Postmeal satiety is shown in regional brain activation by images of high-calorie foods. Regions including the amygdala, nucleus accumbens, and dorsal striatum may alter perception of, and reduce motivation to consume, energy-rich foods, ultimately driving food choice. This trial was registered at clinicaltrials.gov as NCT01631045.

Background: Thyrotropin (TSH)-suppressive doses of levothyroxine (LT4) have adverse effects on bone and cardiac function, but it is unclear whether metabolic function is also affected. The objective of this study was to determine whether women receiving TSH-suppressive LT4 doses have alterations in energy expenditure or body composition. Methods: This study was a cross-sectional comparison between three groups of women: 26 women receiving chronic TSH-suppressive LT4 doses, 80 women receiving chronic replacement LT4 doses, and 16 untreated euthyroid control women. Subjects underwent measurements of resting energy expenditure (REE), substrate oxidation, and thermic effect of food by indirect calorimetry; physical activity energy expenditure by accelerometer; caloric intake by 24-hour diet recall; and body composition by dual X-ray absorptiometry. Results: REE per kilogram lean body mass in the LT4 euthyroid women was 6% lower than that of the LT4-suppressed group, and 4% lower than that of the healthy control group ( p = 0.04). Free triiodothyronine (fT3) levels were directly correlated with REE, and were 10% lower in the LT4 euthyroid women compared with the other two groups ( p = 0.007). The groups of subjects did not differ in other measures of energy expenditure, caloric intake, or body composition. Conclusions: LT4 suppression therapy does not adversely affect energy expenditure or body composition in women. However, LT4 replacement therapy is associated with a lower REE, despite TSH levels within the reference range. This may be due to lower fT3 levels, suggesting relative tissue hypothyroidism may contribute to impaired energy expenditure in LT4 therapy.

Women receiving TSH-suppressive doses of L-T4 do not have central nervous system dysfunction due to exogenous subclinical thyrotoxicosis, but TSH-suppressed and L-T4-replaced women have slight decrements in health status and mood that may be related to self-knowledge of the presence of a thyroid condition or other uncharacterized factors. These mood alterations do not impair cognitive function.

Glucagon-like peptide 1 (GLP-1) has incretin effects that are well-documented, but the independent role of GLP-1 action in human satiety perception is debated. We hypothesized that blockade of GLP-1 receptors would suppress postprandial satiety and increase voluntary food intake. After an overnight fast, 8 normal weight participants (7 men, BMI 19–24.7 kg/m2, age 19–29 yr) were enrolled in a double-blind, placebo-controlled, randomized crossover study of the GLP-1 antagonist Exendin-[9–39] (Ex-9) to determine if the satiating effects of a meal are dependent on GLP-1 signaling in humans. Following a fasting blood draw, iv infusion of Ex-9 (600–750 pmol/kg/min) or saline began. Thirty minutes later, subjects consumed a standardized breakfast followed 90 minutes later (at the predicted time of maximal endogenous circulating GLP-1) by an ad libitum buffet meal to objectively measure satiety. Infusions ended once the buffet meal was complete. Visual analog scale ratings of hunger and fullness and serial assessments of plasma glucose, insulin, and GLP-1 concentrations were done throughout the experiment. Contrary to the hypothesis, during Ex-9 infusion subjects reported a greater decrease in hunger due to consumption of the breakfast (Ex-9 −62±5 Placebo −41±9; P=0.01) than during placebo. There were no differences in ad libitum caloric intake between Ex-9 and placebo. Ex-9 increased glucose, insulin, and endogenous GLP-1, which may have counteracted any effects of Ex-9 infusion to block satiety signaling. Blockade of GLP-1 receptors failed to suppress subjective satiety following a standardized meal or increase voluntary food intake in healthy, normal-weight subjects.

Background: There has been recent debate within the thyroid field regarding whether current upper limits of the thyrotropin (TSH) reference range should be lowered. This debate can be better informed by investigation of whether variations in thyroid function within the reference range have clinical effects. One important target organ for thyroid hormone is the brain, but little is known about variations in neurocognitive measures within the reference range for thyroid function.Methods: This was a cross-sectional study of 132 otherwise healthy hypothyroid subjects receiving chronic replacement therapy with levothyroxine (LT4) who had TSH levels across the full span of the laboratory reference range (0.34-5.6 mU/L). Subjects underwent detailed tests of health status, mood, and cognitive function, with an emphasis on memory and executive functions. Results: Subjects with low-normal (£2.5 mU/L) and high-normal (>2.5 mU/L) TSH levels did not differ on most tests of health status, mood, or cognitive function, and there were no correlations between TSH, free T4, or free T3 levels and most outcomes. There was, however, a suggestion that thyroid function affected performance on the Iowa Gambling Task, which mimics real life decision-making. Subjects with low-normal TSH levels made more advantageous decisions than those with high-normal TSH levels. Conclusions: Variations in thyroid function within the laboratory reference range do not appear to have clinically relevant effects on health status, mood, or memory in LT4 treated subjects. However, decision making, which encompasses many executive functions, may be affected. Unless further studies strengthen this finding, these data do not support narrowing the TSH reference range.