Nonfunctional Pituitary Microadenoma: When to Operate?

[Millypo]

Hi, I have a nonfunctional pituitary microadenoma and was wondering when surgery is indicated.  I have been to MGH for a brief appointment and they suggested that they do surgery when the tumor grows over 1 cm.  This is due to the fact that in their experience, the tumors continue to grow once over 1 cm.  At the time of my appointment last year, my adenoma measured 8mm x 5mm x 7mm.  They thought it would probably never grow.  However, a recent MRI showed that it has slight enlargement at 8mm x 9mm x 7mm.  I have adrenal insufficiency secondary to ACTH insufficiency but no other hormones are deficient yet.  The tumor is located along the right cavernous sinus but doesn't invade the cavernous sinus yet.  I have a few questions about this.

1.  When does the Cleveland Clinic operate on nonfunction pituitary microadenomas?
2.  Do you ever see ACTH as being the only affected stimulating hormone or the first deficient stimulating hormone?

Also, I have some T2 hyperintensities in the deep white matter of the brain consistent with microvascular changes.  I'm only 39 and have some kind of autoimmune process with anticardiolipin antibodies.  Could this be the cause?  Should I be evaluated for something else?  The pattern of the T2 hyperintensities is not consistent with MS.  Could it be caused by Lyme?  Will they progress?

Thank you.

[Joyce K Lee, MD]

Thank you for submitting your question.
I will answer your concerns to the best of my abilities, but please be informed that I am unable to offer a diagnosis based on your history and list of symptoms.
This is solely for educational purposes and should in no way be a substitute for a formal evaluation by a certified physician.
Please also understand that historically, pituitary macroadenomas are handled by our neurosurgery colleagues and I am a neurologist.
I have curbsided my neurosurgery colleagues however to assist in answering your question.

To begin, please allow me to offer an educational segment concerning pituitary adenomas.
Pituitary adenomas are usually slow-growing and invariably benign. They are arbitrarily designated as microadenomas (10 mm in diameter). Functional tumors are more common at younger ages, whereas nonfunctional tumors are seen mostly at older ages. Most nonfunctional pituitary adenomas on morphologic examination reveal secretory granules suggestive of hormonal synthesis, but they fail to secrete functional hormones.

Here is a table I obtained from a Cleveland Clinic website than illustrates the prevalence of different adenoma types
(reference: http://clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/pituitary/pituitary.html.)

Adenoma Type Prevalence (%)

GH cell adenoma 15
PRL cell adenoma 30
GH and PRL cell adenoma 7
ACTH cell adenoma 10
Gonadotroph cell adenoma 10
Nonfunctioning adenoma 25
TSH cell adenoma 1
Unclassified adenoma 2

Abbreviations:
ACTH=Adrenocorticotropic hormone; GH=Growth hormone; PRL=Prolactin; TSH=Thyroid-stimulating hormone

To answer your question, the classic sequential loss of pituitary hormones secondary to a mass effect is in the following order: growth hormone (GH), gonadotropins (LH, FSH), adrenocorticotropic hormone (ACTH) and thyroid-stimulating hormone (TSH).1 The underlying etiology for typical earlier loss of GH and gonadotropins is not known. Isolated deficiencies of various anterior pituitary hormones can also occur.

The goals for treatment of a pituitary tumor include reduction or complete removal of tumor, elimination of mass effect if present, normalization of hormone hypersecretion, and restoration of normal pituitary function. Some patients, especially those with large tumors, may require several therapeutic modalities including medical, surgical, and radiation therapy. The most important factor in pituitary surgery is availability of a good neurosurgeon. The referring physician has the responsibility of referring the patient to an experienced neurosurgeon, who may be available only in a neuroendocrine (pituitary) center. Radiation therapy is used primarily as an adjunctive therapy when surgical or medical therapy is not successful.

