OFF THE PRESS

After her marriage, Christina noticed that she was rapidly gaining weight in her midsection and she began lactating from her breasts.  She thought she was pregnant.  Numerous pregnancy tests proved negative, which prompted her ob-gyn to order a prolactin blood test, which showed that her levels were high.  

Finally, Christina’s doctor suspected that she may have a tumor on her pituitary gland and recommended an MRI.  Christina was terrified to think that she may have a tumor. What did this mean? Was she dying? 

The MRI confirmed that she had an approximate 6mm pituitary tumor. Christina was started on Dostinex and told that this medication would “fix” the tumor and as soon as she wanted to get pregnant to go ahead and go off of birth control pills. Not long after, she went off of the pill and her periods became almost non-existent and she was getting sicker with vertigo and extreme diarrhea.

Christina began searching for information about prolactinomas and found the website for the Pituitary Network Association. She was surprised to find that thousands of people have the same type of tumor. She could finally talk to others suffering from this disease. At www.pituitary.org, she bought “The Pituitary Patient Resource Guide” and took it with her to her primary care physician. She told him about the Pituitary Center at Stanford and asked for a referral. Her doctor was not aware that such a place existed but he wrote the referral, and she made the appointment.

 At Stanford, she was reassured that her symptoms were not uncommon and that she was a perfect candidate for surgery.  On February 22, 2007, Christina arrived at Stanford for tumor surgery. She was terrified thinking about all of the “what ifs…” She remained in the recovery room for three hours and was then moved to a closed observation room for patients who had undergone neurosurgery.

Today, Christina is healthy and well and ready to talk. And she is the proud mother of a healthy baby boy.  For years, breast cancer was a subject people shied away from. Now, it’s time to talk about pituitary disease since 1 in 5 Americans are affected with pituitary disorders. 

ABOUT PITUITARY DISEASE

An estimated 60 MILLION PEOPLE in the United States have pituitary / hormonal disease or disorder and the majority of them are unaware of it

Diagnosing pituitary disease and disorders in the past has been difficult.  Doctors are now beginning to recognize symptoms such as unexplained depression, mood swings, memory loss, eating disorders, sexual dysfunction, weight gain, excessive hair growth and weakness in limbs.

"This is an important finding that indicates pituitary tumors and related hormonal disorders are more common than previously thought and suggests many affected individuals remain undiagnosed,” states Dr. Daniel F. Kelly, Director of the Neuro-Endocrine Tumor Center at Saint John's Health Center and John Wayne Cancer Institute in Santa Monica.  “Given that most pituitary/hormonal disorders are readily treatable, health care professionals should have a low threshold to investigate for such disorders in patients with complaints or symptoms that may be hormonal in origin."

The pituitary is a pea-sized gland at the base of the brain that functions as the “master gland.”  It sends signals to the thyroid gland, adrenal glands, ovaries and testes, directing them to produce thyroid hormone, cortisol, estrogen, testosterone, and more.  These hormones have dramatic effects on metabolism, blood pressure, sexuality, reproduction and other vital body functions.  In addition, the pituitary gland produces growth hormone for normal development of height and prolactin for milk production.

Christina’s advice to others suffering from pituitary disease:
      Trust your body.
      Know that you are not alone.
      Be your own advocate.
      Do not accept mediocrity from medical professionals.
      Join the Pituitary Network Association.

