U.S. Department of Health 

and Human Services

National Institutes of Health

An integrative report and recommendations from the symposium cosponsored by the National Institutes of Health 

(NIH) Office of Research on Women’s Health, the Pediatric and Reproductive Endocrinology Branch, the NIH National 

Institute of Child Health and Human Development of the Department of Health and Human Services (DHHS), the 

National Naval Medical Center and the Pituitary Network Association.

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Understanding Pituitary Disorders and Planning for Future Research

An integrative report and recommendations from the symposium cosponsored by the National 

Institutes of Health (NIH) Office of Research on Women’s Health, the Pediatric and Reproductive 

Endocrinology Branch, the NIH National Institute of Child Health and Human Development 

of the Department of Health and Human Services, the National Naval Medical Center, and 

the Pituitary Network Association. For further information, see http://orwh.od.nih.gov.

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Understanding Pituitary Disorders and Planning for Future Research

October 29, 2004

Family Hormonal Health: Understanding Pituitary Disorders and Planning for Future Research 1

Contents

Foreword from the Director of ORWH .................................................................................................................... 2

Introduction ............................................................................................................................................................. 3

The Pituitary Gland .................................................................................................................................................. 3

Causes and Consequences of Pituitary Gland Malfunction ................................................................................. 3

Pituitary Tumors ....................................................................................................................................................... 5

Etiology of Pituitary Tumors .................................................................................................................................... 6

Diagnosis of Pituitary Tumors ................................................................................................................................ 6

Central Importance of the Pituitary Gland in Normal Functioning and Disease .................................................. 6

Detection of Pituitary Diseases ............................................................................................................................. 6

Current Treatment Options ..................................................................................................................................... 7

Neuroendocrine Effects of Pituitary Disorders on Psychological State and Psychosocial Interactions ............ 8

Patient Perspectives on Pituitary Disorders ........................................................................................................ 10

Moving Forward ..................................................................................................................................................... 12

Additional Information ........................................................................................................................................... 12

Presentations ......................................................................................................................................................... 13
2 Office of Research on Women’s Health Symposium

The Office of Research on Women’s Health (ORWH) 

has been in existence since September 1990, and one 

of its mandates is to set a research agenda for women’ T s 

health for the National Institutes of Health (NIH) and 

the scientific community that NIH funds. In setting that 

agenda, we not only focus on conditions that affect 

women, but also consider projects that address conditions that affect both men and women. This focus is 

a means of learning about sex and gender differences 

and similarities so that diagnoses and treatments can be 

appropriately applied to various populations.

In planning a research agenda, observations and anecdotes may spur our thinking and help us formulate 

scientific hypotheses, but it is the evidence generated by 

biomedical and behavioral research that will change how 

medicine and health care are practiced, how our healthcare professionals are educated, and what individuals will 

do to improve and protect their health. In approaching 

research on women’s health and sex and gender factors, 

we have begun to focus on innovative interdisciplinary 

research, in which there is collaboration between medical and scientific disciplines, and in which the public is 

involved. The interdisciplinary approach to understanding how conditions affect both men and women leads us 

into the realm of pituitary hormonal disorders, 

which are an important consideration in the scientific 

research agenda.

The goals of the scientific symposium on family hormonal health were, first, to increase our awareness and 

scientific understanding of the all-encompassing nature 

of pituitary disorders so that the biomedical community 

can diagnose these conditions in their earliest stages. To 

that end, the symposium included presentations from 

several individuals about their own conditions and 

the effect the lack of early detection has had on their 

health and well-being. A second goal was to disseminate knowledge of state-of-the-art treatments for these 

conditions; this publication is one of several avenues 

for doing so. And third, the symposium was conducted 

to stimulate the thinking of the scientists who attended 

to identify research directions for funding that hold the 

greatest promise for addressing pituitary disorders. 

We recognize that the symptoms of pituitary conditions 

are of many kinds and can be mistaken for symptoms of 

many other disorders or can be considered insignificant. 

We also recognize that pituitary health and pituitary 

conditions affect the entire family and the community 

in which individuals live because of the ramifications 

of those conditions. We know that pituitary tumors, as 

well as other conditions of the pituitary, are probably 

more common than many realize, and that some of 

these conditions may affect women differently than they 

affect men. Thus, we want to encourage interdisciplinary collaboration because of its potential to create 

optimum opportunities for translating research from 

bench to bedside to obtain the best clinical outcomes for 

pituitary conditions. Also, through collaboration among 

Government agencies, public institutions, the private 

sector, and organizations such as the Pituitary Network 

Association, we can optimize service resources and 

delivery to individuals, families, and communities.

I wish to thank some special individuals whose efforts 

were instrumental from the vantage point of ORWH 

for making this symposium a success. In particular, Dr. 

Eleanor Hanna took the lead at ORWH for the symposium and this publication. Dr. George Chrousos of the 

National Institute of Child Health and Human Development (NICHD), a researcher in this area of focus, was 

crucial to designing the scientific program and serving 

as a very effective liaison to the advocacy and scientific 

communities. Dr. Yvonne Maddox, deputy director 

of NICHD, and Dr. Mohamed Shakir of the National 

Naval Medical Center, have been our liaisons and strong 

supporters in this collaborative effort. And, of course, 

Robert Knutzen and the Pituitary Network Association 

have been central to this project in bringing the issues of 

pituitary disorders and hormonal disorders to our attention and for their persistence in ensuring that we grant 

these disorders the public attention that they deserve.

