Neuroendocrine Unit

Clinical

The Neuroendocrine Clinical Unit provides a multidisciplinary evaluation of patients with pituitary and hypothalamic disorders. Our neuroendocrinologists (Drs. Sharon Wardlaw, Pamela Freda, John Ausiello and Gabrielle Page-Wilson) work closely with a neurosurgeon (Jeffrey N. Bruce, MD) and neuroradiologist (Alexander N. Khandji, MD) to develop diagnostic and treatment plans for patients referred to the Unit for evaluation. Other Endocrinology faculty that participate in Neuroendocrine Unit activities are Drs. Thomas Jacobs and Judith Korner.

Our Clinical Neuroendocrine Unit physicians (Drs. Sharon Wardlaw, Pamela Freda, John Ausiello, Gabrielle Page-Wilson treat patients with all types of disorders of the pituitary gland especially Pituitary tumors including Nonfunctioning Pituitary Tumors, Acromegaly, Cushing’s Disease, Prolactinomas and other types of tumors in the region such as Craniopharyngiomas. We also care for patients with Hypopituitarism, Diabetes Insipidus, Lymphocytic Hypophysitis and other diseases that affect the pituitary or hypothalamus. We work closely with Neurosurgery, Neuroradiology, Neuro-oncology and Radiation Oncology in the care of our patients. We also offer diagnostic evaluations such as Petrosal Sinus Sampling, performed by Dr. Khandji, for the evaluation of patients with Cushings syndrome.

For patients undergoing surgery a Specialized Pituitary Surgery Hospital Team of Neuroendocrine physicians and nurses work along with Dr. Bruce and the Neurosurgery team to provide in-hospital and post-operative care, ensuring close follow up on discharge.

A weekly, multi-disciplinary Neuroendocrine rounds is coordinated by our Neuroendocrine Unit physicians and attended by Neuroendocrine Unit physicians, Endocrinology fellows, Neurosurgery (Dr. Bruce) and Neuroradiology (Dr. Khandji) provides a forum for review of radiological studies and discussion of diagnostic and treatment plans and integrates all team members into each patient’s care.

Our Neuroendocrine Unit physicians are also members of The Pituitary Tumor Center of Columbia University.

The Clinical Neuroendocrine Unit has provided comprehensive Endocrinologic care to patients with pituitary disease for 20 years. We treat patients with all types of Pituitary tumors including Nonfunctioning Pituitary Tumors, Acromegaly, Cushing’s Disease, Prolactinomas and other types of tumors in the region such as Craniopharyngiomas. We also care for patients with Hypopituitarism and other diseases that affect pituitary function. We work closely with Neurosurgery, Neuroradiology, Neuro-oncology and Radiation Oncology in the care of our patients. Patients interested in a Consultation or treatment or physicians interested in referring a patient should fax a cover letter and documents supporting their diagnosis to our Neuroendocrine Unit at 212-305-4815 or may call 212-305-2254. We limit our practice to patients with hypothalamic-pituitary disease so that we may best care for patients with diseases within our expertise. We aim to provide a quick review of each case to determine eligibility for our Unit and rapid appointments. Our Clinical Neuroendocrine Unit is located at 180 Fort Washington Avenue, 9th floor, room 970, New York NY 10032.

PITUITARY GLAND DISORDERS OVERVIEW

What is the Pituitary Gland?
The pituitary gland is a small gland that sits in the head, just below the brain and behind the nose. The pituitary gland acts as the master gland of the body, producing hormones and controlling other glands in the body. Hormones travel in the blood throughout the body to many tissues and organs and carry out important functions necessary for life.

