Accepted Manuscript Pituitary Apoplexy: Is it one entity? Kalmon D. Post, M.D PII:
S1878-8750(14)00741-4
DOI:
10.1016/j.wneu.2014.08.020
Reference:
WNEU 2511
To appear in:
World Neurosurgery
Received Date: 7 July 2014 Accepted Date: 14 August 2014
Please cite this article as: Post KD, Pituitary Apoplexy: Is it one entity?, World Neurosurgery (2014), doi: 10.1016/j.wneu.2014.08.020. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title Page
Pituitary Apoplexy: Is it one entity?
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Kalmon D. Post, M.D. Chairman Emeritus Department Neurosurgery Professor Neurosurgery & Medicine Mount Sinai School of Medicine One Gustave L. Levy Place Box 1136 New York, NY 10029 212-241-0933
ACCEPTED MANUSCRIPT
Pituitary apoplexy is often a neurosurgical emergency where prompt intervention may halt and even reverse the neurologic deficits. The condition results from hemorrhage or necrosis of a pituitary tumor, though some would include only those patients with acute hemorrhage.
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There has been extensive interest in the entity. Nevertheless, there has also been considerable debate on what the term pituitary apoplexy encompasses. In fact, there have been reports of silent pituitary apoplexy. 1 Mohr3 estimated the incidence of asymptomatic hemorrhages in pituitary adenomas to be 9.9% as opposed to 0.6% that presented with clinical findings. Other large studies cite similar numbers, with 41% to 86% of all hemorrhages remaining asymptomatic. Onesti4 described 5 patients with subclinical pituitary apoplexy, that is, a clinically silent yet extensive hemorrhage into a pituitary adenoma. Necrotic or cystic degeneration of pituitary adenomas may be asymptomatic as well. The diagnosis of pituitary apoplexy is made clinically by the sudden onset of headache, meningismus, visual impairment, and oculomotor abnormalities in varying combinations. An overall review of the literature has shown that no one type of tumors displays an increased incidence of hemorrhage, and the data actually reflect the relative frequency of each type of tumor.
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It may be caused by a rapidly growing tumor that outgrows its own blood supply resulting in ischemic infarction, or from compression of the superior hypophyseal artery against the diaphragmatic notch, rendering the pars distalis and its tumor ischemic, necrotic, and hemorrhagic. However, even small adenomas may show evidence of hemorrhage. Are there intrinsic tumoral factors that may cause an apoplectic event? A multifactorial explanation for pituitary apoplexy is probably more appropriate. The incidence of pituitary apoplexy is in the 1-2% range in my series of over 4000 patients. Pituitary apoplexy has been considered an endocrine emergency. Hypopituitarism, either partial or complete, is a major manifestation. Low basal or stimulated levels of growth hormone, corticotrophin, thyrotropin, and gonadotropins have all been documented. A worsening of pre-existing endocrine abnormalities is not unusual. Major morbidity and mortality can occur because of failure to treat an evolving Addisonian crisis. Guidelines published in 20115 provided consensus recommendations with three main areas of focus. Glucocorticoid replacement was the single most important aspect of acute treatment for multiple reasons. Those include both endocrine
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deficiency as well as neurologic deficit. A specialized team managing apoplexy patients was suggested for improved results. The actual optimal management however, was still questioned in regard to surgery or medical management. Surgery has been advised for those patients with neurologic deficit including visual loss of acuity or fields, and change of mental status, while controversy is ongoing in regard to ocular palsies. Long-term results with surgery or medical management are similar in patients with ocular palsies, but with intact fields and acuity. The guidelines recommended that surgery for those with acute visual loss be done within the first week. From my experience, I have the impression that the earlier it is done, the better the outcome for recovery of function, but there is a lack of hard data. I have operated upon an octogenarian with three days of complete blindness following apoplexy with full return of function. The predictors of visual recovery are lacking.
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The lack of clarity in treatment paradigms for apoplexy may in part be related to the diversity of apoplexy patients often lumped into one group. In this issue of World Neurosurgery, Jho, Biller, Agarwall, and Swearingen2 have proposed a grading system for pituitary apoplexy that may be very helpful in allowing us to compare apples to apples and oranges to oranges in the future such that we may far better understand what treatment is most appropriate for each level as well as what the best timing may be for treatment. Apoplexy was defined both clinically and radiographically with a spectrum categorized by a clinical grading system. Grade 1 patients have imaging evidence of hemorrhage with minimal symptoms, while grade 2 patients have only endocrinopathy. Grade 3 was assigned to those with headache, while grade 4 patients had ocular paresis and grade 5 patients had visual deficits or a low Glascow coma score such that vision could not be tested. They also have three subgroups for patients with prolactinoma, hemorrhagic Rathke’s cleft cysts, and significant morbidities. These three subgroups were identified as they may suggest medical management as opposed to surgery. Higher grades suggested surgical intervention while lower grades were treated with more elective surgery or medical management. Grades of clinical severity were statistically correlated with tumor size, cavernous sinus involvement, and suprasellar extension. Lower grades (1-3) more frequently had complete recovery of endocrine deficits than higher grades. There was a trend for earlier surgical treatment for higher grades, with good overall outcomes for all grades. Long-term endocrine replacement was necessary in 62-68% of higher grade patients as opposed to 023% of lower grade patients. Using this grading system and parallel treatment paradigms, 92-100% of patients across all grades had good outcomes for visual deficits and ocular palsies.