Foreword from the Director of ORWH

Vivian W. Pinn, M.D.
3

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Introduction

The Office of Research on Women’s Health (ORWH), 

in collaboration with the National Institute of Child 

Health and Human Development (NICHD), the 

National Naval Medical Center, and the Pituitary 

Network Association, convened a National Institutes of 

Health (NIH) Symposium on Family Hormonal Health 

to discuss the impact of pituitary disorders, both from 

the scientific perspective of an internationally recognized 

group of experts and from the personal viewpoint of 

three patients. 

Overall, the goals of the meeting were to increase 

awareness and scientific understanding of the nature of 

pituitary disorders: to improve early diagnosis, to disseminate knowledge of state-of-the-art treatments, and 

to encourage collaboration among scientists and funders 

of research to determine the best way to proceed in 

order to improve treatment options and the quality and 

length of life for both men and women. 

The following sections summarize and integrate the 

scientific discussions on pituitary disorders and the 

insights from three patients who discussed their experiences from detection of their pituitary disorders to their 

treatments. 

The Pituitary Gland

The pituitary is a beanshaped gland attached 

to the base of the 

brain by a thin stalk. 

Essential for growth, 

the pituitary functions as the “Master 

Gland” (see Figure 

1). It receives input 

from the brain and 

the rest of the body, 

integrates that informa

tion, and then responds by producing hormones that 

regulate other glands and bodily functions. The pituitary 

sends signals to the thyroid gland, adrenal glands, and 

-

ovaries or testes, directing them to produce thyroid hormone, cortisol, estrogen, testosterone, and many other 

hormones. These hormones have dramatic effects on 

metabolism, blood pressure, sexuality, reproduction, and 

other vital bodily functions. In addition, the pituitary 

gland produces growth hormone (GH) for normal development of height and prolactin for milk production. This 

all occurs interactively via a system of negative feedback 

loops. The charts on the following page (see Figure 2 and 

Figure 3) detail the hormones produced by the pituitary 

gland and the organs it stimulates to produce other 

hormones.

Causes and Consequences of 

Pituitary Gland Malfunction 

Tumors (primarily benign), inflammation, infections, 

and injury can cause the pituitary gland to malfunction; 

in rare instances, spread of other tumors to the pituitary 

also can cause malfunction. In some cases, radiation 

therapy to the brain can cause normal pituitary cells to 

malfunction. Pituitary malfunctions result in headaches, 

compression of the optic nerve with loss of peripheral 

vision, and a variety of hormonal effects on the heart, 

gut, muscle, bone, and other parts of the body.

Pituitary disorders stunt growth in children and shorten 

the lives of all affected individuals by causing health 

complications such as mood disorders, sexual dysfunction or infertility, diabetes, osteoporosis, arthritis, and 

accelerated heart disease. Although pituitary tumors are 

present in nearly 20 percent of adults worldwide, many 

go undiagnosed for years because of the diffuse array of 

symptoms.

Pituitary disorders frequently go undiagnosed because 

they often signal unrelated conditions; therefore, 

pituitary disorders should be considered as a potential 

diagnosis by health professionals when working with a 

patient who presents a puzzling and diverse constellation 

of complaints and clinical findings. Medical, surgical, 

and radiotherapeutic options do exist for individuals 

with pituitary disorders; however, these therapies cannot 

be used until a patient is diagnosed appropriately.

Family Hormonal Health:

Understanding Pituitary Disorders and Planning for Future Research

Figure 1. As the “Master Gland,” 

the pituitary is essential for 

growth and overall hormonal 

regulation.
4 Office of Research on Women’s Health Symposium

Figure 3. Hormones Under the Control of the Pituitary Gland

This chart illustrates the organs that have been stimulated by the pituitary gland to produce other hormones.

Certain pituitary tumors can cause Cushing’s syndrome, much sugar in the blood, weak muscles and bones, a 

flushed face, and high blood pressure. Other pituitary 

tumors can cause a condition called acromegaly, in 

which the hands, feet, and face are larger than normal; 

in very young people, the whole body may grow much 

a disease in which too many hormones, called glucocorticoids, are released into the bloodstream. This causes 

fat to build up in the face, back, and chest, and the arms 

and legs to become thin. Other symptoms include too 

Hormone Organ Function

Cortisol Adrenals Promotes normal metabolism, maintains blood sugar levels and blood pressure, 

provides resistance to stress, and acts as an anti-inflammatory agent. Cortisol also 

plays a part in regulating fluid balance in the body.

Thyroxine Thyroid Controls many bodily functions, including heart rate, temperature, and metabolism. 

Thyroxine also plays a role in metabolizing calcium in the body.

Estrogen Ovaries Facilitates growth of the tissues of the sex organs and other tissues related to 

reproduction. Estrogen also acts to strengthen bones and has a protective effect 

on the heart.

Progesterone Ovaries Promotes changes in the uterus that occur in preparation for the implantation of a 

fertilized ovum and prepares the breasts for milk production.

Testosterone Testes Responsible for the masculine characteristics of the body, including hair growth 

on the face and body, and muscle development. Testosterone is essential for 

producing sperm and also strengthens bones.

Figure 2. Pituitary Hormones, Targets, and Functions

This chart details the hormones the pituitary gland produces, outlining the targets in the body and the functions of the hormones.

Hormone Target(s) Function

Adrenocorticotropic Adrenals Stimulates the adrenal gland to produce a hormone called cortisol. ACTH is also 

Hormone (ACTH) known as corticotropin.

