Neuroendocrine Clinical Center, Neuroendocrine Unit, Department of Medicine, and Neurosurgical Service (B.S., N.T.Z.), Massachusetts General Hospital, Boston, Massachusetts 02114
Address all correspondence and requests for reprints to: Beverly M. K. Biller, M.D., Neuroendocrine Unit, BUL457B, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114-2696.
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Introduction: development of the Neuroendocrine Clinical Center |
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Since its founding in 1985, the Neuroendocrine Clinical Center has grown substantially in patient volume and personnel to become a major national and international referral center for patients with pituitary and hypothalamic disorders. Initially staffed by 1 endocrinologist, 1 neurologist, and 1 neurosurgeon on 1 afternoon a week, it now is comprised of 3 weekly teaching sessions with a total of 7 endocrine fellows as well as rotating medicine and neurology residents and medical students seeing patients under supervision by 4 staff neuroendocrinologists, 1 neurologist, and 2 neurosurgeons. There are also several separate weekly staff sessions. The total volume at the inception of the Clinical Center was approximately 100 patient visits/yr; it is now well over 1000 visits annually. The most consistent reason for growth of the Center is that referring physicians believe that this type of cohesive multidisciplinary program is needed for patients with complex pituitary and hypothalamic diseases. Despite the fact that many patients come from other states or countries, permission for out of plan coverage is often obtained from insurance carriers because of the unique strengths of the Center. Many patients are referred because of the specific expertise of individual staff endocrinologists in areas such as prolactinomas, Cushings disease, and acromegaly. Referrals are also directed toward the expertise of the neurosurgeons, who are world-renowned for their abilities at curative transsphenoidal adenomectomy with minimal morbidity. With well over 1000 transsphenoidal surgeries performed at Massachusetts General Hospital over the past 15 yr currently undergoing analysis, it is clear that the many years of experience are beneficial to patients. In addition, one of the worlds largest experiences with stereotactic radiosurgery using proton beam therapy for residual/recurrent pituitary adenoma is now available through the Center. The expertise of neuropathologists at Massachusetts General Hospital in the diagnosis and characterization of pituitary adenomas and in pituitary pathology research also plays a key role in the high level of patient care.
The second reason for recent growth of the Center has been that it has served as a major site for the investigation of pathogenesis and the treatment of pituitary disorders. The findings that 1) the majority of clinically nonfunctioning tumors are of gonadotroph origin, 2) pituitary tumors are monoclonal, 3) inhibin subunits may play an important role in tumor phenotype and proliferation, and 4) osteoporosis is a major clinical consequence of hyperprolactinemic hypogonadism in men and women have all emerged from investigations at the Center. The Neuroendocrine Clinical Center was one of the initial sites pioneering the use of octreotide in acromegaly and has worked toward developing the availability of new dopamine agonists, such as CV205502 and cabergoline, for prolactinomas. The Center has designed studies addressing whether adults with acquired GH deficiency should receive long term replacement of this hormone. Many physicians refer their patients to the Center to provide them with access to the most innovative diagnostic or therapeutic approaches. For example, over 100 patients with Cushings syndrome have undergone bilateral inferior petrosal sinus sampling at Massachusetts General Hospital.
A third reason for a recent increase in patient referrals relates to an expanding base of patient awareness groups. There are a number of groups that promote awareness in pituitary disorders, and such groups typically refer patients to major medical centers where there is the combined expertise of neuroendocrinology, neurology, neurosurgery, and radiation oncology so as to provide the most comprehensive approach to pituitary tumors.
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Patterns of patient referrals |
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Patient populations |
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A typical day in a Neuroendocrine Clinical Center session included the following new patients:
A 28-yr-old dentist from South America with a classic history of acromegaly presented with headache and increased difficulty manipulating his dental instruments over the past year because of enlarging hands. He was referred to the Neuroendocrine Clinical Center by a physician in New York to undergo curative transsphenoidal surgery at Massachusetts General Hospital.
A 20-yr-old man who had recently been hospitalized in the neurosurgical intensive care unit for closed head trauma associated with diabetes insipidus. He underwent an insulin tolerance test to determine whether the steroids given for brain edema had suppressed his adrenal axis.
A 57-yr-old panhypopituitary man after craniotomy and radiation therapy for a craniopharyngioma, referred for GH stimulation testing with clonidine to determine eligibility for a clinical research study investigating GH replacement.
