“Facts Do Not Cease To Exist Because They Are Ignored.” ~ Aldous Huxley
On May 8, I was pleased to attend “The Third Annual Seattle Pituitary Symposium: A discussion with leaders in pituitary management”. The event was produced in order to educate and support pituitary patients and their families. I found it a worthwhile program, as patients were able to listen and talk to specialists, and to learn more about the different pituitary diseases and various treatments offered. In this way, patients are able to make informed decisions about their own disease management and to determine which therapies (such as medication, surgery or radiotherapy) may be suitable for their condition(s). Experts such as William H. Ludlam (Seattle Pituitary Center at Swedish), Roberto Salvatori (Johns Hopkins Pituitary Center), and Sylvia L. Asa (University of Toronto) were present, as well as a number of other creditable pituitary and tumor professionals (see complete list of presenters below). It must have been a difficult day for all of them, as they were required to share their time speaking at another concurrent symposium for physicians’ continuing education (called “Advances in Prolactinoma Management”). Although some presenters seemed a little hurried between auditorium sessions, they nevertheless endeavored to make room at the end of each talk to answer individual patient questions. It would have been nice if this time had been a bit longer in some cases, but answers to unique concerns are probably better achieved by scheduling a private appointment with the doctor. Another improvement I would suggest would be for the opportunity for presenters to sit in on each other’s talks so as to avoid the emergence of some seemingly conflicting information, especially when it came to making decisions about prolactinoma surgery.
What this article entails
It is not in the scope of this blog post to provide a comprehensive account of all that was discussed throughout the day, but I have attempted to supply some of the main points. This was nevertheless a sizeable task, and I often considered splitting the report into many smaller postings (i.e., Post #1: First Presentation, Post #2: Second Presentation, and so on). However, I feel that this would have affected the flow and cohesiveness of the various details that were presented at the symposium. While many of the themes and associated facts in this post were collected from the conference itself, I have also attempted to furnish the reader with some personal views about some of the challenging issues often encountered with pituitary disease. Nowadays, I hear a recurrent message from the medical community, for us as patients to be more proactive in our overall health and well-being. It is important to gain knowledge about our own condition(s), so that we can engage in well-versed dialogue with our physicians in the quest to resolve our poor states of health. It seems that the majority of information obtained from medical resources, such as peer-reviewed journals, Internet web sites and visits with the doctor, fail to include the more personal features of the disease (some of the more accommodating links are included below). For example, clinical symptoms frequently include the word “fatigue”, but don’t specifically address the significance of it or how it is likely to affect one’s prognosis in the long-term. A productive part of the symposium dealt with this issue by offering regular breaks, as well as a “Breakout” session where patients could interact and talk about their own specific challenges or triumphs.
Beginning with Breakfast
The event started early with a continental breakfast amongst other pituitary patients and their caregivers, and it didn’t take long for many to unite and spark up similar-themed conversations around the reception hall. Pituitary disease has always been viewed as a relatively rare condition, and so patients can sometimes feel isolated while going through the roller coaster of symptoms and diagnostic tests that are required for proper diagnosis. It is now becoming apparent, however, that one in five people around the globe may have a pituitary growth (see one of my previous posts
here for more information). Although many tumors (also called adenomas) are nonfunctioning and cause no apparent symptoms, some may be very serious and detrimental to one’s health. In fact, in some cases pituitary tumors can be fatal. This gathering was therefore particularly welcomed by those who wanted to compare their stories and to find affiliation with others who would understand. It was certainly an invigorating scene and I had already connected with two patients with Cushing’s disease and another with prolactinoma before the presentations even began. One tiny oddity regarding breakfast, however, was that the food provided mainly comprised sticky and sugary donut type treats, when so many with pituitary disease suffer from metabolic disorders, diabetes or considerable weight issues. Hopefully, we will see some healthy cereals or perhaps even a vegetable or two next year!