Within the pituitary gland are different types of cells, each of which makes a specific hormone. The hormones produced in pituitary gland cells include:

  • Prolactin - needed for production of breast milk and lactation
  • Growth hormone (GH) - necessary for normal growth in childhood and important for metabolism and other functions in adults.
  • Adrenocorticotropin (ACTH) –stimulates the adrenal glands (two glands located just above the kidneys) to produce Cortisol, which is a hormone that is essential for life as it helps keep blood pressure normal and blood sugar normal
  • Thyroid-stimulating hormone (TSH) - stimulates the thyroid gland, to make thyroid hormone (thyroxine) which is also necessary for life and important for metabolism, growth and other functions.
  • Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) - necessary for normal function of the testes in men and ovaries in woman and thus normal fertility and reproduction.
  • Posterior pituitary – releases a hormone Antidiuretic hormone (ADH) (also called vasopressin) that is necessary for maintaining normal water balance in the body.

What disorders can occur in the pituitary gland?
There are many causes of pituitary disease. The most common cause is a pituitary tumor. Up to 20% of people have a pituitary tumor that might be found if they were to have a pituitary MRI, but most of these are small and do not get recognized or need medical attention. Many pituitary tumors produce no symptoms, but are found by chance on a pituitary MRI done for an unrelated reason. These are called “incidentalomas”.

Pituitary tumors can come to medical attention because of physical signs or symptoms caused by hormone excess produced by the tumor or symptoms of low hormones (hypopituitarism) caused by disturbance of the normal pituitary gland. Large tumors can also put pressure on other structures surrounding the pituitary gland such as the nerves of vision producing visual changes or headaches.

Pituitary tumors are growths of pituitary gland cells. These tumors are almost always benign (i.e. not cancer). In the tumor, the cells multiply and produce a ball of cells of one type. Each tumor takes on characteristics of the cell of its origin. Many pituitary tumors originate in hormone producing cells and these tumors are called hormone-secreting. The most common type of hormone secreting pituitary tumors are prolactinomas, these are tumors made up of prolactin cells. Prolactinomas lead to high level of prolactin in the blood (link to prolactinomas section below). Other pituitary tumors are made up of growth hormone (GH) producing cells, a disease called Acromegaly. In Acromegaly high levels of GH and a hormone produced by GH, IGF-1 (insulin like growth factor 1) are found in the blood and patients experience many ill effects of these hormone excesses. Other tumors originate in ACTH producing cells leading to high levels of cortisol in the body and a disease called Cushing’s disease. Many pituitary tumors do not appear to produce a high level of a hormone in the blood and are termed nonfunctioning or non-secreting tumors. Some of these tumors originate in LH or FSH cells, but very few produce high levels of these hormones in the blood. Some pituitary tumors are TSH producing and lead to overactive thyroid function in the body.

Pituitary tumors can cause problems due to hormone over-production, with the nature of the changes in the body depending on the hormone. Pituitary tumors can also cause problems due to pressure on the structures surrounding the pituitary gland and the normal pituitary when they grow large. The nerves of vision sit just above the pituitary gland and pituitary tumors can lead to loss of vision, in particular loss of vision on the sides of the visual field. Pituitary tumors can also cause pressure on the normal pituitary gland which can get compressed by the tumor. Function of the normal pituitary gland can then become compromised, a condition called hypopituitarism. Pituitary tumors can also cause headache, in particular if they grow rapidly or if some bleeding occurs in the tumor, a condition cause apoplexy. Tumors less than 1 centimeter (cm) in size are called microadenomas and tumors 1 cm or larger are called macroadenomas. The larger the tumor, the more likely it is to cause pressure symptoms.

Other types of tumors and cysts can grow in the pituitary region and disrupt pituitary function. Some tumors originate in cells that line the pituitary area. Cysts of the pituitary are common. The most common of these are Rathke’s cleft cysts. Another type of tumor that can grow in the pituitary region is a craniopharyngioma, which also often contains cysts.

Other types of disorders can affect the pituitary. Some infiltrative (or granulomatous) conditions such as sarcoidosis can involve the pituitary gland. Inflammation can also involve the pituitary and produce lymphocytic hypophysitis.

