Canadian population. Method: Twenty-two women with overweight or obesity meeting the BED diagnostic criteria participated in an 8-week open trial. The GSH programme combined a self-help book and weekly support phone calls. Participants were assessed at baseline, at week 4, postintervention, and 12 weeks following its end. Feasibility was measured by attrition rates, participation, and satisfaction. Acceptability was measured by a questionnaire based on the Theoretical Framework of Acceptability. Potential efficacy outcomes were objective binge eating days, eating disorder symptomatology, depressive symptoms, and propensity to eat intuitively. Results: The GSH programme has proven feasible (4.5% attrition, 91% completion, 95.5% satisfaction) and acceptable. Potential efficacy results showed promising improvements on all outcomes (19% abstinence, 70.9% reduction in objective binge eating days). Conclusion: Although preliminary, this programme warrants further study as it may be an efficient and cost-effective way to deliver GSH for BED patients with accessibility barriers.

Background and Aims: To compare the effect of a low-volume walking high-intensity interval training (HIIT) to moderate-intensity continuous training (MICT) on risk of cardiovascular diseases and physical capacity in older women with type 2 diabetes (T2D)., Methods: Thirty inactive older women with T2D were randomized into either HIIT (75 min/week) or MICT (150 min/week). Cardiovascular risk profile (lipid profile; waist circumference and fat mass; resting, post-exercise and ambulatory blood pressure [BP]; VO 2 peak; UKPDS score; ABC's) and physical capacity were assessed before and after a 12-week intervention., Results: While resting systolic and diastolic BP (all p ≤ 0.01) were reduced, ambulatory BP (p ≥ 0.49) and lipid profile (p ≥ 0.40) remained unchanged after the intervention. Although VO 2 peak increased to a similar extent in both groups (p = 0.015), the distance covered during the 6MWT (p = 0.01) and grip strength (p = 0.02) increased to a greater extend in HIIT. The UKPDS risk score decreased in both groups after the intervention (p = 0.03) and 31% of the participants reached the ABC's compared to 24% at baseline., Conclusion: Low-volume walking HIIT is an efficient exercise intervention for older women with T2D as it improved some CVD risk factors and physical capacity. Nevertheless, neither low-volume HIIT nor MICT is sufficient to affect ambulatory blood pressure in T2D patients., Competing Interests: Declaration of competing interest The present manuscript is not under consideration elsewhere, has not previously been published, and has been approved by all authors. Moreover, the authors declare no conflict of interest. The authors declare no conflict of interest., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: The "Life's Simple 7" (LS7) metrics were developed by the American Heart Association (AHA) to assess and promote cardiovascular health in the American population. The purpose of this study was to assess the overall cardiovascular health of French-speaking adults from the Province of Quebec using the LS7 score., Methods and Results: A total of 777 age and sex-representative participants of five different administrative regions in the Province of Quebec (387 men and 390 women; mean age ± SEM: 41.9 ± 0.1 years) were included in these analyses. Metrics of the LS7 score (smoking, physical activity, diet, body mass index, blood pressure, fasting total cholesterol and blood glucose) were analysed to generate a final score ranging from 0 to 7. Only 0.5% of participants met all criteria for ideal cardiovascular health. The diet metric showed the lowest prevalence of "ideal" scores (4.8%) whereas not smoking was the metric with the highest prevalence (88.1%). Women had a higher LS7 score than men, while age and education level (negative and positive association, respectively; p < 0.0001) were also associated with the LS7 score., Conclusion: Consistent with studies conducted among other populations, very few French-speaking adults from the Province of Quebec achieve an ideal cardiovascular health. These data indicate that further public health efforts aimed at promoting the LS7 metrics, focusing primarily on diet, are urgently needed. Specific groups, including older adults and those with lower levels of education, should be targeted when developing cardiovascular health promotion interventions., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess: 1-the spousal concordance of lifestyle and anthropometric characteristics between partners of infertile couples in which the woman is obese; and 2-in men, the influence of these characteristics on their conventional seminal parameters., Design: Cross-sectional study., Setting: Fertility clinic of the Centre hospitalier universitaire de Sherbrooke, Canada, between January 2012 and February 2015., Patients: 97 infertile heterosexual couples in which women were obese and seeking fertility treatments., Intervention: Not applicable., Main Outcome Measures: Weight and percentage of fat mass were evaluated using a scale with foot-to-foot bio-impedance. Abdominal obesity was estimated with waist circumference and lifestyle habits, by a self-reported questionnaire. Seminal parameters were analysed and collected according to the WHO guidelines (Kruger's strict criteria for seminal morphology)., Results: There was a significant spousal concordance for the percentage of fat mass, leisure activities and overall nutritional quality. Accordingly, male participants displayed anthropometric and lifestyle characteristics at higher risk than Canadian men of similar age. Moreover, BMI, daily consumption of fruits & vegetables and sleeping hours in men were independently associated to the total motile sperm count., Conclusion: This is the first study to report concordance for anthropometric and lifestyle characteristics between partners of infertile couples in which the woman is obese. These characteristics in men were more adverse than in the general population and were associated with reduced sperm quality. Altogether, our results suggest that male partners of infertile couples could benefit from participating in the lifestyle intervention that is already recommended for their spouse affected by obesity., Capsule: Because partners of subfertile couples in which the woman is obese share adverse anthropometric and lifestyle characteristics, male partners should be implicated in lifestyle interventions already indicated for their spouse., (Copyright © 2019 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