This month’s PNA spotlight is focused on Dr. Patricia Crock, a member of our Scientific Advisory Panel.  She is an Associate Professor and head of the Department of Pediatric Endocrinology and Diabetes at John Hunter Children’s Hospital in Australia.  She is known for her expertise in lymphocytic hypophysitis and has written extensively on the subject. She has contributed several articles on the subject for the PNA website and Pituitary Patient Resource Guide, and has therefore contributed greatly to the PNA’s ability to educate and enlighten. PNA CEO Robert Knutzen first met Dr. Crock about ten years ago in San Diego through Dr. Sylvia Asa, who is on the PNA’s Scientific Advisory Board.  Mr. Knutzen adds, “Dr. Crock's unfailing courtesy and scholarly demeanor is very reassuring and she has, many times, been a resource of information to parents and patients alike, both from New Zealand and Australia. She has helped, so often and so long, that we named her to our panel of Scientific Advisors.”
Dr. Crock studied medicine at the University of Melbourne in Australia. She completed her internship and residency at St. Vincent's Hospital in Melbourne. She did a fellowship at McGill University/Montreal Children's Hospital in Montreal, Canada.  She is board certified in endocrinology.  Her primary clinical interests include pediatric endocrinology, Prader-Willi Syndrome, pituitary autoimmunity and autoantibodies, congenital hypopituitarism, and septo-optic dysplasia.
She was part of the team that discovered the gene to a rare form of diabetes, associated with neurodegeneration, called Wolfram syndrome.  She is also credited with developing the first immunoblotting (IB) assay for the detection of anti-pituitary autoantibodies as part of a collaboration with the Karolinska Institute in Stockholm, Sweden.  Her laboratory is the only one in Australia to run pituitary autoantibody testing for research.
Dr. Crock is active with the Australasian Paediatric Endocrine Group, which is a nonprofit that represents pediatric endocrinologist in New Zealand and Australia. 

Dr. Crock can be reached at patricia.crock@newcastle.edu.au.

Several PNA-affiliated doctors recently co-authored a fine study entitled “Chronic hypopituitarism after traumatic brain injury: Risk assessment and relationship to outcome.”

Here is the abstract, from the Journal of Neurosurgery, May 2008.
LINICAL STUDIES
Neurosurgery. 62(5):1080-1094, May 2008.
Bavisetty, Sumati B.S.; McArthur, David L. Ph.D., M.P.H.; Dusick, Joshua R. M.D.; Wang, Christina M.D.; Cohan, Pejman M.D.; Boscardin, W. John Ph.D.; Swerdloff, Ronald M.D.; Levin, Harvey Ph.D.; Chang, Dongwoo J. M.D.; Muizelaar, Jan P. M.D., Ph.D.; Kelly, Daniel F. M.D.
Abstract:
OBJECTIVE: Chronic pituitary dysfunction is increasingly recognized as a sequela of traumatic brain injury. We sought to define the incidence, risk factors, and neurobehavioral consequences of chronic hormonal deficiencies after complicated mild, moderate, or severe traumatic brain injury.

METHODS: Patients aged 14 to 80 years were prospectively enrolled at the time of injury and assessed at 3 and 6 to 9 months after injury for hormonal function and neurobehavioral consequences. Major and minor (subclinical) hormonal deficiencies, including growth hormone deficiency (GHD) and growth hormone insufficiency (GHI), were identified. Acute injury characteristics, neurobehavioral, and quality of life measures were compared in patients with and without major hormonal deficits by the use of multivariate analysis.

RESULTS: Out of 70 patients (mean age, 32 yr; median Glasgow Coma Scale score, 7; 19% women) tested at 6 to 9 months after injury, 15 (21%) had at least one major hormonal deficiency, 20 (29%) had minor deficiencies, and 30 (43%) had major and/or minor deficiencies. Patients with major deficiencies included 16% with GHD or GHI, 10.5% with hypogonadism, and 1.4% with diabetes insipidus. None of the patients required adrenal or thyroid replacement. At 6 to 9 months after injury, patients with major hormonal deficits had more abnormal acute computed tomographic findings (P = 0.014), greater acute and chronic body mass index (P < 0.01), and a worse Disability Rating Scale score (multivariate P = 0.04). Compared with the 59 growth hormone-sufficient patients, the 11 patients with GHD or GHI had worse Disability Rating Scale scores (multivariate P = 0.04), greater rates of depression, (90 versus 53%; multivariate P = 0.06), and worse quality of life in the Short Form-36 domains of energy and fatigue (multivariate P = 0.03), emotional well-being (multivariate P = 0.02), and general health (multivariate P = 0.07).

