Pituitary Adenoma

Stanford Pituitary Center

Pituitary adenomas originate within the “master” or pituitary gland, located at the center of the skull base, between a deep air sinus cavity (sphenoid sinus) and the intracranial space (where the brain sits). They are classified as functioning or non-functioning adenomas based on whether they produce excess hormones or not. They are also categorized according to their size into microadenomas (less than 1cm in diameter), macroadenomas (more than 1 cm), and giant adenomas (more than 4 cm). While most adenomas are slow-growing benign tumors, many will invade into neighboring structures, such as the cavernous sinus, clival bone, and intracranial space, becoming difficult to treat and cure.

The Stanford Pituitary Center is aimed at integration of care in a patient-friendly setting for people with pituitary disorders. This multidisciplinary approach allows for total care, from initial triage through surgical intervention and post-operative follow-up. Our surgical team at Stanford, leaded by Dr. Fernandez-Miranda, has pioneered surgical techniques to improve the remission and resection rates in pituitary surgery, while minimizing complications. Patients with the most complex tumors and from several continents have traveled to Stanford to have their pituitary tumor successfully treated.

Symptoms

Non-functioning adenomas cause symptoms by compressing surrounding structures. Compression of the pituitary gland can result in a decrease of hormonal production (infertility -loss of menstruation in women and impotence in men- and fatigue). Mass effect on the lining of the pituitary gland (duramater) may cause difficult-to-treat headaches. Larger tumors will deform the optic apparatus, located just above the gland, resulting on progressive and occasionally severe visual loss. More invasive tumors can cause double vision secondary to mass effect on the nerves that control eye movements; these nerves travel within the cavernous sinus, a venous space located on each side of the pituitary gland, which also contains the internal carotid artery, the main pipeline providing blood supply to the brain.

While all the above symptoms typically appear in a gradual fashion, rarely pituitary tumors can bleed or swell, causing an acute presentation with very severe headaches, visual decline and loss of pituitary function known as “pituitary apoplexy” that requires immediate attention.

Functioning adenomas include prolactin-secreting adenomas known as prolactinomas, adrenocorticotropic hormone (ACTH) secreting adenomas causing Cushing’s disease, growth hormone (GH) secreting adenomas causing acromegaly, and thyroid stimulating hormone (TSH) secreting adenomas causing hyperthyroidism. These types of functioning adenomas may also cause symptoms secondary to mass effect, but more frequently they present with a characteristic hormonal excess syndrome. We will review these in a separate section.

Diagnosis

The Stanford Pituitary Center provides comprehensive, multidisciplinary, and streamlined care for the evaluation and treatment of pituitary tumors and other neuroendocrine disorders.

Other neuroendocrine disorders include acromegaly, prolactinomas, Cushing's syndrome, nonfunctioning pituitary tumors, craniopharygiomas and disorders of the pituitary and hypothalamic region that lead to growth hormone deficiency or adrenal, thyroid, ovarian, or testicular deficiency.

The neuroendocrine clinical program at Stanford, led by Dr. Laurence Katznelson, Medical Director of Stanford Pituitary Center, and Dr. Andrew Hoffman, bring together knowledge and expertise in clinical research and teaching applications to treatment of neuroendocrine diseases. The Stanford Pituitary Center performs diagnostic stimulation tests for community physicians and offers advice on state-of-the-art medical therapeutics and clinical trials. Our endocrinologists are highly experienced in diagnostic strategies, the administration of replacement hormones and drugs to block hormone excess syndromes, as well as investigational drugs for the treatment of pituitary disorders, such as Cushing's disease, acromegaly and growth hormone deficiency.

Our highly trained clinical nursing specialists offer patient education, including teaching self-administration of medications requiring injection, and assist with specialized hormone testing procedures.

Treatment

Our surgical team provides patients the latest surgical techniques for pituitary tumor removal and remission. Dr. Fernandez-Miranda is an internationally renowned surgical innovator and pioneer in endoscopic endonasal surgery for complex pituitary tumors. He has performed more than 1000 endoscopic endonasal operations, many of very high complexity, representing one of the largest endoscopic surgical series to date.

Pituitary tumors at Stanford are treated in a team-approach fashion, with the key participation of our expert ENT endoscopic surgeons, Drs. Hwang, Patel, and Nayak. They provide minimally invasive access to the pituitary gland taking great care to preserve intranasal structures that are relevant for olfaction and healthy breathing.

Our newest state-of-the-art operating rooms have the most advanced technology, including 4K and 3D endoscopic equipment and highly specialized instruments, some designed by Dr. Fernandez-Miranda to improve the gentleness of surgical procedures.