The main purpose of this study was to determine the association between the 6-min walk test distance (6MWTD) and physical functional capacity (PF) in primary care patients, as well as in obese individuals. We studied 351 subjects (age=56.8±14.6 years; BMI=29.4±5.7 kg/m(2); 68% women), including 141 obese subjects (BMI≥30 kg/m(2)), recruited in 10 different family practices. Physical (PCS) and mental component summary of the health-related quality of life (HRQOL) and the 8 sub-scores were measured using the Short Form-36 Health Survey. Anthropometry, vital signs and physical testing were measured according to standardized protocols. Recreational physical activity (LPA) and sedentary levels were determined using the Canadian Community Health Survey. In a stepwise multivariate analysis, 65% of the 6MWTD variance was explained by PF of the HRQOL, age, quadriceps strength, number of chronic diseases, LPA categories, BMI, resting heart rate, PCS, height and TV-viewing categories in primary care subjects. In the obese individuals, PF, age, quadriceps strength and BMI explained 57% of the 6MWTD variance. In these 2 groups, 44% of the 6MWTD variance is explained by PF only. To conclude, the 6MWTD is strongly associated with PF of the HRQOL. Thus, it adequately reflects physical limitations in daily life activities of primary care patients, including obese individuals., (© Georg Thieme Verlag KG Stuttgart · New York.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The objective of this systematic review was to appraise current knowledge on the impact of physical activity (PA) and physical fitness (PF) on the health of class II and III obese subjects and bariatric surgery (BS) patients. All original studies were searched using four databases (Medline®, Scopus®, CINAHL and Sportdiscus). Two independent investigators selected studies assessing the impact of PA or PF on specific health outcomes (anthropometric parameters, body composition, cardiometabolic risk factors, PF, wellness) in adults with a body mass index ≥35 kg m(-2) or in BS patients. Conclusions were drawn based on a rating system of evidence. From 3,170 papers identified, 40 papers met the inclusion criteria. The vast majority of studies were recently carried out with a predominance of women. Less than one-third of these studies were experimental and only three of them were of high quality. Each study reported at least one beneficial effect of PA or PF. However, a lack of high-quality studies and heterogeneity in designs prevented us from finding high levels of evidence. In conclusion, although results support the importance of PA and PF to improve the health of this population, higher-quality trials are required to strengthen evidence-based recommendations., (© 2014 The Authors. obesity reviews © 2014 International Association for the Study of Obesity.)

