Profiling retrospective thyroid function data in complete thyroidectomy patients to investigate the HPT axis set point (PREDICT-IT).

BACKGROUND: The homeostatic euthyroid set point of the hypothalamus-pituitary-thyroid axis of any given individual is unique and oscillates narrowly within substantially broader normal population ranges of circulating free thyroxine (FT4) and thyroid-stimulating hormone (TSH), otherwise termed 'thyroid function test (TFT)'. We developed a mathematical algorithm codenamed Thyroid-SPOT that effectively reconstructs the personalized set point in open-loop situations and evaluated its performance in a retrospective patient sample. METHODS: We computed the set points of 101 patients who underwent total thyroidectomy for non-functioning thyroid disease using Thyroid-SPOT on each patient's own serial post-thyroidectomy TFT. Every predicted set point was compared against its respective healthy pre-operative euthyroid TFT per individual and their separation (i.e. predicted-observed TFT) quantified. RESULTS: Bland-Altman analysis to measure the agreement between each pair of an individual's predicted and actual set points revealed a mean difference in FT4 and TSH of + 3.03 pmol/L (95% CI 2.64, 3.43) and - 0.03 mIU/L (95% CI - 0.25, 0.19), respectively. These differences are small compared to the width of the reference intervals. Thyroid-SPOT can predict the euthyroid set point remarkably well, especially for TSH with a 10-16-fold spread in magnitude between population normal limits. CONCLUSION: Every individual's equilibrium euthyroid set point is unique. Thyroid-SPOT serves as an accurate, precise and reliable targeting system for optimal personalized restoration of euthyroidism. This algorithm can guide clinicians in L-thyroxine dose titrations to resolve persistent dysthyroid symptoms among challenging cases harbouring "normal TFT" within the laboratory ranges but differing significantly from their actual euthyroid set points.

Brown fat activity determined by infrared thermography and thermogenesis measurement using whole body calorimetry (BRIGHT Study).

To assess BAT activity in humans at a population level, infrared thermography (IRT) represents a safe, readily repeatable and affordable alternative to 18F-FDG-PET. Building upon a previously proposed method by our laboratory, we further refined the image computational algorithm to quantify BAT activation in the cervical-supraclavicular (C-SCV) region of healthy young men under thermo-neutral and cold exposure conditions. Additionally, we validated the whole-body calorimeter (WBC) in reliably measuring cold-induced thermogenesis. The temperature gradient between C-SCV-deltoid regions, and the corresponding difference in heat power output, increased upon cold air exposure relative to thermo-neutral conditions (by 74.88 %, p<0.0001; and by 71.34 %, p<0.0001 respectively). Resting and cumulative energy expenditure (EE) rose significantly (by 13.14 % and 9.12 % respectively, p=0.0001) while positive correlations between IRT measures and EE were found with cold air exposure (percentage change in heat power gradient between ROI and deltoid, cold air: r(2)=0.29, p=0.026, Pearson's correlation). IRT and WBC can be used to study BAT activation. The refined algorithm allows for more automation and objectivity in IRT data analysis, especially under cold air exposures.

Associations of physical activity levels and screen time with oral glucose tolerance test profiles in Singaporean women of reproductive age actively trying to conceive: the S-PRESTO study.

AIM: To examine the associations of physical activity and screen time, a proxy for sedentary behaviour, with fasting and post-load glucose levels in Singaporean women enrolled in a multi-ethnic Asian preconception study. METHODS: Moderate and vigorous physical activity and screen time (television and other electronic devices) were self-reported by women enrolled in the S-PRESTO cohort. Fasting, 30-min and 120-min glucose levels before and during a 75-g oral glucose tolerance test were measured. Associations of physical activity and screen time with glucose levels were analysed using multivariable linear marginal regression. RESULTS: A total of 946 women aged 31.4±3.7 years were examined, of whom 72% were of Chinese, 15.5% were of Malay, 9.3% were of Indian and 3.2% were of mixed ethnicity. A total of 32% of women reported being active, 36% watched television ≥2 h/day and 26% used electronic devices ≥3 h/day. In adjusted models, vigorous, but not moderate, physical activity was associated with lower overall glucose levels, and was associated more strongly with post-challenge than fasting glucose levels. Compared to women not engaging in vigorous physical activity, those engaging in physical activity ≥75 min/week had lower mean fasting [-0.14 (95% CI -0.28, -0.01) mmol/l], 30-min [0.35 (95% CI -0.68, -0.02) mmol/l] and 120-min [-0.53 (95% CI -0.16, -0.90) mmol/l] glucose levels (overall P value=0.05). We found no associations of screen time with glucose levels. CONCLUSIONS: Independently of the time spent in non-vigorous physical activity and using screens, engaging in vigorous physical activity may be a modifiable factor to improve glucose regulation in women of Asian ethnicity who are attempting to conceive.

