Saturday, October 9, 2010

Prolactinoma and Pituitary Surgery


“Most of my prolactinoma patients suffer from poor health” 
~ Nurse practitioner (undisclosed) from a specialist U.S. pituitary clinic.

The treatment of prolactin-secreting pituitary tumors with dopamine agonist therapies is not always as straightforward as originally presumed. Indeed, many patients with prolactinomas feel unwell, despite the fact that related symptoms such as profound fatigue, cognitive defects and malaise are often excluded from the majority of medical publications and websites. Additionally, a number of prolactinoma patients may be intolerant to drug therapy or are concerned about the long-term safety of pharmacotherapy. In fact, some specialists are even beginning to consider surgery as a feasible first line treatment for some prolactinoma patients.


What is a prolactinoma?

A prolactinoma is a noncancerous or benign pituitary tumor (also called an adenoma) that secretes too much prolactin (also referred to as hyperprolactinemia). Prolactinomas are the most common type of pituitary tumor. In women, common symptoms may include: breast milk production (lactation), irregular or total loss of menstrual periods not related to menopause, infertility, and decreased libido. Since men don’t have the full range of signs or symptoms as women and are often too embarrassed to tell their physician about symptoms such as impotence or enlargement of breast tissue, they are more likely to go undiagnosed until the tumor becomes large with higher prolactin levels. In such cases, symptoms can include headache and visual loss due to mass effect on the optic nerves or optic chiasm. For more detailed information about pituitary tumors in general, please refer to my previous posts here and here.


Traditional treatment for prolactinomas

When I was first diagnosed with a prolactin-secreting tumor in 2000 (via blood work and an MRI), my endocrinologist followed the usual protocol in prescribing pharmacotherapy. Surgery was never discussed as an option, and at that time I knew nothing about pituitary disease. Like many prolactinoma patients, I was initially prescribed the more cost-effective dopamine agonist called Parlodel® (also known as bromocriptine), but due to unbearable side effects, I soon switched to cabergoline (Dostinex®). Although I still suffered with some dizziness and nausea, I believed it in my best interest to continue with this treatment, so that the tumor would shrink in size and my prolactin levels would reduce. This worked reasonably well for several years until my health started to decline drastically, resulting in my inability to continue with everyday tasks, such as work, leisure activities or social events. Although I had discussed my poor quality of life with numerous medical professionals over the years, no one really seemed to put the pieces together - If your endocrinologist tells you that the prolactinoma is not the cause of your incapacitating symptoms, then this must surely be correct… Right?  I was given a number of medications to help with chronic symptoms, such as overwhelming fatigue, post-exertional malaise and headaches, and thus began my frantic and desperate search to find the cause of my poor health situation. My eagerness to retrieve some sort of semblance of normal life led to innumerable highs and lows with various consultations and lab tests from infectious disease specialists, neurologists, sleep experts, ear nose and throat surgeons, and many more. All practically led to a dead end and I became increasingly disillusioned with the ability of the medical profession to help me get back on to the road to better health.

Dopamine agonists can sometimes be ineffective
or not tolerated, and side effects to these drugs may be so severe that patients are unable to function.


It wasn’t until I revisited my primary health issues and did some in-depth research on pituitary disease that I realized how uninformed many medical professionals were about pituitary tumors. I recognized that I wasn’t the only one whose life had been hijacked by the seemingly inconspicuous prolactinoma. For example, several PNA (Pituitary Network Association) forum members responded to my question about microprolactinomas, cabergoline and debilitating fatigue, and stated that they or their family members had suffered from a poor quality of life (QOL) before embarking upon transsphenoidal surgery in order to remove the prolactinoma. Also, dopamine agonists can sometimes be ineffective or not tolerated by patients. In some patients, side effects to these drugs are so severe that they are hardly able to function. Major side effects of such drugs include: nausea, dizziness, headache, mental fogginess, fatigue, abdominal pain and more (see here for more information). Further, cabergoline has been associated with cardiac valve disease in people with Parkinson’s disease (see here and here for further details relating to cabergoline and cardiac valve disease ). It is believed that the smaller doses used for hyperprolactinemia are safer, although it is not really known whether the long-term use of such drugs would cause a similar outcome. As a precaution, some doctors follow patients who require long-term treatment with cabergoline with careful echocardiographic evaluation – But not all do. In my own situation, a Doppler study revealed that I already had ”slight and physiologic insufficiency of the mitral and tricuspid valves”. I may never know for sure whether cabergoline was the cause of my valvular heart disease, but it is a serious concern in the decision of whether or not to continue pharmacotherapy. Women who plan to become pregnant are also advised to discontinue dopamine agonists (due to unknown risk of birth defects). Without appropriate treatment, there is the potential for regrowth of the pituitary mass, leading to further problems, particularly due to mass effect. Contrary to what many medical professionals believe (except for pituitary specialists), the fact that the tumor is no longer visible on MRI due to shrinkage, does not mean that it has gone. If a patient still requires medication to treat elevated prolactin levels then the tumor must still be functioning. Some prolactinoma patients may, therefore, wish to consider surgical resection as an alternative treatment.