What should you do if you are found to have a pituitary tumor?
Whether the pituitary abnormality is found on MRI done for another reason or a doctor suspects a hormone problem and then begins your evaluation, a detailed Endocrine evaluation that tests your hormones is a necessary initial step. Your Endocrinologist will look for signs on your physical examination or clues from your history of a possible hormone problem and will perform a series of blood tests that will test all your hormones. The Endocrinologist will test for high hormones, evaluating for a possible hormone producing or secreting tumors and for low hormone levels, thus evaluating you for hypopituitarism. You may need treatment with hormone supplements depending on the results of your tests. If you have not already had one, you will need a MRI that looks specifically at your pituitary with thin cuts through the pituitary. Depending on the size and location of your tumor your doctor may ask you to have Visual Field Testing which will determine whether or not your fields of vision are compromised by the tumor.

Depending on the type of tumor and the symptoms you have you may be referred to a Neurosurgeon who specializes in pituitary gland surgery. Prolactinomas are the one type of pituitary tumor that is best initially treated with medication, even if very large. Some pituitary tumors that are not altering your hormones or causing vision disturbance can just be followed with repeat MRI and pituitary hormone testing over time. Most tumors that are hormone secreting and tumors that are threatening or causing a vision problem require transsphenoidal surgery.

NON-FUNCTIONING (NON-SECRETORY) PITUITARY ADENOMAS

Many pituitary tumors are called non-functioning or non-secretory because they do not appear to release an excess of a hormone into the blood. Most of these tumors originate in a cell type that does not produce a hormone, but some come from LH or FSH cells, but these very rarely produce high levels of these hormones in the blood.

Non-secretory tumors do not cause the changes in the body that hormone producing tumors do. Rather, when they become large, they get diagnosed because of problems related to pressure on the structures surrounding the pituitary gland and the normal pituitary. These problems include loss of vision, at first peripheral vision and later more widespread vision loss, pituitary gland insufficiency (hypopituitarism) and headache. Pituitary tumors can also cause headache, in particular if they growth rapidly or if some bleeding occurs in the tumor, a condition cause apoplexy.

Not all growths that appear to be nonfunctioning pituitary adenomas require surgical intervention. A growth in the pituitary can be found when a MRI is done to evaluate an unrelated problem such as neck pain or dizziness. When a pituitary growth is detected in these cases it is called an “incidentaloma”. A lesion found “incidentally” on the pituitary is often a nonfunctioning pituitary adenoma. Such growths do need to be fully evaluated with a physical examination, history and blood tests. In these cases where the growth or tumor is small and not producing any symptoms or hormone excess it can often be followed over time. Surgery would be recommended if symptoms develop or the tumor grows rapidly.

Nonfunctioning pituitary tumors are treated with transsphenoidal microsurgery to remove the tumor when the tumor causes pressure on structures around the pituitary or when vision is threatened. This surgery is performed through the nasal sinuses. After surgery, visual field problems improve in most patients.

After surgery, pituitary MRIs need to be repeated over time to watch for any tumor regrowth. Some tumors do regrow even if all visible tumor is removed by surgery. If surgery cannot remove a large piece of tumor because of the location and size of the tumor or the tumor regrows, another surgery and/or radiation therapy may be needed.

Patients interested in learning more about Research Programs in our Neuroendocrine Unit for patients with Nonfunctioning Pituitary Tumors can contact our Neuroendocrine Research coordinators at 212-305-4921.

ACROMEGALY

Acromegaly is a rare disease causes by a GH producing pituitary tumor. These tumors are made up of GH producing pituitary cells that produce an excess of GH, which leads to high levels of GH in the blood. GH leads to the production of high levels of another hormone, insulin-like growth factors 1(IGF-1). Establishing the diagnosis of acromegaly requires demonstrating high levels of GH and IGF-1 in the blood. Another way to diagnose acromegaly is with an oral glucose tolerance test. In this test, GH levels in the blood are measured after a sugar containing drink. GH levels drop very low (or become suppressed) after glucose normally, but in acromegaly GH levels do not fall and may rise after glucose.