The aim of the study was to evaluate the influence of weight gain and changes in adiposity distribution on insulin resistance and circulating adiponectin variations over 4 years in free-living normal weight young adults. In this prospective observational cohort (n=42 women, 18 men), anthropometric measurements and blood samples were collected in the fasting state at baseline and at 4 years. Insulin resistance was estimated using the homeostatic model assessment (HOMA-IR). Circulating adiponectin levels were determined by radioimmunoassay. To investigate increase in adiposity more specifically, subsidiary analyses were performed in a subgroup of individuals (n=31) who gained adiposity over the course of the 4-year follow-up (defined as gain >1% in percent body fat). Regression analyses were performed to adjust for sex, age, parental education, lifestyle, and fitness levels. At baseline, the participants were young adults (age=20.0 years old) in the normal weight range [body mass index (BMI)=22.7 kg/m2 (IQR=21.1-24.4)]. Median change in body fat percentage was +1.4% (IQR=-0.3-3.4; p=0.01) and in waist circumference was +1.2 cm (IQR=-2.6-5.3; p=0.05). In the subgroup of individuals who gained more than 1% body fat, increase in HOMA-IR was associated with an increase in BMI (r=0.44; p=0.01; p<0.01 in fully adjusted model), while decrease in adiponectin levels was associated with an increase in waist circumference (r=-0.38; p=0.03) but this was no longer significant after adjustment for sex and other potential confounders (p=0.14). In a population of young adults, small variations in adiposity within the normal weight range were associated with increase in insulin resistance., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Over 70% of people who undergo bariatric surgery (BS) develop excess skin (ES). The physical and psychosocial consequences of ES may become a barrier to the practice of physical activity (PA), which is highly recommended to optimize the results of BS. The purpose of this study was to evaluate the impact of ES on the practice of PA in women who have undergone BS., Methods: Questionnaires administered to 26 women having undergone BS 2 ± 0.2 years before (BMI = 29.1 ± 0.8 kg/m2) evaluated the impacts of ES, the practice of PA, physical self-perception, and physical exercise beliefs. We also used the 6-min walking test and muscular endurance tests to evaluate physical fitness and photographs with anatomical markers to quantify ES., Results: Of the women, 76.9% declared mobility limitations due to ES during the practice of PA and 45.2% stated avoiding PA because of ES which caused flapping and unwelcome stares from others. The women who stated that they avoided PA because of ES had significantly lower physical self-perception and physical fitness and reported experiencing more embarrassment during PA despite no significant difference in the magnitude of ES (p = 0.06), BMI, daily life inconveniences, and energy expenditure compared to those women who did not avoid PA., Conclusion: Although ES after BS is a barrier to the practice of PA for some women, it does not in itself prevent the regular practice of PA. The main reason women with ES avoid PA seems to have less to do with the magnitude of ES itself and more with psychosocial inconveniences.

Background: To optimize bariatric surgery results, experts recommend regular practice of physical activity. However, no precise recommendations are available for the pre-surgical period. We aimed to evaluate, in this pilot study, the feasibility of a supervised Pre-Surgical Exercise Training (PreSET) and its short-term clinical impacts in subjects awaiting bariatric surgery., Methods: In addition to the usual interdisciplinary lifestyle management, eight women and four men [40.8 (37.6-47.5) years old, BMI = 51.4 (43.8-53.1) kg/m(2)] underwent the PreSET, which combined both endurance and strength training. They were instructed to perform three physical activity sessions per week during 12 weeks, with at least two sessions per week on site and the possibility to complete missed sessions at home. Before and after the PreSET, anthropometric measures, body composition, physical fitness, quality of life, and physical exercise beliefs were assessed., Results: The subjects participated in 57.3 % of the total supervised exercise sessions proposed and presented high satisfaction rates. Our program resulted in a significant improvement in weight (p = 0.007), physical fitness (p ≤ 0.05), and quality of life score (p = 0.012) as well as for the emotions, social interactions, and sexual life subscales (p < 0.03). Fear of injury (p = 0.028) and embarrassment during physical activity (p = 0.028) were significantly decreased, whereas no significant change in confidence in athletic ability and in beliefs in exercise benefits were noticed after the program., Conclusions: PreSET is feasible in subjects awaiting bariatric surgery and, combined with an interdisciplinary management, results in several short-term benefits.