ACCEPTED MANUSCRIPT
RI PT
These grades give a spectrum of apoplexy that incorporate both imaging and clinical findings that over time may allow us to dictate therapy focused more by individual group than by overall category of apoplexy. I believe the authors have presented a grading system that is logical, practical, and flexible such that we will better understand the entity of pituitary apoplexy in the future.
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1.Findling JW, Tyrrell JB, Aron DC, Fitzgerald PA, Wilson CB, Forsham PH: Silent pituitary apoplexy: subclinical infarction of an adrenocorticotropinproducing pituitary adenoma. J Clin Endocrinol Metab. 1981;52:95-97.
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2.Jho DH, Biller BM, Agarwalla PK, Swearingen B: Pituitary Apoplexy: large surgical series with grading system. World Neurosurgery… 3.Mohr G, Hardy J: Hemorrhage, necrosis, and apoplexy in pituitary adenomas. Surg Neurol. 1982;18:181-189.
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4.Onesti ST, Wisniewski T, Post KD: Clinical versus subclinical pituitary apoplexy: presentation, surgical management, and outcome in 21 patients. Neurosurgery. 1990; 26: 980-986.
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5.Rajasekarnt S, Vanderpump M, Baldeweg S, Drake W, Reddy N, Lanyon M, Markey A, Plant G, Powell M, Sinha S, Wass J: UK guidelines for the management of pituitary apoplexy: pituitary apoplexy guidelines development group. Clin Endocrinol (Oxf) 2011; 74: 9-20.
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Highlights : This is a Perspective comment requested by Dr. Apuzzo for the issue of World Neurosurgery in which the article by Jho et al on a grading system for pituitary apoplexy will be published.
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K. Post
S1878-8750(14)00741-4
DOI:
10.1016/j.wneu.2014.08.020
Reference:
WNEU 2511
To appear in:
World Neurosurgery
Received Date: 7 July 2014 Accepted Date: 14 August 2014
Please cite this article as: Post KD, Pituitary Apoplexy: Is it one entity?, World Neurosurgery (2014), doi: 10.1016/j.wneu.2014.08.020. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title Page
Pituitary Apoplexy: Is it one entity?
AC C
EP
TE D
M AN U
SC
RI PT
Kalmon D. Post, M.D. Chairman Emeritus Department Neurosurgery Professor Neurosurgery & Medicine Mount Sinai School of Medicine One Gustave L. Levy Place Box 1136 New York, NY 10029 212-241-0933
ACCEPTED MANUSCRIPT
Pituitary apoplexy is often a neurosurgical emergency where prompt intervention may halt and even reverse the neurologic deficits. The condition results from hemorrhage or necrosis of a pituitary tumor, though some would include only those patients with acute hemorrhage.
M AN U
SC
RI PT
There has been extensive interest in the entity. Nevertheless, there has also been considerable debate on what the term pituitary apoplexy encompasses. In fact, there have been reports of silent pituitary apoplexy. 1 Mohr3 estimated the incidence of asymptomatic hemorrhages in pituitary adenomas to be 9.9% as opposed to 0.6% that presented with clinical findings. Other large studies cite similar numbers, with 41% to 86% of all hemorrhages remaining asymptomatic. Onesti4 described 5 patients with subclinical pituitary apoplexy, that is, a clinically silent yet extensive hemorrhage into a pituitary adenoma. Necrotic or cystic degeneration of pituitary adenomas may be asymptomatic as well. The diagnosis of pituitary apoplexy is made clinically by the sudden onset of headache, meningismus, visual impairment, and oculomotor abnormalities in varying combinations. An overall review of the literature has shown that no one type of tumors displays an increased incidence of hemorrhage, and the data actually reflect the relative frequency of each type of tumor.