Thyroid-Stimulating Thyroid Stimulates the thyroid gland to secrete its own hormone, which is called thyroxine. 

Hormone (TSH) TSH is also known as thyrotrophin.

Luteinizing Hormone Ovaries (Women) Control reproductive functioning and sexual characteristics. Stimulate the ovaries 

(LH) and Follicle- Testes (Men) to produce estrogen and progesterone and the testes to produce testosterone and 

Stimulating Hormone sperm. LH and FSH are known collectively as gonadotrophins. LH is also referred 

(FSH) to as interstitial cell-stimulating hormone in males.

Prolactin (PRL) Breasts Stimulates the breasts to produce milk. This hormone is secreted in large amounts 

during pregnancy and breastfeeding but is present at all times in both men and 

women.

Growth Hormone (GH) All cells in the Stimulates growth and repair. Research is being carried out to identify the functions 

body of GH in adult life.

Melanocyte-Stimulating Exact role in humans unknown but increases skin pigmentation in amphibians.

Hormone (MSH)

Antidiuretic hormone Kidneys Controls the blood fluid and mineral levels in the body by affecting water retention by 

(ADH) the kidneys. This hormone is also known as vasopressin or arginine vasopressin (AVP).

Oxytocin Uterus Affects uterine contractions in pregnancy and birth, and subsequent release of 

Breasts breast milk.
Family Hormonal Health: Understanding Pituitary Disorders and Planning for Future Research 5

larger than normal. Another type of pituitary tumor can 

cause the breasts to make milk, even though a woman 

may not be pregnant or may be beyond her reproductive 

years. It can also occur in men. Empty sella syndrome 

(ESS) is a disorder that involves the sella turcica, a bony 

structure at the base of the brain that surrounds and 

protects the pituitary gland. Flattening or regression of 

the pituitary gland within the sella turcica cavity may 

result in symptoms such as the ceasing of menstrual 

periods, infertility, fatigue, and intolerance to stress and 

infection. In children, ESS may be associated with early 

onset of puberty, GH deficiency, pituitary tumors, or 

pituitary gland dysfunction.

If symptoms indicate a possible pituitary disorder, 

a doctor may order laboratory tests to see what the 

hormone levels are in the blood. The doctor may also 

order an MRI (magnetic resonance imaging) scan, 

which uses magnetic waves to make a picture of the 

inside of the brain. Other special x rays also may be 

done. The chance of recovery and choice of treatment 

depend on the type of tumor, and the patient’s age and 

general state of health.

Pituitary Tumors

Every year thousands of new patients are diagnosed with 

pituitary tumors in the United States; most pituitary 

tumors are adenomas, and few pituitary tumors are fatal. 

However, the number of pituitary tumors diagnosed is 

much lower than their actual number. Most of these pituitary tumors are benign and, therefore, are not included 

in statistics collected by cancer registries. By examining 

people who have died or who have had routine imaging 

studies of their brain, doctors have found that 15 percent 

to 20 percent of people have pituitary adenomas. Almost 

all individuals with these tumors will not experience any 

symptoms or impairment of their health. 

Although pituitary tumors are the most common, not 

everything that grows within the pituitary is a pituitary 

adenoma. Inflammation can occur from pregnancy, 

infections in a compromised host, injury following a 

head trauma, and a variety of cancers that affect the 

pituitary. Although pituitary tumors are supposed to be 

benign, the recent World Health Organization classification failed to classify pituitary tumors as neoplasms and 

described them as simply adenomas. For individuals 

who have been devastated by a variety of complications 

of pituitary adenomas, a cancer is defined only when 

there is evidence of metastasis from the original tumor 

site. This means that a pituitary adenoma would have 

to spread to other parts of the body, typically within 

the central nervous system, in order to be classified as a 

cancer; however, spread of this nature is rare.

Extremely small and often hormonally inactive pituitary 

tumors are called incidentalomas. Only investigation 

can determine that such tumors can be classified as 

small and not producing hormonal excess. Some incidentalomas may grow rapidly in size and function.

Every year thousands of new patients are 

diagnosed with pituitary tumors in the United 

States; most pituitary tumors are adenomas, 

and few pituitary tumors are fatal.

The patient whose macroadenoma is shown in Figure 

4 died of a pulmonary embolism, as a complication 

of Cushing’s syndrome that was not recognized early 

enough. The major challenge is to identify these adenomas at an early stage.

Most medical schools teach that pituitary tumors are 

unusual lesions that give rise to specific symptoms that 

are clearly either acromegaly or Cushing’s syndrome. 

That characterization is no longer accurate. Results 

of a meta-analysis (Ezzat et al., 2004) showed that, 

across seven autopsy studies and five radiological studies with variable incidences of pituitary tumors, the 

overall estimated prevalence of pituitary tumors in the 

general population is almost 17 percent. Most of these 

patients have nonfunctional tumors. Prolactin-producFigure 4. The patient 

whose macroadenoma 

is pictured died of a 

pulmonary embolism, as a 

complication of Cushing’s 

syndrome that was not 

recognized early enough.
6 Office of Research on Women’s Health Symposium

ing cells found in about one-fourth of the individuals 

in these studies suggest that functional tumors give 

rise to hormonal excess that may have subtle emotional, reproductive, and sexual impact. Most of these 

tumors are microadenomas, but a small percentage are 

macroadenomas; corroborated blood hormone values 

were available in one study, proving that hormones 

are being secreted and are creating a clinical effect. 