Several PNA forum members stated that they or their family members had suffered from a poor quality of life before embarking upon transsphenoidal surgery in order to remove the microprolactinoma.


Pituitary surgery

Due to recent developments in modern technology, pituitary surgery is becoming more straightforward (for microadenomas that are <1 cm in size) and increasingly safer. The surgery itself takes approximately an hour to complete, with the average hospital stay only lasting a day. Surgery is done with the intention of removing the tumor, whilst keeping the normal pituitary gland intact.  Most pituitary tumors can be removed by transsphenoidal resection. This entails going through the sphenoid sinus (one of the facial air spaces behind the nose), as opposed to opening the skull to reach the adenoma (craniotomy). The principal approach is the direct transnasal, which involves making an opening in the back wall of the nose so that the sphenoid sinus can be directly entered. In this case, there is no need for postoperative packing, as the surgeon can use the patient’s belly fat to prevent spinal fluid leakage. It is also feasible to make a cut along the front of the nasal septum (transseptal) or via an incision under the lip/upper gum (sublabial), although these procedures would necessitate postoperative packing and have a longer recovery time than the direct endonasal or endoscopic approach used for transnasal surgery. The success rate for patients with microprolactinoma is extremely high and many patients who decide to undergo pituitary surgery feel a great deal better as a consequence.


Some complications associated with surgery

Although many patients have been shown to do well with pituitary resection, success is dependent upon the amount of experience the surgeon has at carrying out pituitary surgical procedures. A surgeon who is well versed in such matters will generally enable a better likelihood of complete tumor removal and minimal complications thereafter. It is important, however, to take some things into consideration, as like all surgical procedures, this operation carries some risks. Obviously, surgery would be more complicated for some macroadenomas that invade the cavernous sinus. The following list is not exhaustive but it provides some of the main points:

·         Post-operative sinus infection: After undergoing three separate sinus surgeries over the past ten years (for chronic sinusitis), I was perturbed to discover that many patients experience sinus infection after pituitary surgery. Common symptoms include: facial discomfort, stuffy nose, headache, fatigue, brain fog and dark nasal discharge. Although some medical professionals prefer to treat the infection with medications such as prescribed antibiotics and over-the-counter Mucinex-D, not all are in agreement. Antibiotics can be problematic, as they tend to destroy good bacteria along with the bad. In my case, I took Amoxicillin for 10 days, along with almost three whole boxes of Mucinex-D, but my infection hadn’t noticeably improved. My neurosurgeon explained that due to post-operative inflammation, it would likely take several months for the infection to completely clear up. He recommended using the neti pot twice a day in order to keep the area clean. Although I didn’t specifically have a neti pot, I immediately started using the NeilMed sinus rinses, which enabled more pressure and positive results. Although I still have an infection - which has persisted since July - my symptoms are gradually improving. If you really can’t bear the thought of nursing the infection for months on end, you may choose to visit a doctor that specializes in cleaning out the material from the sinus cavities after pituitary surgery.

