Lithium as an adjunct to radioactive iodine for the treatment of hyperthyroidism: a systematic review and meta-analysis.

BACKGROUND: Radioactive iodine (RAI) is commonly used in the treatment of hyperthyroidism but is not uniformly successful. Lithium increases thyroidal iodine retention without reducing iodide uptake, increasing the radiation dose to the thyroid when administered with RAI. Although these actions suggest that adjuvant lithium may increase the efficacy of RAI, its role as an adjunct to RAI remains contentious. OBJECTIVE: To evaluate the safety and efficacy of adding lithium to RAI to treat hyperthyroidism. METHODS: Relevant studies were identified by a search of Medline and the Cochrane Central Register of Controlled Trials. To be included, a study had to be a controlled trial comparing the effect of RAI alone to RAI with lithium in the treatment of hyperthyroidism. Relevant data were extracted and meta-analyses were performed. RESULTS: Of the 75 identified studies, 6 met the inclusion criteria; 4 of these studies were interventional and 2 were observational trials. Meta-analysis of the observational trials (N = 851), both of which were retrospective cohort studies, showed significant improvement in the primary outcome (i.e., cure rate) with adjunctive lithium (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.24 to 2.96). The combined interventional trials (N = 485) also showed an improvement in cure rate, but the difference did not reach statistical significance (OR, 1.28; 95% CI, 0.85 to 1.91). Adjunctive lithium reduced time to cure and blunted thyroid hormone excursions after RAI. Lithium-related side effects were infrequent and usually mild. CONCLUSION: The observational trials demonstrated significant improvement in the cure rate of hyperthyroidism when lithium is added to RAI. The improvements shown in the interventional trials did not reach statistical significance due to the effect of a single, large negative trial.

Changes in serum TSH and free T4 during human sleep restriction.

STUDY OBJECTIVES: To examine whether recurrent sleep restriction is accompanied by changes in measures of thyroid function. DESIGN: Two-period crossover intervention study. SETTING: University clinical research center and sleep laboratory. PARTICIPANTS: 11 healthy volunteers (5F/6M) with a mean (+/- SD) age of 39 +/- 5 y and BMI 26.5 +/- 1.5 kg/m2. INTERVENTION: Randomized exposure to 14 days of sedentary living with ad libitum food intake and 5.5- vs. 8.5-h overnight sleep opportunity. MEASUREMENTS AND RESULTS: Serum thyroid-stimulating hormone (TSH) and free thyroxine (T4) were measured at the end of each intervention. Partial sleep restriction was accompanied by a modest but statistically significant reduction in TSH and free T4, seen mainly in the female participants of the study. CONCLUSIONS: Compared to the well-known rise in TSH and thyroid hormone concentrations during acute sleep loss, tests obtained after 14 days of partial sleep restriction did not show a similar activation of the human thyroid axis.

Mutation of the alpha2A-adrenoceptor impairs working memory performance and annuls cognitive enhancement by guanfacine.

Norepinephrine strengthens the working memory, behavioral inhibition, and attentional functions of the prefrontal cortex through actions at postsynaptic alpha2-adrenoceptors (alpha2-AR). The alpha2-AR agonist guanfacine enhances prefrontal cortical functions in rats, monkeys, and human beings and ameliorates prefrontal cortical deficits in patients with attention deficit hyperactivity disorder. The present study examined the subtype of alpha2-AR underlying these beneficial effects. Because there are no selective alpha2A-AR, alpha2B-AR, or alpha2C-AR agonists or antagonists, genetically altered mice were used to identify the molecular target of the action of guanfacine. Mice with a point mutation of the alpha2A-AR, which serves as a functional knock-out, were compared with wild-type animals and with previously published studies of alpha2C-AR knock-out mice (Tanila et al., 1999). Mice were adapted to handling on a T maze and trained on either a spatial delayed alternation task that is sensitive to prefrontal cortical damage or a spatial discrimination control task with similar motor and motivational demands but no dependence on prefrontal cortex. The effects of guanfacine on performance of the delayed alternation task were assessed in additional groups of wild-type versus alpha2A-AR mutant mice. We observed that functional loss of the alpha2A-AR subtype, unlike knock-out of the alpha2C-AR subtype, weakened performance of the prefrontal cortical task without affecting learning and resulted in loss of the beneficial response to guanfacine. These data demonstrate the importance of alpha2A-AR subtype stimulation for the cognitive functions of the prefrontal cortex and identify the molecular substrate for guanfacine and novel therapeutic interventions.

