There are children who always feel hungry and who are very overweight because their sense of satiety is 'broken'. These children also have hormonal problems, can have a disturbed day-night rhythm and sometimes temperature dysregulation, which makes them uncomfortable. The Hypothalamic Syndrome has enormous consequences for growing children and their families. This rare condition is often discovered late and there is no cure yet. About the Hypothalamic Syndrome, UMC Utrecht pediatric endocrinologist Hanneke van Santen and other international experts wrote an article that recently appeared in the renowned scientific journal Nature reviews | Disease Primers.

The young patients with Hypothalamic Syndrome - which Van Santen is researching - have problems with their hypothalamus. The hypothalamus is part of the brain and controls the autonomic nervous system responsible for breathing, heart rate and regulating body temperature. The hypothalamus also controls the hormonal system. This is controlled by the production of hormones and via the bloodstream by influencing the pituitary gland. The hypothalamus also regulates the day and night rhythm and the energy balance with the help of hunger or the feeling of satiety.

Patients with a hypothalamic syndrome often come to pediatrician Hanneke van Santen because they have become unexplainedly fat, or because the growth in height or puberty development is lagging. In part of these children, it is genetic, in another part a benign brain tumor is discovered that is attached to the pituitary gland: a Craniopharyngioma. The prognosis for this tumor is good. However, the quality of life after treatment can deteriorate sharply. “This low-grade brain tumor is located in a vulnerable area,” says Van Santen. “We treat these children in the Princess Máxima Center because the team you need for this complicated tumor is the neuro-oncology team.” Quality of life after surgery is determined by the degree of damage to the hypothalamus. This can be damaged by the tumor, but also by surgery. Van Santen is investigating how this damage can be prevented or limited as much as possible. “In collaboration with colleague Marc van de Wetering and Prof. Eelco Hoving (Princess Máxima Centre), we are developing ways to limit neurosurgical damage, such as by developing an organoid model with drug screens and the introduction of intraoperative MRI. We are also introducing new treatments for hypothalamic obesity such as dexamfetamines.”

Patients with a malfunctioning hypothalamus can experience various complaints: a constant feeling of hunger, a slowed metabolism, a disturbed temperature regulation of the body and a disturbed sleep-wake rhythm. A combination of complaints also occurs and the picture changes as children get older. “I see parents come in with a toddler who is not eating well and has growth problems. Through scientific research, we know that this toddler will probably tend to overeat constantly by the age of 10. This has to do with the maturation of the hypothalamus. Parents who first must actively encourage their child to eat, must therefore motivate their child to eat less a few years later. That cover can be complicated for parents. When one child in a family is always hungry and becomes overweight more quickly, it affects daily life for all members of the family. Just think how food is part of our culture; every holiday is accompanied by food such as Easter eggs or orange tompouces. Such a holiday is often not so festive for these families, but again a difficult day with struggles over food. It requires intensive full-time supervision.”

Prevention
Van Santen has set up a multidisciplinary team to optimally guide children with hypothalamic syndrome. The pediatric endocrinologist, psychologist, child psychiatrist, dietician, physiotherapist, neurologist, rehabilitation physician and oncologist work closely together. “As a team, we are building expertise on this rare condition, and we are also gaining more insight into its symptoms. That differs per patient. We see that complaints often existed longer before the hypothalamic syndrome was recognized by the general practitioner or pediatrician. That's not surprising because it's rare. Creating awareness is therefore important," she says. “If alarm signals are better recognized, we can detect small tumors in the pituitary gland earlier with an MRI and they can be treated well. However, once the hypothalamus is damaged you have a problem. A damaged hypothalamus leads to (morbid) obesity, behavioral problems, and diabetes insipidus without adequate thirst, which is very difficult to treat. The optic nerve is also located in this area. Early recognition of hypothalamic dysfunction can prevent vision loss and even blindness in the case of a tumor in this area.”

European cooperation
“My goal is to actually be able to offer patients with hypothalamic dysfunction something in the future,” Van Santen acknowledges. “I notice that there is a lot of support for this research theme within the WKZ, the Child Health spearhead and the Princess Máxima Center. Within the UMC Utrecht there is also a valuable collaboration with internist-endocrinologist Aline Stades and Professor of Endocrinology Gerlof Valk, which guarantees the transition of patients. This support and the recognition of the Dutch Federation of University Medical Centers as a center of expertise for rare hypothalamic disorders motivates me enormously to further expand the research from Utrecht.”

Van Santen opts for international cooperation. “The condition is rare, so we need collaboration for research and increasing knowledge. As with many rare diseases, it helps to set up international studies. I hope to set up a European consortium so that we can jointly investigate which interventions can help these patients.”

More awareness is also needed about the hypothalamic syndrome so that it is recognized earlier. “That is why I am developing a tool together with my colleague doctor and professor Dr. Hermann Müller (Oldenburg) with which we can classify patients in a uniform manner. This allows you to recognize characteristics at an early stage. The picture differs per patient, but I am convinced that if certain patterns become clear, we can do more for these patients.”