👤 Jessica Duis

Hyperphagia is a hallmark of both congenital and acquired rare melanocortin-4 receptor (MC4R) pathway diseases. Currently, the medical community has no standard treatment guidelines or approach to establishing treatment benefit. This narrative review discusses current understandings of the pathophysiology, burden, and treatment of hyperphagia and summarizes findings from a systematic literature review of validated instruments for assessing the response to hyperphagia treatment. Hyperphagia can result from dysfunction within, or damage impacting, hypothalamic pathways including the MC4R pathway, a key regulator of energy balance. The burden of hyperphagia is substantial, with negative effects experienced across physiologic, emotional, and social domains. Approaches for hyperphagia management include environmental control, lifestyle intervention, pharmacotherapy, neurocognitive approaches, and neurostimulation. There are varied approaches to determine treatment response; however, standard methodology has not been determined and largely relies on questionnaires. Studies of rare MC4R pathway diseases have improved understanding of the etiology of hyperphagia and established the need for indication-specific treatment. Targeted treatments are limited, and methods for determining treatment efficacy are varied. There is a need for consensus guidelines to establish a standard approach for the management of hyperphagia and related assessment of treatment response to improve patient morbidity. Show less

The aim of this study was to review bariatric procedure outcomes among patients with Prader-Willi syndrome (PWS), melanocortin 4 receptor (MC4R) mutations, Bardet-Biedl syndrome, and hypothalamic obesity. Systematic published literature review used the following search terms: "Prader-Willi syndrome," "Bardet-Biedl syndrome," "hyperphagia," "bariatric surgery," "MC4R"/"melanocortin 4 receptor", "hypothalamic obesity," and "bariatric procedure." Information collected included demographics, genetics, anthropometry, procedure type, outcomes, and complications, with inclusion of case series and clinical reports given the rarity of the disorders. For PWS, postoperative weight-change percentage and BMI up to 14 years following surgery were analyzed using general linear mixed models, with descriptive outcomes for other conditions. A total of 54 publications were identified, with variable follow-up periods for 202 patients (114 with PWS, 43 with MC4R mutations, 7 with Bardet-Biedl syndrome, and 38 with hypothalamic obesity) among bariatric procedures. Weight loss of patients with PWS was greatest within 1 year of surgery, with weight-change percentage not significantly different from 0 at 5 years. Long-term results in other conditions were variable and featured suboptimal weight loss and increased reoperation risk. Bariatric procedures among hyperphagic individuals, including those with PWS, report variable results and outcomes. Benefits of bariatric surgery may be less durable in hyperphagic disorders in comparison with other patients with severe obesity. Show less