Nonfunctioning pituitary tumors
Dr. Molitch presented the first topic, which was about nonfunctioning pituitary tumors. He explained the difference between the terms “micro” and “macro” that are used to convey tumor size. An arbitrary division is made at 1 cm, signifying that those less than 1 cm are microadenomas and those greater are considered macroadenomas. Another distinction can be made between tumors that produce either endocrine or mass effects. In some instances, the tumor can create over production of one or more hormones, such as prolactin, cortisol or growth hormone. For example, if a pituitary tumor causes excess amounts of prolactin, it is referred to as a prolactinoma. In the case where the tumor secretes too much cortisol, it is known as Cushing’s disease. Although not specifically mentioned by Dr. Molitch, it is now also understood that in some cases the tumor may be co-functioning (a plurihormonal adenoma), resulting in the secretion of more than one type of hormone (although this is less common). For example, it is possible for a patient to have both prolactinoma and Cushing’s disease. Despite the fact that some tumors may not produce excess hormone levels (nonfunctioning), its increasing size may put pressure on the pituitary gland and result in symptoms such as headache, visual field defects, diabetes insipidus (DI) or hypopituitarism (when the pituitary gland fails to produce the correct amount or number of hormones). In some instances, however, microadenomas produce no clinical symptoms (asymptomatic) and are often found as incidental findings. An example given was that of a person who would be sent to MRI following recent head trauma (such as a motorcycle accident), and the pituitary tumor was discovered as a secondary finding. In such cases, they are referred to as incidentalomas. In instances where a nonfunctioning macroadenoma is causing major symptoms due to its mass, however, it is necessary to consider suitable treatment options.
An Overview of Acromegaly
Dr. Ludlam talked about one of the most conspicuous and serious forms of pituitary diseases, called acromegaly. Most of us have seen photographs of the Guinness Book of Records’ World’s tallest man or woman, or heard other remarkable stories about “giants” that just kept growing. Such a condition is not a new phenomenon, and it is even believed that some ancient rulers suffered from acromegaly or gigantism. The caption to this segment was taken in the auditorium during the symposium. If you look carefully, you will distinguish that the slide depicts portraits of Akhenaten, pharaoh of 18th dynasty in Egypt, and Roman Emperor Gaius Julius Versus Maximinus “Thrax” 235 AD. (“Acromegaly”, editors: van der Lely AJ. Et al, 2007, Informa Healthcare). On closer observation, you may notice that the facial features of both rulers are rather coarse. In around 10% of cases, pituitary tumors cause an excess production of growth hormone (GH), which causes a myriad of difficult physical and subjective signs and symptoms. A distinction is made between children and adults, as excess growth hormone in children results in taller stature because their bones haven’t yet fused (called pituitary gigantism). In respect of adults, where bones are fused, excessive growth hormone results in marked bony and soft tissue changes (referred to as acromegaly). This can lead to an altered facial appearance due to enlargement of the forehead (called frontal bossing) and jaw. Other symptoms of acromegaly include enlarged hands and feet, spreading of teeth, enlarged tongue, deepened voice, accelerated cardiovascular disease and more. The condition is also associated with other diseases such as sleep apnea, osteoarthritis and diabetes mellitus. Acromegaly affects both body and mind. Not only does the patient suffer from physical discomforts, such as joint pain and cognitive impairment, but also on a social level it can cause personality changes and disorders, depression, fatigue and decreased libido. Although acromegaly progresses gradually over the years, if not caught in its earliest stages, permanent disfigurement may result. While acromegaly is considered rare, it is believed that many patients are undiagnosed. The diagnosis of acromegaly can be confirmed by observing levels of insulin-like growth factor (IGF-1) and GH and applying a glucose tolerance test.
There are many treatment methods for dealing with GH excess and tumor growth. The primary option for acromegaly is transsphenoidal pituitary surgery (further details are given below), which may be followed by irradiation and/or medical therapy. Pharmacotherapy includes the use of somatostatin analogs (octreotide LAR or lanreotide), dopamine agonists (cabergoline or bromocriptine), or a GH receptor blocker (pegvisomant). Tumor size and biochemical management of GH and IFG-1 levels affect long-term outcomes
Advances in Pituitary Radiotherapy
Dr. Suh began this presentation by explaining that pituitary adenomas are very common, representing around 10-15% of all intracranial tumors (tumors within the skull). Around 3-25% are discovered as incidentals in autopsy reports. Some clinically evident cases can, however, cause severe morbidity. Around 70% of pituitary adenomas secrete hormones, such as prolactin (PRL), Growth Hormone (GH), Thyroid Stimulating Hormone (TSH), Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH). Also, mass effect from growing tumors can lead to visual defects, headaches, cranial nerve deficits and PRL secretion. There are many treatment options available for pituitary adenomas. A nonfunctioning incidental microadenoma may merely be observed with imaging studies over a period of time. In instances where the tumor is producing clinical symptoms, treatments may include medical therapy, surgery and/or radiotherapy (radiosurgery or radiation therapy).