·         Damage to the pituitary gland: Although normally unanticipated, such a situation is more likely to occur with macroadenomas than with microadenomas. In my case, I was told that damage to the gland was most probably caused by the tumor itself (I assume that long-term growth and shrinkage of the tumor eventually led to the injury). In the event that damage to the anterior (or front portion) of the pituitary has occurred, new hormone replacements may be required, including: growth hormone, cortisol and thyroid hormone. Damage to the posterior (or back part) of the pituitary gland may lead to diabetes insipidus (see below).

·         Diabetes insipidus (DI): Diabetes insipidus occurs when there is damage to the posterior part of the pituitary gland, and as a result the kidneys are no longer able to adequately conserve water. This causes the patient to frequently urinate large volumes, which in turn leads to excessive thirst in order to prevent dehydration. DI can be diagnosed through symptom history and laboratory testing, which may include the water retention test. This test can be quite a lengthy undertaking and can take a day or even longer before any conclusions can be made. So, make sure you take some good reading material with you (but no fluids or food!) My own recent experience involved sitting in a comfortable chair and being requested to produce a urine sample and to undergo lab work every hour. Although many post-operative patients experience DI initially after surgery, it is important to be aware of your symptoms during the whole recovery period. For instance, it wasn’t until about six weeks after surgery that I was diagnosed with DI. In most cases, DI is temporary after pituitary surgery, and can be treated with the oral medication, DDAVP (Desmopressin). Your electrolytes should also be monitored to make sure that you are on the right dose.

·         Electrolyte imbalance: The balance of electrolytes in the human body is necessary for normal function of our cells and organs. Electrolytes include: potassium, chloride, sodium, magnesium and bicarbonate. Common symptoms of electrolyte imbalance include: confusion, nausea and vomiting. Electrolyte imbalance can be diagnosed through blood testing and can be treated with electrolyte replacement.

·        Cerebral spinal fluid (CSF) leak: A CSF leak is an abnormal drainage of the fluid that surrounds the brain and spinal cord. Common signs and symptoms include: a positional headache (that is worse when sitting up but better when laying down), a clear watery liquid or bloody discharge from the nose, or a dripping down the back of the throat that leaves a salty taste in the mouth. Depending on the severity of the CSF, it can be resolved with as little as bed rest and a substantial intake of fluids, or as much as repeat surgery. To prevent CSF leakage, a small piece of fat (about 2 cm) is taken from the abdomen and packed into the pituitary cavity.

·         Meningitis: This is a rare complication from pituitary surgery. Common symptoms include: high fever, severe headache, stiff neck, nausea or vomiting, flu-like feeling, confusion and difficulty concentrating. Meningitis is usually a result of CSF leak and is normally treated with antibiotics.

·         Visual loss: The optic chiasm may be damaged during surgery. Although rare, post-operative bleeding may flow into the area around the pituitary gland or into any tumor tissue that remains. This can put pressure on the optic nerves and cause vision loss. In such circumstances, an additional procedure may be needed to remove any blood clots.

·         Stroke: There is a very small chance of damage being caused to the carotid arteries that are located close to the pituitary gland, in an area known as the cavernous sinus. This can cause and interruption of blood supply to the brain, potentially leading to stroke, severe blood loss or even death. Such a situation is, however, highly unlikely when surgery is performed by an experienced surgeon.

·         Tumor regrowth: Even after having surgery, there remains a chance that post-operative blood work may reveal another (microscopic) tumor or residual tumor that the neurosurgeon was unable to see during the procedure. In such cases, the patient may be required to receive further treatments, such as pharmacotherapy, an additional pituitary surgery or radiation therapy. For instance, my post-operative PRL level was above 10 mg/ml and it is continually rising, so with my next MRI we shall be looking out for another adenoma. I have become intolerant to medical therapy, so will inevitably have to undergo a second transsphenoidal surgery at some point in time.


Final comments


While most medical professionals continue to prescribe dopamine agonists for the treatment of prolactinomas, surgery may be a good option for some patients. The list of complications associated with pituitary surgery may seem daunting, but many of these are rare occurrences. As pituitary surgery has evolved technologically over the past few years, in the hands of a specialist it is a minimally invasive and low-risk procedure. Total surgical removal of the tumor results in complete “cure” (or what many doctors prefer to call remission), although this cannot be guaranteed. Success after surgery is based on an individual case, and it is important that you do your own research. Please talk to your pituitary endocrinologist and neurosurgeon for information about the likely outcome of you having surgery.