High levels of GH and IGF-1 produces may changes in the body from changes in physical appearance to changes in organs and metabolism. Often, the physical changes occur so gradually that they go unnoticed by people who see the patient every day, even the patient’s regular physician. A relative or physician who has not seen the patient in a long time may notice the changes. Most patients with acromegaly are diagnosed between 40 and 50 years of age, but the physical changes and symptoms may be present as long as 10 years before the diagnosis is made.

The most common physical changes are enlargement of the hands and feet and because of this acromegaly patients often enlarge their rings or get wider shoes. Facial appearance can change with coarsening of the facial features, thickening of the lips and enlargement of the bones of the forehead and the lower jaw. Patients can have a change in their bite and increased spacing of the teeth. Patients often have excess sweating, oily skin and acne. Many patients with acromegaly develop high blood pressure and diabetes mellitus. Many patients have joint pain, arthritis or numbness and tingling of the fingers due to carpal tunnel syndrome. Snoring is common and sleep apnea (breathing repeatedly stops and starts during sleep) can develop. Colon polyps are more common in patients with acromegaly.

In children, acromegaly is very rare, but if it occurs before puberty and before the growth plates of the bones have closed, the child can grow very tall due to the excess GH stimulating growth. This is called Gigantism.

Some patients with acromegaly also have prolactin elevation, which can lead to loss of menstrual periods in woman and low testosterone levels in men. Some patients with acromegaly have pituitary insufficiency, which can produce symptoms of low thyroid, low cortisol (from the adrenal glands) or dysfunction of the ovaries in women or testes in men which can include menstrual disorders, reduced sexual desire or infertility.

Patients with acromegaly, as with any type of pituitary tumor, can have symptoms due to pressure on structures surrounding the pituitary such as vision problems such as peripheral vision loss and headaches.

Acromegaly is treated initially by removal of the pituitary tumor by transsphenoidal microsurgery. Surgery is the most effective treatment for acromegaly because it removes the tumor mass thus relieving pressure on surrounding structures and protecting from future vision loss, it results in rapid reduction in GH and IGF-1 levels with improvement in symptoms and produces long term normalization of hormone levels in most patients. Surgery can lead to remission of acromegaly in most patients, but not all patients can be cured. The chance of remission after surgery depends on the size and location of the tumor. In some cases where medical problems make surgery unsafe, initial treatment may be given with medication such as a somatostatin analog.

After surgery, patients undergo detailed testing of their IGF-1 level and GH after the glucose drink to determine whether levels are normal or not. For patients with persistent elevations of GH and IGF-1 after surgery a number of medications are available including long-acting somatostatin analogs and a GH receptor antagonist. Some patients are also treated with radiotherapy to the remaining pituitary tumor. Treatment with medication will be necessary until radiation therapy takes effect, which usually takes years. Some patients need a number of therapies to achieve remission. Many of the problems experienced by patients get better and some can completely resolve with effective treatment of acromegaly. Headache can improve rapidly as can abnormal glucose levels, sweating. Much of the thickening of tissues in the hands and feet will reduce in size gradually after treatment. Bone changes such as enlargement of the lower jaw will not reverse.

Patients interested in learning more about Research Programs in our Neuroendocrine Unit for patients with Acromegaly can contact our Neuroendocrine Research coordinators at 212-305-4921.

For patients undergoing surgery a Specialized Pituitary Surgery Hospital Team of physicians and nurses provide in-hospital and post-operative care, ensuring close follow up on discharge. In addition to hospital care by the Neurosurgery service, patients are seen routinely in the hospital and post-operatively by the Neuroendocrine Service. The team employs standardized, validated protocols for the management of peri-operative adrenal hormone replacement and monitoring of fluid balances, electrolytes and diabetes insipidus. The goals of this program are to ensure optimal care of Endocrine function while allowing for an early and safe hospital discharge. Most patients return home after surgery on postoperative day 2, well below the US average of 5 days for pituitary surgery. Members of this team include Dr. John Ausiello (Neuroendocrine Unit), Dr. Gabrielle Page-Wilson (Neuroendocrine Unit), Meghan Smith NP (Neurosurgery) and the Endocrinology Fellows of the Division of Endocrinology.