To be quite honest with you, I am not aware of a an exact number cut-off that our surgeons use to determine whether to operate or not.
I believe that most of their decision is based on the patient's personalized profile and on the size, location and nature of the tumor itself.
In the patients that I have seen undergo surgery however have had a transphenoidal approach and did markedly well post-operatively.
It is important however to mention that hypopituitarism can be seen after tumor removal and require hormonal supplementation.

All in all, if for some reason you would like another formal opinion with one of the Cleveland Clinic neurosurgeons, I highly recommend Dr. Robert Weil. He specializes in pituitary tumors and is a wonderful surgeon.

As for your additional question, I would not become too perplexed over these T2 HI seen on your MRI -- we see these a lot.
These are non-specific changes, often grouped as "small vessel disease" or "microvascular changes" by the radiologists.
The autoimmune process you mentioned does predispose you to vessel occlusive disease (i.e. strokes and cardiac disease) so you should definitely have this managed appropriately by a vascular medicine specialist, but I cannot attribute these MRI changes entirely to this disease process.
Most importantly, stay on top of your routine medical care -- take aspririn to prevent stroke and heart attacks, stop smoking if you are a current smoker, watch what you eat, check your cholesterol, stay fit, etc.

Hope this help,
Best of luck,
JKL, MD

[neehama]

A related discussion, Pituitary nonfunctional macroadenoma 23x23x18 was started.

[Millypo]

Fiona,

Thanks for your message.  Actually I'm 39 and have just recently seen a reproductive endocrinologist/fertility specialist (RE) to see if I could by any chance have a child.  Unfortunately, recent test results indicate that my FSH is swinging from one extreme to the other, which has been occurring for about five years, and my RE told me a couple of weeks ago that I definitely cannot have children.  I could possibly have an egg donor pregnancy but given the ongoing mild pulmonary hypertension issue, along with the autoimmune issues, a pregnancy would be too risky.   The RE also suggested I may have some kind of polyendocrine disease due to my premature ovarian insufficiency and adrenal insufficiency, but I don't think I fall into any of the common disease categories for polyendocrine or autoimmune disease.  The RE will probably talk to my endocrinologist about all of this, but I am about to give up completely on discovering what is driving my health problems.   I have excellent doctors now who are all well-known professors at a well-known medical school and I just think that whatever is happening to me must be so rare as to almost be unheard of since no one seems to have seen patients with my same history or collection of problems.  

On that note, thanks for sharing the information on Dr. Couvaras in Phoenix.  Given my APA has almost always been low positive, my doctors don't think much of this result.  I have noticed in the past that BC pills, Lupron and HRT exacerbate circulation problems in me, though, especially during elevations in my ANA and APA, causing sharp headaches, numbness in arms and legs, and sharp lung pains.   So I am wondering if those medications along with the ANA/APA could be connected to the other health problems.  My rheumatologist is watching the APA and ran the APA tests again last week to see if they have gone up after stopping the aspirin.   I'll be curious to see what he discovers.

As for brain tumors, I'm sorry to hear that you have to deal with a brain tumor, too.  It adds stress when you go to MRIs and don't know whether you are following a complete fiction or a problem that could be life-threatening.  Preferring the fiction option, I was prepared to totally dismiss my pituitary problem until my last MRI showed that it had grown a few millimeters.  Now what do I do?  lol  I only have a millimeter or so to go before MGH would recommend surgery.  The idea of having transphenoidal brain surgery is mind boggling, to say the least.  (Pun intended, lol)   A large part of me just wants to go into denial as to the significance of this particular problem.  However, losing my eyesight doesn't sound like a good way to rediscover the problem in the future, either.  On the other hand, a local neurosurgeon once told me that my tumor was so close to my carotid artery that surgery would be so dangerous he would not only refuse to do the surgery, he wouldn't even stand anywhere near the operating room if someone else was doing the surgery.    

No easy answers, I guess.  I hope all goes well with you.  Thanks again for the information about Dr. Couvaras and his clinic.  I'll definitely visit his website and research his clinic.

