Patients with brain tumors who participated in the study were diverse. The subjects differed by histology of the tumor and its localization in the brain. The selection of patients was limited because the study included only those patients who already finished treatment in one clinical centre.
Current studies in patients who completed oncological therapy describe various abnormalities of carbohydrate metabolism. An excessive weight gain is the most frequent observed complication [7
]. Many authors emphasize that the main cause of obesity during or after oncology management is the neoplastic process itself (tumors of h-p area), steroid treatment in brain edema prophylaxis, pituitary insufficiency - particularly growth hormone deficiency, other endocrinopathies, lifestyle changes and accompanying neurological symptoms [18
Childhood Cancer Survivor Study [9
] evaluated adults treated for brain tumors in childhood. It reveal that the risk of obesity comparing to healthy adults is similar. On the other hand, Pietilä et al. [8
] describe significant frequency of obesity and carbohydrate metabolism abnormalities in patients after brain tumors management. Patients in this study underwent treatment for brain tumors of various locations. In few patients tumors were situated in hypothalamus
and sella turcica area. The majority of patients were treated exclusively with surgery. Obesity was diagnosed in 35% of patients (21% with the central one). Adiposity was observed more frequently in patients receiving radiotherapy for the whole brain, after damage of hypothalamic-pituitary area by neoplastic process, in patients with growth hormone deficiency and with decreased physical activity [8
In our study the group with the highest risk of developing obesity were patients treated for tumors located in hypothalamic-pituitary area (60% of all patients with excessive weight gain).
No dependence between weight gain and chemotherapy or radiotherapy was noted.
Numerous authors inform that excessive weight gain frequently correlates with increased appetite. It relates mostly to patients treated for hypothalamic-pituitary tumors [8
]. As far as some authors are concerned, hypothalamic obesity may develop even some years after hypothalamic tumors management , though there are observations that first symptoms may be present shortly after surgery [23
Excessive weight gain related to an increased appetite is most common for patients after surgical treatment or radiotherapy of craniopharyngioma
]. Meuric et al. [24
] evaluated patients with craniopharyngioma after extensive treatment and primary damage of hypothalamus and observed correlation between weight gain and increased insulin secretion. Hyperinsulinemia can develop either before the surgical treatment or after completed therapy [21
]. The cause of increased insulin concentration in the serum indirectly explained animal studies. The damage of ventromedial nucleus in hypothalamus of rats was the cause of hyperphagia and increased serum insulin concentration, which led to obesity [26
]. In this study the correlation between hyperinsulinemia and increased activity of parasympathetic system was shown. Other studies also confirm the hypothesis that increased insulin secretion may cause the hypothalamic obesity. It is considered that positive influence of Octreotide treatment in this type of obesity is by insulin secretion inhibition [14
Pinto et al. [23
] observed that carbohydrate metabolism abnormalities intensified during and after oncology treatment. There is a hypothesis, that the craniopharyngioma itself and the surgery in addition modified the insulin secretion. The correlation between hyperinsulinemia and the weight gain is described for healthy population as well [28
In our study, in half of the patients who underwent surgical treatment for h-p tumors, elevated insulin concentrations after treatment were observed. The location of the tumor in this area had a significant influence on weight gain and hyperinsulinemia. There was dependence between hyperinsulinemia and an excessive weight gain. For the patients receiving complex treatment for tumors outside the h-p area increased fasting insulin concentrations were noted only in 5% of patients and elevated insulin concentrations in OGTT were seen in 15% of patients. In this group only 27% were overweight or obese. 20% of patients surgically treated for tumors outside the h-p area revealed weight gain. Elevated insulin concentrations in OGTT were noted for 13% of them. The imbalance between patients with tumors of different areas testifies that the tumor location in the h-p area has the greatest influence on weight gain and insulin resistance after treatment.