Research

Complimenting our clinical programs are many clinical research programs that are funded by the National Institutes of Health and other sources. These programs offer patients the opportunity to receive novel diagnostic and therapeutic options for their pituitary tumors above and beyond those routinely available. These include the clinical management of prolactinomas, Cushing's disease and acromegaly. Dr. Freda is currently testing several new approaches to the evaluation and treatment of acromegaly in a large cohort of acromegalic patients. She is studying novel treatments and effects on body composition and metabolism. Dr. Freda has also initiated a comprehensive prospective study of nonfunctioning pituitary adenomas. Drs. Wardllaw and Page-Wilson have been studying new approaches to diagnosing Cushings syndrome based on tumor specific differences in the processing of ACTH and its precursor, proopiomelanocortin (POMC). In more basic studies Dr. Wardlaw has been studying the role of hypothalamic POMC and the brain melanocortin system in the regulation of neuroendocrine function and energy balance in animals models. Ongoing clinical studies are developing biomarkers to assess brain melanocortin activity in humans. Collaborative studies with Drs. Judith Korner, Rudolph Leibel and Michael Rosenbaum focus on understanding and reversing the neuroendocrine changes induced by weight loss in order to help maintain weight loss after dieting. Related clinical research focuses on the mechanisms responsible for the hypothalamic obesity seen in some patients with hypothalamic tumors.




The Central Melanocortin System and the Regulation of Energy Balance.
(Dr. Sharon Wardlaw (PI))
The long-term objective of this project is to understand how the brain senses levels of peripheral energy stores and integrates these signals to maintain energy balance. This project focuses on the melanocortin neuropeptide system which plays a key role in regulating appetite and body weight and is an important target for leptin and insulin in the hypothalamus. Studies center on the regulation of proopiomelanocortin (POMC) and the POMC-derived peptides, α-MSH, γ-MSH and ß-EP, together with agouti related protein (AgRP) which is synthesized in the hypothalamus and is a potent antagonist of the MSH peptides. Transgenic and knockout mouse models are being used to study role of the melanocortin system in modulating metabolic responses to energy excess on a high fat diet and to food restriction and to characterize underlying mechanisms with respect to changes in body weight/composition and glucose and fat metabolism with a focus on energy expenditure and fuel oxidation. An important focus is on the regulation pf POMC peptide processing with respect to energy balance. These studies are highly relevant to human energy balance as mutations in POMC, POMC processing enzymes and in melanocortin receptors have all been associated with human obesity and there are many parallels with rodent models of melanocortin deficiency.

    • Lee M and Wardlaw SL: The central melanocortin system and the regulation of energy balance. Frontiers in Bioscience 12: 3994-4010, 2007.
    • Lee M, Kim A, Chua SC, Obici, S, Wardlaw SL: Transgenic MSH overexpression attenuates the metabolic effects of a high fat diet. Am J Physiol Endocrinol Metab 293: E121-E131, 2007.
    • Plum L, Lin HV, Dutia R, Tanaka J, Aizawa KS, Matsumoto M, Kim AJ, Cawley NX, Paik J, Loh YP, DePinho RA, Wardlaw SL, Accili D. The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake. Nature Medicine 15: 1195- 201, 2009.
    • Wardlaw, SL: Hypothalamic proopiomelanocortin processing and the regulation of energy balance. European J of Pharmacology 660: 213-219, 2011.
    • Dutia R, Meece K, Dighe S, Kim AJ, Wardlaw SL: ß-Endorphin antagonizes the effects of α-MSH on food intake and body weight. Endocrinology 153: 4246-4255, 2012.