17 comments:

  1. Thank you for sharing this! I'm so sorry you have had to stuggle with this for so long! Are you going to go through with the surgery??? It is one of my greatest fears for myself, but I know it may have to happen one of these days as a last resort. Keep me posted! Shy

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  2. You’re very welcome! Thank you for your kind words. Although I underwent pituitary surgery in the summer, post-op elevated prolactin levels suggest that I have tumor regrowth (which is relatively rare). Consequently, I will probably need another surgery (I am intolerant to drug therapy). I’m due for my next MRI at the beginning of next year, so I should have some idea about the rate of growth by then. I’ve heard of so many other prolactinoma patients who have felt so much better after undergoing transsphenoidal surgery, so I shall persevere and hopefully the next one will do the trick. Pituitary surgery has come along way over the last few years and is far less invasive nowadays. I spent only one night in the hospital and even benefited from a shower before returning home the next morning. The most crucial thing is to make sure that you find a neurosurgeon who has lots of experience with pituitary resections. This makes all the difference. If you have any further questions or concerns, please don’t hesitate to let me know (you can also email me at gallantstrides@yahoo.com). Best wishes, Di.
    PS. I enjoy reading your interesting Prolactinoma blog.

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  3. @Shy I too had surgery for a prolactinoma, last December - and I can honestly say that it wasn't as bad as I thought it would be. It felt like a blocked nose and bad cold for a while, and I had my usual headaches for about two weeks afterwards, but other than that, I was just fine. The worst part is the anticipation I found.
    Good luck, I hope all goes well for you and that your second surgery, @Diplead, goes well for you. I was sorry to read that you have to have a second surgery at all :( It's a possibility for me too depending on how my MRIs and blood tests go in the next few months :(

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  4. @E.F.D. I’m pleased your prolactinoma surgery went well and hope your follow up testing will demonstrate that there is no residual adenoma or recurrent growth (an elevated prolactin level within 24 hours of surgery can often be an indication). I also hope that you are feeling better and that college life is treating you well. After undergoing a 4th sinus surgery and being told by my ENT doctor that the inside of my sinuses had been practically destroyed by the transsphenoidal transection, I admit that I am somewhat hesitant to undergo yet another pituitary surgery. I’m due to commence follow up pituitary hormone testing in a few days, so I will see if my prolactin levels, although elevated, are stable before making a final decision (without pharmacotherapy, my neurosurgeon tells me that Gamma Knife radiosurgery is another option, although I also have my reservations about that). I guess I will just have to cross that bridge when I come to it! Please do keep me posted about how you are progressing. Best wishes.

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  5. Hello! I am from Hungary and I was operated with a prolactinoma in a transphenoidal operation 3 years ago. 5-6 days later I got a stroke (ischemic). And I was always said that the stroke had nothing to do with the former surgery. I do not know but here above I saw that maybe.
    Can you say something about it?

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  6. Hello Felhőűző – I am so sorry you experienced such a traumatic incident after transsphenoidal resection and hope you have been able to recover from your ordeal. I’m not a medical professional, but from what I understand, ischemic stroke is unlikely to occur when an experienced pituitary surgeon performs the procedure. However, if the carotid arteries (located on both sides of the pituitary gland) become damaged during surgery, this can halt blood flow, which can lead to stroke. Do you know if your surgeon was particularly well versed in pituitary surgery?

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  7. thank you for sharing. My Daughter has been diagnosed for over 10 years, she is now 26 and it has grown to a macro-prolactinoma. Also, it is considered a pre-existing condition and we are VERY limited as to which and where we go for treatment//surgery. 1st visit went very quick and I don't feel we were given any opportunity to discuss methods of treatment, let alone as ANY questions. Her next appt. is with the Endo, so he will get an earful, as Stephanie is has realized SHE DOES HAVE A SAY in her medical treatment. I have copied this website and sent it to her. I know she will be get a lot out of it... THANK YOU FOR SHARING! EVERYONE

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  8. Hi there! glad to drop by your page and found these very interesting and informative stuff. Thanks for sharing, keep it up!
    - pituitary tumor

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    1. Thanks for visiting my page, Myrtle. I'm glad you found the information helpful and hope you are doing well. Best wishes.