Carbohydrate metabolism disorders as diabetes mellitus and impaired glucose tolerance were described after treatment for brain tumors in hypothalamic-pituitary area [29
]. Crowley et al. diagnosed diabetes mellitus in 11.5% of patients after surgical treatment of craniopharyngioma [29
]. Furthermore, in Deepak et al. study diabetes mellitus was diagnosed in 9% of those patients [30
]. In the other survey [31
] diabetes mellitus incidence was 3.7%. In our present study type 2 diabetes mellitus was diagnosed only in one patient (1.6%) treated with surgery for craniopharyngioma. Impaired glucose tolerance was noted in one patient treated for h-p tumor and another treated exclusively with chemotherapy for optic nerve glioma. The highest average HbA1c value was observed in patients treated for h-p tumors [32
For patients with abnormal glucose or insulin concentrations, the insulin resistance assessment is required. It can be evaluated by indirect calculation of insulin resistance indices. A more adequate method is the glucose clamp technique [33
], but because of the complexity of the method, it is not routinely used in the clinical practice. Yeni-Komshian et al. [35
] compared different insulin resistance indices with the glucose clamp technique and observed that fasting insulin concentration was the most sensitive insulin resistance index. A fasting glucose to insulin ratio and HOMA-IR index also showed high sensitivity, however they were less sensitive than fasting insulin.
In our study elevated fasting insulin concentrations, HOMA-IR and Matsuda abnormal values were noted more frequently in patients treated surgically for h-p tumors. Some patients treated with surgery followed by radio- and chemotherapy for tumors outside the h-p area also revealed insulin resistance. This was mostly accompanied by overweight and obesity. In the literature only few authors assessed insulin resistance indices for patients after complex treatment of brain tumors. Usually patients with h-p tumors and craniopharyngioma were described [15
]. There are also studies concerning patients after treatment of acute lymphoblastic leukemia [37
]. In those groups increased percentage of abnormal values of assessed indices has been observed comparing to control groups [15
Steroid treatment in cancer therapy is an important factor influencing carbohydrate metabolism abnormalities [38
]. The steroid use in therapeutic protocols of acute lymphoblastic leukemia (ALL) increases frequency of obesity and carbohydrate metabolism abnormalities [40
]. On the other hand, in the studies assessing large population of ALL survivors, prophylactic radiotherapy was essential factor influencing obesity rate. Exclusive chemotherapy did not influence the obesity rate [43
]. In our study correlation between chemotherapy and radiotherapy with the excessive weight gain was not observed. In brain tumor therapeutic schedules in children steroid treatment is used commonly in pre-operative period in order to decrease intracranial pressure, and less frequently in later treatment stages. Our results did not confirm correlation between carbohydrate metabolism disorders and the type of treatment.
An important constituent of the abdominal obesity assessment is a measurement of waist and hip circumferences and calculation of indices. In our study WHtR (waist-to-height ratio) index was used. It is widely accepted as a very good index assessing abdominal obesity and it is an excellent prognostic factor for abdominal obesity complications, especially in children [4
]. In our study 26% of patients treated for h-p tumors revealed abnormal values of this index. Lower prevalence of abdominal obesity was noted in patients with tumors of other than h-p location.
While analyzing the causes of obesity, mainly abdominal type, hypopituitarism and decreased growth hormone secretion has to be taken into consideration. Many authors mentioned growth hormone deficiency (GHD) as one of the main factors increasing the risk of obesity and dyslipidemia in patients after treatment of brain tumors [46
] and other neoplasms, mainly ALL [49
]. In the present study patients with damaged hypothalamic-pituitary area by neoplastic process with accompanying GHD, more frequently revealed excessive weight gain and dyslipidemia. After the year of treatment with recombinant growth hormone significant reduction of SDS BMI was observed.
In our previous study influence of treatment with recombinant growth hormone (rGH) on metabolic functions in patients after craniopharyngioma with pituitary insufficiency was assessed [48
]. Growth hormone therapy caused significant BMI, LDL-cholesterol and HbA1c reduction one year after treatment.