CONCLUSION: Chronic hypopituitarism warranting hormone replacement occurs in approximately 20% of patients after complicated mild, moderate, or severe traumatic brain injury and is associated with more severe brain injuries and increased disability. GHD and GHI are also associated with increased disability, poor quality of life, and a greater likelihood of depression. The clinical significance of minor hormonal deficits, which occur in almost 30% of patients, warrants further study. Given that major deficiencies are readily treatable, routine pituitary hormonal testing within 6 months of injury is indicated for this patient population.
Copyright (C) by the Congress of Neurological Surgeons

Click here for the full study.

The PNA Spotlight for July focuses on a man who is perhaps Europe’s most preeminent endocrinologist, Aart-Jan van der Lely, M.D. Dr. van der Lely has served on the PNA’s Scientific Advisory Board for years and is Chief and Professor of Clinical Endocrinology at the Department of Medicine at the Erasmus MC in Rotterdam, The Netherlands. PNA CEO Bob Knutzen met Professor van der Lely at a European medical conference about 15 years ago and admired the traits that make him a great doctor; he is very thoughtful, bright and intense. As a result, the PNA regularly refers European patients to him.

Dr. van der Lely is also Scientific Director of the Erasmus Institute of Neuro-endocrinology (ERINE) in Rotterdam. . Dr. van der Lely is an expert in acromegaly and in excessive growth hormones. His recent work has focused on ghrelin, a peptide released by the stomach that affects growth hormone. He has published his research extensively and serves as an editor for a number of medical journals, including Clinical Endocrinology (Oxford), the Journal of Endocrinological Investigation, Clinical Interventions in Aging, Journal of Clinical Endocrinology and Metabolism and Nature Clinical Endocrinology and Metabolism.

The PNA recently came up with a list of facts about pituitary disease that bear repeating.  They form the basis of what we do – and the message we are intent on spreading.  Words to live by!

1.)  The pituitary is the master gland of the human body.  It is so called because many parts of the body are directly or indirectly affected by its function.

2.)  The pituitary is the center of human sexuality and reproduction. Other parts of the body do most of the work but the pituitary initiates and controls the processes! We know that between 30 and 40% of the population suffers sexual dysfunction at sometime in their life.

3.)  The pituitary controls the life hormone, ACTH, or (simplified) cortisol without which we would soon die. Cushing's disease, then, from the adrenal or pituitary gland is a deadly and very difficult disease both to diagnose and treat.  

4.) The pituitary controls/regulates the thyroid gland. Rarely, if ever, does one function well without the other. This is often overlooked by many doctors.

5.) The pituitary, to a very large extent, regulates the metabolism in your body. How much or how little you eat, and disorders such as bulimia and anorexia, primarily stem from pituitary function.  So, of course, do obesityand simple (but often hard to correct) weight gain.

6.) The pituitary regulates mood, behavior and a startling number of mental and emotional health issues. (Bi-polarity has been linked to the pituitary gland).7. Your size, shape and height are directly linked to growth hormone, which is also produced by the pituitary gland.

8.) By a separate hormone, the pituitary regulates thirst and urinary output (diabetes insipidus results).

9.) Breast milk, the opening of the birth canal and regulation of the menstrual cycle are also pituitary gland functions!

There are many more things to know, but you can find it all in the Pituitary Patient Resource Guide.  However, and this is the key: next time someone asks "What is so special about the pituitary gland?"  Your answer should be - EVERYTHING!  It is a HUGE issue, but a very small gland!

A report by Edward R. Laws, Department of Neurosurgery
Brigham and Women’s Hospital and Robert Knutzen, Chair/CEO, Pituitary Network Association

In the 1930s a young investigator at the Mayo Clinic in Rochester, Minnesota, had a unique opportunity. Robert Costello conducted a careful and systematic analysis of pituitary glands obtained at post mortem examination from patients who had no obvious symptoms of endocrine disorders. The results were published in 1936. 1 In this study of 1,000 human pituitary glands, he discovered more than 200 benign tumours, most of them quite small.  This unexpected finding went relatively unnoticed by the general medical community at the time. This may have been because it was published in a pathology journal, or because it came at a time when tumours and cysts of other endocrine glands were being recognised and reported. At that time, the recognition of acromegaly occurred quite rarely and cases of Cushing’s disease were few and far between. Most of the pituitary adenomas being diagnosed and treated in the era before magnetic resonance imaging (MRI) scans and sophisticated endocrine laboratory test were macroadenomas that produced headache and progressive visual loss. In those days it was thought that pituitary adenomas accounted for only about 6% of primary brain tumours.