A 40-yr-old woman with Cushings syndrome (diagnosed by her neighbor who had read a magazine article) referred by her internist for evaluation and treatment.
Follow-up patients seen that day were:
A 32-yr-old woman from Connecticut 5 yr after surgery and cranial irradiation for a chrondrosarcoma, evaluated on an annual basis for the development of hypopituitarism.
Three premenopausal women with microprolactinomas doing well on dopamine agonist therapy.
A 27-yr-old woman with hyperprolactinemia induced by neuroleptics and a 3-mm abnormality on head magnetic resonance imaging, stable on follow-up scan.
Two patients several years posttranssphenoidal surgery for nonfunctioning macroadenomas, doing well with no evidence of recurrence clinically or radiographically.
A 34-yr-old patient with residual acromegaly after transsphenoidal surgery and radiation, under control with sc octreotide injections.
Hyperprolactinemia.
The most common diagnosis seen in the
Center is pituitary adenoma, accounting for 45% of cases. The major
tumor subtypes are seen in Fig. 1. Hyperprolactinemia accounts for
nearly half of these cases and includes idiopathic, micro- or
macroprolactinomas, and drug-induced types. Several new
idiopathic/microprolactinomas are seen each week; medical treatment
with bromocriptine or cabergoline is begun if the patient has
hypogonadism, infertility, or clinically significant galactorrhea.
Macroprolactinoma patients have historically been treated with
bromocriptine, but currently many such patients are being offered
participation in a new cabergoline trial because of its high rate of
patient acceptance due to the low incidence of side-effects and only
once a week treatment. The dose escalation in prolactinoma patients
with visual compromise proceeds much more rapidly than with other
patients, and visual field testing is repeated at frequent intervals to
document the expected rapid improvement. Surgical intervention is used
for prolactinomas when there is absence of response to medical therapy
in a macroadenoma (often due to a cystic component), an episode of
acute hemorrhage/apoplexy, complete intolerance to all dopamine
agonists in some patients with infertility or hypogonadism, and
patients taking neuroleptics who need control of a mass lesion.
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Approximately
30% of patients with pituitary tumors seen at the Center have
clinically nonfunctioning adenomas. Patients with these tumors
typically present with symptoms due to mass effect, such as headaches
or visual field loss. Others present with central hypogonadism,
hypothyroidism, or hypoadrenalism, leading to the finding of a sellar
mass. However, it is more common for these disorders to go undiagnosed
until a mass is seen on brain imaging, with the symptoms of hormone
deficiencies present in retrospect. At least half of the patients with
nonfunctioning pituitary adenomas present incidentally, such as when a
skull film or computed tomography scan is performed after a head injury
or when sinus films are ordered, such as in a patient with recurrent
sinusitis. Patients with sellar masses and no clinical evidence of
acromegaly, Cushings disease, or prolactinoma undergo detailed
hormone testing confirming that the lesion is biochemically
nonfunctioning. The use of specialized glycoprotein hormone subunit
serum assays, such as -subunit or FSHß can confirm the pituitary
origin of sellar masses. Patients with clinically nonfunctioning
macroadenomas larger than 1 cm typically undergo transsphenoidal
surgery to protect the adjacent neurological structures such as the
optic chiasm and cranial nerves IIIVI. In many cases, large
nonfunctioning macroadenomas can be completely resected, particularly
if there is no lateral extension into the cavernous sinuses.
Substantial recovery of bitemporal hemianopsia is seen in up to 70% of
cases even if there have been long standing deficits. A typical
hospital stay after transsphenoidal surgery is now 24 days, with
out-patient sodium measurements arranged for the week after discharge
to monitor for late SIADH. The morbidity rate is extremely low,
approximately 1% or less for serious complications in over 1000
patients with all types of pituitary tumors (visual worsening, 0.4%;
meningitis, 0.4%; cerebrospinal fluid rhinorrhea requiring repair,
1%; epistaxis requiring embolization, 0.002%). The mortality rate for
both of the pituitary neurosurgeons at Massachusetts General Hospital
is zero. Patients are routinely retested for recovery of pituitary
function postoperatively, as many patients no longer need hormone
replacement after decompression of the normal pituitary gland. Long
term follow-up of patients from 115 yr after transsphenoidal surgery
reveals a low rate of hypopituitarism directly attributable to surgery
alone. Only 10% of patients who do not receive radiation after surgery
require replacement of at least one hormone more than a year after
surgery, and many of these patients were hypopituitary before surgery
due to the compressive effects of the tumor. In contrast, after a
combination of surgery and radiation, 45% of patients require adrenal
replacement, and 55% require thyroid replacement.
