Craniopharyngiomas (CP) are rare embryonal tumors of low-grade histological malignancy, located in the sellar/para- and supra-sellar region of the skull base [1]. The WHO 2021 classification of central nervous system tumors defines adamantinomatous and papillary CP for the first time as two distinct tumor entities [2]. The adamantinomatous CP is mainly diagnosed in children and adolescents (<18 years), whereas the papillary CP is diagnosed almost exclusively in the adult age group. The median age at diagnosis of adamantinomatous CP ranges from 5 to 9 years and from 55 to 69 years for papillary CP. The diagnosis of childhood-onset (CO) CP is often made late—sometimes years after the initial appearance of symptoms [1], [3], [4]—with clinical picture at time of diagnosis often dominated by non-specific manifestations of intracranial pressure. Among adult-onset (AO) CP the diagnosis is maid mainly on visual symptoms but also on longstanding endocrine insufficiencies [5]. The incidence of CP is 0.5–2.0 new CP cases per million persons per year [1]. Whereas patients with CP present with a favorable overall short-term survival rate (90–96 %), health-related quality of life (QOL) after CP diagnosis is frequently impaired due to age at diagnosis, tumor- and/or treatment-related sequelae including neuroendocrine, and hypothalamic dysregulation [1], *[6].

Patients with CP frequently present with neuro-endocrine sequelae due to the proximity of the tumor to the pituitary gland and the hypothalamus [7]. Additionally, visual impairment can occur due to mechanical compression of optic chiasm and/or optic nerves by tumors or cysts with suprasellar location [8]. The hypothalamus processes and controls information to ensure the body’s homeostasis – information from the environment (pain, smell, light, temperature), information from the body (blood glucose, blood pressure, serum osmolality), release of hormones through the hypothalamic-pituitary axes (HPA), and information from the central nervous system [9]. Accordingly, hypothalamus and HPA regulate hunger, satiety, and thirst, circadian rhythm, body temperature, circulatory function, stress response, sexual and reproductive function, and growth. Neurons in the ventromedial nucleus, dorsomedial nucleus, paraventricular nucleus, and lateral hypothalamic area control food intake (Fig. 1).

The mortality rate of survivors of CP, including both CO and AO CP, is higher than in the general population [10] with a standardized overall mortality rate (SMR) between 2.88–9.28 [11]. In addition, mortality was higher among females (SMR, 11.4) than males (SMR, 4.79) (9). Based on mixed populations (both CO and AO CP) the risk of cardio- and cerebrovascular mortality was particularly enhanced (SMR, 3.21; 95 % CI: 1.29–6.61) [5]. In a more recent study, the overall CO mortality was much higher SMR 17 (6.3–37) and the AO mortality was 3.5 (2.6–4.6) [12]. The overall survival rates in recent years range from 89 % to 94 % at 5-years and from 85 % to 90 % at 10-years follow-up [13], [14], and an average of 62–76 % at 20 years [15], [16]. The cause specific late mortality, after 20 years, was multi-factorial, but rarely due to disease progression [15]. Survival is, however, associated with the choice of therapy which is depending on tumor size extension and of recurrence of the tumor. Karavitaki et al. [13] recorded no significant difference in the 10 years survival rates between patients treated with gross total removal (100 %) and partial removal (86 %). A multivariate survival analysis adjusting for age showed a protective effect of radiotherapy (hazard ratio, 0.3; 95 % CI: 0.1–0.8) and an increased risk of death after recurrence (hazard ratio, 4.4; 95 % CI: 1.4 –14), but no obvious effect of radicality at surgery [5].

In a systematic review, hypopituitarism was associated with an excess mortality (weighted SMR of 1.55; 95 %-CI: 1.14–2.11) irrespective of the condition that had led to endocrine deficits. Especially in patients with CP involving hypothalamic structures, an elevated mortality risk was observed [17]. Adult patients with CO CP and hypothalamic involvement have persistently increased cardiovascular (CVD) risk. Conventional hormone substitution is insufficient to normalize CVD risk, suggesting an important role for irreversible hypothalamic involvement [18]. Pereira et al. [19] recorded again an increased CVD morbidity among females. White matter lesions caused by obstruction of small cerebral vessels are associated with stroke risk, which is the leading cause of mortality among CP. CO CP have significantly increase in white matter lesions volume (mL) [20] and treatment with cranial radiotherapy vs. no radiotherapy was associated with increased white matter lesions volume. These patients also had higher CVD manifestation. Again, CVD risk factors should be carefully monitored in these patients.