It was not until the 1970’s that the current ‘explosion’ in the diagnosis and treatment of pituitary tumours began and the importance of Dr. Costello’s study was validated. The factors that have led to our current state of knowledge include advances in a number of areas.  The revival of the trans-sphenoidal microsurgical approach provided a new, safe way of approaching the sellar area where these tumours begin.  The concept of the microadenoma, a small benign tumour that could cause disease because of its endocrine hyperactivity, was critical.

The pituitary microadenoma was a lesion that could be removed selectively using microsurgical techniques while preserving normal pituitary function. The advent of accurate hormone testing allowed these tumours to be diagnosed at a relatively early stage, and the actual incidence of pituitary tumours began to be recognised.  Over the past 100 years systematic attempts were gradually made to link hormonal excess or deficiency to symptoms and patient complaints.  The most common symptoms were enlarged extremities (acromegaly) and obesity/striae (Cushings’s). Important related symptoms such as mood swings, infertility, psychological problems, high blood pressure, arthritis, depression and apathy were often attributed to health issues unconnected to hormonal disorders.  Between 30 and 40% of the population experiences sexual dysfunction – an important symptom of pituitary disease.  Obesity is a major national health concern, along with osteoporosis and diabetes mellitus.  All are unmistakably linked to hormonal issues.

The pioneering neurosurgeon and pituitary psychologist Harvey Cushing produced a clear, compelling and decisive exposition of the findings in patients with pituitary adenomas. The true significance of these findings, and the extent of the prevalence and importance of pituitary disease, has yet to be fully appreciated.  The total number of pituitary adenomas has probably not changed over the 70 years since Dr. Costello’s initial discovery of the prevalence of pituitary adenomas.

A recent meta-analysis of this prevalence was conducted on behalf of the Pituitary Network Association (PNA) by a multidisciplinary team of quality researchers. 2 Their examination of series of both autopsy and imaging studies from Dr. Costello’s time to today essentially confirmed his numbers.  Therefore, the surprise is not the high number of adenomas found, but that the medical community has been generally unaware of the true prevalence of these lesions. The discovery of advanced pituitary imaging, first with computed tomography (CT) and then with MRI, allowed for the detection of pituitary tumours of all sizes and for the development of effective medical, surgical and radiotherapeutic treatments.  Furthermore, the results of treatment could be thoroughly evaluated with imaging and laboratory follow-up.  It is likely that Dr. Costello would be pleased to see the current state of the diagnosis and treatment of pituitary adenomas that derived from the findings of his laborious studies.

We now have data showing that pituitary adenomas account for 20% of surgically treated primary brain tumours. A large number of these adenomas are treated with medication alone or with surgery and radiosurgery. In some cases they are not treated at all. Doctors can recommend continued observation of the tumours and follow them with a “wait and see” attitude, anticipating that neither tumour growth nor possible infarct or haemmorrhage will interfere with the patient’s survival or quality of life. This conservative philosophy demands rigorous and frequent follow-up imaging and visual and laboratory testing.

