Dr. McCutcheon has helped countless Cushing's patients with anything from a second opinion on an MRI to transsphenoidal surgery to remove a pituitary tumor. He is a champion in many ways to the Cushie community for his relentless endeavors in awareness and treatment for Cushing's. In the following article, published on the PNA site, he continues the same:
Pituitary Tumors in Women
by Ian E. McCutcheon, M.D., FRCSC
Professor of Neurosurgery
The University of Texas M.D. Anderson Cancer Center
by Ian E. McCutcheon, M.D., FRCSC
Professor of Neurosurgery
The University of Texas M.D. Anderson Cancer Center
Pituitary tumors represent a special clinical problem in women. Although their diagnosis is relatively straight forward once the suspicion has been raised, patients with pituitary tumors can go undiagnosed for years in spite of symptoms that should raise such suspicion and lead to definitive testing. This article seeks to highlight the symptoms that such tumors produce, to describe the best way of confirming the presence of the tumor, and the most appropriate ways of treating such lesions.
Diagnosis
Pituitary tumors can cause symptoms by either of two methods. In some, they compress the adjacent normal pituitary gland, and thereby impair hormone secretion and produce a lack of one or more of the hormones produced by the gland. Alternatively, the tumor can itself produce hormones in excess, leading to high levels of hormones, each of which produces a specific clinical syndrome. Others symptoms of significance include visual loss, caused by a tumor large enough to reach from the pituitary to the optic chiasm running above the sella. Typically a tumor must be greater than 1.5 cm in diameter to create loss of vision, and many patients with tumors larger than that have intact vision. In addition, headache is commonly seen in patients with pituitary tumors. In some of them the tumor causes the headache by local dural compression or infiltration. In many, however, headache represents a second, unrelated issue which will not necessarily clear if the tumor is eliminated.
The most common pituitary tumor is the "clinically nonfunctional" adenoma, representing 40-45% of cases. Such tumors make no clinically significant hormone and are usually found incidentally, by virtue of low hormone levels they produce, or because of visual loss when a tumor is relatively large. The second most common is the prolactin producing tumor "prolactinoma" representing 30% of cases. These are the tumors most likely to be seen in a gynecological practice, given their impact on reproductive function, the menstrual cycle, and the libido. Prolactinomas tend to be relatively small and to exert their effects by virtue of the raising of serum prolactin levels that accompanies them. To be secure in the diagnosis of prolactinoma, a patient should have a prolactin >100 ng/ml. Because certain drugs (e.g., Respirtol or other phenothiazines) raise prolactin levels to a similar degree, they must be excluded by history before concluding that the patient with a high prolactin level has a pituitary tumor. Patients with lower levels of prolactin that are still super normal (i.e., >25 ng/ml) may have either a prolactinoma or a nonfunctional tumor exerting "stalk effect", namely a distortion of the gland from local pressure which blocks the tonic hypothalamic inhibition of prolactin secretion and thus allows prolactin levels to rise. The distinction is important because prolactin excess caused by tumor secretion is treated in the majority of patients with Dopamine agonist therapy, whereas prolactin elevation due to stalk effect suggests that such therapy will be ineffective. The distinction is not always an easy one and an endocrinologist should be involved for any patient suspected of having a pituitary tumor. They can offer help in deciding whether a tumor is nonfunctional (with stalk effect) versus a true prolactinoma, and can in addition perform hormonal screening for all areas of pituitary function. It is not sufficient simply to check prolactin and perhaps thyroid hormone levels, as is often done in women in whom a pituitary tumor is suspected. A full hormone panel should be drawn and the new onsets in interpreting this make involvement of an endocrinologist very helpful.
Other tumor types include those which secrete growth hormone (causing acromegaly), those secreting ACTH (causing Cushing's disease), and those rare tumors secreting TSH (producing a hyperthyroid state commonly misdiagnosed as primary hyperthyroidism and often treated inappropriately with thyroid ablation). Three quarters of all pituitary tumors will, however, be either nonfunctional or prolactin secreting adenomas, and understanding of which is vital in any gynecological practice.
