The Difficult Treatment of Pediatric Hypothalamic Obesity Due to a Craniopharyngioma
As part of my Anatomy and Physiology class, we wrote various research papers and my final one was about pediatric hypothalamic obesity and craniopharyngiomas, a very specific kind of brain tumor. This paper covers an introduction to this topic, the specific medical background to this chronic illness and some methods that have been researched to see how they affect hypothalamic obesity. This is a demonstration of my research abilities and highlights my interest in the various physiological systems that play a role in our everyday lives.
Abstract:
In order for the body to function at a high level, the body must produce, secrete and transport hormones to the tissues and organs that rely on them. There are many different parts of the brain that function to maintain the body’s level of hormone homeostasis including the hypothalamus and pituitary gland. These two glands play a vital role in the production and secretion of hormones directed into the bloodstream. The overarching coordination of hormones and glands is combined to form the endocrine system which if harmed, can have major consequences for hormone regulation. In the case of a craniopharyngioma brain tumor, the hypothalamus and pituitary gland are damaged so much that various health conditions arise post-surgery including hypothalamic obesity. This condition proves to be difficult, demanding, and intense making it hard for children to manage. Many methods have been tried to reduce weight gain caused by hypothalamic obesity, but most have been unsuccessful. A more successful method is specific dieting practices such as calculated carbohydrate counting. This review will discuss the potential benefits of a highly restricted carbohydrate diet as well as existing pharmaceutical treatments that have not been successful for reducing the negative effects of pediatric hypothalamic obesity.
Keywords: craniopharyngioma, hormones, endocrine system, hypothalamus, hypothalamic obesity, hyperphagia, satiety, carbohydrates, metabolism, insulin, weight gain, weight loss
Word count: 1,649
Introduction:
A craniopharyngioma tumor usually grows in close proximity to the hypothalamus and the pituitary gland therefore it damages and disrupts the endocrine system (1). These tumors can be found anywhere along the path of development of embryonic squamous epithelial parts of Rathke’s pouches. These extend downwards towards the hypothalamus and pituitary regions that are important for hormone regulation and satiety (2). This type of tumor is located in the sellar and parasellar regions of the brain (1). These are slow-growing, benign tumors, meaning that they are non-cancerous (1). Due to its presence in the hypothalamic region of the brain, the resection of a craniopharyngioma results in decreased growth rates, puberty delay, hyperinsulinemia, diabetes insipidus and significant obesity. These deficiencies require significant hormone replacements through various medications 85-90% of the time (2). Children usually suffer from growth hormone deficiency, adrenocorticotropic deficiency, thyroid-stimulating deficiency, and follicle-stimulating hormone and luteinizing hormone deficiency due to the pituitary axis deficits (3). While there is a good overall survival rate of craniopharyngioma resections in children, there are many endocrine dysfunctions as a result of the tumor. One of the dysfunctions is hypothalamic obesity (HO), a serious condition which develops in 50-60% of patients, which can be deadly if not managed properly (2, 3). .
In healthy individuals, the body manages energy intake and makes sure that it is equal to the energy output. (4). With obesity situations, the brain is unable to control such energy homeostasis (4). Usually the body detects energy excess or deficits by sensing levels of circulating hormones released by the pituitary glands via the autonomic nervous system. That energy is transmitted to the neurons in the hypothalamus which plays a huge role controlling food intake and body weight. There are particular regions in the hypothalamus such as arcuate nucleus (ARC) and the third ventricle that access the nutrients and hormones from the blood brain barrier. (4) These regions sense adiposity signals such as leptin and insulin which signal the status of body energy storage (4). Leptin is the most abundant hormone produced by adipocytes (5). It regulates food intake, energy expenditure and glucose homeostasis as well as insulin sensitivity (5). Insulin is normally released in the bloodstream in response to eating carbohydrates. When carbohydrates are consumed, they are broken into smaller molecules once of which is glucose. Glucose is absorbed from the small intestines into the bloodstream which takes it to the rest of the body to be used as energy or to be stored. Glucose relies on insulin to leave the bloodstream and enter the cells. If excess glucose remains in the bloodstream it is sent to the liver to be stored as glycogen and once that supply is at maximum capacity, the remaining glucose is converted into fat (6).
The hypothalamus, which is largely involved in regulating homeostatic functions of hormones, is linked directly through synaptic connections to the limbic system that mediates the motivation to eat (7). Disruptions in those synaptic connections result in an increased hunger which leads to obsessive food seeking behavior known as hyperphagia (6). Other challenges include musculoskeletal problems, diabetes mellitus, sleep apnea, and depression later in life (1). The HO damage to the ARC, dorsal hypothalamic area, paraventricular nucleus disrupts regulation of satiety and energy balance through neural and humoral connections. (7). The loss of satiety and reductions of metabolic rate, physical activity, hyperinsulinemia and leptin resistance results in rapid weight gain due to decreased energy expenditure and increased energy storage in adipose cells (7). Under normal conditions, circulating leptin crosses the blood brain barrier and synapses on neurons of hypothalamus and induces a series of hormone actions that decrease appetite which leads to less food intake (9).
What is the best way to help lose HO weight and maintain a healthy body mass index?
Hypothalamic obesity is labeled a “difficult to treat” disease for a reason. It is noted that this obesity does not respond to caloric dieting or exercise interventions that are normally prescribed to help people achieve their goal weight and body size (8). One of the most recently discovered successful methods for treating HO has been carbohydrate restriction with a diet high in fats and proteins (7). “Hungry for Solutions”, a book written by Marcia Serota, a registered dietician nurse, describes the nutritional strategies that she created because her son weighed 180 pounds at age ten and was near liver failure. These strategies induced weight loss of up to 40 pounds in her son who suffered from a craniopharyngioma tumor and HO. This intervention uses a very low and controlled carbohydrate count of 50-100g per day with very low sugar and processed foods intake (6). It is important for this eating plan to be supplemented with physical activities (6). The reason for trying this method is to help regulate and limit insulin release. A HO individual stores extra fat and never feels full which results in excess insulin release that increases hunger, ultimately causing irritability and weight gain regardless of most dietary restrictions. The carbohydrates that are consumed should be naturally made and high in fiber and consciously eaten in spread out mealtimes (6). The less sugar and flour the carbs contain the better. This is a strict diet with specific measurements for every type of food which requires significant adult supervision (6). Many people who spend time around individuals with HO and hyperphagia have to lock the fridge and pantry to prevent sneaking of food. While it requires aggressive management, this plan can produce life-changing effects.
In contrast to this method, octreotide, a synthetic long-lasting somatostatin analog that binds to SSTR5 receptors on the B cell in the Islets of Langerhans in the pancreas, inhibits calcium influx and attenuation of insulin release and works to control obesity (8). Unfortunately, in a pilot study of the effects of octreotide in hyperinsulinemia of HO patients, results showed that all of the participants developed diarrhea and abdominal discomfort (7). Furthermore, another study conducted at Novartis Pharmaceuticals in 2004 failed to change the BMI of participants (7). It seems to be a difficult medication for long term adherence (7). Another downside to octreotide is that HO craniopharyngioma survivors are already consuming other synthetic hormones and drugs to maintain the other hormone imbalances in their body. Craniopharyngiomas also cause damage to the pituitary gland so the body stops maintaining hormones such as cortisol and thyroxine. Most common anterior and post pituitary defects are through growth hormone deficiency (10). Excessive cortisol replacement can contribute to weight gain and prevent weight loss (6). Some CP survivors who have secondary hypothyroidism also require thyroid replacement. All of these added elements on top of the side effects make it hard to see the benefits of adding more medication to an HO patient’s already extensive list. Working with the limited carbohydrate diet has better outcomes, especially for children.
Lack of research and success rates on the treatment of pediatric hypothalamic obesity
There are currently no commonly accepted medications or surgery treatments that can cure hypothalamic obesity (6). Treatment options and cures remain a bit of a mystery to doctors and specialists. The mechanisms for HO weight loss such as carbohydrate dieting and physical exercise need more research in order to know what type and how much exercise and how rigorous the diets must be to prevent weight gain (2). There have been limited researched drug interventions, many of which have led to side effects (7). More research is needed to understand if more than one therapy is needed to replace the various hypothalamic mechanisms of disturbed homeostasis and the effectiveness of combinations of certain agents or surgical therapies on HO (7). While this newer restricted carbohydrate diet was highly effective for one patient, it has not been clinically tested for many children. More information is needed on the success rates and how realistic it is for children and their families. Besides diets and pharmaceuticals there is also the possibility of bariatric surgery, but more studies are needed to evaluate those methods, especially on children (11). In order to understand the most successful treatment plan, protocols need to be researched so that side effects can be identified, and benefits can be weighed against risk to determine the most beneficial option for HO patients (11).
Possible outcomes and further development to improve hypothalamic obesity conditions
Further research is needed on the pathogenic role of neurotransmitters in the brain which could help predict the likelihood of HO (2). A limited amount of studies looked at pharmacological treatment such as calexcitin which is an oxytocin analogue (6). The combination of low dose intranasal oxytocin and naltrexone (effective in determining hedonic eating), have shown to enhance oxytocin effects (6). Results from those studies showed improved satiety and decreased hyperphagia but further exploration and trials are needed (6). More clinical trials and information needs to be collected about the results of severely restricted carbohydrate diets to see how successful it is with children of different ages (6).
Conclusion:
Hypothalamic obesity is a daunting journey for children and their parents to take on but with a carefully managed diet, it is possible for the weight to be maintained at a healthy level. Hypothalamic obesity regulation requires the careful management of hormonal deficits, including cortisol, growth, thyroid, and insulin production (6). Since the endocrine system controls so many different mechanisms throughout the body, changing one thing such as diet can have a strong positive impact on body function. Along with diet, it is important for HO individuals to continue engaging in physical activity such as weightlifting and cardiovascular exercises (6). The amount and type of physical activity and specific kinds of diets must be considered under the supervision of a medical professional who can assist and monitor the effects of such measures, ensure progress, and help to facilitate the best ways for HO survivors to sustain a healthy lifestyle for the present and future years.
Works Cited
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