[Fionajnz]

I am sorry you are having to deal with all these health issues.  I am thinking that its time to seek a second endocrinology opinion.  If your Drs are not on the same page, you are pushing poop up hill in many ways.  I feel your pain in more ways than one, I developed adrenal insufficiency secondary to cardiomyopathy, a suspected PE and some neurological issue, that they treated with high dose steroids.  My liver and kidneys started failing and I was in a pretty dismal state for many mths, it took me almost 2 yrs to get off the hydrocortisone and even now, I have really bad days.  Interestingly they also found a brain tumor in my pineal gland, which is 6 mm or so in size.  Its right beside the pituitary gland.  I am monitored closely every yr or 6 mths depending on symptoms.  They think its benign but are not sure it will not become malignant at some point and its too deep to biopsy.

Have you ever sought a reproductive endocrinologist opinion?  If not it may be worth considering.  I cannot exactly remember your age, but I think in your 40's.  A great guy to see is Dr Couvaras in, PHx AZ.  He is pretty cutting edge and has done a great deal of research around ANA and APA issues and sees a pt base broader than just fertility issues, he is an expert on hematology (works with Dr Sharon Ondreyco in Scottsdale, AZ) and hormonal issues.  You can find him online at www.ivfphoenix.com.  It just may give you the pulled together info you are seeking.

Best wishes.

Fiona

[Millypo]

Thank you for your response and information.  On the topic of isolated anterior hormone deficiencies caused by pituitary adenomas, I have come across some disagreement among doctors.  My current endocrinologist does not believe that my adrenal insufficiency, for which I must take daily cortisol replacement, is caused by my pituitary tumor because only my ACTH/cortisol has shown to be deficient.   He believes that other hormones must also be deficient for my adrenal insufficiency to be caused by my pituitary disease.  My TSH is usually in the low normal range, my FSH has been swinging widely for the last five years with premature menopause and is often high, and even my IGF-1 has tested high once, but is usually normal.  He believes my adrenal insufficiency was caused by four Kenalog joint shots given to me by a former rheumatologist, all in one day.  I had symptoms of adrenal insufficiency, however, for many years prior to the joint shots and did not have any other exposure to steroids.  So I think it's possible that the joint shots did not cause my adrenal insufficiency but did result in an acute adrenal crisis, which is how my pituitary problems were finally diagnosed.  The cortisol replacement started at that time resolved many symptoms I had suffered for years, such as severe fatigue, muscle weakness and hypoglycemia.  But, given my endocrinologist believes the joint shots caused the adrenal insufficiency, he has suggested withdrawing the cortisol replacement.  My current rheumatologist is keeping me on the cortisol.  Now my recent MRI has shown that my pituitary adenoma is slightly larger, but the radiologist doesn't believe the growth is significant.  Anyway, it's all very confusing.  I'm not sure whether to take the pituitary adenoma seriously or not, but I know how sick I will become if we withdraw the cortisol.  I had to live that way for many years and could do very little.

Thank you for the information about Dr. Weil.  I'll keep him in mind for the future.

Also, I was wondering if you know of a vascular medicine specialist?  I have a strange collection of vascular problems that have developed over the years, including Raynauds, exercise induced pulmonary hypertension that appears primary in form but is responsive to calcium channel blockers, focal nodular hyperplasia of the liver, the T2 hyperintensities in the brain, occasional outbreaks of petechiae on my hips, and the high ANA with low positive anticardiolipin ABs.  Also, I had to take hormone pills for many years due to severe endometriosis.  The most serious condition I have is the pulmonary hypertension, which rapidly progresses without 240 mg of diltiazem daily.  I'm not sure why I have this problem.  I do not have any thromboembolic disease of the lung apparent by VQ scan.

Also, thanks for the advice on staying in shape.  I firmly believe in exercise and staying fit and try to keep a BMI around 18-19.  Never smoke and don't drink.   I was taking aspirin but recently my rheumatologist stopped this treatment due to an outbreak of petechiae on my hips.

Thanks again for your response. It's greatly appreciated.