The hormone system most vulnerable to extrinsic pressure is the pituitary gonadal axis. Minor disturbances of the pulsatile rhythms of FSH or LH production can affect fertility and libido and can disrupt the menstrual cycle. Thus, any pituitary tumor can cause infertility, and the search for such tumors should be part of any infertility workup, particularly when low levels of FSH and/or LH can be shown. Low levels of prolactin are not considered to be significant or to require intervention. High levels of prolactin will cause galactorrhea, which can be the presenting symptom of this condition. Here, too, menstrual irregularity is common as are infertility and loss of libido. If the excess production of prolactin is prolonged, osteoporosis becomes an issue as well. Thus, endocrinologists will typically perform bone density testing on patients with incompletely treated prolactinomas and intervene pharmacologically if density is shown to be insufficient.
Psychosocial Aspects
Patients with pituitary tumors routinely express symptoms consistent with psychological disruption and with impaired quality of life. The most profoundly affected are those with Cushing's disease in whom excess cortisol can produce a host of psychological symptoms ranging from moderate depression to frank mania. Psychiatric disorders per se are not more common in patients with pituitary tumors than in the general population. Nonetheless, their often overwhelming sense of malaise is expressed either as a direct emotional dysphoria or is somaticized into any number of physical symptoms. These include (but are not limited to) headache, tenderness, tingling or numbness, memory loss, and impairment of cognition. Depression, anxiety, behavioral disturbance, and personality change may reflect the adjustments that pituitary tumor patients must make to deal with the physical symptoms caused by alterations in the various hormonal axes affected by the tumor. However, it is equally possible (although at this time unprovable) that the pituitary tumor may itself not be the direct cause of the emotional or cognitive changes experienced by the patient. It is entirely possible or even likely that disruption within the hypothalamus on a molecular rather and structural level may trigger the formation of the pituitary tumor and concomitantly may directly produce the psychosocial disruption the patient feels. Connections from the hypothalamus to other limbic structures (e.g. prefrontal cortex) may cause alternations in personality and mood. Intervention for this constellation of psychological disruption is feasible but may require intervention by
psychiatrists in those most profoundly affected. Generally treatment begins with optimization of hormone levels but may in addition require drug therapy including antidepressants. Psychological testing can yield a detailed profile of the specific areas of impairment and suggest compensatory strategies. In particular, pituitary tumor patients complainof depression, fatigue, and poor memory function. These are real symptoms of physical disease, but the treatment for them is complex and often requires multidisciplinary input.
Radiology
The best way of diagnosing pituitary disease is radiographically by an MRI focused on the sella. CT scan has insufficient resolution to show small tumors and does not confer the anatomic detail found in MRI. A standard MRI of the brain is also inadequate for showing pituitary disease, as it may result in the pituitary being shown by only 1 or 2 slices that are too thick and too spaced to show a pituitary lesion properly. Therefore, if a pituitary tumor is suspected, it is wise to order an MRI of the sella upfront to avoid having to send the patient back for repeat scanning.
Treatment
Once a diagnosis has been made or is at least entertained with a strong level of suspicion, the referral to an endocrinologist and a neurosurgeon is advisable. Even a "simple" prolactinoma may have ramifications on the pituitary - an organ axis that are not immediately obvious from the gynecological perspective. In our practice all patients referred for pituitary tumors are seen by both the endocrinologist and the neurosurgeon to provide opinions from a medical and surgical perspective respectively. A further word of caution is important here. Most endocrinologists can perform an effective workup of a pituitary tumor and make appropriate diagnosis and, where appropriate, medical treatment recommendations from that workup. However, within the neurosurgical community a wide spectrum of expertise in pituitary disorders exists. Patients with resources tend to consult a relatively small cadre of nationally prominent subspecialists in this area while many neurosurgeons with the theoretical ability to do pituitary surgery actually see only 1 or 2 patients per year, an insufficient number to develop true facility with such procedures. Statistics have been compiled that show true expertise (as judged by success in achieving cure and in avoiding complications) comes only when a surgeon has completed 500 or more transsphenoidal surgeries. Thus, for optimal care, referral to a known center of excellence is advisable. The referral practice at The University of Texas MD Anderson Cancer Center is the largest within the state of Texas or any neighboring state.
