Association of pancreatic MRI R2* with blood glucose and cardiac MRI R2* among thalassemia major patients in <scp>I</scp> ndonesia
Authors: Pustika Amalia Wahidiyat, Damayanti Sekarsari, Nitish Basant Adnani, Siti Ayu Putriasih, Vasili Berdoukas
Journal: American Journal of Hematology (2017)

Advancements in technology has encouraged the use of magnetic resonance imaging (MRI) T2* and R2* to evaluate organ iron overload in thalassemia major (TM) patients due to its sensitivity, reproducibility, availability, and relative non-invasiveness.1 While cardiac and hepatic MRI have largely replaced conventional methods to evaluate organ siderosis, the use of MRI in other organs is still under investigation. In recent years, MRI has also been used to evaluate pancreatic iron overload, which offers promising prospects as a predictor of pancreatic iron accumulation. Currently, fasting blood glucose (FBG) and 2-h postprandial blood glucose (PPBG) examinations are widely used to monitor endocrine complications in TM patients. However, the relationship between pancreatic iron overload and glucose dysregulation has not been well defined and warrants further investigation.2 Moreover, controversies still remain as to whether cardiac siderosis is a predictor of pancreatic siderosis in TM patients. This study aims to evaluate the presence of iron overload among TM children patients in Indonesia based on the pancreatic MRI R2* results as well as to determine its association to FBG, 2-h PPBG, and cardiac MRI R2* results. This study was conducted at the Thalassemia Center in Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia. Eligible subjects included TM patients receiving routine blood transfusion with no history of other diseases known to cause glucose intolerance. After obtaining fasting blood samples, oral administration of glucose load of 1.75 g/kg of body weight were provided and the 2-h PPBG were obtained. Normal cut-off values for impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus were used to evaluate the blood glucose examination results. Pancreatic and cardiac MRI were conducted using 1.5 Tesla MRI Scanner (Siemens Avanto Germany). Pancreatic MRI R2* results < 30 Hz were considered normal, 30–100 Hz as mild pancreatic siderosis, 100–400 Hz as moderate pancreatic siderosis, and > 400 Hz as severe pancreatic siderosis. Likewise, cardiac R2* results < 50 ms were considered normal, 50–72 Hz as mild cardiac siderosis, 72–100 Hz as moderate cardiac siderosis, and > 100 Hz as severe cardiac siderosis.3 Correlations between pancreatic MRI R2* results and FBG, 2-h PPBG, and cardiac MRI R2* were evaluated using the Pearson correlation test. Following the grouping of pancreatic MRI R2* results into normal, mild, moderate and severe pancreatic siderosis, the one-way ANOVA test was used to evaluate the associations of these groups to FBG and 2-h PPBG. Sixty-one subjects fulfilled the inclusion criteria, with a mean age of 13.28 (± 3.05) years old, ranging from 7 to 19 years old. Following MRI examination, 25 participants were found to have normal pancreatic MRI R2* (40.98%), 27 had mild pancreatic siderosis (44.26%), and 9 had moderate pancreatic siderosis (14.76%). However, 58 (95.08%) subjects had normal cardiac iron stores, 2 (3.28%) had mild cardiac siderosis, and 1 (1.64%) had severe cardiac siderosis. The mean FBG and PPBG were 85.18 (± 8.43) mg/dL and 89.05 (± 18.12) mg/dL, respectively. No subjects had IFG, and 1 subject was classified as having IGT, with a 2-h PPBG of 147 mg/dL and normal FBG. The Pearson correlation test showed no correlation between pancreatic MRI R2* and both FBG (r = 0.128, P-value = .327) and 2-h PPBG (r = −0.040, P-value = .761). Following grouping the subjects based on degree of pancreatic siderosis, there were no significant differences in both FBG (P = .673) and 2-h PPBG (P = .063) among the groups with the one-way ANOVA test. The Pearson correlation test showed no correlation between pancreatic and cardiac MRI R2* (r = −0.042). Of the two subjects who had mild cardiac siderosis, one also had moderate pancreatic siderosis, and the other had normal pancreatic iron stores. One subject had severe cardiac siderosis along with moderate pancreatic siderosis. In this study, a significant degree of pancreatic iron loading has not occurred and toxicity from the small degree of iron load was not seen. With an age range of 7–19 years old, the subjects may have only received iron chelation therapy for a relatively shorter period of time and therefore long-term exposure to iron that would have caused pancreatic damage may not have occurred yet. Among the subjects, 27 (44.2%) had mild and 9 (14.8%) had moderate pancreatic iron overload. In contrast, none had IFG and only 1 had IGT, which may suggest that MRI R2* can detect pancreatic iron accumulation at a much earlier stage, even before abnormalities can be seen in the FBG and 2-h PPBG results. Two factors that are thought to account for this in our population are the lack of availability of oral iron chelating agents at that time and poor compliance of DFO consumption. Furthermore, previous studies also report that while pancreatic R2* may be sensitive for glucose dysregulation, most patients may still have no symptoms and normal blood glucose, indicating the presence of a preclinical iron burden.4 The weak negative correlation between pancreatic and cardiac MRI R2* are in contrast to another demonstrating that pancreatic iron load are good predictors of cardiac iron load.5, 6 However, the fact that only 3 of the subjects had abnormal cardiac iron stores is in conjuction with the Noetzli et al. (2009) study, which suggests that pancreatic iron loading generally precedes cardiac siderosis and may occur up to a decade prior.6 In conclusion, this study highlights the importance of iron load monitoring in TM patients receiving routine transfusion. As only few centers in Indonesia are able to conduct MRI examinations to evaluate organ siderosis, the findings from this study reflects the need to modify the current guideline for TM management in Indonesia to include this examination as a monitoring strategy to improve patient treatment. Further studies should aim to identify the potential link between pancreatic MRI R2* and blood glucose levels, and whether conducting MRI R2* at an earlier age would be beneficial for TM patients.