Dr. Fernandez-Miranda is recognized worldwide as a master in surgical neuroanatomy, the basis for accurate, safe, and gentle surgery. He has developed new surgical techniques for pituitary tumors invading the cavernous sinus and extending into the brain space that allow for higher rates of complete tumor removal and long-term remission in functional tumors. These are several of our innovations:

Pituitary tumors with Cavernous Sinus Invasion

Pituitary tumors with cavernous sinus invasion represent a neurosurgical challenge. Safe and effective surgery in this area requires deep understanding of the cavernous sinus anatomy from an endonasal perspective. Dr. JFM has been studying the cavernous sinus for over 15 years and has developed a surgical anatomy-based classification of the cavernous sinus with demonstrated utility for preoperative surgical planning and intraoperative guidance in pituitary surgery.

Four cavernous sinus compartments are described based on their spatial relationship with the cavernous carotid artery: superior, posterior, inferior, and lateral. Each compartment has distinct boundaries and dural and neurovascular relationships.

This essential knowledge has been successfully applied by Dr. JFM in hundreds of patients with invasive pituitary tumors. Selected pituitary adenomas with cavernous sinus invasion can now be completely removed at the Stanford Pituitary Center.

Surgical Approach

Selective Resection of the Medial Wall of the Cavernous Sinus

Pituitary adenomas often invade the medial wall of the cavernous sinus, but this structure is generally not surgically removed because of the risk of vascular and cranial nerve injury. This results on incomplete tumor resections and persistent disease in functional tumors.

Dr. JFM has meticulously investigated the medial wall of the cavernous sinus introducing a classification of the parasellar ligaments and their role in anchoring the medial wall, and has developed an innovative technique for selective resection of the medial wall when invaded by tumor.

At Stanford Pituitary Center, tumors invading the medial wall of the cavernous sinus can now be removed safely and effectively, with minimal morbidity and excellent resection and remission rates in hormonal-secreting adenomas causing Cushing's disease, Acromegaly, or Hyperprolactinemia.

Transoculomor Triangle Approach for Adenomas Invading the Roof of the Cavernous Sinus

Pituitary adenomas may extend into the parapeduncular space by invading through the roof of the cavernous sinus. Currently, a transcranial approach is the preferred choice, with or without the combination of an endonasal approach.

Dr. Juan Fernandez-Miranda has described a novel surgical approach that takes advantage of the natural corridor provided by the tumor to further open the oculomotor triangle and resect tumor extension into the parapeduncular space.

The endoscopic endonasal transoculomotor approach is an original alternative for removal of tumor extension into the parapeduncular space in a single procedure.

Complex Adenomas with Multilobular Shape and Subarachnoid Invasion

While most pituitary adenomas do not require extracapsular subarachnoidal dissection, there are complex adenomas with subarachnoidal invasion and multilobulated morphology, that require a combination of internal debulking, extracapsular and subarachnoidal dissection. The technique presented here allows for complete tumor resection, avoiding the risk of postoperative apoplexy of residual adenoma, and facilitates identification of perforating branches and neural structures that require meticulous preservation.

Endoscopic Endonasal Approach for Pituitary Tumor Removal

Approach to the Patient Undergoing Pituitary Surgery

Endoscopic Endonasal Approach for Complex Macroadenoma with Subarachnoid Invasion

Endoscopic Endonasal Trans-oculomotor Triangle Approach for Invasive Pituitary Adenoma

Stanford Pituitary Center
Patient Education
Day

Innovations in Pituitary Surgery: Step-wise Anatomically-based Resection of the Medial Wall of the Cavernous Sinus

References

Chabot, Joseph D., Chirag R. Patel, Marion A. Hughes, Eric W. Wang, Carl H. Snyderman, Paul A. Gardner, and Juan C. Fernandez-Miranda. “Nasoseptal Flap Necrosis: A Rare Complication of Endoscopic Endonasal Surgery.” Journal of Neurosurgery 128, no. 5 (May 2018): 1463–72. https://doi.org/10.3171/2017.2.JNS161582.

Chivukula, Srinivas, Maria Koutourousiou, Carl H. Snyderman, Juan C. Fernandez-Miranda, Paul A. Gardner, and Elizabeth C. Tyler-Kabara. “Endoscopic Endonasal Skull Base Surgery in the Pediatric Population.” Journal of Neurosurgery. Pediatrics 11, no. 3 (March 2013): 227–41. https://doi.org/10.3171/2012.10.PEDS12160.

