Delineating Small Pituitary Tumors

New Visualization Technique Delineates Pituitary Adenomas for Precise Surgical Resection and Preservation of the Pituitary Gland

In the Surgical Molecular Imaging Laboratory at Brigham and Women’s Hospital (BWH), led by Nathalie Agar, PhD, researchers have developed a new visualization technique using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) to aid neurosurgeons in delineating small pituitary tumors.

Clinical Need Drives Innovation

Microadenomas, including many associated with Cushing syndrome, are often not visible on preoperative magnetic resonance imaging (MRI), making exact location difficult. In addition, discriminating pituitary tumor from normal pituitary gland to define the boundaries of these tumors during surgery, even with advanced intraoperative imaging tools, is extremely challenging. Current methods to detect hormone levels do not fit the time restraints of surgery.

“The result can be incomplete resection or the removal of normal pituitary tissue,” said Edward R. Laws, MD, surgical director of the Pituitary and Neuroendocrine Center at BWH. “Our goal in each patient’s case is to completely remove the tumor while preserving function of the pituitary gland, so we have a real clinical need to address these issues.”

Examining Large Molecules

Dr. Laws, Dr. Agar, and BWH neuropathologist Sandro Santagata, MD, PhD, collaborated with a team in the Surgical Molecular Imaging Laboratory to develop a test designed to assess the distribution of pituitary hormones, including prolactin, growth hormone, adrenocorticotropic hormone, and thyroid stimulating hormone levels in pituitary tissue.

“We have been studying mass spectrometry-based techniques that evaluate smaller molecules for use during the surgical resection of other brain tumor types and have demonstrated the tests’ clinical usefulness,” said Dr. Agar. “Our team developed this test to analyze much larger molecules with very high specificity in order to visualize the hormone levels found in pituitary tumors, as compared with normal pituitary tissue.”

In a proof of concept study published in August 2015 (Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):9978-83.), they analyzed six non-pathological (NP) human pituitary glands and 45 hormone secreting and non-secreting (NS) human pituitary adenomas using MALDI MSI. The team found that it is possible to determine the peptide and protein hormone composition of pituitary tumor resection samples in less than 30 minutes, making it feasible to use the test for near-real-time detection and delineation of pituitary tumors for intraoperative surgical decision making. The team anticipates beginning clinical study of the new test within the year among patients undergoing surgery for small pituitary tumors.

Expert Evaluation and Treatment

A multidisciplinary team in the Pituitary and Neuroendocrine Center at BWH, including neuroendocrinologists, neurosurgeons, neurologists, neuro-radiologists, neuro-ophthalmologists, neuropathologists, radiation oncologists, neuro-oncologists, psychiatrists, and others, delivers expert evaluation and treatment for hundreds of patients each year. Throughout his career, Dr. Laws has performed nearly 6,000 pituitary procedures and has pioneered new approaches designed to preserve the pituitary gland. An early adopter of the 3D endoscope, Dr. Laws has performed more than 600 3D endoscopic transsphenoidal pituitary procedures with preservation of the pituitary gland in more than 96 percent of patients.

  • Nathalie Agar, PhD
    Director, Surgical Molecular Imaging Laboratory
  • Edward R. Laws, MD
    Surgical Director, Pituitary and Neuroendocrine Center