Medical therapy is rarely used for nonfunctioning adenomas because of
the lack of effectiveness in most patients; recurrences are treated
with radiation and/or repeated transsphenoidal surgery. A minority of
patients with -subunit-secreting tumors may show a small degree of
mass reduction with somatostatin analog therapy. Rarely, patients who
are not surgical candidates because of concurrent medical problems may
be treated with radiation as a primary modality. In such cases, serum
hormone markers confirming a pituitary adenoma are essential for
appropriate radiation dosing and management.
A number of patients are seen for "incidentalomas" with a sellar lesion of 1 cm or smaller, and these patients are typically followed, if there is no evidence of hormone abnormalities, visual field, or cavernous sinus involvement. This includes a detailed evaluation for evidence of subtle hypersecretion from "silent" tumors, including insulin-like growth factor I (IGF-I), PRL, and urinary free cortisol levels. The first follow-up scan is performed at 36 months, then annually (and subsequently at increasing intervals if no change is seen), with transsphenoidal surgery performed if there is enlargement of the lesion.
Cushings syndrome.
Sixteen percent of pituitary tumor patients seen at the Neuroendocrine Clinical Center have Cushings disease. Patients with Cushings syndrome are most often referred to the Neuroendocrine Clinical Center by endocrinologists who have already performed an evaluation and are requesting bilateral inferior petrosal sinus sampling with CRH to distinguish between pituitary and ectopic Cushings or are requesting a second opinion in a complex case. There has been a significant increase in the number of patient self-referrals as well. Bilateral inferior petrosal sinus catheterization is performed as an out-patient procedure by the Vascular Radiology Department and is arranged in advance so that the patient spends 2448 h in Boston with the results typically available in 2 days. Many such patients who are confirmed to have pituitary Cushings subsequently undergo transsphenoidal surgery at Massachusetts General Hospital because of the high neurosurgical cure rate. Over the 18 yr since 1978, the cure rate for microadenomas, defined as profound hypoadrenalism postoperatively (urinary free cortisol, <30 µg/24 h; serum cortisol, <3 µg/dL), is 84%. Diagnostic and surgical techniques have improved, and over the past 4 yr, the cure rate for newly diagnosed Cushings microadenomas is 96%, with 48 of 50 patients cured. Forty-six of these were cured with a single transsphenoidal operation; 2 patients required a second operation, usually performed within a few weeks of the initial procedure. The recurrence rate since 1978 is 6%. No patients cured over the past 4 yr have yet recurred. In those Cushings disease patients whose long term postoperative care will be at the Neuroendocrine Clinical Center, the endocrinological focus is on providing as rapid a steroid taper as possible without inducing steroid withdrawal symptoms. The comprehensive recovery program for cured Cushings patients may also include coordination with physical therapy for patients with severe proximal myopathy and with psychiatry for patients with affective symptoms. Most patients are markedly improved clinically within 6 months and fully recovered by 1 yr, including intact hypothalamic-pituitary-adrenal axis function.
Acromegaly.
Acromegaly represents approximately 10% of the pituitary adenomas seen at the Neuroendocrine Clinical Center. Such patients are most often referred by endocrinologists, with the goal of providing the patient with the best chance of curative transsphenoidal surgery. However, many are referred by other specialists, such as the gastroenterologist who realized that a patient with multiple colon polyps had acromegaly as their source, the otolaryngologist seeing a patient for hearing loss who noted overgrowth of palatal soft tissue, or the plastic surgeon performing a bilateral carpal tunnel release and noting fleshy palms. In addition to the standard evaluation with IGF-I and/or oral glucose suppression of GH, the Neuroendocrine Clinical Center has recently described the use of serum IGF-binding protein-3 levels as an additional diagnostic method in cases where conventional tests yield borderline results.
Transsphenoidal adenomectomy remains the primary therapeutic modality in patients with acromegaly. Using a normal IGF-I as a definition of cure, 100% of microadenomas associated with acromegaly (10 of 10) have been cured over the past 4 yr. However, most acromegalics present with macroadenomas. Over the past 4 yr, 45 of 55 acromegalics seen in the Center have sellar masses of 1 cm or greater. Sixty-nine percent of such patients were cured with transsphenoidal surgery. Among macroadenoma patients not cured surgically, over three quarters had tumor invasion of the cavernous sinus and/or sphenoid sinus and were, therefore, not considered surgically curable, but were debulked. Those patients not cured experienced a 45% decline in IGF-I from preoperative levels. There have been no recurrences among cured acromegalics.