Even when these tumors are clinically nonfunctioning 

and do not secrete excess hormone, they give rise to 

pressure effects such as headache; they can press on 

the optic nerve giving rise to loss of peripheral vision, 

and they can compromise normal function of the gland 

with patients developing hypopituitarism.

Etiology of Pituitary Tumors

Scientists do not know exactly what causes most pituitary tumors. During the past few years, great progress 

has been made in understanding how certain changes 

in a person’s DNA can cause cells in the pituitary 

to produce a tumor. About 3 percent of all pituitary 

tumors are caused by a condition that is inherited; 

these pituitary tumors usually occur in adults, and 

genetic testing of family members is available.

... pituitary disorders can progress for 10 or 

15 years without diagnosis or appropriate 

treatment. It is critical that endocrinologists 

instruct other healthcare providers to make 

the clinical diagnosis of a pituitary disorder 

at an earlier stage.

Much less is known about the causes of nonhereditary 

pituitary tumors; although, recent studies indicate about 

40 percent of growth hormone-secreting adenomas 

have an acquired mutation in a specific protein called 

Gs-alpha. Several other genetic abnormalities have been 

found in other types of pituitary adenomas, but it is not 

clear whether abnormal genes are essential for pituitary 

tumor formation. What is known is that there is a loss 

of the normal regulatory mechanism that keeps the 

glandular cells from overproducing their hormone and 

growing; this is likely the result of gene alterations.

Diagnosis of Pituitary Tumors 

The first step in diagnosing a pituitary tumor is for the 

doctor to take a complete medical history to check for 

risk factors and symptoms. The doctor should know if 

anyone in the patient’s family has had a pituitary gland 

tumor, hyperparathyroidism (overactive parathyroid 

gland), multiple kidney stones, multiple stomach ulcers, 

hypoglycemia (low blood sugar), or adrenal gland 

tumors, because these conditions raise the possibility 

that the patient may have inherited the gene for multiple 

endocrine neoplasia, type 1. A general physical exam and 

visual exam provide other information about signs of 

pituitary tumors and other health problems. Other diagnostic tools include biochemical testing, venous blood 

sampling, imaging tests, MRI scans, and examination of 

pituitary tissue specimens.

Central Importance of the Pituitary Gland 

in Normal Functioning and Disease

If untreated, pituitary complications can lead to reduced 

survival. Pituitary patients can suffer from tumors as 

well as other diseases. Functional abnormalities, such 

as nonneoplastic mass lesions, hypoplasia, cysts, and 

inflammatory lesions, can affect the pituitary and its 

function. A pituitary disorder can be merely an incidental finding, and some pathologists identify pituitary 

lesions on autopsy in the absence of any evidence that 

those lesions affected the living patient. More often, 

health complications arise from these disorders, affecting everything from mood and sexual function to metabolic disorders such as diabetes mellitus, osteoporosis 

and arthritis, and accelerated heart disease.

Metabolic disorders in adults can be subtle. Patients 

suffer from lethargy, cardiovascular dysfunction, water 

and electrolyte imbalance, emotional dysfunction, and 

reproductive and sexual dysfunctions. These complex 

and nonspecific findings may be difficult to associate 

with pituitary disease, and a definitive diagnosis may 

take many years during which time the patient does not 

receive appropriate treatment.

Detection of Pituitary Diseases 

Advancements in Detection. Tremendous advancements 

have occurred in detecting pituitary tumors clinically, 

biochemically, and radiologically. The advent of MRI 

scans allowed radiological detection of even smaller 

tumors than computed tomography (CT) scans could 
Family Hormonal Health: Understanding Pituitary Disorders and Planning for Future Research 7

observe. During the last several decades, the ability to 

refine biochemical testing has improved, for detecting 

both decreased levels of circulating pituitary hormones 

and elevated levels of pituitary hormones in their targets, such as insulin-like growth factor 1 (IGF-1) and 

gonadal hormones. Despite these advances, pituitary 

disorders can progress for 10 or 15 years without 

diagnosis or appropriate treatment. It is critical that 

endocrinologists instruct other healthcare providers to 

make the clinical diagnosis of a pituitary disorder at an 

earlier stage. 

Patient Presentation. The relatively asymptomatic state 

of pituitary disease and the constellation of nonspecific 

complaints are a major barrier to early diagnosis; often 

the diagnosis is delayed and the pituitary tumor remains 

asymptomatic for a prolonged period of time. Patients 

with pituitary disorders present to various medical specialties a wide variety of often nonspecific complaints. 

Some patients can even be asymptomatic, but once an 

endocrine disorder is suspected, patients are referred to 

endocrinologists.

Increased awareness is the most 

important first step in diagnosing pituitary 

tumors. Medical professionals who are 

knowledgeable about the pituitary are more 

likely to be able to put together the pieces 

of this puzzle when confronted with a 

constellation of clinical complaints.