The medical therapies available for pituitary adenomas are varied, depending on the type of hormone that is being secreted. Excess PRL levels with a prolactinoma are treated with bromocriptine, quinagolide or cabergoline. Somatostatin, octreotide or pegvisomant are prescribed to patients with excess growth hormone levels. To suppress cortisol production associated with Cushing’s disease (CD), mitotane, ketoconazole or cyproheptadine may be recommended. Octreotide or somatostatin are shown to be effective for treating TSH-secreting adenomas.
Where surgery has been unsuccessful (due to incomplete resection, recurrent tumors, or inoperable patients), pituitary radiotherapy may be used as an alternative treatment. It has also been utilized to reduce the requirement for long-term medical therapy. Because radiation therapy is administered in small doses, it can take many years for hormone regulation when offered for hormone-secreting tumors. Nevertheless, it is effective at preventing tumor growth within only a matter of months after commencing treatment, despite taking longer (sometimes years) to actually shrink the mass. Because medical and surgical therapies show a more immediate response when addressing pituitary tumors, radiotherapy is not often used as a first line of treatment. With recent technological advances, there has been an improvement in benefit and safety of radiotherapy, and although conventional (external beam) and stereotactic radiation therapy are used, most patients now opt for the stereotactic techniques, unless the tumor is particularly large. This method has the ability to match up to the shape of the tumor, thus reducing radiation exposure to proximate brain tissue. There are still, however, some concerns about damage caused to normal surrounding tissues and this can result in endocrine dysfunction, vascular injury, optic neuropathy (< 1%) and radiation necrosis (<1-2%). Recently, there are now single dose techniques, such as Gamma Knife® radiosurgery, which give out a more intense magnitude of beams to the pituitary tumor. Radiosurgery seems faster at reducing excess hormone production from sectretory adenomas than radiation treatments. Future work is required to refine the role of radiation in treating pituitary tumors.
Medical Treatment Options in Cushing’s Disease
Dr. Heaney presented a talk about pharmacotherapy options for patients with Cushing’s disease (CD). I have also included some information obtained from Dr. Grossman’s presentation on medical therapy for pituitary tumors in general.
Despite the fact that most CD tumors are tiny (less than 5 mm in diameter), CD is the most serious and life-endangering condition caused by a pituitary tumor. It is also one of the most challenging pituitary diseases to treat. CD is caused due to pituitary adrenocorticotropic hormone (ACTH) hypersecretion, which results in excess cortisol production from the adrenal glands. Too much cortisol can cause many disabling and sometimes life-threatening symptoms, which can vary but include abnormal and rapid weight gain (upper body obesity), severe fatigue, high blood pressure, diabetes, osteoporosis, muscle weakness, coronary artery disease, psychological disturbances (irritability, anxiety and depression), fragile and thinning skin, poor sleep quality, hair loss, purplish stretch marks, and more.
Some patients may have a cyclical form of Cushing’s disease, which means that cortisol levels fluctuate between high and very low. In such instances, the patient may not experience the same patterns of weight gain as a classic Cushing’s patient (such as rounded face or the classic “buffalo hump”). Unfortunately, many physician’s fail to recognize this and misdiagnose patients with PCOS or attribute symptoms to other nonspecific illnesses such as Chronic Fatigue Syndrome (CFS). It is crucial that patients obtain a proper diagnosis as early as possible, as CD is linked to high morbidity and eventually mortality, if left untreated. |
While many acromegaly and prolactinoma patients can be treated with medical therapy alone, there are no real effective drug therapies currently available for ACTH-secreting pituitary tumors. Drugs can be useful at controlling hypercortisolism (excess cortisol levels), but they do not prevent tumor growth. A medication commonly used for CD is called ketoconazole, which is an antifungal agent. It acts on the adrenal glands to reduce cortisol levels (and also lowers testosterone), but has shown to be less effective for long-term use. Ketoconazole is taken in pill form 2 or 3 times a day and is generally well tolerated by patients, although there are sometimes side effects associated with liver function (which can be monitored), edema and skin rash. Other oral medications that work upon the adrenal glands include metyrapone, aminoglutethimide, mitotane and etomidate, although these have a higher rate of side effects, such as dizziness, nausea, skin rash, edema and hirsutism (excessive hairiness in females). Other drug treatments used for CD patients include neuromodular therapies that act at the hypothalamic-pituitary level, such as serotonin antagonists (cyproheptadine, retanserin, ketanserin) and dopamine agonists (cabergoline and bromocriptine).