Further risk factors included younger age at CP diagnosis, female sex, radiation therapy, AVP-D, and hypogonadism. In retrospective analyses, left ventricular failure and myocardial infarction were sequelae that contributed to premature mortality [15]. Besides cardiovascular and cerebrovascular complications [21], respiratory adverse events such as respiratory tract infections, pneumonia, and respiratory arrest were observed in CP patients with fatal outcome [15]. Furthermore, endocrine deficiencies resulted in increased mortality risk of patients with CP. Being on cortisol replacement therapy due to secondary or tertiary adrenal insufficiency, patients need to immediately and flexibly adapt the dose of cortisol substitution according to stress requirements. Acute adrenal crisis is a life-threatening medical emergency. Therefore, patients and their families and caregivers should be educated for quick and correct actions in such emergency situations [17].

In the German KRANIOPHARYNGEOM Registry 2019 including CO CP, 70 % of recruited patients presented with visual impairments at the time of CP diagnosis. Three months after initial CP diagnosis, 51 % of these patients had persisting visual impairment and 54 % of CP patients at three years follow-up after CP diagnosis [22]. In a study by Bulow et al. [5], initial symptoms among AO CP at diagnosis were visual failure (47 %), endocrine deficiencies (35 %) and symptoms of increased intracranial pressure (18 %). At 10-years follow-up of 121 patients one quarter of the adults or children were unable to work in their previous occupation or were behind the expected school status [13]. In a long term follow up of 54 patients (majority AO CP) neurological morbidity was high: short term memory loss 40 %, personality changes 31 %, and visual morbidity 40 % [19]. In addition, inability to resume work or impaired school performances was seen among 57 %. A report from the KIMS data base on 241 AO and 152 CO CP on growth hormone therapy, showed a particularly a low QOL among AO vs. CO CP [23].

Hypothalamic syndrome is an umbrella term describing multiple complaints and clinical symptoms that frequently occur in patients with damage or dysfunction of hypothalamic structures [9]. Causes of hypothalamic syndrome are non-cancerous parasellar masses as germ cell tumors, gliomas and particularly CP. Furthermore, cysts of Rathke's pouch and Langerhans cell histiocytosis as well as with genetic neurodevelopmental syndromes, such as Prader-Willi syndrome and septo-optic dysplasia.

Hypothalamic syndrome is not synonymous with hypothalamic obesity. Hypothalamic syndrome consists of several clinical symptoms and its manifestations might be different for each patient [24]. Van Santen et al. described five clinical domains for the definition and diagnosis of hypothalamic syndrome among CO CP: eating disorders, behavioral disorders, sleep disorders, temperature dysregulation, and endocrine dysfunction [25].

Eating disorders include hyper- or hypophagia, showing extensive hunger, binge-eating, overweight, obesity or the failure to thrive, underweight, which is more prone to appear at the time of CP diagnosis and before surgical treatment [25], [26]. At long-term follow up among CO CP, total energy intake was significantly lower in patients vs. controls (- 430 kcal / 24 h) [27]. The relative contributions to dietary energy from fat, protein, and carbohydrates were similar in patients and controls. The percentage of light meals (i.e. soup, salad, or omelet) was significantly higher in patients compared with controls, and this was particularly seen in the female patients. Significantly higher scales of cognitive restraint, i.e. thinking of not eating, but with no differences in disinhibition (loss of control) or hunger, were recorded in the patients. Furthermore, it has been suggested that reduced physical activity rather than increased energy intake is responsible for HO in these patients [28].