Pituitary diseases may present differently to different 

specialists. A dermatologist might see a patient with oily 

diaphoretic skin, which, for an endocrinologist, would 

serve as proof of acromegaly, but may not be so recognized by a dermatologist. Similarly, many other medical 

specialists will see pituitary patients because of specific 

complaints related to their disease, complaints that hint 

at the full medical picture. Infertility, menstrual irregularities, and galactorrhea are the presenting symptoms 

to a gynecologist or an obstetrics specialist. Urologists 

may see hypogonadism, impotence, or low testosterone 

levels. Carpel tunnel syndrome or headaches may be 

the presenting symptoms in patients with as-yet-undiagnosed acromegaly who seek out a neurologist. Proximal 

muscle weakness may be the presentation of Cushing’s 

syndrome. The pituitary tumor may put pressure on the 

optic chiasm, resulting in visual field defects, diplopia, 

and blurred vision, all of which would be presented 

to an ophthalmologist. Enlarging feet size and bone 

abnormalities may be the complaints presented to a 

podiatrist. The primary care physician sees patients with 

all of these complaints and might also see patients with 

pituitary disease who suffer from depression, fatigue, 

and polyuria. In most cases, all of the above-mentioned 

medical professionals do not initially consider a diagnosis of a pituitary tumor, but after some time and for 

a variety of reasons, these patients eventually receive a 

workup from a healthcare professional who makes the 

diagnosis of a pituitary tumor.

Diagnosis. Increased awareness is the most important 

first step in diagnosing pituitary tumors. Medical professionals who are knowledgeable about the pituitary are 

more likely to be able to put together the pieces of this 

puzzle when confronted with a constellation of clinical 

complaints. Once patients become or are made aware 

of the possibility of pituitary disease, and therefore 

seek the advice of an endocrinologist, the endocrinologist examines blood and urinary hormone levels and 

conducts MRI scans to document the presence of an 

abnormality in the brain.

Tumor Classification. Pathologists classify tumors based 

on their clinical function or clinical silence, and then, 

based on the type of cell in the pathology specimen, different tumor types are identified based on transcription 

factors, hormone production, and the architecture that 

holds the cells together. Pathologists can measure hormones from the target organ in order to accurately diagnose the abnormality, and they can localize transcription 

factors in hormones to prove that the patient’s pituitary 

tumor is the reason for the clinical presentation. Tests 

such as electromicroscopy, immunohistochemistry, and 

molecular analyses can show specific parts of tumors 

that are responsible for hormone production.

Current Treatment Options

Treating pituitary tumors depends on the type of tumor 

and how far it has invaded into the brain, as well as the 

patient’s age and overall health. Three kinds of treatment 
8 Office of Research on Women’s Health Symposium

are used: surgery to remove the tumor, radiation therapy 

using high-dose x rays or proton beams to kill tumor 

cells, and drug therapy to shrink and sometimes eradicate the tumor. Drugs can also block the pituitary gland 

from making too much hormone. 

Surgery remains the mainstay of treating pituitary 

tumors, and new methods are continually being identified. In the past, surgical procedures for patients with 

pituitary tumors were limited to invasive brain surgery. 

Today, many patients are being treated using advances 

in surgical therapy that have improved patient outcome. 

Two different approaches to tumor removal are a transsphenadal operation, in which the tumor is removed 

through a cut in the nasal passage or upper lip, leaving 

no external scar, and a craniotomy, in which the tumor is 

removed through a cut in the skull. 

Dopamine agonists are widely used for medical management of prolactinomas. Octreotide has become a 

mainstay of medical therapy after surgical failure for 

acromegaly; for patients with unique tumors that fail 

to respond to octreotide, new drugs are in development. For pituitary-related depression, new treatments 

being explored include corticotropin-releasing hormone 

(CRH) and other peptide antagonists, anticonvulsants, 

neurotropic agents, serotonin transporter agents, and 

nerve growth factors.

To summarize, normalizing measurable symptoms will 

restore most people with pituitary disorders to a normal 

quality and length of life.

Neuroendocrine Effects of Pituitary 

Disorders on Psychological State 

and Psychosocial Interactions

Growth factors are made in the pituitary gland by pituitary cells and also from sources around and outside of 

the pituitary. Multiple mechanisms give rise to a tumor: 

Mutations can result in abnormal cell clones that will be 

stimulated to grow; a pathway can exist where growth 

factors and hormonal stimulation are the primary problem; and other events can occur within hyperplastic cells 

to give rise to expansion and tumor formation.

Children and Adolescents. Growth and development are 

affected in children with pituitary disorders. The effects 

of hormones on growth include the following:

◗ Stature: children may stop growing or may overgrow. 

◗ Body composition: children may lose muscle and 

may gain abnormal fat that could affect the rest of 

their lives.

◗ Puberty: children could experience puberty too early 

or too late.

◗ Attentional problems and psychopathology: children 

and adolescents may suffer the concurrent effects 

of attentional problems or psychopathology, both of 

which may be associated with later adult pathology.

Pituitary disorders in adolescents are particularly difficult to diagnose properly. All the psychological and 

emotional problems of being a “normal” adolescent 

appear—growth and development, societal pressure, 

drug-related issues, and peer pressures all impinge on 

the pituitary system. For adolescents, it is critical to 

sort out those issues that are endocrine-based and for 

which medical intervention can be successful, while also 

attending to all the other “normal” adolescent issues.

Depression. Depression is a systemic disorder. Pituitary 

dysregulation helps to sustain and perpetuate major 

depression and the hormonal abnormalities that are part 

of its overall pathophysiology. Stress precipitates depression and influences its incidence, course, and severity. 

The stress response and some forms of depression share 

phenomena, mediators, and circuitries. Each can be 

associated with fear, mood, and cognition, as well as 

alterations in arousal, autonomic function, and neuroendocrine regulation. 