There are also GABA agonists (sodium valproate) and somatostatin receptor ligands (octreotide and lanreotide). For example, research has shown that peroxisome proliferator-activated receptor gamma (PPARy) agonists effectively suppress ACTH secretion in the mouse/rat cell line, but the few studies so far conducted with CD patients have produced inconsistent results. In one investigation, 14 patients were treated with rosiglitazone (8 mg-16 mg) for 1-7 months, resulting in normalization of urinary free cortisol (UFC) in 6 patients (42.9%) and mild improvement in clinical features. Other similar studies using rosiglitazone have also shown effective use in a subset of patients, but further work is required in order to identify the medicinal potential of PPARy agonists in CD patients. Some of the side effects include weight gain, edema, bruisability and hypertension (high blood pressure). Presently, many doctors believe that rosiglitazone is currently of little value in treating Cushing’s disease.
One thing that puzzles me is that cabergoline is generally effective at reducing both prolactin levels and tumor size in prolactinoma patients. I have also been advised by several MDs that cabergoline decreases cortisol levels in CD patients. It seems odd therefore that a medication would shrink tumors secreting excess prolactin but not those producing ACTH. In my own case, I am suspected of a co-functioning tumor due to both elevated prolactin and random cortisol levels. My prolactinoma has been managed with cabergoline therapy over the past 10 years, and the tumor has sometimes presented on MRIs but not on all (this does not mean that the tumor has disappeared, especially if the patient still requires medication to suppress excess hormone production. In fact ~ 30% of pituitary tumors do not present themselves on MRI due to issues such as tumor size, position, angle, or type of machine used). I have been advised to discontinue cabergoline therapy whilst undergoing further testing for Cushing’s disease, as cabergoline suppresses cortisol and testing needs to be performed when cortisol levels are high. So, does this mean that my tumor would not have shrunk at all if it were not co-functioning with prolactinoma? Another oddity is that one of my previous MRIs has not only revealed a 5 mm adenoma, but also a smaller 2-3 mm lesion on my pituitary gland. This is thought to represent either a second pituitary tumor or a Rathke’s cleft cyst. I just wonder whether the larger tumor is the prolactinoma and the tiny one (more typical of Cushing’s) is responsible for my elevated cortisol levels. I suppose only time will tell and I will certainly update this information after I have consulted with my pituitary endocrinologist in June.
*NB: Before testing for CD, make sure you check your current medications with your doctor. I went through a whole ICT test kit before realizing that I should have discontinued both cabergoline and estrogen. Whether you take estrogen in birth control form or as hormone replacement therapy (HRT) following a hysterectomy, it should be discontinued for 2-3 months prior to testing for CD so as not to skew lab results. |
Although octreotide and lanreotide are more effective at treating acromegaly than CD patients, the good news is that Dr. Heaney informed us about another somatostatin analogue drug-based therapy called pasireotide (SOM230), which is being developed to successfully target CD tumors. Somatostatin is a hormone made in the hypothalamus, which reduces the creation of several pituitary hormones. Pasireotide binds multiple somatostatin receptors (1, 2, 3, and 5) to mimic the action of natural somatostatin. Pasireotide requires injection once a day but is likely to develop into a once a month treatment. One analysis showed that after 15 days of pasireotide therapy 76% of patients had a reduction in UFC levels, and 17% of these had normal UFC levels. Although the drug has potential for lowering cortisol, it isn’t yet effective at reducing levels into the normal range. Pasireotide drug-therapy looks very promising and is currently awaiting approval from the FDA.