Behavioral disorders include obsessive compulsive symptoms, rage, or hoarding. Sleep disorders can include sleep apnea, hyposomnia, daytime sleepiness, fatigue, or insomnia [25]. Temperature regulation disorders include hypothermia, hyperthermia and temperature dysregulation (cold or warm hand, feet, face at unusual moments) [25]. Central precocious puberty, delay in pubertal development, and hormonal deficits are endocrine dysfunctions described for hypothalamic syndrome [25], *[29]. Longitudinally, patients with hypothalamic syndrome face an increased risk of cardiovascular and metabolic disorders [9]. All the above-mentioned domains of hypothalamic syndrome clearly affect health-related QOL of patients with CP.

Behavioral disorder also includes cognitive dysfunction in CO CP [30]. Particularly adults with CO CP with hypothalamic damage suffered from decreased scores in episodic memory, and verbal memory for immediate and delayed recall and recognition [30]. Furthermore, they had also attention deficits [30]. Diffusion tensor imaging (DTI) illustrates the white fibers of the brain [31] and shows clearly how the hypothalamus is connected to frontal and temporal lobe of the brain and damage may lead to deficits in attention, executive function and memory [32]. Hippocampus is also connected to the hypothalamus and frontal lobe important for encoding and retrieving sequences of events that compose particularly the episodic memory [33]. Ventral cingulum is connected to the medial temporal lobe important for episodic memory. DTI showed a decrease in episodic visual memory significantly associated to white matter alterations in the left ventral cingulum, for both immediate and delayed memory recall [34]. Uncinate fasciculus, is a white matter tract important for general knowledge, which is connected to hippocampus and temporal lobe. Increased white matter alteration in this tract was associated to a decrease in general knowledge [34]. Such white matter alterations are explained by demyelination or oedema in these fibers. CO CP had smaller hippocampal volume compared to controls [34]. A lower general knowledge raw score was significantly correlated to smaller hippocampus volume. Thus, cognitive function is severely affected among CP with hypothalamic damage also shown in other studies [35]. Interestingly, no such differences were shown among CP with intact hypothalamus [34].

At a median age of 29 years, CO CP patients had a self-reported psychosomatic and emotional health comparable to the normal population [34]. No significant difference was found on the total score for social interaction, but patients had significantly lower adequacy of integration compared to controls. Among the social network parameters, no significant difference was found between patients and controls. The highest level of education among patients and matched controls was elementary school 17 % vs. 5 %, secondary school 44 % vs. 41 %, and university 39 % vs. 54 % (P = 0.19). Forty-eight percent of the patients and 62 % of the control group were employed at the time of the study (P = 0.15). Received income as unemployment benefits was comparable between patients (7 %) and controls (12 %). None of the controls were receiving long-term sick leave or early pension, which was the case for 14 % of the patient group. Dekkers et al. [36] reported decreased QOL in a mixed cohort of AO and CO CP with a mean follow-up time of 20 years. This could be explained by a greater sense of loss among patients diagnosed with CP in adult life. Müller et al. [37] showed that after 4.5 years, children with CP had a low QOL and the group with hypothalamic involvement was most affected. Others have reported relatively well-preserved QOL after 7 years of follow-up with an improvement with time since operation. A possible explanation is an adaption to the disease, which is known as the phenomena of response shift [38], which seems to take time and is expressed as the present life satisfaction. On the other hand, CO CP patients with hypothalamic involvement were less satisfied with their social interaction and social participation, which may negatively impact general health. In addition, patients with hypothalamic involvement had a lower level of employment; fewer had reached university education, and all patients on long-term sick leave or disability pension belonged to this group [34].

During long-term follow-up, approximately 50 % of CO CP patients with hypothalamic lesions develop hypothalamic obesity [39], *[40]. Rovani et al. observed overweight or obesity in 54 % of patients with CP. Risk factors associated with the long-term development of obesity were female sex, hypothalamic involvement, and a BMI > 2 SDS at baseline [41]. Beckhaus et al. could show, that also familial disposition for obesity (maternal and paternal BMI at CP diagnosis) is associated with the development of morbid hypothalamic obesity in patients with CP [42]. In a mixed cohort of AO and CO CP patients, the percentage of hyperphagia or excessive weight gain was increasing between 10 (39 %) to 20 years of follow up (67 %) [13].