The stress response increases the anticipation of 

harm and fear-related behaviors and the shift to wellrehearsed automatic programs. The stress response 

leads to breakdown of muscle, bone, and other tissues 

for fuel; long-term effects related to loss of muscle and 

increased fat tissue (no change in weight but change in 

body composition); loss of bone and long-term osteoporosis; priming of the immune system to anticipate possible injury, which is an inflammatory state; priming of 

the coagulation system as a defense against blood loss; 

and increased heart rate and blood pressure, resulting in 

hypertension and cardiac disease.
Family Hormonal Health: Understanding Pituitary Disorders and Planning for Future Research 9

As seen in Figure 5, the pituitary plays a central role in 

the regulation of the stress response. The hypothalomic 

pituitary-adrenal (HPA) axis, shown on the left, together 

with the autonomic system, shown on the right, are 

activated during stress to protect against the cause of 

stress. Thus, when an individual is stressed, the pituitary 

is stimulated by the releasing factors CRH and AVP to 

produce ACTH, which in turn stimulates the adrenals 

to produce cortisol. In parallel, the autonomic system is 

activated to produce the catecholamines, Norepinephrine (NE) and Epinephrine (E), two other key stress 

hormones. Figure 5 shows how the HPA axis and autonomic system interact with each other; how the growth 

and thyroid axes are suppressed by the HPA axis; and 

how cortisol, the catecholamines, and CRH influence 

inflammation. The amygdala is the fear-generating system in the brain and locus coeruleus (LC) is the arousal 

system. IL-6 is the inflammatory cytokine interleukin-6. 

Reproduction, growth, thyroid function, and immune 

function are all distressed in the presence of major depression. Emerging data indicate that young children with 

obsessive-compulsive disorder and depression are shorter, 

starting relatively early in life; although this result needs 

to be replicated, it points to the possibility of alterations 

in pituitary function as a consequence of depression. 

Melancholic depression is a state of pathological 

hyperarousal. The pituitary is involved in all of the characteristics of melancholic depression. Patients with melancholia are very anxious, especially about themselves, 

and they feel worthless and dread the future. There 

is a loss of cognitive flexibility in patients with major 

depression—they have difficulty concentrating and 

formulating complex plans—and they exhibit decreased 

sleeping, decreased food intake, decreased sexual activity, and diversion of energy away from growth and 

reproduction. Thirty percent of the major depressions 

are melancholic and are characterized by this pathological hyperarousal, but 20 percent to 25 percent of the 

major depressions are atypical. Patients with atypical 

depression are characterized by profound lethargy and 

fatigue; they feel much less alive than usual; they have 

increased appetite; and they sleep more. Emotional 

memory is influenced by pituitary adrenal activity, and 

serious, life-altering disorders are often associated with 

pituitary dysregulation. 

Stress hormones profoundly increase the strength of 

the negatively charged emotional memory trace. This 

represents a mechanism by which the unconscious 

memory of a previous life-threatening situation can 

provide reflexive responses to promote survival. MelFigure 5. HPA Axis Stress Response 

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10 Office of Research on Women’s Health Symposium

ancholic depression seems like a continuous state of 

negative emotional memory recall without access to the 

contextual content. Atypical depression may be a loss 

of contact with emotional memory and, hence, a loss of 

connection to one’s self and one’s past, which at times, 

can feel like a terrible state of emptiness. Both forms of 

depression are characterized by a loss of the capacity to 

experience pleasure.

Another message common to all three 

was the need for health practitioners to 

recognize and help them and their families 

cope with the psychosocial aspects of 

pituitary disorders.

Major depression doubles the risk of mortality in 

patients of any age, independent of smoking and other 

risk factors for poor health; doubles in the incidence of 

premature coronary artery disease, also independent of 

smoking; and more than doubles the risk for premature 

osteoporosis. These phenomena are reasons for diagnosing and treating depression or any hormonal disorder at 

the earliest possible stage.

Patient Perspectives on Pituitary Disorders

The previous sections summarize the scientific discussions at the symposium; however, an important part of 

the story comes from the patients themselves. A woman 

with Cushing’s syndrome, a man with a pituitary tumor, 

and a man with acromegaly provided examples of the 

devastating consequences they faced during the process 

of detecting, diagnosing, and ultimately finding treatment for their pituitary disorders. With early diagnosis, 

expert care, and the support of multiple medical specialists, these three individuals give hope to the millions of 

people who suffer from pituitary disorders that they can 

regain control of their lives. 

All three patients experienced a significant delay in 

diagnosis, an average of 9 years. Consequently, they 

urge all health practitioners to check symptoms that 

could indicate an endocrine disorder in order to make 

a timely diagnosis. All three also emphasized the need 

for health practitioners to recognize and help them 

and their families cope with the complex psychosocial 

aspects of pituitary disorders.

The following are excerpts from testimonials from 

patients who provided personal insights into their 

struggles with pituitary disorders.

Sharmyn McGraw

Cushing’s Syndrome

My story about Cushing’s is not much different than 

that of most people trying to get a diagnosis for this 

horribly misunderstood disease.

I sought help from more than 15 highly recommended 

physicians, and, with each new doctor, I showed photographs of myself, hoping that the drastic physical 

changes would convince them that there was something 

medically wrong with me. Some were very sympathetic, 

but most of them just offered prescription drugs and 

were convinced I was a compulsive overeater with a 

mental disorder. Some labeled me a hypochondriac and 

others labeled me prediabetic or premenopausal. They 

told me I had fibromyalgia, a spastic colon, acid reflux, 

and a sleep disorder. I had many painful and expensive 

medical tests, including two upper endoscopies, a horrible colonoscopy, a bone marrow biopsy, multiple CT 

scans and ultrasounds, and the removal of my thyroid.