Patients with acromegaly who are not cured because of large tumor size
and/or extension into the cavernous sinus have access to radiation
therapy, including conventional fractionated radiation and single dose
stereotactic radiosurgery with proton beam, which minimizes the
radiation to adjacent structures. With the availability of effective
medical therapy, the indications for radiation therapy have become less
clear, and this will be an important issue to address in the future.
Because of the morbidity and increased mortality associated with
acromegaly, medical therapy is administered to all patients with
biochemical evidence of residual tumor after surgery, regardless of
whether they have received radiation. Many patients are first given a
limited (34 months) therapeutic trial of bromocriptine, particularly
those with minimally elevated IGF-I levels postoperatively, despite its
low rate of success in normalizing serum IGF-I levels (8% in
combined series), because it is available orally and costs
significantly less than octreotide. For the majority of those patients
with active acromegaly who do not achieve biochemical control with
bromocriptine, octreotide therapy is initiated. Patients are taught sc
octreotide self-injection by the Neuroendocrine Clinical Center nurse,
and compliance is excellent. Patients who require more frequent dosing
to achieve IGF-I normalization or headache control are offered a sc
minipump for constant drug delivery. Neuroendocrine Clinical Center
patients are offered access to new investigative agents as they become
available; all acromegalics who initiated treatment with octreotide
here will be contacted when longer acting somatostatin analogs become
available for research use in the United States.
Postradiation patients.
The second most frequent diagnosis group seen in the Center, representing 21% of the cases, includes patients who have received radiation therapy to the hypothalamic or pituitary region for a number of central nervous system tumors, including meningiomas, chordomas, chondrosarcomas, and other parasellar lesions. These patients are followed prospectively, from the time of radiation, to monitor the development of hypopituitarism. The most common laboratory abnormality in the first several years after radiation is hyperprolactinemia, which develops in association with destruction of hypothalamic dopaminergic neurons. Often the first clinical symptoms are oligomenorrhea in a woman or decreased libido and impotence in a man, which respond well to bromocriptine therapy to normalize PRL levels, if the gonadotroph axis remains intact. Although hypopituitarism can occur within months of radiation, most patients develop no abnormalities for several years. There is a wide variability in the number of axes affected, with some patients developing panhypopituitarism, and others being normal or experiencing only partial pituitary deficiency up to 10 yr later. Annual evaluations in all patients with a history of parasellar radiation include cortrosyn stimulation testing, free T4 index, menstrual history in women, and testosterone levels in men. Patients are instructed in the need for lifelong hormone monitoring after radiation therapy and in the symptoms of hypopituitarism so that they can seek attention between visits if needed.
Other neuroendocrine disorders.
Miscellaneous neuroendocrine disorders comprise the remaining patients referred to the Center. Some are patients who benefit from the participation of a staff neurologist at the Clinical Center, such as those who have neurological disorders associated with endocrine dysfunction. These conditions include catamenial seizures, catamenial migraine and other headaches, and parasellar tumors, such as tuberculum sella meningiomas and craniopharyngiomas. A final subgroup of patients seen at the Neuroendocrine Clinical Center includes the several patients a year who are referred with pituitary apoplexy, often in transfer from another hospital where a hemorrhagic sellar mass has been found on evaluation of severe headache and/or third cranial nerve palsy. Such patients are treated as neurosurgical emergencies, with high dose steroids to reduce edema and preclude acute adrenal crisis and immediate transsphenoidal decompression. Most patients experience full neurological recovery but become panhypopituitary. Recurrence of the underlying tumor, which is often necrotic on pathology, is uncommon.
Even in this clinic, which is comprised of many patients with rare diseases, there are "zebras." For example, there are several patients with unusual sellar lesions, such as granular cell tumors, dysgerminomas, and Rathkes pouch cysts. A number of patients are followed with unusual causes of hypopituitarism, such as neurosarcoid, histiocytosis, Sheehans syndrome, and bilateral carotid artery aneurysms. Other cases seen at the Center include lymphocytic hypophysitis in a postmenopausal woman, a case of biopsy-proven intrasellar salivary gland, and an actor who, during a fencing duel scene, sustained a rapier injury through the nares to his pituitary gland.