Physiologically, the homeostasis of satiety and weight development is maintained through anorexigenic (e.g., leptin, insulin) and orexigenic (e.g., ghrelin, neuropeptide Y) pathways [43]. In case of hypothalamic obesity, these pathways are impaired due to tumor- and/or treatment-related damage of the nucleus tractus solitarius and the hypothalamic ventromedial/arcuate nuclei [43]. This can result in insulin and leptin resistance. An imbalance of appetite and satiety i.e., inappropriate food intake can be observed as a clinical consequence [44]. In patients with CP, parasympathetic dominance of the autonomic nervous system due to vagal hyperactivation causing hyper-insulinemia with hunger craving, resulting in accumulation of fat in the liver and lipoproteins in blood together with increased lipogenesis in fat cells lead to hypothalamic obesity [44]. The decreased sympathetic activity reduces total energy expenditure with a decrease in lipolysis. Furthermore, patients with hypothalamic obesity often exhibit lower levels of α-melanocyte-stimulating hormone, a key regulator of energy expenditure. Once morbid obesity levels are reached, weight reduction is difficult to achieve [44] and patients seem to reach stable plateau of high BMI [17]. To date, no “one size fits all” therapeutic solution is available in these clinically complicated and challenging situations [43]. Current approaches include prevention of hypothalamic damage by hypothalamus-sparing surgical strategies, novel irradiation techniques (e.g., proton beam therapy), and novel pharmacological agents for management of hypothalamic obesity [8]. In addition, among papillary CP with a high likelihood of BRAF V600E mutation, there are promising pharmacological treatment with BRAF-inhibitors [45].

Major clinical manifestations of hypothalamic syndrome are disturbances of circadian rhythms and sleep disorders. Common experienced sleep disorders in patients with CP are excessive daytime sleepiness, insomnia, secondary narcolepsy, sleep fragmentation, circadian rhythm sleep-wake disorders and sleep-related breathing disorders (e.g., sleep apnea) [46]. Hypersomnia is defined as the clinically relevant form of excessive daytime sleepiness, while having normal quality of sleep and normal timing of nocturnal sleep. Individuals with hypersomnia and increased daytime sleepiness may struggle to stay awake during the day, often feeling an urge to nap or fall asleep in inappropriate situations [46]. Müller et al. analyzed 115 patients with CO CP and observed abnormal daytime sleepiness in 35 cases (30 %) [47]. Four patients presented with symptoms of secondary narcolepsy, and three patients were diagnosed with hypersomnia [47]. In these reported cases, improvements of daily activity and daytime sleepiness were observed under medication with central stimulating agents such as methylphenidate and modafinil [47].

Polysomnographic signs of excessive daytime sleepiness were observed in 80 % of patients (n = 110) with CO CP [48]. Fatigue and self-reported QOL were not significantly associated with daytime sleepiness and BMI z-score was predictive for hypersomnia [48]. Furthermore, posterior hypothalamic involvement was a risk factor for hypersomnia. In a sample of 70 patients with CO CP, 41 % (n = 29) were diagnosed with hypersomnia after surgical intervention but before irradiation [49]. Sterkenburg et al. assessed survivors of CO CP regarding fatigue [17]. Higher scores on the physical fatigue domain and reduced motivation were observed in survivors of CP with hypothalamic involvement [17]. Circadian rhythm disorders, increased daytime somnolence, and insomnia were also reported as results of tumor-associated neurological impairments [46]. Besides direct effects, also indirect influence of depression, anxiety, and stress due to the coping with sequelae of CP can affect the sleep quality and exacerbate sleep disorders [46]. A questionnaire study of AO and CO CP on growth hormone therapy (n = 72 patients) showed a high percentage of antidepressants use [27]. Fatigue has a massive impact on QOL of CP survivors [17].