I borrowed a friend’s computer and looked up “cortisol,” 

and there on the computer screen was Cushing’s syndrome, a hormone disorder caused by prolonged exposure 

of the body’s tissue to high levels of the hormone cortisol. 

I carefully read the rest of the article, and that is when I 

realized I had actually diagnosed myself with Cushing’s. 

In most cases, pituitary disease can be treated either 

medically or surgically if a timely diagnosis is made. 

Oftentimes, quality of life is much improved once proper 

medical treatment has been started. Unfortunately, most 

people affected by this debilitating disease go far too 

long before finding the source of the problem, becoming permanently disabled. The psychological aspects of 

Cushing’s, or any pituitary disorder, is devastating. Many 

patients are treated medically for many years as having a 

mental disorder, whereas, in reality, they have a hormonal 

imbalance caused by a treatable pituitary tumor. 
Family Hormonal Health: Understanding Pituitary Disorders and Planning for Future Research 11

Diagnosing Cushing’s requires more than looking at the 

patient; running appropriate tests is the only way to get 

a correct diagnosis. High levels of cortisol cause a horrible psychological imbalance and significantly impact 

the quality of life. Healthcare providers should remember that a patient’s laundry list of symptoms could very 

well be caused by a treatable pituitary tumor.

Bram Levy

Prolactinoma

I was very fortunate at the age of 19 to have a doctor 

who said, “Let’s look at the pieces, and we’ll start to put 

things together. You were growth-hormone deficient as 

a child, and you have headaches. We need to take a CT 

scan to rule out the possibility of a pituitary tumor.” 

Had it not been for that doctor, I would be somewhere 

else today, with more severe headaches and facing the 

possibility of long-term infertility and all the other side 

effects that come with having a pituitary tumor. It took 

one doctor who happened to know that certain pieces 

of a puzzle fit together, and who knew to give me a CT 

scan. He found that I have a very large—about 21⁄2 to 

3 centimeter—prolactinoma. My prolactin level was 

around 2,000; normal is less than 20.

That was the scariest day of my life. I was told I had a 

tumor in my brain. I would not say I was happy, but there 

was a sense of relief. I now knew that I looked young for 

a reason, and I knew there was some reason for having 

those headaches. I was glad that I was going to begin 

some form of treatment. That is how I was diagnosed. 

The most important part that my family and I played 

was that we were our own advocates. If we had listened 

to what each doctor told us to do, we would have gone 

straight ahead with one doctor or two doctors and done 

exactly what they told us. But we took the time to find 

out exactly what our treatment options were, and we 

got as many opinions as we possibly could and found 

out what the best course of action was for my case; not 

what was best for a prolactin case or for a child who 

has prolactinoma, but what was best for me, Bram Lev

I do not consider myself cured, as I do not think it is 

possible to have a pituitary tumor and ever be cured. I 

do consider myself managed, and that is about the best 

I can hope for. I will continue to be monitored for the 

rest of my life, and I will continue to take most of the 

y. 

medications for the rest of my life. I take adult growth 

hormone now, which helps with body composition, and 

I am happy with the results so far.

Robert Knutzen

Acromegaly

Acromegalics have an insidious and often well-hidden 

series of severe complications that are still far beyond 

most physicians’ abilities to diagnose, predict, or understand—and therefore beyond their ability to fully treat.

I was born with large hands, which my mother unsuccessfully tried to hide under the blanket so that her first 

born would not be thought of as being deformed. I had 

constant migraine headaches, but no one looked for an 

underlying cause. I had a series of remarkable, at least 

to me, sexual problems: I almost lost a testicle in my late 

30s and premature ejaculation was the norm. 

An ugly, hot temper followed me most of my life. I was 

aggressive and verbally abusive, and often terrified my 

own family for reasons that were rational to me but 

in retrospect clearly unacceptable to others. Today, we 

know this as acromegalic rage. 

Neurosurgeons and endocrinologists distanced themselves from me because they did not understand that 

who and what I had become was as a result of my 

illness, not a result of willful misbehavior. My prostate 

grew, my cholesterol level increased, and my blood pressure shot up, but all of these problems have been controlled with medications. I now have a support system 

of family, friends, physicians, and surgeons who guide 

me and advise me along the way. 

Far too few patients are diagnosed in a timely fashion. 

Far too few are treated by experts for the myriad medical problems that often befall a pituitary patient. Far 

too few understand that pituitary disorders, acromegaly 

among them, first attack our mental and emotional 

well-being, then our sexual well-being, then our internal 

organs—long before we are recognizable as patients. 

Medical schools must teach that only by listening to a 

patient’s stories can an accurate and thorough workup 

be ordered that will diagnose that patient. A Cushing’s 

patient or an acromegalic patient cannot be diagnosed 

merely by looking at them, except in the late stages of 

their disease.
12 Office of Research on Women’s Health Symposium

Moving Forward

Increased awareness of pituitary disease should result 

in early diagnosis and treatment before its multiple 

complications are beyond repair. Unfortunately, this is 

not always the case. Although it is critical that advances

continue to be made in identifying the causes of pituitary 

tumors and devising improved and specific targeted treatments with fewer complications, the experts at the meeting pointed to the need to facilitate research that focuses

on the psychosocial consequences of pituitary disorders 

for the patient and his or her family in order to educate 

and involve more medical specialties in understanding 

pituitary disorders and treating the whole patient. This 

knowledge will be helpful in managing the psychological

complications of patients with endocrine disorders, as 

well as in identifying endocrine manifestations among 

patients with diagnosed psychological disorders. 