So it seems that drug-based therapies can sometimes be helpful but are not generally effective as a sole treatment for CD at the current time. Pharmacotherapy, however, can be a suitable option for patients with severe cortisol levels that are awaiting surgery, are medically unfit for surgery, have poorly controlled diabetes and/or hypertension, or who decline pituitary surgery. The first line of treatment for Cushing’s disease for most patients therefore is pituitary surgery. Around 76% of microadenomas can be successfully resected via transsphenoidal pituitary surgery. The outcomes for macroadenomas are less successful (around only 30% of cases). It is not uncommon for CD patients to have several surgeries due to recurrent tumor growth.
Although CD patients are currently unable to rely on medical therapies as sole treatments, Dr. Heaney notified us of some preclinical drugs that have potential for use as treatments for hypercortisolism. For instance, mifepristone is a glucocorticoid receptor antagonist, which blocks the effects of cortisol. Its efficacy and safety for Cushing’s syndrome are currently under investigation. The trial involves giving subjects oral mifepristone for up to 24 weeks, and is suitable for those who have had failed or recurred pituitary surgery or radiation therapy. The study requires close monitoring for possible severe hypokalemia (low blood calcium), hypertension and clinical signs of adrenal insufficiency.
More information can be found here.
Another preclinical drug that both Drs. Heaney and Grossman mentioned was Retinoic acid (ligand for RXR/RAR nuclear receptor). Further details can be found here.
Breakout: Patient Small Group Discussions
After lunch, attendees were given the opportunity to separate into various groups, relating to type of pituitary disease they were interested in. Although I have a prolactinoma, I decided to join the Cushing’s crowd, as I am also suspected of Cushing’s disease. Patients present were at different stages of treatment: some undergoing testing for diagnosis, some planning surgery, and others who had undergone at least one surgery. This is the first time I had been in the company of fellow pituitary disease sufferers, and I confess that I felt quite emotional at times. It was a relief to know that I wasn’t the only one who felt discouraged by the inability to carry out simple daily tasks. Others had also occasionally questioned themselves and felt as though they were losing their minds. It’s amazing how well pituitary patients look despite how dreadfully ill they are inside, and it can sometimes take a long time to receive serious attention and proper diagnosis from the medical community. Sometimes it can even take years because physicians often fail to recognize the symptoms and put all the pieces together. In fact, I was surprised to discover that the failure of my GP to refer me to a pituitary specialist was not an isolated incident. I was fortunate in having PPO insurance, which enabled me to ditch this stubborn physician and find another who would provide that much needed referral. Others weren’t so fortunate and resorted to threatening to slap their GPs with lawsuits if they had to go elsewhere for diagnosis. This often had the desired effect, although personally I wouldn’t want to keep such a physician in my list of medical contacts. Another individual, however, put a positive spin on it by suggesting that a return to the offending physician could lead to better education within the medical community. In fact, some GPs have even been known to apologize.
Unless someone has specifically gone through the same challenging set of circumstances as a pituitary patient, he or she would be unable to fully understand the disease in all its complexities |
Many patients disclosed that they found it difficult to stay in employment, drive a car, or deal with minor stressful events. Additionally, some struggled to get out of bed, at times spending days, or even weeks totally bedridden. Doing the housework or taking care of children seemed yet another milestone for many, and the general consensus was that it was easier to focus on the mere necessities in order to avoid living in complete filth! Some patients chose the option of seeking assistance from other sources. Although a number of patients suffered with mood swings and periods of anxiety, one individual in particular was concerned about the psychotic episodes she regularly experienced. Such occurrences had become so profound that she was unable to return to work, and her children had been taken away so that she wouldn’t harm them. She was totally aware of the serous nature of this state of affairs, but hadn’t really come any closer to resolving them.
One of the biggest concerns for most patients relates to the lack of emotional support received from some family members and friends. Although relatives may be present during surgery and “recovery” periods, they were still unable to identify with the various battles encountered by someone with lifelong pituitary disease. I suppose the fact that patients present themselves as walking and talking individuals translates to many that they must be fine. Several at the meeting were in agreement with the fact that unless a person has specifically gone through the same challenging circumstances, they would be unable to fully understand the disease in all its complexities.
