Hanneke van Santen, who has been Professor of Paediatric Endocrinology for a year, focusing on the hormonal consequences for children with cancer, gave her inaugural lecture on 9 January. It was a call to dare to build new bridges to innovative solutions for complex problems. ‘What seems impossible today may be closer tomorrow if you persevere and build the right partnerships.’
Hanneke van Santen began researching hormone problems in children with cancer in 1999, because there was a suspicion that children with cancer had many more hormone problems than were then apparent. Her PhD thesis focused on thyroid damage in children with cancer, and her co-supervisor asked her to bridge the gap between endocrinology and oncology. Now, as a paediatric endocrinologist, 27 years later, she literally walks across the bridge that connects the paediatric endocrinology department of the Wilhelmina Children’s Hospital with the Princess Máxima Centre, the national paediatric oncology centre, where all children with cancer in the Netherlands have been treated since 2018.
Nowadays, more children with cancer are being cured of the disease. However, this also means that the number of children and adults experiencing negative side effects from their treatment, such as hormone problems, is increasing. Damage to a hormone-producing organ can be caused by the tumour, chemotherapy or radiation. A hormone deficiency can lead to short stature, chronic fatigue, obesity, diabetes, infertility or brittle bones. This has a major impact on these children and their parents.
Hormones are signalling substances that regulate physical processes. From the head, the hypothalamus and pituitary gland control the other hormone-producing organs in the body to produce hormones such as growth hormone, thyroid hormone and puberty hormone. If there is enough or too much hormone, a signal is sent back to the hypothalamus and pituitary gland, keeping people in optimal balance. Hormones are essential for growth and development, but they are also essential for our daily well-being.
During or after cancer treatment, a hormone deficiency may occur, for example due to damage to the pituitary gland. A hormone may also be produced in excess or too early. For example, a 5-year-old who is already entering puberty. In that case, doctors must slow down the system. The system can also adapt during an illness, such as lowering thyroid hormones during sepsis, and we must respect any imbalance. This is the work of the paediatric endocrinologist: supplementing a hormone deficiency if it is too low or slowing it down if it is too high.
The research conducted by Hanneke van Santen and her team focuses on identifying and treating hormonal problems in children with and after childhood cancer treatment more effectively, focusing on the most serious hormonal problem: hypothalamic dysfunction. “General practitioners often fail to recognise it because it is very rare. Damage to the hypothalamus itself is often irreparable and has a major impact on daily life. Because the hypothalamus is connected to other areas of the brain, particularly the prefrontal cortex, the amygdala and the hippocampus, damage to the hypothalamus can also cause complex behavioural problems.”
Since the centralisation of care and the arrival of Maxima in 2018, major strides have been made in improving the outcomes for children with cancer in terms of long-term effects. “We are seeing less hypothalamic obesity and fewer patients with hypothalamic syndrome. This is thanks to multidisciplinary collaboration between surgeons, intensive care physicians, paramedics and nurses, and by combining the knowledge and expertise at Maxima and the WKZ. We can greatly strengthen each other.”
Hanneke will focus on preventing damage to the hypothalamus and pituitary gland – the hormone centres in the brain – and on developing innovative treatments for this. “I will be doing this in close collaboration with colleagues in the lab and with national and international partners in endocrinology and beyond. I will also be working with partners from industry who are developing exciting new tools, from medication to smart wearables, such as smartwatches that can help measure body temperature, stress, sleep and daily activity.”