Aim: To compare the effectiveness and cost of two lifestyle-modification programmes in individuals at high risk of developing type 2 diabetes., Methods: Forty-eight men and women with a body mass index ≥27 kg/m(2) and prediabetes were randomly assigned to either a 1-year interdisciplinary intervention including individual counseling every 6 weeks and 25 group seminars (group I; n=22) or a group intervention comprising seminars only (group G; n=26). These interventions were compared in terms of weight loss and improvement of anthropometric measures, metabolic variables and costs., Results: Participants in group I lost an average of 4.9 kg (95% CI: -7.3, -2.4; P<0.01) and 5 cm in waist circumference (95% CI: -7.0, -3.0; P<0.01), whereas no significant change was noted in those assigned to group G. Among the participants in group I, 50 and 27% lost at least 5 and 10% of their initial weight, respectively, compared with only 12 and 4%, respectively, in group G. Fasting glucose, 2-hour glucose and lipid profiles improved significantly in group I, and no participant (zero on 22) developed diabetes compared with 11.5% (3/26) in group G. Most participants (nine on 11) with impaired fasting glucose in group I returned to normal. The direct cost of the individual intervention was estimated to be $733.06/year per subject compared with $81.36/year per subject for the group intervention., Conclusion: This study demonstrates that a low-cost, moderate-intensity, individual interdisciplinary approach combined with group seminars leads to clinically significant weight loss and metabolic improvement in people with prediabetes. Group seminars alone were not effective in this population (www.ClinicalTrial.gov, Identifier: NCT00991549)., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The six-minute walk test (6MWT) is an inexpensive, quick and safe tool to evaluate the functional capacity of patients with heart failure and chronic obstructive pulmonary disease. The aim of this study was to determine the reproducibility of the 6MWT in overweight and obese individuals. We thus undertook a prospective repeated-measure validity study taking place in our academic weight management outpatient clinic. The 6MWT was conducted twice the same day in 21 overweight or obese adult subjects (15 females and 6 males). Repeatability of walking distance was the primary outcome. Anthropometric measures, blood pressure and heart rate were also recorded. Participant's mean BMI was 37.2+/-9.8 kg/m(2) (range: 27.0-62.3 kg/m(2)). Walking distance in the morning (mean=452+/-90 m) and in the afternoon (mean=458+/-97 m) were highly correlated (r=0.948; 95% Confidence Interval 0.877-0.978; p<0.001). Walking distance was negatively correlated with BMI (r=-0.47, p=0.03), waist circumference (r=-0.43, p=0.05) and pre-test heart rate (r=-0.54, p=0.01). Our findings indicate that the 6MWT is highly reproducible in obese subjects and could thus be used as a fitness indicator in clinical studies and clinical care in this population., (Georg Thieme Verlag KG Stuttgart New York.)

Objectives: This study aims to evaluate clinical practice of primary care physicians regarding common thyroid disorders., Materials and Methods: A sample of 210 primary care physicians was randomly selected in three Quebec's administrative regions. Four clinical vignettes (V1 to V4) were presented by mail: two cases of subclinical hypothyroidism (women of 25 years - V1 - and 70 - V2 - years of age) for which physicians had to choose to either treat or not with thyroid replacement and two cases of hyperthyroidism (women of 30 - V3 - and 66 - V4- years of age) for which they had to choose a course of action (observation, treatment or referral to a specialist). V1 and V2 where followed by four sub-questions presenting supportive elements that could influence the decision to treat (presence of antithyroid antibodies, accumulation of symptoms, LDL cholesterol and thyreostimulin levels)., Results: The overall response rate was 22%. Forty-two percent of respondents would have treated V1 outright and 49% would have treated V2. The therapeutic approach in the face of these two vignettes, independently of the presence or absence of supportive clinical or biochemical elements, did not vary according to geographic practice area. However, one region was significantly more conservative for V4. The number of years in practice or assistance to continuous medical education activities did not affect management of vignettes., Conclusion: This study outlines the importance of clinical practice guidelines and tools to facilitate their application in clinical management of thyroid disorders.