New cases of pituitary tumours are diagnosed in about 17 people per million on the general population per year. At any given time, as many as 100 people per 100,000 are living with pituitary tumours. It is distinctly possible that a similar number of cases go unreported or undiagnosed each year, even though the characteristic symptoms may be evident to a practiced endocrine professional or pituitary surgeon.  There is a legitimate concern about the large number of pituitary tumours that remain undiagnosed and untreated. The symptoms of these tumours include some of the most common complaints that individuals may experience.  Putting them together in an accurate diagnosis is a major challenge for many physicians. Raising awareness among the public, medical practitioners, public health authorities and federal health agencies (e.g. the National Institutes of health [NIH] and National Communicable Disease Center [NCDC] is an inescapable need and remains an important goal. 3

Four very important segments of society are in dire need of pituitary/endocrine/hormonal education. The first segment is the general medical community, (this means the medical professionals, nurses, nurse practitioners, physicians’ assistants and doctors) who usually see the patient first.  This is the critical “tipping point” for most patients. They wonder: “Will I be believed, tested, diagnosed and referred to an expert for confirming the diagnosis and recommending expert treatment?”  If so, the patient is among the lucky few.  Too often, the answer is “no”. Doctors tell them that their symptoms do not match the classic criteria for clinical symptoms.  If the patient’s symptoms do not match the doctor’s knowledge and experience of pituitary disease, they may be wrongly attributed to other conditions.

The second segment of society that needs education on hormonal issues is the mental health community. This is where patient turns for solutions to sexual failure (lack of libido), mood swings, inability to concentrate or focus on the task at hand, workplace insubordination and other psychological problems.  The correct diagnosis is often not forthcoming because the mental health practitioner s trained to look for signs of a difficult family background, environmental factors, workplace stress and other correlates of behavioural difficulties, rather than hormonal imbalance.
Hormonal failure (excess of insufficiency) is rarely suspected or discussed.  Hence, another treatment opportunity is often lost.

The third segment comprises the patient and the patient’s family.  They can easily identify a host of symptoms and complaints, yet the very significant symptoms -   the results of a malfunctioning master gland – are rarely recognized  or considered in the search for a diagnosis.  Finally, society at large is undereducated on the subject of hormonal health. 

Only recently have we begun to understand the many types of diabetes and thyroid problems, to mention but two recognizable issues.  Most other hormonal problems, of equal value to the patient’s well being, are sadly neither diagnosed nor treated in a satisfactory fashion.

• Costello, R.T., Subclinical adenoma of the pituitary gland, Am J Pathol. 1936 12: 205-14
• Ezzat, S., Asa, S., Couldwell, W. et al., The prevalence of pituitary adenomas, Cancer, 2004, (101)3 613-19
• Ezzat, S., Knutzen, R., Dispelling the myths about rarely diagnosed pituitary disorders, U.S. Endo Rev., 2005,1-3

How Doctors Think by Jerome Groopman, M.D., (2008), Houghton Mifflin Company, publishers.
By Linda M. Rio, M.A., MFT

PNA Board of Directors This book provides a helpful insight into the thought process of today’s physicians. For pituitary patients and their family members, I think it is a must-read as a guidepost through the confusing and frustrating maze of modern medicine. Pituitary patients deal with an uphill battle to just get a doctor to listen to their list of seemingly unconnected physical and emotional symptoms. Finally, a doctor - an insider - has written about how important it is for a good physician to listen to the patient. He highlights the importance of the doctor-patient relationship! In an age of managed care by third-party insurance and business executives, it is refreshing to hear that good doctoring still requires the doctor to remember to be a human being.

In spite of advances in technology, Groopman states, “the best way to get that information (about client symptoms) is by establishing rapport with the patient.” He also states that good clinical intuition is “a complex sense that becomes refined over years and years of practice.”

The other benefit of this book is that it also puts patients on alert about their own inability to provide doctors with enough information. Patients, Dr. Groopman states, “should politely but freely broach the issue with their doctor, “I sense that we may not be communicating well.” He also pulls back the veil on the medical profession in several ways. He interviews several other doctors and cites research that talks about misdiagnoses and the reasons for mistakes in medicine. Often misdiagnoses are not due to inaccurate knowledge, but to blocks in the physicians thinking. He cautions doctors to, “not be so ready to match a patient’s symptoms and clinical findings against their mental templates or clinical prototypes…seemingly unusual or atypical presentations often get short shrift.”