Based on accelerometric analyses, CO CP patients showed lower levels of physical activity when compared with BMI-matched healthy controls [28]. Also in adulthood, the CO CP reported lower degrees of physical activity than controls [27]. The degree of physical exercise during spare time was significantly lower for patients in both summer and winter. The number of steps recorded by the pedometer during 3 days was significantly lower for CP patients. Furthermore, patients with CP and severe hypothalamic obesity presented with increased levels of daytime sleepiness [50]. CP patients showed lower early morning and nocturnal melatonin concentrations in saliva, which were associated with increased daytime sleepiness and hypothalamic obesity. Under oral melatonin substitution (6.0 mg/d), patients with CP achieved a normalization of melatonin saliva concentrations and short-term improvements of daytime sleepiness and physical activity [51]. However, reports on long-term effects of melatonin medication on daytime sleepiness and hypothalamic obesity are still missing.

Patients with CP, severe hypothalamic obesity and increased daytime sleepiness, presented with polysomnographic sleep patterns typical for hypersomnia and secondary narcolepsy (i.e., high frequency of sleep-onset rapid eye movement phases / SOREM). Daytime sleepiness significantly improved under medication with central stimulating agents such as modafinil or methylphenidate in these patients [47].

The development of hypothalamic obesity in patients with CP is associated with changes in metabolic rate. Lower ratio of energy intake / REE was associated with a CP involvement of the third ventricle. Additionally, decreased total energy expenditure may also be caused by reduced levels of physical activity due to neurological/visual impairments and/or increased daytime sleepiness [28], [52]. About 20 years after operation, CO CP had significantly lower basal metabolic rate (90 kcal / 24 hours) after adjustment for weight and sex age [27]. Furthermore, the energy intake/BMR ratio was also significantly lower in the patients.

Approximately 80–90 % of patients with CP develop complete pituitary insufficiency after surgical intervention [13], [53]. Patients surgically treated via transcranial approach more frequently present with pituitary deficiencies than patients treated via transsphenoidal surgical approach. Gross total resection is mostly associated with higher rates of posttreatment endocrinopathies than subtotal resection or subtotal resection followed by irradiation. For certain endocrinopathies, the addition of radiooncological treatment increases the rate of deficient hypothalamic-pituitary-axes when compared with subtotal resection alone.

Insufficient endocrine substitution is associated with a high risk of severe sequelae such as adrenal crisis or short stature [17]. Growth hormone replacement therapy that is initiated during childhood results in growth improvement without affecting overall- or progression-free survival [54]. Early initiation of growth hormone substitution during pediatric age has beneficial effects on long-term QOL [55]. Growth hormone substitution therapy in the presence of growth hormone deficiency does not increase the risk of CP relapse or progression [56], [57], [58], [59]. Fixed intervals between the end of tumor treatment and the initiation of growth hormone replacement therapy—as suggested in malignant cancers—are not necessary in patients with CP and growth hormone deficiency. Growth hormone substitution beginning early after CP diagnosis may be associated with improvements in weight control and QOL [55]. AO CP patients present with 3- to 19-fold higher cardiovascular mortality than the general population [19]. Growth hormone replacement therapy decreases cardiovascular risks and helps to maintain body composition and normal bone density. The Growth Hormone Research Society (GRS) recently published a consensus statement summarizing available evidence and concluding that growth hormone replacement therapy is safe in patients with CP [56]. While growth hormone substitution does not cure hypothalamic obesity, it has beneficial effects on body composition, metabolic derangements of hypothalamic obesity and QOL in survivors of CP [55].

In the case of frequently encountered tumor- and/or treatment-associated adrenocorticotropin deficiency in CP patients, hydrocortisone substitution therapy and flexible dose adaptation with regard to stress situations is mandatory [60]. Non-physiological overreplacement of hydrocortisone may promote the development of obesity. Perioperative cortisone medication for edema treatment and perioperative prophylaxis of stress-induced adrenal crisis can led to perioperative weight gain. However, the risk of long-term obesity was not associated with perioperative cortisone treatment and appropriate physiologic replacement doses should not cause increased weight gain or risk of obesity [61]. A well-balanced and flexibly adapted dosage of hydrocortisone is beneficial for stabilizing weight development as well as preventing adrenal crisis and hypoglycemia. Patient and parental training on the perception of stress situations and appropriate and rapid intervention in life-threatening emergency situations such as acute adrenal crisis is of vital importance [62].