Oxytocin in metabolic homeostasis: implications for obesity and diabetes management.

Oxytocin was once understood solely as a neuropeptide with a central role in social bonding, reproduction, parturition, lactation and appetite regulation. Recent evidence indicates that oxytocin enhances glucose uptake and lipid utilization in adipose tissue and skeletal muscle, suggesting that dysfunction of the oxytocin system could underlie the pathogenesis of insulin resistance and dyslipidaemia. Murine studies revealed that deficiencies in oxytocin signalling and oxytocin receptor expression lead to obesity despite normal food intake, motor activity and increased leptin levels. In addition, plasma oxytocin concentration is notably lower in obese individuals with diabetes, which may suggest an involvement of the oxytocin system in the pathogenesis of cardiometabolic disease. More recently, small scale studies demonstrated that intranasal administration of oxytocin was associated with significant weight loss as well as improvements in insulin sensitivity and pancreatic ß-cell responsivity in human subjects. The multi-pronged effects of oxytocin signalling on improving peripheral insulin sensitivity, pancreatic function and lipid homeostasis strongly suggest a role for this system as a therapeutic target in obesity and diabetes management. The complexity of obesity aetiology and the pathogenesis of obesity-related metabolic complications underscore the need for a systems approach to better understand the role of oxytocin in metabolic function.

Smaller size of high metabolic rate organs explains lower resting energy expenditure in Asian-Indian Than Chinese men.

BACKGROUND: In Singapore, the obesity prevalence is disproportionately higher in the Asian-Indians and Malays than the Chinese. Lower resting energy expenditure (REE) may be a contributory factor. OBJECTIVE: We explored the association between ethnicity and REE in Chinese, Asian-Indian and Malay men living in Singapore and determined the influence of body composition, mass/volume of high metabolic rate organs, represented by brain volume and trunk fat-free mass (FFM), and physical activity on ethnic differences. DESIGN: Two hundred and forty-four men from Singapore (n=100 Chinese, 70 Asian-Indians and 74 Malays), aged 21-40 years and body mass index of 18.5-30.0 kg m(-2), were recruited in this cross-sectional study. REE was assessed by indirect calorimetry and body composition by dual-energy X-ray absorptiometry. Brain volume was measured by magnetic resonance imaging. Physical activity was assessed by the Singapore Prospective Study Program Physical Activity Questionnaire. RESULTS: REE was significantly lower in Asian-Indians compared with that in Chinese after adjusting for body weight. FFM (total, trunk and limb) and total fat mass were important predictors of REE across all ethnic groups. Brain volume was positively associated with REE only in Malays. Moderate and vigorous physical activity was positively associated with REE only in Asian-Indians and Malays. The difference in REE between Asian-Indians and Chinese was attenuated but remained statistically significant after adjustment for total FFM (59±20 kcal per day), fat mass (67±20 kcal per day) and brain volume (54±22 kcal per day). The association between REE and ethnicity was no longer statistically significant after total FFM was replaced by trunk FFM (which includes heart, liver, kidney and spleen) but not when it was replaced by limb FFM (skeletal muscle). CONCLUSIONS: We have demonstrated a lower REE in Asian-Indians compared with Chinese who may contribute to the higher rates of obesity in the former. This difference could be accounted for by differences in metabolically active organs.

Mastication effects on the glycaemic index: impact on variability and practical implications.

Glycaemic variability challenges the accuracy and use of the glycaemic index (GI). The purpose of the current study was to determine the role of mastication on GI. Using a randomized, controlled, crossover, non-blind design, 15 healthy young subjects returned on 5 separate days for three glucose and two rice test sessions. At the rice sessions, subjects chewed each mouthful either 15 or 30 times. Rice chewed 15 times produced a total glycaemic response (GR; 155 mmol min/l), peak GR (2.4 mmol/l) and GI (68) significantly lower than when chewed for longer (30 times) (184 mmol min/l, 2.8 mmol/l and 88, respectively). The study shows that the GI of rice is affected by the degree of mastication. Chewing 15 times compared with 30 times significantly attenuates the GI, suggesting that mastication may potentially contribute to the glycaemic variability of rice. While future work must establish the extent and limits to which mastication affects glycaemia, it could also explore the potential of using mastication to reduce the glycaemic load of rice.