Geographic scope.
From what geographic area are patients
served? One third of patients are derived from the Boston urban area.
Thirty to 45% of patients are from elsewhere in Massachusetts, and an
additional 1020% are from other parts of New England. Twelve to 20%
of patients come from the rest of the United States, and approximately
7% are referred from abroad (Fig. 2).
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Clinical research |
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Educational initiatives |
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A major component of Neuroendocrine Clinical Center education is that it serves as an essential aspect of the Massachusetts General Hospital Endocrine Fellowship Training Program. Three weekly Neuroendocrine Clinic sessions provide the fellows a unique opportunity to follow a pituitary tumor patient from initial evaluation and diagnosis through long term care. Fellows perform a comprehensive office evaluation under staff supervision, and during the visit conduct dynamic diagnostic testing, such as cortrosyn stimulation, glucose-suppressed GH, or insulin tolerance testing. Each fellow follows his or her patients longitudinally, if the Center has primary responsibility for endocrine management, for at least a year and can choose to maintain their Neuroendocrine Clinic patients for all 3 of the fellowship years. The fellows also have the opportunity to observe their patients procedures, such as bilateral inferior petrosal sampling and transsphenoidal surgery. When a patient has undergone pituitary adenomectomy, the fellows manage the perioperative endocrine issues, such as monitoring for diabetes insipidus and/or SIADH, administering steroids, and testing the hypothalamic-pituitary-adrenal axis before discharge. If the surgery was performed for Cushings disease, the fellow evaluates for cure during the hospitalization, because a second transsphenoidal operation is usually immediately performed in the few cases not initially cured. Patients are seen by the same fellow at the 6 week postoperative follow-up visit to ascertain whether there has been any damage to (or recovery of) the hypothalamic-pituitary-gonadal or thyroidal axes and to determine whether the tumor has been cured biochemically and/or in terms of tumor mass, depending on the tumor type. Pathology findings, including immunocytochemical staining for all anterior pituitary hormones, are reviewed. Options for adjunctive therapy (medical and radiation) are reviewed in detail with patients who have residual tumors. If the patient will be returning to a referring physician, the fellow receives instruction about communicating the perioperative history, pathology results, and long term treatment recommendations to provide a smooth transition. In addition, the weekly multidisciplinary Clinical Case Conference provides a venue for fellows, medical students, and residents to participate in a group discussion of all cases seen that week at the Center, including a review of laboratory test results and magnetic resonance imaging scans, thereby expanding their experience beyond only those cases they have seen themselves.
Neuroendocrine conference.
A monthly Neuroendocrine scientific conference addressing current clinical and research topics in pituitary and hypothalamic diseases is attended by Massachusetts General Hospital physicians as well as endocrinologists in the community. There are two purposes of these conferences. The first goal is providing the Endocrine Fellows, residents, and primary care providers with a thorough didactic overview of neuroendocrinology; this is conducted during the first half of the academic year by having staff physicians in all divisions of the Center provide an annual lecture curriculum covering such topics as the evaluation of patients with Cushings syndrome, history and method of transsphenoidal surgery, hypothalamic disorders, radiation of sellar region tumors, pituitary pathology, neuroophthalamological evaluation of patients with sellar masses, and sellar neuroradiology. The second purpose of the Center is to provide staff endocrinologists with a forum for current clinical and basic science research. Some of these sessions, which occur during the second half of the academic year, are conducted by members of the Neuroendocrine Clinical Center, with staff presenting their research work; others are by invited speakers, with recent topics including "Growth Hormone Releasing Peptides," "Somatostatin Receptors: Structure and Physiology," "Adrenal Insufficiency in H.I.V.-Associated Disease", "Genetics and Management of Endocrine Neoplasia Syndromes," and "Clinical Vignettes from the Sella."
Massachusetts General Hospital housestaff elective.
The Neuroendocrine Clinical Center offers a 2-week intensive elective course in neuroendocrinology to medical residents at the Massachusetts General Hospital. The resident attends the daily general endocrinology visit rounds, then participates in all of the fellow and staff neuroendocrine clinics during the week. Arrangements are made for the resident to attend the transsphenoidal surgeries performed during the elective course, and he/she then takes primary responsibility for the in-patient hormonal management. A syllabus and regular didactic sessions reviewing the principles of neuroendocrinology are also provided, and teaching cases, which include photographs of patients, are discussed with the staff preceptor. Special emphasis is placed on considering pituitary disorders in the differential diagnosis of patients in the medical residents clinics and on knowing how to evaluate properly for hypopituitarism. Because these problems are not routinely emphasized on the in-patient medical wards, participants in this elective course have been very enthusiastic about the unique experience it provides.