Medical therapy generally consists of replacing hormones when levels are low or of suppressing them when they are high. Prolactinomas are generally treated with medical therapy as the first line approach due to the fairly good success achievable with Dopamine agonists such as Bromocriptine (Parlodel) or Cabergoline (Dostinex). These drugs will not be effective in patients with pituitary tumor types other than prolactinoma, but in the prolactinoma category they do have excellent success in lowering prolactin levels and reasonable (but lesser) success in causing tumor shrinkage. Patients with prolactinomas come to surgery for several reasons. In some, the drug is ineffective or produces debilitating side effects, typically gastrointestinal in nature. In others, drug therapy has been successful but not completely so, and debulking the tumor is felt to be helpful in allowing medical therapy a better chance to work on a smaller volume of disease. Finally, a number of patients present for surgery because of what one might term "medication fatigue," namely a desire to free themselves of the necessity for taking what may amount to lifelong medication requirement. For patients with Cushing's disease or acromegaly, the first line treatment is almost always surgical; and for patients with nonfunctional tumors causing hypopituitarism or large enough to endanger vision by compressing the optic chiasm, surgery is also the first line choice. Radiation therapy is used mainly as a backup for tumors that have been treated by other means and yet have recurred, are that small group of invasive, hormonally functional tumors that surgery cannot cure and which have proven refractory to medical therapy.
Transsphenoidal surgery is the most common method of removing a pituitary tumor today. Over 95% of pituitary tumors will prove amendable to that approach, of which there are several variations (endonasal versus sublabial, endoscopic versus microscopic, etc.). The transsphenoidal approach is popular because it provides a relatively direct route of access that travels along the septum of the nose, through the sphenoid sinus, to the sella just behind it. When properly performed, this method avoids the brain altogether and is a very safe procedure. Craniotomy is only necessary for tumors that show special features such as persistent recurrence in the
suprasellar space, lateral extension in the cavernous sinus or around the supraclinoid carotid artery, or for tumors too large to be dealt with by transsphenoidal surgery. Because the brain must be retracted somewhat to expose the sella during a craniotomy for pituitary tumor, the
transsphenoidal approach tends to be safer.
Summary of Important Points
Diagnosis
Pituitary tumors can cause symptoms by either of two methods. In some, they compress the adjacent normal pituitary gland, and thereby impair hormone secretion and produce a lack of one or more of the hormones produced by the gland. Alternatively, the tumor can itself produce hormones in excess, leading to high levels of hormones, each of which produces a specific clinical syndrome. Others symptoms of significance include visual loss, caused by a tumor large enough to reach from the pituitary to the optic chiasm running above the sella. Typically a tumor must be greater than 1.5 cm in diameter to create loss of vision, and many patients with tumors larger than that have intact vision. In addition, headache is commonly seen in patients with pituitary tumors. In some of them the tumor causes the headache by local dural compression or infiltration. In many, however, headache represents a second, unrelated issue which will not necessarily clear if the tumor is eliminated.
The most common pituitary tumor is the "clinically nonfunctional" adenoma, representing 40-45% of cases. Such tumors make no clinically significant hormone and are usually found incidentally, by virtue of low hormone levels they produce, or because of visual loss when a tumor is relatively large. The second most common is the prolactin producing tumor "prolactinoma" representing 30% of cases. These are the tumors most likely to be seen in a gynecological practice, given their impact on reproductive function, the menstrual cycle, and the libido. Prolactinomas tend to be relatively small and to exert their effects by virtue of the raising of serum prolactin levels that accompanies them. To be secure in the diagnosis of prolactinoma, a patient should have a prolactin >100 ng/ml. Because certain drugs (e.g., Respirtol or other phenothiazines) raise prolactin levels to a similar degree, they must be excluded by history before concluding that the patient with a high prolactin level has a pituitary tumor. Patients with lower levels of prolactin that are still super normal (i.e., >25 ng/ml) may have either a prolactinoma or a nonfunctional tumor exerting "stalk effect", namely a distortion of the gland from local pressure which blocks the tonic hypothalamic inhibition of prolactin secretion and thus allows prolactin levels to rise. The distinction is important because prolactin excess caused by tumor secretion is treated in the majority of patients with Dopamine agonist therapy, whereas prolactin elevation due to stalk effect suggests that such therapy will be ineffective. The distinction is not always an easy one and an endocrinologist should be involved for any patient suspected of having a pituitary tumor. They can offer help in deciding whether a tumor is nonfunctional (with stalk effect) versus a true prolactinoma, and can in addition perform hormonal screening for all areas of pituitary function. It is not sufficient simply to check prolactin and perhaps thyroid hormone levels, as is often done in women in whom a pituitary tumor is suspected. A full hormone panel should be drawn and the new onsets in interpreting this make involvement of an endocrinologist very helpful.