Differences in insulin secretion and sensitivity in short-sleep insomnia.

OBJECTIVE: Short-sleep insomnia is associated with increased risk of diabetes. The role of altered insulin secretion and action in this association is poorly understood. DESIGN: Observational study. SETTING: Academic clinical research center. PARTICIPANTS: Nondiabetic individuals with insomnia (mean [standard deviation] age 48 [9] y, body mass index 25.6 [3.9] kg/m(2)) with ≤ 6 h (short sleep, n = 14) and > 6 h of sleep (n = 14) during overnight laboratory polysomnography. MEASUREMENTS AND RESULTS: Standard oral glucose testing was used to assess glucose tolerance, beta-cell function (homeostasis model assessment [HOMA-B]; second-phase insulin secretion) and insulin resistance (HOMA-IR; insulin sensitivity index). There was no significant difference in hemoglobin A1C and fasting or 2-h blood glucose concentrations between sleep groups. Short-sleep insomnia sufferers had lower fasting and postchallenge serum insulin concentrations associated with lower estimates of fasting and glucose-stimulated insulin secretion, and increased insulin sensitivity. CONCLUSIONS: Individuals with short-sleep insomnia appear to have higher indices of systemic insulin sensitivity and secrete less insulin without changes in overall glucose tolerance.

Exposure to recurrent sleep restriction in the setting of high caloric intake and physical inactivity results in increased insulin resistance and reduced glucose tolerance.

CONTEXT: Epidemiological data indicate that reduced sleep duration is associated with increased incidence of type-2 diabetes. OBJECTIVE: The aim of the study was to test the hypothesis that, when part of a Western-like lifestyle, recurrent bedtime restriction may result in decreased glucose tolerance and reduced insulin secretion and action. DESIGN AND SETTING: We conducted a randomized crossover study at a university clinical research center and sleep research laboratory. PARTICIPANTS: Eleven healthy volunteers (five females and six males) with a mean (+/-sd) age of 39 +/- 5 yr and body mass index of 26.5 +/- 1.5 kg/m(2) participated in the study. INTERVENTION: The study included two 14-d periods of controlled exposure to sedentary living with ad libitum food intake and 5.5- or 8.5-h bedtimes. MAIN OUTCOME MEASURES: Oral and iv glucose challenges were used to obtain measures of glucose tolerance, glucose effectiveness, insulin secretion, and insulin sensitivity at the end of each intervention. Secondary measures included circulating concentrations of the glucose counter-regulatory hormones, cortisol, GH, epinephrine, and norepinephrine. RESULTS: Bedtime restriction reduced daily sleep by 122 +/- 25 min. Both study periods were associated with comparable weight gain; however, recurrent sleep restriction resulted in reduced oral glucose tolerance (2-h glucose value, 144 +/- 25 vs. 132 +/- 36 mg/dl; P < 0.01) and insulin sensitivity [3.3 +/- 1.1 vs. 4.0 +/- 1.6 (mU/liter)(-1) x min(-1); P < 0.03], and increased glucose effectiveness (0.023 +/- 0.005 vs. 0.020 +/- 0.005 min(-1); P < 0.04). Although 24-h cortisol and GH concentrations did not change, there was a modest increase in 24-h epinephrine and nighttime norepinephrine levels during the 5.5-h bedtime condition. CONCLUSIONS: Experimental bedtime restriction, designed to approximate the short sleep times experienced by many individuals in Westernized societies, may facilitate the development of insulin resistance and reduced glucose tolerance.