Visiting physician/scientist preceptorship.
A recent addition to the Neuroendocrine Clinical Center teaching program has been a visiting physician/scientist preceptorship program. Initiated in response to requests by physicians from abroad, the visiting endocrinologist typically spends time in the Center observing patient evaluations, hearing case presentations, and attending conferences and transsphenoidal surgeries. It has been an interesting forum for exchanging information about different approaches to the evaluation and treatment of pituitary tumor patients.
Speakers bureau and newsletter.
Two activities of the Neuroendocrine Clinical Center provide education beyond the setting of Massachusetts General Hospital and Harvard Medical School. The staff of the Center provides a speakers bureau, which has been used both nationally and internationally, offering a variety of clinical and research topics in neuroendocrinology. Some are reviews geared at a general audience, such as for Medical Grand Rounds, whereas others provide an in-depth discussion of a focused topic appropriate for endocrinologists. Speakers have also been used in a visiting professor capacity, reviewing complex neuroendocrine cases at other institutions and discussing possible approaches. Neuroendocrine staff typically provide more than 3040 off-campus lectures regarding neuroendocrine topics annually throughout the United States. In addition, staff members have chaired scientific meetings related to neuroendocrine topics including the International Pituitary Congress and Pituitary Symposia at Endocrine Society meetings. The Center publishes an annual newsletter, mailed to physicians in New England, in which current neuroendocrine topics of interest are reviewed. Recent articles have included "Advances in Recombinant Human Growth Hormone Replacement Therapy in Adults," "Clinical Uses of Corticotropin-Releasing Hormone in the Evaluation of Patients with Cushings Syndrome," and "Clinically Nonfunctioning Pituitary Adenomas: Characterization and Diagnosis." The Neuroendocrine Clinical Center is also on the internet (http://Neurosurgery.mgh.harvard.edu) at a site that contains the full text of the newsletter. Internet services include the educational material provided above and access to all service facilities and clinical research programs of the Neuroendocrine Clinical Center.
Beyond these formal teaching activities, there are also many informal interactions about patient care conducted at the Neuroendocrine Clinical Center. The neuroendocrine staff typically receives 1025 calls each week from physicians requesting to "run a case by." These phone requests can range from less than 1 min, such as asking where to find a particular assay or asking how to refer a patient to Boston for bilateral inferior petrosal sinus sampling, to more than half an hour reviewing detailed lab results and requesting suggestions for the next step in a specific patients care. The majority of such queries are from endocrinologists, but calls from general internists and gynecologists have been increasing rapidly over the past few years as physicians are under pressure to avoid subspecialty referrals.
Finally, the educational role of the Neuroendocrine Clinic has recently extended to patients, with preparation of educational pamphlets such as a "A Patients Guide to Acromegaly" and editing an NIH patient brochure entitled "Cushings Syndrome." The Center has also served as a base for patient support groups that conduct meetings at Massachusetts General Hospital. Recently, a Pituitary Awareness Day was held at the Massachusetts General Hospital for patients and their families in conjunction with the Pituitary Tumor Network Association. Similar events have also been conducted at several other major pituitary centers in the United States. Patient education is a key aspect of the role of the neuroendocrine nurse who conducts a weekly clinic, providing direct patient teaching, such as in the use of im testosterone or sc octreotide injections.
In summary, 10 yr of the Neuroendocrine Clinical Center at the Massachusetts General Hospital have seen it grow into an international referral center for the evaluation and treatment of both pituitary tumors and disorders of the hypothalamic-pituitary region. It has served as a major facility for clinical research as well as basic science investigations regarding the pathogenesis and treatment of pituitary tumors. The key feature of this Center is its multidisciplinary composition, with close involvement of pituitary endocrinologists, experienced pituitary neurosurgeons, neurologists, radiation oncologists, and endocrine nursing as well as availability of neuroophthalmologists to provide an integrated approach to patient care that includes access to innovative clinical research programs.
Received November 6, 1996.
Accepted January 10, 1997.
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