Surgical Treatment Options for Pituitary Lesions
This was an exciting presentation provided by Dr. Mayberg (specialist in microsurgery for pituitary tumors), who diverged from using the customary didactic graphs and diagrams but instead provided video footage of recent pituitary surgeries. I found this very helpful, as symposium attendees were able to observe pituitary surgeries on the screen, whilst Dr. Mayberg provided practical narration. He confidently assured us about recent advancements in modern technology, and said that pituitary surgery was becoming more straightforward (for microadenomas) and increasingly safer. He also stated that the success rate for patients with microprolactinoma was 100%. In fact, he basically said that if prolactinoma patients get tired of taking the [cabergoline] pill, then it’s easy enough to take the tumor out. It’s a personal choice. Obviously, surgery would be more complicated for some macroadenomas that invade the cavernous sinus.
Surgery should be carried out with the aim of removing the tumor, whilst keeping the normal pituitary gland intact. The most common type of pituitary surgery performed is the transsphenoidal resection. This involves going through the sphenoid sinus (an air space behind the nose), as opposed to opening the skull to reach the tumor (craniotomy). The primary approach is the direct transnasal, which involves making an incision in the back wall of the nose so that the sphenoid sinus can be entered directly. In this instance, no postoperative packing is required, as the surgeon can simply use fat taken from the belly to prevent spinal fluid leakage. It is also possible to make an incision along the front of the nasal septum (transseptal) or via an incision under the lip/upper gum (sublabial), although these methods would require postoperative packing and have a longer recovery time than the direct endonasal or endoscopic approach used for transnasal surgery.
The Role of the Pathologist in Pituitary Patient Management
Dr. Asa provided some interesting data relating to the spectrum of pituitary disease, and detection (clinical, biochemical and radiologic). When the pituitary malfunctions it can cause mass effects, resulting in headaches, pressure on the optic nerve with loss of peripheral vision, and it can compromise normal function, resulting in an insufficient number or amount of hormones (hypopituitarism). A malfunctioning pituitary can also lead to hormone excess states, causing health problems such as sexual dysfunction/infertility, osteoporosis/arthritis, diabetes mellitus, mood disorders and accelerated heart disease.
New results from a Meta-analysis study (Ezzat et al, Cancer 2004; 101(3):613-9) show that pituitary tumors are more common than once believed. The overall estimated prevalence is 16.7%, although this also includes nonfunctioning and asymptomatic lesions. Approximately one third to a quarter of tumors are believed to be prolactin secreting. The majority of tumors are micro (< 10 mm). Around 40% of patients with Cushing’s disease do not have detectable tumors on MRI. About a third of patients with infertility and elevated prolactin do not have observable tumors. It is thought that 4/100,000 lose pituitary function in the absence of a large pituitary growth (Clin Endocrinol (Oxf) 2001;55:735-740). Dr. Asa’s main theme was to increase awareness, in order that physicians consider pituitary disease as a likelihood when faced with a specific group of symptoms and/or laboratory results. In such cases, the patient may need to undergo testing for blood and urinary hormone levels and MRI.
Around 40% of patients with Cushing’s disease do not have detectable tumors on MRI.
About a third of patients with infertility and elevated prolactin do not have visible tumors on mri |
The role of the pathologist is to manage the clinical laboratory and to offer clinically related and accurate diagnostic tests for pituitary function and assessment. One fascinating revelation for me was that it is possible for pathologists to use a practical approach in diagnosing pituitary specimens taken from surgery. Pituitary adenomas can be assessed using several special stains and “immunohistochemical” markers in order to classify the pathologies. In this way, it is possible for the pathologist to distinguish certain clinical characteristics and to predict targeted therapies for patients with pituitary tumors. It is important, therefore, that the neurosurgeon endeavors to send the surgically removed tumor to the pathologist for evaluation (apparently, this doesn’t always happen).
Medical Management of Prolactin Secreting Pituitary Tumors
Dr. Salvatori provided the final presentation of the day by discussing one of the most common types of pituitary tumor, the prolactinoma. This is also one of the less serious types of pituitary adenomas as it can generally be easily treated with pharmacotherapy. This tumor secretes too much prolactin (also called hyperprolactinemia). Symptoms in females include breast milk discharge from the nipples, irregular or complete loss of menstrual periods, infertility, and low libido. Men may have enlarged breasts and loss of libido. Because men don’t have the full range of signs or symptoms as women, they often go undiagnosed until the tumor becomes large with higher prolactin levels. In such cases, symptoms include headache and visual loss from mass effect on the optic nerves or optic chiasm.