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    2. OH WOW!!! This page was sooo informative!!! Let me begin by saying: Hello, my name is Luvenia. 19 years ago today I had a surgical resection of my pituitary prolactinoma. It was a very scary experience in the beginning but I am thankful to the Almighty God for giving me the strength and courage to endure the experience. (I had just lost my baby sister Christmas day 1990) I learned I had a pituitary tumor February 1991. My gynecologist discovered it because I was having secretions of breast milk and missed menstrual cycles for months at a time!! I cried and cried because I didn't know it was benign (THANK GOD FOR THAT!!) November 10, 1994 with a ENT specialist and a brain surgeon present I awakened from my operation. With the exception of the headache pain in my head, the packing in my nose and a deep scar from the tissue removed from my outer right thigh, I was comforted in knowing ALL the tumor was gone!!! TODAY....I am still living with my pituitary prolactina with the assistance of Cabergoline 0.5 (1/2 once a week). Yes, four years after my surgery MY TUMOR RETURNED! This time with a new symptom of migraine headaches!!! I have been out of work for 10 years now. My headaches come unannounced most of the time so I live when I don't have my migraines and when I have them... THAT'S A WHOLE OTHER ISSUE!! The ER doctors recognize me when I They call me by name! I receive a combination of three drugs in an IV or three separate shots in my hip which make the pain subside at each onset. I have pain meds at home which work sometimes and sometimes NOT. I am a recipient of disability due to the severity of the debilitating pains!! With ALL this being said......... I am so thankful to be alive and I am happy to have encountered someone who can understand my battle. Thank you for your blog and everyone who have shared their experiences on it. My email address is msvena1@cs.com I can also be found on Facebook under my name Luvenia Brinkley.

      God bless you all and may the heavens smile upon you!!

      ~Luvenia Brinkley

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    3. Hi Luvenia. Thank you for sharing your story. I’m sorry that you have been through so much pain and understand how debilitating migraines can be. Like you, I have been unable to work for many years, mainly due to exhaustion, but I’m hoping that medical care for pituitary tumors will continue to improve. It appears that doctors are still learning! Do you have a good pituitary endocrinologist to regularly check and adjust your hormones? This is important as some more general endocrinologists sometimes fail to adequately test all relevant hormones (in my case, it took several years for me to obtain diagnoses for growth hormone deficiency, diabetes insipidus and hypothyroidism). Please keep in touch. Wishing you well. Di

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  9. Hello, did you have your second surgery? I had my micro removed in May and within two weeks my prolactin levels were up to 600. I knew then what was going on (though my endo and GP implied I was imagining it) and insisted on an MRI. Lo and behold, a tumour. I'm waiting for a second surgery in January but to be honest I'm terrified as my faith in the surgeon has gone. I still don't understand how you can operate on a 5mm tumour and leave 3mm behind (which is basically what happened). I went through a coma and hemorrhaged and he just took 2mm away. I asked him how that was possible (when he knew how much mass he was aiming for) and he said "it looked big on the screen". Which effectively means he closed me up before he'd taken it out to measure it. Or didn't bother to measure it.

    He's supposed to be the best surgeon in London for this. I'm intolerant to medication and just don't know what to do.

    I know there's more chance of pituitary damage with a secondary surgery and also he said he was going to "shave up to a third of the gland away" to make sure they get it this time. I got very worried as can't bear the thought of being on hormone replacements which are really bad for you (being on hydrocortisone for three weeks after surgery was bad enough and indicative of what might happen to my cortisol in future). He assured me that I had a 99% chance of no pituitary damage. I think shaving up to a third of the gland away makes these odds ridiculous. He said because it was a healthy gland I would have a very good chance of recovery, even with a third of it gone.

    The tumour is on the anterior part.

    I would love to know what you (who has obviously read as much as me about all this) think. And if you had a second surgery how things are looking? I wish I could see stats for this surgeon's performance. I feel like I'm being lied to.

