Neuroendocrine Clinical Research Program

Overview

Our goal is to conduct research that will ultimately improve clinical care for patients with neuroendocrine disorders.

Research at the Neuroendocrine and Pituitary Tumor Clinical Center at Massachusetts General Hospital is divided into four major areas including:

1. Pathogenesis and regulation of human pituitary adenomas;
2. Pathophysiology of neuroendocrine disorders;
3. Relationship between neuroendocrine factors and body composition including anorexia nervosa and obesity and;
4. Development of novel therapies for patients with pituitary and hypothalamic disorders.

How Our Clinical Mission Drives Research

Our clinical mission is to advance the diagnosis and treatment of patients with pituitary and neuroendocrine disorders. The Neuroendocrine Unit is an internationally recognized research center in neuroendocrinology, body composition, and pituitary disease. Investigators in the Center have been awarded 14 NIH and federal research grants. In addition, funding from industry and private foundation support for investigator initiated research. Research in the Neuroendocrine Unit incorporates both clinical and translational laboratory investigations in neuroendocrinology. In vitro and in vivo investigations have allowed basic studies of pituitary tumor pathogenesis and regulation to be brought directly into the clinical research arena.

Investigators in the Neuroendocrine Unit have played key leadership roles in the establishment and implementation of nationally recognized research programs in neuroendocrine disorders and have pioneered novel therapies for patients with secretory pituitary tumors, including the use of GH receptor antagonists and somatostatin receptor subtype specific analogues.

Key Collaborations

Another major focus of research is the relationship between the neuroendocrine axis and body composition. In recent collaborative work with the bioimaging groups in Psychiatry and Radiology, we are investigating the impact of psychiatric disorders and associated hormone disorders on specific brain regions, and the use of novel imaging modalities to investigate the effects of hormone deficiency states on body composition.  In collaboration with Neuropathology, we are investigating the role of novel tumor suppressors in pituitary tumor development.  In collaboration with the Department of Radiology, we are using novel imaging techniques to assess body composition and metabolism.  In our collaborations with the Departments of Neurosurgery and Radiation Oncology, we have improved patient care for patients following cranial irradiation and have and completed investigations and have published work regarding the effects of surgery and radiotherapy on hypothalamic/pituitary function. The creation and expansion of the Neuroendocrine Center has provided a patient base for obtaining tumor tissue for in vitro experiments, conducting clinical studies, as well as providing continued care to these patients.

Learn more about Pediatric Endocrine/Neuroendocrine/Sports Endocrine Research.

Research Projects

Neuroendocrine regulation of bone mass and body composition

Research projects and highlights include:

1. The regulation of bone mass and fat depots by GI/neuroendocrine factors including PYY and Ghrelin;
2. The investigation of the GHRH, GH/IGF-1 axis on bone density, bone architecture and visceral adiposity in adults and children including studies in anorexia nervosa and obesity;
3. The contribution of GH resistance to the bone loss seen with anorexia nervosa; effects of GH versus rhIGF-1 administration;
4. The impact of anorexia and undernutrition on bone mass accretion and pubertal development. The role of  rhIGF-1 as a selective stimulator of bone formation in states of undernutrition to increase peak bone mass in children with anorexia nervosa and its relationship to gonadal steroids is under investigation;
5. Endogenous growth hormone (GH) secretion as a major determinant of cardiovascular risk in obese adults and adolescents;
6. The role of endogenous hypercortisolemia on body composition and neurocognitive function.

Neuroendocrine mediators of psychiatric disease

Research projects and highlights include:

1. Abnormalities in appetite regulatory circuitry in anorexia nervosa using PET bioimaging paradigms and genetic approaches;
2. Estrogen and gonadal steroid effects on cognition in women with schizophrenia or depression; neuroprotective effects of estrogen;
3. Effects of glucocorticoids as mediators of cognition in patients with depression;
4. Neuroendocrine regulation of oxytocin and physiologic effects of oxytocin in humans.

Novel therapies for pituitary tumors

Research projects and highlights include:

1. Use of novel somatostatin SSTR 2 and 5 targeted analogues to inhibit ACTH  secretion and proliferation in human pituitary adenomas;
2. Investigation of the long term effects of GH deficiency in patients with pituitary tumors on cardio-vascular risk
3. New therapies for Acromegaly
4. Effects of cortisol receptor blockade in Cushing’s syndrome