Although advances are encouraged and will continue 

to be made in identifying the etiology of and perfecting 

treatments for pituitary disorders, the experts at the 

workshop identified the following as significant researc

needs for the future:

◗ To develop and teach screening methods for earlier 

diagnosis of pituitary disorders before their multiple 

complications are beyond repair. 

◗ To explore the psychosocial consequences of pituitary disorders in the patient and his or her family.

◗ To determine the nature of pituitary dysfunctions 

associated with psychiatric disorders.

h 

Additional Information

More information about pituitary disorders can be 

found on the following Web sites:

◗ The Office of Research on Women’s Health 

(ORWH) stimulates and coordinates trans-NIH 

research efforts that focus on sex and gender differences in disorders that primarily affect or have 

implications for women’s health. Visit 

http://orwh.od.nih.gov. 

◗ The National Institute of Neurological Disorders and 

Stroke (NINDS) is the primary NIH Institute for research 

on pituitary disorders. Visit www.ninds.nih.gov. 

◗ Other NIH Institutes conducting research on 

or related to pituitary disorders include the 

National Institute of Child Health and Human 

Development (NICHD) at www.nichd.nih.gov, the 

National Institute of Diabetes and Digestive and 

Kidney Diseases (NIDDK) at www.niddk.nih.gov 

and the National Institute of Mental Health 

(NIMH) at www.nimh.nih.gov.

◗ The Pituitary Network Association is an international 

nonprofit organization for patients with pituitary 

tumors and disorders, their families, and the physicians 

and healthcare providers who treat them. Visit 

www.pituitary.org.

Reference

Ezzat, S., Asa, S. L., Couldwell, W. T., Barr, C. E., 

Dodge, W. E., Vance, M. L., et al. (2004, August 1). The 

prevalence of pituitary adenomas: A systematic review. 

Cancer, 101(3):613–619. 
Family Hormonal Health: Understanding Pituitary Disorders and Planning for Future Research 13

This document is not a typical meeting summary, but is based on what happened at the meeting. All content was 

derived from the following presentations:

Introduction and Opening Remarks

Vivian W. Pinn, M.D.

Associate Director for Research on Women’s Health

Director, Office of Research on Women’s 

Health, National Institutes of Health

Family Hormonal Health: The Broader Picture 

Yvonne T. Maddox, Ph.D. 

Deputy Director, National Institute of Child Health and 

Human Development, National Institutes of Health 

Hormonal Disease Is No Apparent 

Impediment to Good Health 

Captain Mohamed K. Shakir, M.D., FACP, FRCP

Director, Department of Endocrinology, National Naval 

Medical Center, Professor of Medicine, Uniformed 

Services University of the Health Sciences

Session I

Session Chair: Ian McCutcheon, M.D.

Professor of Neurosurgery, University of 

Texas, M.D. Anderson Cancer Center

The Pituitary Gland in Health and Disease 

Sylvia Asa, M.D., Ph.D. 

Professor, Department of Laboratory Medicine 

and Pathobiology, University of Toronto

Pathologist-in-Chief, University Health Network 

and Toronto Medical Laboratories

Impact of Hormonal Disorders in Childhood 

George P. Chrousos, M.D.

Chief, Pediatric and Reproductive Endocrinology 

Branch, National Institute of Child Health and 

Human Development, National Institutes of Health

The Transition Years: Neither Child Nor Adult 

Alan Rogol, M.D., Ph.D.

Professor of Pediatrics, University of Virginia

The Endocrinology of the Stress Response 

and Its Relevance to Depression, 

Anxiety, and Other States 

Philip W. Gold, M.D.

Chief, Clinical Neuroendocrinology Branch, National 

Institute of Mental Health, National Institutes of Health

Three Personal Perspectives on 

Living with Hormonal Disorders 

Sharmyn McGraw, Bram Levy, and Robert Knutzen 

Session II 

Session Chair: Edward Oldfield, M.D. 

Chief, Surgical Neurology Branch, National 

Institute of Neurological Diseases and 

Stroke, National Institutes of Health

The Young Male: What Are His 

Options and Choices? 

Marc R. Blackman, M.D.

Chief, Endocrinology, National Center for Complimentary 

and Alternative Medicine, National Institutes of Health

A Young Woman’s Hormonal World 

James Segars, M.D.

Staff Clinician, National Institute of Child Health and 

Human Development, National Institutes of Health

Hormonal Needs and Disorders 

in the Mature Female 

Jennifer Larsen, M.D.

Professor and Section Chief of Diabetes, 

Endocrinology and Metabolism, University 

of Nebraska Medical Center

Presentations
14 Office of Research on Women’s Health Symposium

Surgical Treatment of Pituitary Disorders 

Edward Laws, M.D., FACS

Professor of Neurosurgery and Medicine, 

University of Virginia 

Difficult Pituitary Problems: Options and Solution 

Ian McCutcheon, M.D.

Professor of Neurosurgery, University of Texas, 

M. D. Anderson Cancer Center

Panel Discussion: What Do We Know, 

Where Do We Go from Here, and What 

Is the Future Role of Research?

Drs. McCutcheon, Asa, Chrousos, Rogol, Laws, 

Oldfield, and Larsen

Moderator: Shereen Ezzat, M.D.

Professor of Medicine and Oncology 

Head, Endocrine Oncology, University of Toronto 

A videocast of the symposium is available at: 

http://orwh.od.nih.gov/news/pastmeetings.html.

NIH Publication Number 06-6074