Cohen-Cohen, Salomon, Paul A. Gardner, Joao T. Alves-Belo, Huy Q. Truong, Carl H. Snyderman, Eric W. Wang, and Juan C. Fernandez-Miranda. “The Medial Wall of the Cavernous Sinus. Part 2: Selective Medial Wall Resection in 50 Pituitary Adenoma Patients.” Journal of Neurosurgery 131, no. 1 (July 2019): 131–40. https://doi.org/10.3171/2018.5.JNS18595.

Dedhia, Raj C., Christopher A. Lord, Carlos D. Pinheiro-Neto, Juan C. Fernandez-Miranda, Eric W. Wang, Paul A. Gardner, and Carl H. Snyderman. “Endoscopic Endonasal Pituitary Surgery: Impact of Surgical Education on Operation Length and Patient Morbidity.” Journal of Neurological Surgery. Part B, Skull Base 73, no. 6 (December 2012): 405–9. https://doi.org/10.1055/s-0032-1329620.

Fernandez-Miranda, Juan C., Paul A. Gardner, Milton M. Rastelli, Maria Peris-Celda, Maria Koutourousiou, David Peace, Carl H. Snyderman, and Albert L. Rhoton. “Endoscopic Endonasal Transcavernous Posterior Clinoidectomy with Interdural Pituitary Transposition.” Journal of Neurosurgery 121, no. 1 (July 2014): 91–99. https://doi.org/10.3171/2014.3.JNS131865.

Fernandez-Miranda, Juan C., Paul A. Gardner, Carl H. Snyderman, Kenneth O. Devaney, Primož Strojan, Carlos Suárez, Eric M. Genden, Alessandra Rinaldo, and Alfio Ferlito. “Craniopharyngioma: A Pathologic, Clinical, and Surgical Review.” Head & Neck 34, no. 7 (July 2012): 1036–44. https://doi.org/10.1002/hed.21771.

Fernandez-Miranda, Juan C., Daniel M. Prevedello, Paul Gardner, Ricardo Carrau, Carl H. Snyderman, and Amin B. Kassam. “Endonasal Endoscopic Pituitary Surgery: Is It a Matter of Fashion?” Acta Neurochirurgica 152, no. 8 (August 2010): 1281–82. https://doi.org/10.1007/s00701-009-0487-y.

Fernandez-Miranda, Juan C., Daniel M. Prevedello, Ricky Madhok, Victor Morera, Juan Barges-Coll, Katharine Reineman, Carl H. Snyderman, Paul Gardner, Ricardo Carrau, and Amin B. Kassam. “Sphenoid Septations and Their Relationship with Internal Carotid Arteries: Anatomical and Radiological Study: Sphenoid Septa.” The Laryngoscope 119, no. 10 (October 2009): 1893–96. https://doi.org/10.1002/lary.20623.

Fernandez-Miranda, Juan C., Matthew Tormenti, Fernando Latorre, Paul Gardner, and Carl Snyderman. “Endoscopic Endonasal Middle Clinoidectomy: Anatomic, Radiological, and Technical Note.” Neurosurgery 71, no. 2 Suppl Operative (December 2012): ons233-239; discussion ons239. https://doi.org/10.1227/NEU.0b013e3182690b6b.

Fernandez-Miranda, Juan C., Nathan T. Zwagerman, Kumar Abhinav, Stefan Lieber, Eric W. Wang, Carl H. Snyderman, and Paul A. Gardner. “Cavernous Sinus Compartments from the Endoscopic Endonasal Approach: Anatomical Considerations and Surgical Relevance to Adenoma Surgery.” Journal of Neurosurgery 129, no. 2 (August 2018): 430–41. https://doi.org/10.3171/2017.2.JNS162214.

Fraser, Shannon, Paul A. Gardner, Maria Koutourousiou, Mark Kubik, Juan C. Fernandez-Miranda, Carl H. Snyderman, and Eric W. Wang. “Risk Factors Associated with Postoperative Cerebrospinal Fluid Leak after Endoscopic Endonasal Skull Base Surgery.” Journal of Neurosurgery 128, no. 4 (April 2018): 1066–71. https://doi.org/10.3171/2016.12.JNS1694.

Gardner, Paul A., Matthew J. Tormenti, Harshita Pant, Juan C. Fernandez-Miranda, Carl H. Snyderman, and Michael B. Horowitz. “Carotid Artery Injury during Endoscopic Endonasal Skull Base Surgery: Incidence and Outcomes.” Neurosurgery 73, no. 2 Suppl Operative (December 2013): ons261-269; discussion ons269-270. https://doi.org/10.1227/01.neu.0000430821.71267.f2.