“Patients exposed to BRC for at least one month are more likely to have tumor, and possibly less likely to be cured by surgery” ~ Roberto Salvatori, MD |
The treatment goals associated with prolactinoma include shrinkage of the mass, preservation or recovery of pituitary function, and prevention of recurrences. It is also important to prevent long-term complications of hypogonadism (low levels or impaired production of sex hormones), which can lead to osteoporosis. Dopamine agonists such as bromocriptine (Parlodel®) or cabergoline (Dostinex®) are generally effective at reducing tumor size and prolactin levels. Personally, I found cabergoline more tolerable than bromocriptine, and it is certainly the drug of choice if surgery might be considered as a future option. Pituitary tumors are generally soft in nature but prolonged use of bromocriptine can increase the consistency, making them hard and thus more difficult to remove.
Physicians often work with the patient by recommending a withdrawal protocol. If the drug has been successful at managing prolactin levels for at least a year, and the tumor is no longer evident on MRI, the patient is able to gradually discontinue the medication. Some patients may stay in long-term remission after a period of several years of dopamine agonist therapy. However, this is not always the case. In my own situation, I have attempted to taper off cabergoline numerous times over the past ten years, but a three-month follow up has always demonstrated elevated prolactin levels. I was always told that I would need to continue cabergoline therapy until I reached 52 (the natural age of menopause). Since undergoing a premature hysterectomy last year, however, I realized that this was incorrect. Medical therapy needs to be continued (with breaks if possible) for life, or the tumor will likely grow larger and increase prolactin levels. Just because the tumor no longer presents itself on MRI due to shrinkage, it doesn’t mean it is no longer there. Indeed, if a patient still requires medication to treat elevated prolactin levels then the tumor must still be functioning.
One thing to consider is the fact that dopamine agonists such as cabergoline carry the serious risk of cardiac valve disease. It is important to note here, however, that the research conducted included Parkinson’s disease patients who were generally on far higher doses than those with prolactinoma. Further, the patients treated for Parkinson’s disease differ in age (are generally older). It is believed that the smaller doses used for prolactinoma are safer, although it is not really known whether the long-term use of such drugs (say in 20, 30 or 40 years) would cause a similar outcome. For those patients requiring long-term treatment with cabergoline, it is recommended that regular echocardiographic evaluation should be carried out. Hopefully, larger studies will be conducted in the foreseeable future.
Although medication is the first line of treatment for prolactinoma patients, surgery may be performed when medication is ineffective at reducing tumor growth and/or prolactin levels. In such instances, the tumor has grown into a macroadenoma prior to undergoing surgery. However, surgery may also be preferred as treatment for microadenomas where the patient no longer wishes to continue long-term drug therapy. For instance, the patient may not be able to tolerate the medication or perhaps is unable to afford the high cost of the drug due to lack of medical insurance.
Although I hear physicians state repeatedly that patients with prolactinoma shouldn’t suffer with poor quality of life when treated with medical therapy, I have come across a number of patients (both online and now in person) that actually do. For example, several members of the Pituitary Network Association (PNA) responded to my question on the forum about microprolactinoma, cabergoline and debilitating fatigue. In fact, due to their poor QOL some of them decided to undergo surgery and are now feeling a great deal better. I also came across one of the few peer-reviewed journals relating to QOL for patients treated for microprolactinoma. The study can be found
here.
Final Comments
Although this article is not intended as an all-inclusive review of pituitary disease, I hope you will find my notes from the Seattle pituitary symposium informative. However, I am not a medical professional and I may have misunderstood some of the information offered. Please consult a trained physician for your own individual care. Should you find any errors or wish to add any pertinent information, please let me know. Wishing you and your family well in your road to recovery and good health.
Useful Links
Dr. William Ludlam talking about Pituitary Disease
The Pituitary Network Association (PNA)
Cushing’s Help and Support
Cushing’s Help Organization
The Magic Foundation
Cabergoline heart valve long-term use