We summarize here the studies examining the association between thyroid function and cognitive performance from an aging perspective. The available data suggest that there may be a continuum in which cognitive dysfunction can result from increased or decreased concentrations of thyroid hormones. Clinical and subclinical hypothyroidism as well as hyperthyroidism in middle-aged and elderly adults are both associated with decreased cognitive functioning, especially memory, visuospatial organization, attention, and reaction time. Mild variations of thyroid function, even within normal limits, can have significant consequences for cognitive function in the elderly. Different cognitive deficits possibly related to thyroid failure do not necessarily follow a consistent pattern, and L-thyroxine treatment may not always completely restore normal functioning in patients with hypothyroidism. There is little or no consensus in the literature regarding how thyroid function is associated with cognitive performance in the elderly.

Objective: Prevention would be the ideal public health strategy to face the current obesity epidemic. Adoption of healthy lifestyles during the first years of college or university could prevent the onset of weight gain associated with this period of acquired independence and eventually decrease the incidence of obesity., Design: Randomized-controlled trial over a period of 2 years. The subjects received an educational/behavioral intervention (small group seminars) designed to help maintain a healthy lifestyle or no specific intervention (control group)., Subjects: One-hundred and fifteen non-obese freshmen in a Faculty of Medicine., Measurements: Anthropometric measurements, physical activity level, fitness level, food intake and lipid profile were recorded at predetermined intervals., Results: The control group gained weight, whereas the intervention group lost a slight amount of weight over 2 years. The difference between the two groups was 1.3 kg at the end of the follow-up, the trend of weight gain differing between the two groups during the 2-year intervention period (P=0.04). There was no detectable difference in fitness, physical activity level or total caloric intake between the two groups during follow-up. However, plasma triglyceride levels increased in the control group and decreased in the intervention group (P=0.04)., Conclusion: In this randomized-controlled trial, a small-group seminar educational/behavioral intervention successfully prevents weight gain in normal weight young healthy university students. Such small absolute changes in body composition and lipid profile, if maintained over a prolonged period, could result in significant long-term health benefits for the general population.

Obesity has now reached epidemic proportions. Epidemiological studies in the past decades have shown that adults gain weight and adiposity from the early twenties until their sixties. In the paediatric population, growing numbers of children and adolescents put on unhealthy weight. Many environmental, socio-economical and biological determinants that predispose to weight gain have been identified thus far. The aim of the present review is to summarize the current knowledge on the role of the circulating levels of adipokines and other entero-insular hormones and biological markers of obesity to predict weight gain in humans. The review focuses on relationship between hormonal and biochemical markers (insulin, insulin-like growth factors, gastrointestinal hormones, leptin, adiponectin, resistin, inflammatory proteins and cytokines) and weight gain in prospective studies. The complex relationships displayed by these hormonal factors with future weight gain in humans are critically reviewed and integrative models are proposed. Overall, most of the studies reported to date made adjustments for baseline body mass index but failed to consider dietary intake and physical activity as confounding factors. Outstanding questions are raised and new directions for future prospective studies are proposed in order to improve our understanding of the role of biological determinants of energy balance and development of obesity in humans.

Resistance to thyroid hormone (RTH) is a syndrome caused by a mutation in the carboxyl-terminal domain of the thyroid hormone receptor beta (TRbeta) gene. 3,5,3'-triiodothyroacetic acid (Triac) has been used on an empirical basis to treat RTH but its efficacy is still controversial. In previous studies, we demonstrated that Triac has TR isoform- and TRE-specific effects. In this report, we used five natural RTH mutations of the ligand-binding domain in both TRbeta1 and TRbeta2 isoforms for the evaluation of the effect of T3 and Triac on regulation of transcription and binding affinity. We show that Triac has superior activity on negatively and positively regulated promoters and higher binding affinity than T3 for a majority of TRbeta1 and TRbeta2 mutants. However, the difference of transcriptional activity and binding affinity between both ligands is less for RTH mutants than for wild type receptors. These results suggest that Triac could be a potential treatment for RTH patients.