Iodine-131 therapy for hyperthyroidism prescribed by endocrinologist - our preliminary experience.

INTRODUCTION: Radioiodine (I-131) is a useful therapeutic modality of hyperthyroidism when medical therapy fails. Traditionally, the nuclear physicians undertake the prescription of I-131 therapy. However, endocrinologists are increasingly being recognized for their competence in prescribing individualized doses of I-131 for the treatment of various thyroid disorders. METHODS: In this pilot prospective study, we collaborated with our nuclear medicine colleagues to determine the outcomes of 80 patients with hyperthyroidism who underwent I-131 ablation as prescribed by the endocrinologist. Doses administered were based primarily on thyroid volume with adjustments contingent on adverse factors, and fixed assumptions on target absorbed dose (R) and uptake (U) were used. Seventy-three had Graves' disease (GD) and seven had toxic nodular goitre (TNG) or toxic adenomas (AFTN). Therapeutic success was defined as achievement of hypothyroidism or euthyroidism. RESULTS: 95.9 percent (70 of 73) of GD patients and 85.7 percent (6 of 7) of those with TNG/AFTN achieved successful outcomes after a single dose of endocrinologist-directed I-131 therapy. More than 50 percent of patients became hypothyroid by three months and about two-thirds became hypothyroid by six months post I-131 therapy. CONCLUSION: Our results indicate that the success rate of endocrinologist-directed I-131 therapy exceeds 95 percent with a single dose and compares favourably with nuclear physician-directed therapy outcomes.

Thyrotoxicosis and acute abdomen--still as defying and misunderstood today? Brief observations over the recent decade.

BACKGROUND: Clinicians managing thyrotoxic patients with acute abdomen face challenging diagnostic and risky therapeutic dilemmas. AIM: To analyse the frequency of medical vs. surgical acute abdomen, and to characterize the poorly understood thyrotoxic medical acute abdomen phenomenon. DESIGN: Retrospective review of case notes. METHODS: All case files with a simultaneous diagnosis of thyrotoxicosis and acute abdomen admitted between 1994 and 2004 were traced and audited. RESULTS: Thirteen had a history of thyrotoxicosis while 12 were newly diagnosed. The commonest cause was Graves' disease. Twenty-three (92%) cases were thyrotoxic, of whom six (24%) had thyroid crisis, while two (8%) had subclinical thyrotoxicosis. The provisional diagnosis of acute abdomen was correct in 14 cases (56%), but discordant with the final diagnosis in 11 cases (44%). Eight cases (32%) without any demonstrable pathology were medical, vs. four (16%) with surgical acute abdomen, while 11(44%) had gastritis, hepatobiliary-pancreatic disorders or diverticulitis conservatively managed. The epigastrium and/or central abdomen (72.7%) were the commonest affected regions in medical acute abdomen. CONCLUSION: Although the majority of acute abdomen in thyrotoxicosis was medical in nature, our experience indicates that surgical conditions were not uncommon. Thus, serious causes requiring life-saving surgery should be excluded before attributing it to medical acute abdomen.

Pulmonary function and exercise capacity in survivors of severe acute respiratory syndrome.

The aim of this study was to investigate pulmonary function and exercise capacity in a group of survivors of the severe acute respiratory syndrome (SARS). At 3 months after hospital discharge, 46 survivors of SARS underwent the following evaluation: spirometry, static lung volumes and carbon monoxide transfer factor (TL,CO). In total, 44 of these patients underwent cardiopulmonary exercise testing. No abnormalities were detected in the pulmonary function tests in 23 (50%) of the patients. Abnormalities of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC and TL,CO were detected in seven (15%), 12 (26%), one (2%) and 18 (39%) patients, respectively. All of these abnormalities were mild except in one case. In 18 patients (41%), the maximum aerobic capacity was below the lower limit of the normal range. Breathing reserve was low in four patients and significant oxygen desaturation was detected in a further four patients. Comparison of the measured exercise capacity with resting pulmonary function tests showed many cases of discordance in impairment. In conclusion, pulmonary function defects were detected in half of the recovered severe acute respiratory syndrome patients 3 months after hospital discharge, but the impairment was mild in almost all cases. Many patients had reduced exercise capacity that cannot be accounted for by impairment of pulmonary function.