Other tumor types include those which secrete growth hormone (causing acromegaly), those secreting ACTH (causing Cushing's disease), and those rare tumors secreting TSH (producing a hyperthyroid state commonly misdiagnosed as primary hyperthyroidism and often treated inappropriately with thyroid ablation). Three quarters of all pituitary tumors will, however, be either nonfunctional or prolactin secreting adenomas, and understanding of which is vital in any gynecological practice.
The hormone system most vulnerable to extrinsic pressure is the pituitary gonadal axis. Minor disturbances of the pulsatile rhythms of FSH or LH production can affect fertility and libido and can disrupt the menstrual cycle. Thus, any pituitary tumor can cause infertility, and the search for such tumors should be part of any infertility workup, particularly when low levels of FSH and/or LH can be shown. Low levels of prolactin are not considered to be significant or to require intervention. High levels of prolactin will cause galactorrhea, which can be the presenting symptom of this condition. Here, too, menstrual irregularity is common as are infertility and loss of libido. If the excess production of prolactin is prolonged, osteoporosis becomes an issue as well. Thus, endocrinologists will typically perform bone density testing on patients with incompletely treated prolactinomas and intervene pharmacologically if density is shown to be insufficient.
Psychosocial Aspects
Patients with pituitary tumors routinely express symptoms consistent with psychological disruption and with impaired quality of life. The most profoundly affected are those with Cushing's disease in whom excess cortisol can produce a host of psychological symptoms ranging from moderate depression to frank mania. Psychiatric disorders per se are not more common in patients with pituitary tumors than in the general population. Nonetheless, their often overwhelming sense of malaise is expressed either as a direct emotional dysphoria or is somaticized into any number of physical symptoms. These include (but are not limited to) headache, tenderness, tingling or numbness, memory loss, and impairment of cognition. Depression, anxiety, behavioral disturbance, and personality change may reflect the adjustments that pituitary tumor patients must make to deal with the physical symptoms caused by alterations in the various hormonal axes affected by the tumor. However, it is equally possible (although at this time unprovable) that the pituitary tumor may itself not be the direct cause of the emotional or cognitive changes experienced by the patient. It is entirely possible or even likely that disruption within the hypothalamus on a molecular rather and structural level may trigger the formation of the pituitary tumor and concomitantly may directly produce the psychosocial disruption the patient feels. Connections from the hypothalamus to other limbic structures (e.g. prefrontal cortex) may cause alternations in personality and mood. Intervention for this constellation of psychological disruption is feasible but may require intervention by
psychiatrists in those most profoundly affected. Generally treatment begins with optimization of hormone levels but may in addition require drug therapy including antidepressants. Psychological testing can yield a detailed profile of the specific areas of impairment and suggest compensatory strategies. In particular, pituitary tumor patients complainof depression, fatigue, and poor memory function. These are real symptoms of physical disease, but the treatment for them is complex and often requires multidisciplinary input.
Radiology
The best way of diagnosing pituitary disease is radiographically by an MRI focused on the sella. CT scan has insufficient resolution to show small tumors and does not confer the anatomic detail found in MRI. A standard MRI of the brain is also inadequate for showing pituitary disease, as it may result in the pituitary being shown by only 1 or 2 slices that are too thick and too spaced to show a pituitary lesion properly. Therefore, if a pituitary tumor is suspected, it is wise to order an MRI of the sella upfront to avoid having to send the patient back for repeat scanning.
Treatment
Once a diagnosis has been made or is at least entertained with a strong level of suspicion, the referral to an endocrinologist and a neurosurgeon is advisable. Even a "simple" prolactinoma may have ramifications on the pituitary - an organ axis that are not immediately obvious from the gynecological perspective. In our practice all patients referred for pituitary tumors are seen by both the endocrinologist and the neurosurgeon to provide opinions from a medical and surgical perspective respectively. A further word of caution is important here. Most endocrinologists can perform an effective workup of a pituitary tumor and make appropriate diagnosis and, where appropriate, medical treatment recommendations from that workup. However, within the neurosurgical community a wide spectrum of expertise in pituitary disorders exists. Patients with resources tend to consult a relatively small cadre of nationally prominent subspecialists in this area while many neurosurgeons with the theoretical ability to do pituitary surgery actually see only 1 or 2 patients per year, an insufficient number to develop true facility with such procedures. Statistics have been compiled that show true expertise (as judged by success in achieving cure and in avoiding complications) comes only when a surgeon has completed 500 or more transsphenoidal surgeries. Thus, for optimal care, referral to a known center of excellence is advisable. The referral practice at The University of Texas MD Anderson Cancer Center is the largest within the state of Texas or any neighboring state.