Hypothyroidism due to insufficient substitution of L-thyroxine can promote weight gain. Accordingly, L-thyroxine doses leading to thyroxine serum concentrations in the upper normal range are recommended in CP patients with hypothalamic obesity.

Gonadotrophin deficiency may necessitate pubertal induction and medically assisted reproduction [63]. Not surprisingly, rates of sexual activity are lower and psychosexual dysfunction higher in adult patients treated during childhood [63].

Based on hypothalamic origin, oxytocin deficiency is observed in CP patients with tumor- and/or treatment-associated hypothalamic involvement leading to hypothalamic syndrome. Accordingly, decreased salivary concentrations of basal and/or stimulated oxytocin have been observed in CP patients [64], [65], [66], [67] when compared with healthy controls. Reduced oxytocin saliva levels were associated with anxiety [68] and worse social cognition [69]. CP patients with anterior hypothalamic lesions were observed with lower saliva levels of oxytocin and best neuropsychological response to a single nasal oxytocin administration [65], [66] when compared with CP patients with lesions of posterior hypothalamic structures and normal controls. The results suggest that oxytocin-based therapeutics could be useful in treating CP patients with hypothalamic syndrome *[9], [70].

Patients with AVP-D are more likely to develop hypothalamic obesity due to hypothalamic damage, particularly in posterior hypothalamic areas. Accordingly, AVP-D can serve as a marker of hypothalamic damage and risk factor for hypothalamic obesity and impaired QOL [71].

An algorithm for individualized treatment of CO CP patients was published by van Iersel et al. [44]. After initial diagnostic evaluation, interventions for management of hypothalamic syndrome may be initiated in one or more of six appropriate clinical domains (Fig. 2). Beneficial effects on symptoms of hypothalamic syndrome are indicated in each step of the treatment algorithm. It may be prudent to apply certain intervention steps that have been studied only in a specific age group to other age categories. However, this should be done with caution, as adverse effects may differ for specific age groups (e.g., dextroamphetamine medication in adults or non-reversible bariatric interventions in the pediatric age group).

Morbid obesity due to hypothalamic damage is mostly non-responsive to conventional lifestyle modifications such as dietary interventions or physical exercise. Stimulating agents such as dextroamphetamine, methylphenidate, and tesomet increase the metabolic rate and suppress appetite [72], [73]. A systematic review observed weight reduction or stabilization in 89 % of patients [44]. Central stimulating agents may also have beneficial effects on increased daytime sleepiness, fatigue, psychosocial disorders, and hyperphagia [44].

Antidiabetic medications (i.e., metformin, diazoxide, fenofibrate, glucagon-like peptide (GLP)-1 receptor agonists, pioglitazone, or combinations) can reduce weight gain and improve insulin sensitivity. In combination with lifestyle interventions, metformin seems to stabilize and reduce weight gain with the least side effects. However, long-term effects of metformin medication on hypothalamic obesity remain unknown [74]. The effects of GLP-1 receptor agonists on weight control in adult patients with hypothalamic obesity are controversial. Benefits of improved glycemic control and a decrease in food intake were reported [75], [76]. However, Shoemaker et al. [76] reported decrease in food intake, but also a decrease in total energy expenditure after treatment once weekly with exenatide. The decrease in energy expenditure was disproportionate to weight loss and not explained by change in physical activity or leptin. With the same dose of exenatide, Perez et al. [77] reported a greater reduction in adiposity in relation to greater hypothalamic damage. The incretin liraglutide is registered for the long-term use in general obesity and has been used in adult CP with hypothalamic obesity with some success (reduction of 9–22 kg) [78], [79], [80]. Semaglutide has been approved for the treatment of obesity in adolescents achieving a median BMI decrease of 17 %. It is speculated that semaglutide and GLP-1 receptor agonist exenatide could have beneficial effects on weight development of patients suffering from hypothalamic obesity as well [81], [82].