3,5,3'-triiodothyroacetic acid (Triac) is a naturally occurring triiodothyronine (T(3)) analog, which has been used on an empirical basis to treat the syndrome of resistance to thyroid hormone (RTH). The aim of our studies was to compare the effects of Triac and T(3) on negative and positive thyroid hormone response elements (TREs). We used transient transfections with luciferase reporter genes to show that on palindromic, inverted palindrome and human TRH reporters, Triac is more potent than T(3) for transcriptional regulation by TRbeta1 and TRbeta2 isoforms, while regulation by TRalpha1 is equivalent for both ligands. Other TREs (direct repeat, hTSHalpha and hTSHbeta) are not regulated differently by Triac and T(3). Dose-response curves show that the difference between Triac and T(3) is maximal in the 1-10 nM range. Receptor-binding studies reveal a greater affinity of Triac than T(3) for TRbeta1 and TRbeta2 isoforms, which could explain its isoform-specific effects. These data suggest that the TRE- and TR isoform-specific effects of Triac favor its use in RTH.

Purpose: To report a case of severe coronary artery disease complicating pheochromocytoma, managed with combined coronary artery bypass grafting (CABG) and adrenalectomy., Clinical Features: A 55-yr-old woman presented with poorly controlled hypertension and investigation revealed an active pheochromocytoma of her left adrenal gland. During medical preparation for adrenalectomy, she developed an acute myocardial infarct complicated with unstable angina. This required urgent CABG, and combined surgery for the triple vessels coronary artery disease and the pheochromocytoma was planned. We explain the details of medical preparation before surgery and the anesthetic considerations during the surgical procedure. Postoperative recovery was normal and no complication occurred. Even if the pheochromocytoma was malignant, her urinary catecholamines two months after the surgery were normal and remain normal after more than two years of follow-up., Conclusion: We report a patient who underwent combined CABG and adrenalectomy for pheochromocytoma. The CABG was done first, followed by the adrenalectomy with invasive monitoring. The procedure was well tolerated with cure of the two underlying conditions. So we propose that combined procedure should be considered in this clinical setting.

Negative regulation by thyroid hormone is mediated by nuclear thyroid hormone receptors (TRs) acting on thyroid hormone response elements (TREs). We examine here the role of human TR-beta2, a TR isoform with central nervous system-restricted expression, in the regulation of target genes whose expression are decreased by triiodothyronine (T3). Using transient transfection studies, we found that TR-beta2 achieved significantly greater ligand-independent activation on the thyrotropin-releasing hormone (TRH) and common glycoprotein alpha-subunit genes than either TR-beta1 or TR-alpha1. A chimeric TR-beta isoform containing the TR-beta2 amino terminus linked to the TR-alpha1 DNA- and ligand-binding domains functioned like the TR-beta2 isoform on these promoters, confirming that the amino terminus of TR-beta2 was both necessary and sufficient to mediate this effect. By constructing deletion mutants of the TR-beta2 amino terminus, we demonstrate that amino acids 89-116 mediate this function. This domain, important in ligand-independent activation on negative TREs, is discrete from a previously described activation domain in the amino-terminal portion of TR-beta2. We conclude that the central nervous system-restricted TR-beta2 isoform has a unique effect on negative regulation by T3 that can be mapped to amino acids 89-116 of the amino terminus of the human TR-beta2.

Resistance to thyroid hormone (RTH) is due to mutations in the beta-isoform of the thyroid hormone receptor (TR-beta). The mutant TR interferes with the action of normal TR to cause the clinical syndrome. Selective pituitary resistance to thyroid hormone (PRTH) results in inappropriate TSH secretion and peripheral sensitivity to elevated thyroid hormone levels. Association of the PRTH phenotype with in vitro behavior of the mutant TR has proved elusive. Alternative exon utilization results in two TR-beta isoforms, TR-beta 1 and TR-beta 2, which differ only in their amino termini. Although the TR-beta 1 isoform is ubiquitous, the TR-beta 2 isoform is found predominantly in the anterior pituitary and brain. To date, in vitro evaluation of RTH mutations has focused on the TR-beta 1 isoform. Site-directed mutagenesis was used to create several PRTH (R338L, R338W, V349M, R429Q, I431T) and generalized RTH (delta 337T, P453H) mutations in both TR-beta isoforms. The ability of mutant TRs to act as dominant negative inhibitors of wild type TR-beta function on positive and negative thyroid hormone response elements (pTREs and nTREs, respectively) was evaluated in transient transfection assays. PRTH mutants had no significant dominant negative activity as TR-beta 1 isoforms on pTREs found in peripheral tissues or on nTREs found on genes regulating TSH synthesis. PRTH mutants, in contrast, had strong dominant negative activity on these same nTREs as TR-beta 2 isoforms. Cotransfected retinoid X receptor-alpha was required for negative T3 regulation via the TR-beta 1 isoform but was not necessary for negative regulation via the TR-beta 2 isoform in CV-1 cells. The differing need for retinoid X receptor cotransfection demonstrates two distinct negative T3-regulatory pathways, one mediated by the TR-beta 1 and the other mediated by TR-beta 2. The selective effect of PRTH mutations on the TR-beta 2 isoform found in the hypothalamus and pituitary vs. the TR-beta 1 isoform found in peripheral tissues suggests a molecular mechanism for the PRTH disorder.

