- Foundation for the Development of Internal Medicine in Europe
Short final reports of the 2020 Clinical Research Bursary recipients
Below you will find the short final reports of the 2020 Clinical Research Bursary recipients. Because they are not easy to read in all aspects by lay people, we have added a few sentences in the beginning to explain.
“Towards Treatment Optimization in autoimmune Pancreatitis (the TOP Study)”
Identifying predictors for long-term metabolic, infectious, and treatment-related complications in autoimmune pancreatitis patients
I am deeply thankful to FDIME for granting me the opportunity to carry on my project on autoimmune pancreatitis in the marvelous frame of the Karolinska Institute, Stockholm, Sweden.
Type 1 autoimmune pancreatitis (AIP) is a rare form of immune-mediated pancreatitis that belongs to the Immunoglobulin-G4 related disease (IgG4-RD) spectrum, sharing its most peculiar features such as serum IgG4 level elevation and a lymphoplasmacytic infiltrate in the affected organs. AIP carries a high risk of metabolic and infectious complications, related to pancreatic insufficiency and biliary strictures or immunosuppressive treatment, respectively. Moreover, AIP it is prone to relapse, requiring multiple courses of glucocorticoids that might exacerbate pancreatogenic (Type 3c) diabetes. In addition, the chronic inflammation in the hepatobiliary district might represent a trigger for subsequent malignant transformation, but a causal link has not been assessed yet.
Yet, to date there are only scant data on predictors of disease relapse, while data related to risk factors for long-term metabolic and infectious complications are absent. Given these premises, AIP management is far from being personalized and ‘one-size fits all’ treatment still represents the medical standard, ultimately resulting in over- or under-treatments.
Thanks to FDIME grant I have created a synergistic enterprise involving more than twenty tertiary care centers dealing with AIP, totaling more than 1000 AIP patients. As a result of this endeavor, we have now created the first European registry of AIP patients from which more data on the natural history of AIP will stem, focusing on AIP epidemiology, response to treatment, and risk factors for disease relapse.
Moreover, after merging the data Karolinska Institute and San Raffaele scientific Institute, I have unveiled how maintenance treatment with glucocorticoid represents a risk factor for new onset diabetes mellitus and infectious cholangitis, thus pointing out the relevance for alternative immunosuppressive agents.
Last, I had the chance to shedding more light also on type 2 AIP, a recently recognized form of AIP characterized by a dense neutrophils infiltrate of the pancreas. Thanks to a combined effort we disclosed the strong interplay between type 2 AIP and inflammatory bowel disease, both in terms of clinical presentation and response to treatment.
Overall, I am deeply confident that the FDIME research grant contributed to my professional and personal growth, boosting my career and providing a fertile soil for further international studies in the field of autoimmune disease.
Link to published articles:
Musculoskeletal comorbidities and changes in body composition in acromegaly
Acromegaly is a clinical syndrome resulting from constantly elevated concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-I) due to a somatotroph pituitary adenoma in almost all cases. If not adequately treated, GH excess is associated with an increased morbidity and mortality.
The metabolic effects of GH include anabolic actions on the muscle and bone, and catabolic actions on adipose tissue. This results in a disease specific distribution of adipose tissue, as well as in potential skeletal fragility, malformations and arthropathy.
For the characterization of a disease specific profile of musculoskeletal abnormalities a longitudinal, retrospective analysis was performed. We included 201 out of 516 patients diagnosed with acromegaly treated at the Bicêtre hospital, who had at least one DEXA measurement for the assessment of bone mass and microarchitecture, as well as body composition. In addition, results of x-rays of the spine for the assessment of vertebral fractures, as well as of the larger joints for the assessment of malformations were analyzed.
The effect of acromegaly treatment on changes in body composition was our first research question. Here we investigated specific effects of treatment vs ageing on changes in body composition and compared patients evaluated both at the time of active and controlled disease (A>C; n=31) and patients evaluated two times while the disease was controlled (C>C; n=32).
Patients from A>C and C>C groups were comparable for age, sex, BMI and follow-up duration (p=n.s.). Treatment of acromegaly was associated with an increase in fat mass and a decrease in lean mass in the A>C group, which was four and eight times more pronounced compared to the C>C group (fat mass: +39±34 vs +10±15%, p<0.001; lean mass: -8±8 vs -0.2±6%, p<0.001, respectively).
Changes in fat mass were negatively associated with IGF-I (r=-0.450;p=0.011) and independent of the individual therapy. In the whole cohort a correlation of IGF-I with fat (r=-0.369;p<0.001) and lean mass (r=0.383;p<0.001) could be found.
These results show that treatment of acromegaly has a strong impact on body composition. This is characterized by an increase in fat mass and a decrease in lean mass until biochemical disease remission. Thereafter, body composition changes are similar to what is observed with ageing.
Our second research question was the impact of acromegaly on musculoskeletal complications. Therefore, the prevalence of vertebral fractures as well as of malformations of the joints and the spine will be assessed in the whole cohort of patients. In addition, longitudinal changes in bone quantity and quality will be analyzed in the A>C group and the C>C group to investigate the treatment specific effects. The analysis of these parameters is currently ongoing.