Search

Summary Single-minded homolog 1 (SIM1) is a transcription factor that plays a role in the development of both the hypothalamus and pituitary. SIM1 gene mutations are known to cause obesity in humans, and chromosomal deletions encompassing SIM1 and other genes necessary for pituitary development can cause a Prader–Willi-like syndrome with obesity and hypopituitarism. There have been no reported cases of hypopituitarism linked to a single SIM1 mutation. A 21-month-old male presented to endocrinology clinic with excessive weight gain and severe obesity. History was also notable for excessive drinking and urination. Endocrine workup revealed central hypothyroidism, partial diabetes insipidus, and central adrenal insufficiency. Genetic evaluation revealed a novel mutation in the SIM1 gene. No other genetic abnormalities to account for his obesity and hypopituitarism were identified. While we cannot definitively state this mutation is pathogenic, it is notable that SIM1 plays a role in the development of all three of the patient’s affected hormone axes. He is now 6 years old and remains on treatment for his pituitary hormone deficiencies and continues to exhibit excessive weight gain despite lifestyle interventions. Learning points: Mutations in SIM1 are a well-recognized cause of monogenic human obesity, and there have been case reports of Prader–Willi-like syndrome and hypopituitarism in patients with chromosomal deletions that contain the SIM1 gene. SIM1 is expressed during the development of the hypothalamus, specifically in neuroendocrine lineages that give rise to the hormones oxytocin, arginine vasopressin, thyrotropin-releasing hormone, corticotropin-releasing hormone, and somatostatin. Pituitary testing should be considered in patients with severe obesity and a known genetic abnormality affecting the SIM1 gene, particularly in the pediatric population.

Although obesity and mental health disorders are two major public health problems in adolescents that affect academic performance, few rigorously designed experimental studies have been conducted in high schools.The goal of the study was to test the efficacy of the COPE (Creating Opportunities for Personal Empowerment) Healthy Lifestyles TEEN (Thinking, Emotions, Exercise, Nutrition) Program, versus an attention control program (Healthy Teens) on: healthy lifestyle behaviors, BMI, mental health, social skills, and academic performance of high school adolescents immediately after and at 6 months post-intervention.A cluster RCT was conducted. Data were collected from January 2010 to May of 2012 and analyzed in 2012-2013.A total of 779 culturally diverse adolescents in the U.S. Southwest participated in the trial.COPE was a cognitive-behavioral skills-building intervention with 20 minutes of physical activity integrated into a health course, taught by teachers once a week for 15 weeks. The attention control program was a 15-session, 15-week program that covered common health topics.Primary outcomes assessed immediately after and 6 months post-intervention were healthy lifestyle behaviors and BMI. Secondary outcomes included mental health, alcohol and drug use, social skills, and academic performance.Post-intervention, COPE teens had a greater number of steps per day (p=0.03) and a lower BMI (p=0.01) than did those in Healthy Teens, and higher average scores on all Social Skills Rating System subscales (p-values0.05). Teens in the COPE group with extremely elevated depression scores at pre-intervention had significantly lower depression scores than the Healthy Teens group (p=0.02). Alcohol use was 12.96% in the COPE group and 19.94% in the Healthy Teens group (p=0.04). COPE teens had higher health course grades than did control teens. At 6 months post-intervention, COPE teens had a lower mean BMI than teens in Healthy Teens (COPE=24.72, Healthy Teens=25.05, adjusted M=-0.34, 95% CI=-0.56, -0.11). The proportion of those overweight was significantly different from pre-intervention to 6-month follow-up (chi-square=4.69, p=0.03), with COPE decreasing the proportion of overweight teens, versus an increase in overweight in control adolescents. There also was a trend for COPE Teens to report less alcohol use at 6 months (p=0.06).COPE can improve short- and more long-term outcomes in high school teens.This study is registered at www.clinicaltrials.gov NCT01704768.