In obesity, it is well known that basal growth hormone (GH) levels can be suppressed and they may show an impaired response to various stimuli like hypoglycemia, stress, and GHRH. However, the inhibitory effect of hyperglycemia on GH in this condition has not been well studied. We analyzed the GH response to an oral glucose tolerance test (OGTT) in 25 unselected patients with morbid obesity who were not diabetic, glucose intolerant or affected by renal or hepatic disease. Ten (40%) of the 25 subjects had an abnormal response of GH to the OGTT, expressed by a lack of suppression of GH levels below 2 micrograms/L within 60 minutes of glucose administration. Three subjects even had a paradoxal increase of GH levels of more than 50% of the basal level. There was no significant difference between these subjects regarding their age, BMI and, serum levels of glucose, insulin, C peptide, or insulin/glucose ratio. After weight loss, three of four patients normalized their GH response. Thus, we conclude that patients with morbid obesity frequently have an abnormal response of GH to OGTT (40% vs 4-8% in normal subjects). This finding must be taken into consideration when interpreting GH levels in these patients. A normalization of this response can be expected after weight loss.

A 63-year-old female patient was referred to our hospital in February 1994 for a pituitary tumor. On a previous examination, in 1973, she had a goiter, nonspecific symptoms and only an elevated serum T3. In 1984 she had become hypothyroid, her goiter had increased, serum T4 was 69 nmol/L, TSH 34.4 mU/L, and TPO antibodies were positive. Hypothyroidism due to autoimmune thyroiditis was diagnosed and she received L-T4 100 micrograms/day. In 1985 and 1986, serum TSH had decreased but remained slightly elevated, while T4 was at the upper limits of normal. From 1987 to 1989 her serum TSH rose from 9 to 20 mU/L and remained at that level for the ensuing 4 years in spite of increasing L-T4 up to 150 micrograms/day. In October 1993, after discontinuing L-T4 for 6 weeks, TSH was 23.7 mU/L, T4 170 nmol/L, 131I thyroid uptake 52%, and the CT scan showed a large pituitary tumor with suprasellar extension. On preoperative investigation TSH was 40-51 mU/L with no response to TRH or GnRH. The alpha-subunit was increased at 6.33 micrograms/L with the alpha-TSH/TSH molar ratio of 1.23. Prolactin was elevated, but plasma cortisol, FSH, and LH were low. At surgery, we found a large chromophobe adenoma with few PAS-positive granules and with immunostaining positive for TSH and prolactin. From the clinical and biological data, we can conclude that the patient had probably a TSH-secreting adenoma since the goiter was first detected. The development, however, of autoimmune thyroiditis with hypothyroidism considerably modified the presentation of the disease and may have accelerated the growth of the tumor.

We report a case of rapid 99mTc-methoxyisobutylisonitrile (MIBI) clearance from a parathyroid adenoma. A double-phase 99mTc-MIBI parathyroid scintigraphy was performed on a 62-yr-old female evaluated for primary hyperparathyroidism. A large parathyroid adenoma was visualized caudal to the left lobe of the thyroid gland with an unusually rapid washout of the tracer from tumor tissue. Histologic tissue examination confirmed the presence of a parathyroid adenoma and the absence of oxyphil cells. Care should be taken in interpretation of 99mTc-MIBI parathyroid scintigrams because some adenomas can present a rapid release of the radiotracer in a double-phase study. Technetium-99m-MIBI retention could be related to the number of mitochondria-rich cells in parathyroid adenomas or to hyperplasia.