Cerebrospinal Fluid Neuropeptide, Hormonal and Metabolomic Analysis in Human Energy Balance.
(Drs. Sharon Wardlaw (PI), Gabrielle Page-Wilson, Judith Korner and Richard Smiley)
This proposal will focus on cerebrospinal fluid (CSF) POMC and AgRP measurements as a surrogate for hypothalamic melanocortin activity, as related to CSF leptin, insulin and nutrient levels. Recent studies in the rodent show that levels of the intact POMC prohormone in CSF reflect hypothalamic POMC activity. We have confirmed that the POMC prohormone is the predominant POMC peptide in human CSF and are examining the relationship of CSF POMC to BMI and adiposity. An important goal is to identify biomarkers in CSF that could predict responses to dieting and to pharmacotherapy for obesity that target the melanocortin system.

    • Xiao E, Kim AJ, Dutia R, Conwell I, Ferin M, Wardlaw SL: Effects of estradiol on cerebrospinal fluid levels of agouti-related protein in ovariectomized rhesus monkeys. Endocrinology 151: 1002-1009, 2010.
    • Page-Wilson G, Reitman-Ivashkov E, Meece K, White A, Rosenbaum M, Smiley RM, Wardlaw SL: Cerebrospinal fluid levels of leptin, proopiomelanocortin and agouti-related protein in human pregnancy: Evidence for leptin resistance. J Clin Endocrinol Metab 98:264-271, 2013.




New approaches to the Treatment of Prolactinomas and Elevated Prolactin Levels
Elevated prolactin levels are commonly caused by pituitary tumors that produce prolactin (prolactinomas). These tumors are primarily treated with medications instead of surgery. Both bromocriptine and cabergoline lower prolactin levels and promote tumor shrinkage. However, these medications can have side effects and their prolonged use may be associated with heart valve disease.

Ropinirole is a medication that is FDA approved for use in patients with Parkinson's disease and Restless Leg Syndrome that has been show to lower prolactin levels in patients with Parkinson's disease and in healthy volunteers with few side effects.

The purpose of these studies is to determine if ropinirole can be used to effectively lower prolactin levels without significant side effects in patients with elevated prolactin levels. Study 1 evaluates how ropinirole affects prolactin levels over 24hrs. Study 2 examines the long-term effectiveness of ropinirole for treating high prolactin levels.

Please click here for more information.




New Approaches to the Diagnosis of Cushing’s Disease.
(Drs. Gabrielle Page-Wilson (PI), Sharon Wardlaw, Pamela Freda, Alexander Khandji and Jeffrey Bruce)
New assays are being evaluated that will improve the differential diagnosis of ACTH-dependent Cushing’s syndrome based on tumor specific differences in the processing of ACTH and its precursor, proopiomelanocortin (POMC). This is being evaluated in conjunction with petrosal sinus sampling in order to develop a less invasive way to distinguish between pituitary and ectopic sources of ACTH secretion.

    • Page-Wilson G, Freda PU, Jacobs T, Khandji AG, Bruce JN, Meece K, White A, Wardlaw SL: Elevated plasma POMC and AgRP levels in ectopic ACTH tumors: Use in the differential diagnosis of ACTH-dependent Cushing’s syndrome. 94th Annual Meeting of the Endocrine Society, Houston, TX, 2012.




New Approaches to Evaluation and Treatment of Acromegaly.
(Pamela U. Freda MD (PI), Tirissa J. Reid MD, Jeffrey N. Bruce MD, Anthony Ferrante MD, Kalmon Post MD, Fernando Arias-Mendoza MD, PhD)
These NIH supported studies focuses on patients with acromegaly, a rare disease characterized by excess GH and IGF-I and their multi-system adverse effects. For these studies we utilize a large cohort of newly diagnosed and postoperative patients with acromegaly. The studies examine a novel GH-IGF-I excess specific dysregulation of adipose tissue (AT) and lipodystrophy, which we believe contributes to insulin resistance, adipokine and appetite hormone dysregulation, endothelial cell dysfunction and ultimately increased CV risk in active acromegaly. During treatment, as GH/IGF-I normalize, reversal of the lipodystrophy markedly increases central AT, macrophage infiltration and inflammation in AT and systemic inflammation. We are testing these hypotheses utilizing techniques novel to the study of acromegaly and the GH/IGF-I axis including examinations of muscle lipid by MRI and 1HMRS, hepatic lipid by 1HMRS, adipose tissue for macrophage infiltration and inflammation and function of biopsied endothelial cells. We will also relate these clinical endpoints to our modern biochemical markers of acromegaly and thereby establish clinically validated biochemical guidelines for acromegaly therapy.

