“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.
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.
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.
Mediasite presentation: Advances in the surgical treatment of prolactin-producing pituitary adenomas
Mediasite presentation: Potential complications including valvular heart disease associated with dopamine agonist therapy
Clinical study: Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients