Researchers from the Icahn School of Medicine at Mount Sinai are presenting several new studies at ENDO 2013, The Endocrine Society’s Annual Meeting & Expo (ENDO) from June 15-18 in San Francisco.
Mount Sinai researchers demonstrate new data on diabetes self-management, as well as the role of prostastic acid phosphatase (PAP) in Prostate Cancer (PCa) bone metastases; identify new molecules that can stimulate the thyroid gland; reveal the prevalence of primary aldosteronism (PA) in an urban population; and show how thyroid autoimmunity may be triggered by endoplasmic reticulum (ER) stress.
Highlights of Mount Sinai research at ENDO 2013:
Availability of Reliable Home Blood Glucose Data at Diabetes Appointments and Correlation with Hemoglobin A1C
Medicaid and Medicare patients with uncontrolled diabetes, who brought their glucose meters to appointments, and monitored levels at home, lowered their Hemoglobin A1c by 1.2 percent, whereas all other patients saw no change in their A1c. The research highlighting diabetes self-management was conducted by Ronald Tamler, MD, PhD, CDE, Clinical Director of the Mount Sinai Diabetes Center and Associate Professor of Medicine at The Mount Sinai Medical Center and his team, and presented in an ENDO 2013 poster session. “These results show that there is still much work to be done in educating patients about the benefits of glucose monitoring,” said Dr. Tamler. “We also need to focus our resources on the population most likely to benefit from this kind of monitoring. After all, the effect seen in Medicare and Medicaid patients rivals that of adding another medication.”
The team reviewed data on 500 adult patients at the Mount Sinai Diabetes Center and determined that 30 percent of the patients (almost all insulin-treated) brought glucose meters to their visits. “Hand-written glucose logs can be misleading,” said Gillian Boyd-Woschinko, MD, Chief Endocrine Fellow at Mount Sinai and lead author of the study. “Past research has shown then when comparing hand written logs to meter data, it can be inaccurate due to under-reporting and over-reporting. Both occur as a result of human error, the desire to please the physician, and lack of understanding of the utility of accurate data. We encourage all patients to bring their blood glucose meters to their appointments, so we can download them.”
Prostatic Acid Phosphatase in Prostate Cancer Bone Metastases: Rank Ligand as a Mediator
Levels of prostatic acid phosphatase (PAP), the oldest tumor marker, are elevated in men with prostate cancer (PCa) bone metastases, according to research presented by Alice C. Levine, MD, Professor of Medicine in the Division of Endocrinology, Diabetes and Bone Diseases at the Icahn School of Medicine at Mount Sinai and her team in a highlighted poster session. According to Dr. Levine, PCa has a tendency to spread to the bone where it becomes incurable and blood PAP levels are higher in men with PCa bone metastases.
“Currently, there are no curative therapies for this stage of the disease,” said Dr. Levine. “Our study could have wide-ranging clinical applications for men with advanced PCa that has spread to bone.”
Researchers studied two PCa cell lines and a mouse preosteoblast (OB) line. All three cell lines expressed measurable amounts of two proteins, RANK Ligand (RANKL) and Osteoprotegerin (OPG) mRNA/protein that are known to be essential regulators of bone formation and breakdown. The results suggested that PAP secreted by PCa cells in bone metastases modulates RANKL/OPG expression in both PCa and OB cells and therefore inhibitors of PAP may effectively target the RANKL/OPG system and treat bone metastases.
The study took place from February 2012 until April 2013 and was funded through an Exploration Hypothesis Award from the Department of Defense Prostate Cancer Research Program.
Pathways to Thyroid Stimulation: Identification of New Potent and Selective Small Molecular Agonists to the TSH Receptor
Mount Sinai researchers have identified two novel and potent small molecular compounds proven to be effective in stimulating the thyroid gland and producing more thyroid hormone.
For this study, Terry F. Davies, MD, the Florence and Theodore Baumritter Professor of Medicine at the Icahn School of Medicine at Mount Sinai and his research team screened 50,000 molecules, narrowed them down to 20 molecules which had activity and then identified two molecules with high potency and specificity.
“One of the two molecules identified has a very impressive potency and the potential to be used as a diagnostic tool and therapeutic agent in individuals,” said Dr. Davies, who is giving an oral presentation at ENDO 2013. “This newly- identified molecule could lead to the pharmaceutical development of a very effective form of human thyroid-stimulating hormone (TSH), similar to Thyrogen. This drug works by binding to TSH receptors on normal thyroid cells or on thyroid cancer tissue and helps to determine if there are any thyroid cells or thyroid cancer cells remaining after removal of the thyroid gland. Our identification of such novel and potent molecules could have the potential to develop new treatments for thyroid dysfunction, including thyroid cancer, in the future.”
Prevalence of Primary Aldosteronism in an Urban Hypertensive Population
With 65 million people in the U.S. diagnosed with hypertension, Dr. Levine and her research team at Mount Sinai will present data showing that primary aldosteronism (PA) is under diagnosed and undertreated in patients. PA is a disorder where the adrenal glands make too much of the hormone aldosterone, which was once thought of as a very rare cause of high blood pressure in patients with hypertension, with or without low blood potassium levels,
The data from this study shows that 4.7 percent of patients tested in the study had blood aldosterone and renin levels indicating they may have PA. Those patients are currently undergoing further testing for the diagnosis. “It is important to ascertain whether PA is a common cause of high blood pressure in our urban population since many of the drugs we currently employ would not be effective if this is the underlying cause,” said Dr. Levine. “Medical and surgical therapies are now available that could properly target this disease.”
According to Dr. Levine, physicians do not generally screen hypertensive patients for this disorder unless they have very severe high blood pressure and also have low blood potassium levels.
“Testing for PA involves a very simple blood screening test which can be done in almost all hypertensive patients without even discontinuing their drugs,” said Dr. Levine. “As a result of our research, many more screening tests have been done by physicians at Mount Sinai, and previously unsuspected cases have been confirmed and patients have been properly treated.”
For the study, the first of a large urban population in the United States, researchers screened 260 individuals for PA who had previously been diagnosed with hypertension. Researchers measured the levels of aldosterone and renin through two separate blood tests. The study was conducted with patients in New York City from August 2012 until May 2013.
Pinpointing Interpheron-alpha in Thyroid Autoimmunity: The Role of Endoplasmic Reticulum Stress
Thyroid autoimmunity might be triggered by a process called Endoplasmic Reticulum (ER) stress, which can even occur following a viral infection, according to Angela Lombardi, PhD, a post-doctoral fellow at the Icahn School of Medicine at Mount Sinai who is making an oral presentation. Dr. Lombardi was mentored by Yaron Tomer, MD, FACP, Chief of the Hilda & J. Lester Gabrilove Division of Endocrinology, Diabetes and Bone Disease at The Mount Sinai Medical Center.
ER stress is a process in which cell production and packaging of newly-synthesized proteins is perturbed. This can trigger an autoimmune response which can lead to inflammation and cause cell death. In this study, a human thyroid cell line and human primary thyroid cells were exposed to interferon-alpha (IFN-a), a protein which is secreted during infections. The cells were then tested for markers of ER stress. As a result, both the cell line and the primary thyroid cell cultures showed high levels of ER stress.
“This study showed that one of the main proteins produced by cells in response to infection can also cause ER stress in thyroid cells which can trigger thyroid autoimmunity,” said Dr. Tomer. “This discovery will enable us to test ER stress blockers for their effectiveness to treat and prevent thyroid immunity in the future.”
The Mount Sinai Hospital / Mount Sinai School of Medicine