    I hope you are feeling alright, so sorry for your sinuses and thank you so much for sharing this info.

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    1. Hello – Thanks for sharing your story.

      Despite my initial prognosis, oddly my prolactinoma situation seems to have remedied itself over time. Although still elevated, my prolactin levels have gradually reduced without pharmacotherapy, and my last MRI did not reveal the tumour. Hence, my endocrinologist is still continuing to monitor the hyperprolactinemia at this point in time. However, if my prolactin level starts to rise again, like you, I will likely have the option of undergoing either another pituitary surgery or radiation therapy. I believe this is becoming less likely the more time that passes though. Have your prolactin levels remained fairly constant or are they still increasing?

      I am very sorry to hear of your plight and understand your reluctance to have another surgery, especially by the same neurosurgeon. It sounds as though you went through an incredibly rough ordeal. Would it be possible for you to select another surgeon elsewhere, who may perhaps be more experienced in the area of pituitary tumours? I understand that he is touted as the best neurosurgeon, but does he specifically have sufficient expertise with pituitary tumours? I actually had 2 different neurosurgeons perform surgeries during the same year but for different types of brain tumour: one for the pituitary and the other for a lesion in my temporal lobe. Despite the fact that both were very reputable neurosurgeons, I would by no means consider swapping their tasks. Perhaps you don’t have this choice with the NHS in the UK though?

      Indeed, although there may be some risk of pituitary damage following surgery, I have heard of some patients who have demonstrated some type of healing over time (e.g., many with temporary diabetes insipidus). In my case, I only have about 50% of my pituitary gland left, so I need to take some hormone supplementation such as DDVAP for diabetes insipidus (posterior lobe), TSH and growth hormone for adult growth hormone deficiency (anterior lobe). I do know of one patient who stopped taking GH after about 8 years when her pituitary gland started to produce it again, so I live in hope!

      I am sorry that I can’t be of more comfort to you but hope that this information is of some help. Please feel free to contact me with any further questions. You can also email me directly at: gallantstridesblog@gmail.com

      Hoping that your next surgery will go well and that your recovery will be speedy.

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  10. Hello. I am a 12 years old. I had a pituitary tumor and got surgery on september 5 2013. Its been almost 3 months that I've had my surgery and about aweek ago my nose was bleeding. Its been bleeding eversense. I think its because my friend ran into my nose with her head. I told my mom and she wanted to take me to the hospita but I said that it was nomal. I just want to know if it is normal that my nose bleeds after 3 months of surgery.

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    1. Hello Valentina. I’m sorry that you had to undergo pituitary surgery but hope that you will have a positive outcome. I did experience a similar situation, where my husband accidentally elbowed me in the nose shortly after my procedure but all was thankfully well. Although, hopefully, there is nothing to worry about, it is important for you to get checked by your pituitary doctor in order to make sure that there is no hemorrhaging. I hope that you will make an appointment with him/her soon. Best wishes, Di

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  11. Hello. My husband was diagnosed with Prolactinoma in 2008. In 2009, he was also diagnosed with Acromegaly. They attempted surgery, which they said would take three hours. Five hours later, they came back to me and stopped surgery because they were unable to find the tumor. My husband has been on Cabergoline for quite some time and recently, began experiencing some of the same symptoms as he had before he was diagnosed. he is feeling extremely fatigued to the point where he cannot even stay awake. His body has been hurting in ways it had not been hurting for quite some time. his endocrinologist feels we should continue monitoring it as the tumor itself is not changing. I just don't know. I feel like something is being missed here. If anyone has any thoughts, opinions, etc., I would love to hear them.

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  12. Hello,

    24 year old male here. It is so great to read this blog entry. Thank you for sharing. On Tuesday (07/15/2014), I will undergo resection of a micro-prolactinoma. I would love to hear from any of you who have tips for recovery and preparation. Email me at ckdallas1221@icloud.com.

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Thank you for your comment – I appreciate you taking the time to write to me, and hope you will find my blog helpful. All comments are moderated, so your post will appear soon. You may also email me directly at: gallantstrides@me.com if you are concerned about leaving any personal information.

Wishing you and your family good health and happiness for the future!