ENDOCRINE/BONE DISEASE

Director
Dr. Frederick Singer 

Assistant Director
Dr. Nancy Greep 

Goals and Areas of Research

Women’s Health

We are interested in the general health of postmenopausal women who have been treated for breast cancer. In addition to being at risk for recurrence of breast cancer, commonly encountered problems in such women relate to sex hormone deficiency and include bone loss, hot flashes and loss of libido. The management of these problems is challenging since these women cannot take hormone replacement therapy. Our research relates to the mechanism of bone loss in women treated with chemotherapy, the development of nonhormonal treatments for hot flashes, a better understanding of the sex hormone changes associated with chemotherapy, and molecular markers of breast cancer.

Parathyroid

Hyperparathyroidism is a relatively common condition in which the four parathyroid glands in the neck secrete too much parathyroid hormone, resulting in an elevation of blood calcium which can lead to bone loss and kidney stones. Usually the disease is caused by a single benign parathyroid tumor (85%) or by enlargement of all four glands (10-15%). The only definitive therapy for this disease is surgical removal of the diseased glands, but surgery can be difficult because the glands are small and may be difficult for the surgeon to locate. We are interested in determining prior to surgery whether one or all four glands are responsible for the problem and if one gland is the cause where it is located. Such information would reduce the duration of an operation and increase the overall success of surgery.

Prostate Cancer

Prostate cancer is the most common malignancy in males. Dr. Singer is working in collaboration with Dr. Hoon in Molecular Oncology to study genetic markers in the serum of prostate cancer patients to determine if this type of test can improve the management of prostate cancer patients in the future.

Paget’s Disease

Paget's disease is the second most common bone disease and affects one to two million Americans. Dr Singer is collaborating with investigators at the University of Pittsburgh and the University of Texas at San Antonio on genetic and viral influences in the development of Paget’s disease.

Recent Research Achievements

Health of Breast Cancer Survivors

Our research has shown that chemotherapy is harmful to bone health not only because it causes estrogen deficiency but also because it may be directly toxic to bone. We have also participated in a multicenter trial which found that the selective serotonin re-uptake inhibitor paroxetine (Paxil®) is more effective than placebo in suppressing hot flashes. We are planning future studies on the impact of chemotherapy on serum androgens in women to determine if a decline in these levels could explain impaired libido.

Hyperparathyroidism

The department’s recent research has focused on four issues related to parathyroid tumors:

(1) What are the clinical characteristics of patients with primary hyperparathyroidism who have positive versus negative scans? Are those with negative scans more likely to have milder disease, smaller tumors, or particular types of tumors? And if negative scans are due to small glands, what is the smallest size gland that reliably can be detected by the scan?

(2) Is it possible to catch the disease so early that the parathyroid hormone level is still in the normal range even though the blood calcium is already elevated? If so, then early cases might escape diagnosis and develop more advanced disease.

(3) Is it possible to improve the sensitivity of the parathyroid scan?

(4) Is it possible to distinguish patients with single parathyroid tumors from those with four gland disease by analyzing the pattern of proteins in the parathyroid tissue and blood of patients who have had successful surgery?

We have determined that patients with negative sestamibi scans usually, but not always have small parathyroid tumors and that the smallest gland which can be reliably detected is about 250mg. We have found that early in the course of hyperparathyroidism the serum parathyroid level can be in the normal range and so the disease could escape diagnosis without a high index of suspicion. Our research also has shown that the molecular mechanism of a positive parathyroid scan when a benign parathyroid tumor is present is due to the turning off of a gene which codes for a cell membrane pump capable of removing foreign substances from cells. When the gene is switched on and the membrane transporter is active-as in normal tissue-, the radioactive tracer used for scanning is extruded quickly from parathyroid cells so the gland does not show up on the scan.

In future studies, we hope to administer a drug which reversibly shuts down the membrane transporter in order to allow the accumulation of the scanning agent and thus visualization of the abnormal gland(s). This technique will hopefully allow the "hot spots" to show up on the scan, resulting in more accurate and effective treatment for the patient.

At present we are analyzing the protein patterns in patients with single tumors and four gland disease to see if there are differences which distinguish the two types of primary hyperparathyroidism.

Prostate Cancer

Data are presently being analyzed in the Molecular Oncology laboratory which should show the value of serum genetic markers in the evaluation of prostate cancer patients.

Paget's Disease of Bone

A study which has evaluated the incidence of a specific genetic mutation in in the blood cells of patients with Paget’s disease in the United States is currently under review.