Medical therapy generally consists of replacing hormones when levels are low or of suppressing them when they are high. Prolactinomas are generally treated with medical therapy as the first line approach due to the fairly good success achievable with Dopamine agonists such as Bromocriptine (Parlodel) or Cabergoline (Dostinex). These drugs will not be effective in patients with pituitary tumor types other than prolactinoma, but in the prolactinoma category they do have excellent success in lowering prolactin levels and reasonable (but lesser) success in causing tumor shrinkage. Patients with prolactinomas come to surgery for several reasons. In some, the drug is ineffective or produces debilitating side effects, typically gastrointestinal in nature. In others, drug therapy has been successful but not completely so, and debulking the tumor is felt to be helpful in allowing medical therapy a better chance to work on a smaller volume of disease. Finally, a number of patients present for surgery because of what one might term "medication fatigue," namely a desire to free themselves of the necessity for taking what may amount to lifelong medication requirement. For patients with Cushing's disease or acromegaly, the first line treatment is almost always surgical; and for patients with nonfunctional tumors causing hypopituitarism or large enough to endanger vision by compressing the optic chiasm, surgery is also the first line choice. Radiation therapy is used mainly as a backup for tumors that have been treated by other means and yet have recurred, are that small group of invasive, hormonally functional tumors that surgery cannot cure and which have proven refractory to medical therapy.
Transsphenoidal surgery is the most common method of removing a pituitary tumor today. Over 95% of pituitary tumors will prove amendable to that approach, of which there are several variations (endonasal versus sublabial, endoscopic versus microscopic, etc.). The transsphenoidal approach is popular because it provides a relatively direct route of access that travels along the septum of the nose, through the sphenoid sinus, to the sella just behind it. When properly performed, this method avoids the brain altogether and is a very safe procedure. Craniotomy is only necessary for tumors that show special features such as persistent recurrence in the
suprasellar space, lateral extension in the cavernous sinus or around the supraclinoid carotid artery, or for tumors too large to be dealt with by transsphenoidal surgery. Because the brain must be retracted somewhat to expose the sella during a craniotomy for pituitary tumor, the
transsphenoidal approach tends to be safer.
Summary of Important Points
- Prolactin levels allow the important distinction between a true
prolactin producing adenoma and a nonfunctional adenoma with stalk
effect to be made with relative security in most patients. - Patients with prolactin secreting pituitary tumors (prolactinomas)
should be treated as first line with Dopamine agonist therapy, while
nonfunctional or other tumors should not. - Surgery may still be necessary in a prolactinoma and is almost always
needed as first line treatment in patients with other functional
pituitary tumor types. - Because the hormonal systems of the pituitary are complex, a wide
variety of clinical syndromes can be caused by tumors.
However, because the majority of pituitary tumors are either
prolactinomas or nonfunctional tumors, the symptoms of those two
types (menstrual disruption, infertility, galactorrhea, headache,
and/or visual disturbance) should raise the issues of a pituitary tumor
in patients who complain of one or more elements of that constellation. - The cognitive and psychosocial disruption exhibited by patients with
pituitary tumors is real and should be viewed as manifestation of
physical disease that can be amenable to appropriately directed
therapies. - Although women with pituitary tumors may be diagnosed by their
obstetrician/gynecologist, ultimate treatment of such tumors should be
carried out under the joint care of an endocrinologist and
neurosurgeon.
I love Dr. McC!
ReplyDeleteI really need to send that to my ex-obgyn. *cough*misdiagnosis*cough*
Hi, Lisa...me, too. He was the first neurosurgeon who saw my pituitary tumor.
ReplyDeleteHe was the 5th neurosurgeon I interviewed to perform the resection of my pit tumor. He is a terrific physician and I will always be in debt to him. thank you Dr. Mc C for your kindness and skill!
ReplyDeleteDr. McC did both my resection and gamma knife surgeries on my pituitary. I will be forever grateful for his expertise.
ReplyDeleteIs anyone else having vision issues after resection? As of about 6-8 months ago, I have been having trouble with one eye following the other, being lazy to move with the other. I am 10 years post surgery and wondering if perhaps scar tissue or some other consequential event is happening to cause my vision issues. Anyone else having trouble with vision?
ReplyDelete