  • Freda PU, Wendy K. Chung, Naoki Matsuoka, Jane E Walsh, M. Nabi Kanibir, George Kleinman, Yuanjia Wang, Jeffrey N. Bruce, Kalmon D. Post. Analysis of GNAS Mutations in 60 Growth Hormone Secreting Pituitary Tumors; Correlation with Clinical and Pathological Characteristics and Surgical Outcome Based on Highly Sensitive GH and IGF-I Criteria for Remission Pituitary 10(3); 275-282, 2007
  • Freda PU, Shen W, Heymsfield SB, Geer EB, Reyes-Vidal CM, Gallagher D. Lower visceral and subcutaneous, but higher intermuscular adipose tissue depots in patients with GH and IGF-I excess due to acromegaly. J Clin Endocrinol Metab 93(6); 2334-2343, 2008.
  • Freda PU. Medical management of the patient with acromegaly. In Pituitary Tumors; Diagnosis and Management. Humana Press, Inc. Ed. Biller BMK & Swearingen B. 2008, pp. 151-170.
  • Reid TJ, Post KD, Bruce JN, Kanibir MN, Reyes-Vidal CM, Freda P. Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006; Acromegaly remains under-recognized and under-diagnosed. Clin Endocrinol. 2009 May 16 [Epub].
  • Freda PU, Shen, W, Reyes-Vidal CM, Geer EB, Arias-Mendoza F, Gallagher D, Heymsfield SB. Skeletal Muscle Mass in Acromegaly Assessed by Magnetic Resonance Imaging and Dual Photon X-ray Absorptiometry. J Clin Endocrinol Metab. 2009 Aug; 94(8): 2880-6.




Prospective Study of Clinically Non-functioning Pituitary Adenomas.
(Pamela U. Freda MD (PI), Sharon L. Wardlaw MD (Co-I), Jeffrey N. Bruce (Co-I), Steven Isaacson MD, Yaakov Stern, PhD, Kalmon Post MD)
This NIH funded, multi-disciplinary collaborative study is first comprehensive prospective study of clinically non-functioning pituitary adenomas (CNFA). This project prospectively studies asymptomatic pituitary lesions that do not require surgical intervention in order to determine the appropriate initial evaluation and follow up as well as the safety of their conservative, non-surgical management. We also prospectively assess the outcome of symptomatic CNFAs treated with surgery, the safety of conservative follow up for patients with small tumor remnants after surgery and determine which patients need radiotherapy(RT) by examining the risks vs. benefits of post-operatively RT for residual/recurrent tumors. This project also examines for the first time, prospectively, the impact of the disease and our therapies on quality of life and neurocognitive function in patients with CNFAs and establish a novel bank of pituitary tumor specimens from our cohort that will be linked to the extensive clinical data collected in our prospective study.

  • Ausiello JC, Bruce JN, Freda PU. Postoperative assessment of the patient after pituitary surgery. Pituitary 11(4); 391-401, 2008.
  • Freda PU, Bruce JN. Surgery: Risks of pituitary surgery in the elderly. Nat Rev Endocrinol. 2010 Nov;6(11):606-8. No abstract available. PMID: 20962868
  • Freda P, Beckers AM, Katznelson L, Molitch M, Montori VM, Post KD, and Vance ML. Pituitary Incidentaloma: An Endocrine Society Clinical Practice Guideline. J. Clin Endocrinol Metab 2011 Apr;96(4):894-904.