The neuropeptide oxytocin suppresses appetite and hunger sensation. In individuals with CP, the change in salivary oxytocin concentrations in response to meals and exercise appeared to be associated with BMI and eating behavior, thereby demonstrating a potential benefit of oxytocin medication in patients with hypothalamic obesity [83]. However, there are still many unanswered questions regarding mechanisms of action and dosage of oxytocin in treatment of patients with CP and hypothalamic syndrome.

Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, originally developed for treating congenital hypothalamic obesity caused by proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency [84], is known to stimulate remaining (hypothalamic) MC4R neurons. Disruptions of the MC4R-pathway lead to hyperphagia and consecutive hypothalamic obesity. Impressive reduction of BMI (mean BMI reduction of 15 % ± 10 %) together with clinically relevant mitigating effects on hyperphagia and beneficial effects on QOL were observed in a recent phase-2 study in adults and children [85]. A prospective blinded randomized trial over a 12-month treatment period is ongoing. Setmelanotide might be a promising agent to target hypothalamic obesity [86] (Table 1).

Bariatric interventions demonstrated notable effectiveness in weight loss and safety in patients with CP [87], [88] (Table 2). In 2013, Bretault et al. [87] reviewed in their individual-level meta-analysis a total of 21 cases and found significant weight loss at 6 months and 12 months after bariatric surgery (-20.86 %TWL / 6 months, −15.14 %TWL / 12 months). The greatest weight reduction was achieved after Roux-en-Y gastric bypass (RYGB). Compared to the results in normal controls total weight reduction during 2 years was lower for other interventions but RYGB [87]. At present, the follow-up after bariatric interventions among CP are short, only 2 years [87]. In pediatric patients, the application of none-reversible bariatric techniques such as bypass interventions is ethically and legally controversial and should be made by multidisciplinary teams in the context of national / international trials [89]. The Endocrine Society’s Clinical Practice Guideline for Treating Pediatric Obesity [90] suggests that only adolescents with morbid obesity and advanced pubertal development, who have reached near final or final height and are adherent to diet and exercise interventions, should be considered for bariatric surgery. It is also important to be aware of the postoperative complications of bariatric surgery, including iron-deficiency anemia, diarrhea, and dumping syndrome following RYGB, folic acid and vitamin D deficiency, impaired effectiveness of oral desmopressin medication following sleeve gastrectomy, and dysphagia, vomiting following laparoscopic gastric banding (LAGB), all of which may have more profound impact on patients with hypothalamic obesity [89]. As patients with hypothalamic obesity have varying hypothalamic and pituitary functions, the net benefit from bariatric interventions on hypothalamic obesity is uncertain, and they should be evaluated individually to decide whether to operate and by which bariatric procedure.

Eveslage et al. could show that preoperative hypothalamic involvement, or surgical lesions of anterior and posterior hypothalamic nuclei were associated with impaired QOL in patients with CP. Furthermore, complete surgical resection resulted in lower QOL after CP when compared to incomplete surgical resection (Fig. 3) [91]. Presurgical hypothalamic involvement especially of posterior hypothalamic areas is a risk factor for impaired prognosis after CP. These adverse effects of preoperative hypothalamic involvement as a priori risk factor for sequelae can be modified by risk-adapted hypothalamus-sparing surgical strategies aiming at prevention of additional surgical hypothalamic lesions. Surgical hypothalamic lesions confined to anterior hypothalamic areas resulted in less adverse effects, whereas posterior surgical hypothalamic lesions were clinically relevant risk factors for the development of hypothalamic syndrome and impaired QOL [92]. A strong association between hypothalamic volume and fat mass was recorded among adult CO CP [34]. Thus, a reduced volume of < 600 mm3 (normal volume about 800 mm3) showed a particular increase in fat mass and risk of hypothalamic obesity. Accordingly, surgical strategies and approaches should avoid posterior hypothalamic damage. However, such strategies are frequently associated with a higher rate of recurrence and progression of residual tumor. Radio-oncological treatment is effective in treatment and prevention of relapse/progression after CP and therefore plays an important role in hypothalamus-sparing treatment strategies for CP [1], [93].