He also states that doctors like to be right (don’t we all). “Physicians, like everyone else, display certain psychological characteristics when they act in the face of uncertainty. There is the overconfident mind-set: people convince themselves they are right because they usually are.” Elaborating further on this topic, he says that, “While uncertainty itself imposes a significant burden on physicians”, the greater burden is “the obligation to keep these uncertainties in mind and acknowledge them to patients.” This becomes particularly relevant to pituitary patients because so many have great difficulty in obtaining a proper diagnosis. This book helps, I think, explain some of the reasons for this because pituitary tumors cause such a wide array of symptoms and are often difficult to identify, especially when other diagnoses may appear more readily available. Often, it seems, modern medicine treats the surface symptoms and fails to look further.

“Finding something may be satisfactory, but not finding everything is suboptimal.” Dr. Groopman writes about problems with imaging (MRI, CT etc.) and cites studies on how mistakes happen. He relays many patient stories that I think that anyone who goes to a doctor will find his information enlightening, helpful, and empowering.

By Robert Knutzen, PNA CEO, Founder

In a discussion with one of our Scientific Advisors the focal point of Pituitary Diseases/disorders came into view and we concluded a discussion we have touched upon many, many times before. How do we classify, describe and categorize pituitary tumors?

For 18 years we’ve been listening to patients clearly and lucidly (at least sometimes) describe their many physiological symptoms/problems/disorders, only to come to an awkward pause in the conversation when the staff member asks about issues of depression, mood swings, anger, etc. From some patients we hear words of denial/feigned ignorance and outright anger for our impudence in linking them with emotional/mental health issues! For the majority, however, the relief is palpable and often times they become very emotional when they realize that they are not alone. A great number of patients already know this about themselves but are either reluctant or frightened to bring it up or confess to it. When patients are told that a large majority face the same unanswered uncertainty in their own medical quest for help, it sometimes helps enormously.

The stigma of mental/emotional disorders still lingers, particularly among the ignorant and spiteful members of society. (Those with any semblance of common sense know that issues from PMS to Alzheimer’s are not self-induced or the result of bad parenting or early potty-training ). So it is with pituitary/hormonal disorders. You don’t give it to yourself, but even when you seek help from the medical community you are often told that your physical/physiological complaints are in no way related to your feelings, emotions and behavior. That is absolutely wrong.

For many years, probably since time immemorial, someone among us starts to act strangely and we realize he/she is not “normal”, whatever that means. From Plato to Dr. Harvey Cushing, it is quite clear that a vaguely outlined problem existed but it was rarely talked about nor treated until, I believe, the advent of pills and other medication. There are virtually no psychiatrists or psychologists who broadly speak about or train the general medical community in recognizing or dealing with emotional/hormonal issues. Why? Is an appropriate question we have asked many, many times, yet no viable answer is forthcoming!

The facts, again, are plain and up-front. The American Psychiatric Association has a section in its diagnostic manual mentioning the problem.

Let’s read from the International Classification of Diseases, Ninth Edition, Clinical Modification, Chapter V. “They are for reference use by trained mental health clinicians, HIPAA requires ICD-9 not DSM coding. Under heading 306: Physiological malfunction arising from mental factors, psychogenic: physical symptoms or physiological manifestations, neither involving tissue damage (* this part might exclude Pituitary tumors)

     306.6: Endocrine

The American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders (DSM IV), lists in Appendix G, page 818, Endocrine Diseases (including acromegaly, Cushing’s etc.) as ICD-9 medical codes (at least they are listed).

Few, if any, are willing to deal with it. The readers can all (doctors, nurses, family and patient) contact your doctor, insurance company, Representative and Senator, all the way up to the White House. Explain the situation(s) you are experiencing and ask them to take action. A failure to act after knowledge is gained may simply not allow the doctor or the insurance company to escape legal liability! We know that many insurance companies turn down requests for coverage of mental health problems. Most patients (and we suspect doctors) are not willing to fight for us or themselves. Therefore we, as patients, must take up the task ourselves.

More about this in the next Issue of HIGHLIGHTS.