AC C
EP
TE D
It may be caused by a rapidly growing tumor that outgrows its own blood supply resulting in ischemic infarction, or from compression of the superior hypophyseal artery against the diaphragmatic notch, rendering the pars distalis and its tumor ischemic, necrotic, and hemorrhagic. However, even small adenomas may show evidence of hemorrhage. Are there intrinsic tumoral factors that may cause an apoplectic event? A multifactorial explanation for pituitary apoplexy is probably more appropriate. The incidence of pituitary apoplexy is in the 1-2% range in my series of over 4000 patients. Pituitary apoplexy has been considered an endocrine emergency. Hypopituitarism, either partial or complete, is a major manifestation. Low basal or stimulated levels of growth hormone, corticotrophin, thyrotropin, and gonadotropins have all been documented. A worsening of pre-existing endocrine abnormalities is not unusual. Major morbidity and mortality can occur because of failure to treat an evolving Addisonian crisis. Guidelines published in 20115 provided consensus recommendations with three main areas of focus. Glucocorticoid replacement was the single most important aspect of acute treatment for multiple reasons. Those include both endocrine
ACCEPTED MANUSCRIPT
SC
RI PT
deficiency as well as neurologic deficit. A specialized team managing apoplexy patients was suggested for improved results. The actual optimal management however, was still questioned in regard to surgery or medical management. Surgery has been advised for those patients with neurologic deficit including visual loss of acuity or fields, and change of mental status, while controversy is ongoing in regard to ocular palsies. Long-term results with surgery or medical management are similar in patients with ocular palsies, but with intact fields and acuity. The guidelines recommended that surgery for those with acute visual loss be done within the first week. From my experience, I have the impression that the earlier it is done, the better the outcome for recovery of function, but there is a lack of hard data. I have operated upon an octogenarian with three days of complete blindness following apoplexy with full return of function. The predictors of visual recovery are lacking.
AC C
EP
TE D
M AN U
The lack of clarity in treatment paradigms for apoplexy may in part be related to the diversity of apoplexy patients often lumped into one group. In this issue of World Neurosurgery, Jho, Biller, Agarwall, and Swearingen2 have proposed a grading system for pituitary apoplexy that may be very helpful in allowing us to compare apples to apples and oranges to oranges in the future such that we may far better understand what treatment is most appropriate for each level as well as what the best timing may be for treatment. Apoplexy was defined both clinically and radiographically with a spectrum categorized by a clinical grading system. Grade 1 patients have imaging evidence of hemorrhage with minimal symptoms, while grade 2 patients have only endocrinopathy. Grade 3 was assigned to those with headache, while grade 4 patients had ocular paresis and grade 5 patients had visual deficits or a low Glascow coma score such that vision could not be tested. They also have three subgroups for patients with prolactinoma, hemorrhagic Rathke’s cleft cysts, and significant morbidities. These three subgroups were identified as they may suggest medical management as opposed to surgery. Higher grades suggested surgical intervention while lower grades were treated with more elective surgery or medical management. Grades of clinical severity were statistically correlated with tumor size, cavernous sinus involvement, and suprasellar extension. Lower grades (1-3) more frequently had complete recovery of endocrine deficits than higher grades. There was a trend for earlier surgical treatment for higher grades, with good overall outcomes for all grades. Long-term endocrine replacement was necessary in 62-68% of higher grade patients as opposed to 023% of lower grade patients. Using this grading system and parallel treatment paradigms, 92-100% of patients across all grades had good outcomes for visual deficits and ocular palsies.
ACCEPTED MANUSCRIPT
RI PT
These grades give a spectrum of apoplexy that incorporate both imaging and clinical findings that over time may allow us to dictate therapy focused more by individual group than by overall category of apoplexy. I believe the authors have presented a grading system that is logical, practical, and flexible such that we will better understand the entity of pituitary apoplexy in the future.
SC
1.Findling JW, Tyrrell JB, Aron DC, Fitzgerald PA, Wilson CB, Forsham PH: Silent pituitary apoplexy: subclinical infarction of an adrenocorticotropinproducing pituitary adenoma. J Clin Endocrinol Metab. 1981;52:95-97.
M AN U
2.Jho DH, Biller BM, Agarwalla PK, Swearingen B: Pituitary Apoplexy: large surgical series with grading system. World Neurosurgery… 3.Mohr G, Hardy J: Hemorrhage, necrosis, and apoplexy in pituitary adenomas. Surg Neurol. 1982;18:181-189.
TE D
4.Onesti ST, Wisniewski T, Post KD: Clinical versus subclinical pituitary apoplexy: presentation, surgical management, and outcome in 21 patients. Neurosurgery. 1990; 26: 980-986.
AC C
EP
5.Rajasekarnt S, Vanderpump M, Baldeweg S, Drake W, Reddy N, Lanyon M, Markey A, Plant G, Powell M, Sinha S, Wass J: UK guidelines for the management of pituitary apoplexy: pituitary apoplexy guidelines development group. Clin Endocrinol (Oxf) 2011; 74: 9-20.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Highlights : This is a Perspective comment requested by Dr. Apuzzo for the issue of World Neurosurgery in which the article by Jho et al on a grading system for pituitary apoplexy will be published.
AC C
EP
TE D
M AN U
SC
RI PT
K. Post