Koutourousiou, Maria, Paul A. Gardner, Juan C. Fernandez-Miranda, Alessandro Paluzzi, Eric W. Wang, and Carl H. Snyderman. “Endoscopic Endonasal Surgery for Giant Pituitary Adenomas: Advantages and Limitations.” Journal of Neurosurgery 118, no. 3 (March 2013): 621–31. https://doi.org/10.3171/2012.11.JNS121190.

Koutourousiou, Maria, Paul A. Gardner, Juan C. Fernandez-Miranda, Elizabeth C. Tyler-Kabara, Eric W. Wang, and Carl H. Snyderman. “Endoscopic Endonasal Surgery for Craniopharyngiomas: Surgical Outcome in 64 Patients.” Journal of Neurosurgery 119, no. 5 (November 2013): 1194–1207. https://doi.org/10.3171/2013.6.JNS122259.

Koutourousiou, Maria, Paul A. Gardner, Julia K. Kofler, Juan C. Fernandez-Miranda, Carl H. Snyderman, and L. Dade Lunsford. “Rare Infundibular Tumors: Clinical Presentation, Imaging Findings, and the Role of Endoscopic Endonasal Surgery in Their Management.” Journal of Neurological Surgery. Part B, Skull Base 74, no. 1 (February 2013): 1–11. https://doi.org/10.1055/s-0032-1329619.

Koutourousiou, Maria, Francisco Vaz Guimaraes Filho, Juan C. Fernandez-Miranda, Eric W. Wang, Susan Tonya Stefko, Carl H. Snyderman, and Paul A. Gardner. “Endoscopic Endonasal Surgery for Tumors of the Cavernous Sinus: A Series of 234 Patients.” World Neurosurgery 103 (July 2017): 713–32. https://doi.org/10.1016/j.wneu.2017.04.096.

Najera, Edinson, Carl H. Snyderman, and Juan C. Fernandez-Miranda. “Endoscopic Endonasal Approach for Complex Macroadenoma with Suprasellar and Retrochiasmatic Extension.” Journal of Neurological Surgery. Part B, Skull Base 79, no. Suppl 3 (April 2018): S284. https://doi.org/10.1055/s-0038-1625969.

Paluzzi, Alessandro, Juan C. Fernandez-Miranda, Carlos Pinheiro-Neto, Victor Alcocer-Barradas, Beatriz Lopez-Alvarez, Paul Gardner, and Carl Snyderman. “Endoscopic Endonasal Infrasellar Approach to the Sellar and Suprasellar Regions: Technical Note.” Skull Base: Official Journal of North American Skull Base Society ... [et Al.] 21, no. 5 (September 2011): 335–42. https://doi.org/10.1055/s-0031-1280682.

Paluzzi, Alessandro, Juan C. Fernandez-Miranda, S. Tonya Stefko, Sue Challinor, Carl H. Snyderman, and Paul A. Gardner. “Endoscopic Endonasal Approach for Pituitary Adenomas: A Series of 555 Patients.” Pituitary 17, no. 4 (August 2014): 307–19. https://doi.org/10.1007/s11102-013-0502-4.

Shin, Samuel S., Paul A. Gardner, Jason Ng, Amir H. Faraji, Nitin Agarwal, Srinivas Chivukula, Juan C. Fernandez-Miranda, Carl H. Snyderman, and Sue M. Challinor. “Endoscopic Endonasal Approach for Adrenocorticotropic Hormone-Secreting Pituitary Adenomas: Outcomes and Analysis of Remission Rates and Tumor Biochemical Activity with Respect to Tumor Invasiveness.” World Neurosurgery 102 (June 2017): 651-658.e1. https://doi.org/10.1016/j.wneu.2015.07.065.

Shin, Samuel S., Matthew J. Tormenti, Alessandro Paluzzi, William E. Rothfus, Yue-Fang Chang, Hanady Zainah, Juan C. Fernandez-Miranda, Carl H. Snyderman, Sue M. Challinor, and Paul A. Gardner. “Endoscopic Endonasal Approach for Growth Hormone Secreting Pituitary Adenomas: Outcomes in 53 Patients Using 2010 Consensus Criteria for Remission.” Pituitary 16, no. 4 (December 2013): 435–44. https://doi.org/10.1007/s11102-012-0440-6.

Stefko, S. Tonya, Carl Snyderman, Juan Fernandez-Miranda, Elizabeth Tyler-Kabara, Eric Wang, Lance Bodily, Richard A. Bilonick, and Paul A. Gardner. “Visual Outcomes after Endoscopic Endonasal Approach for Craniopharyngioma: The Pittsburgh Experience.” Journal of Neurological Surgery. Part B, Skull Base 77, no. 4 (August 2016): 326–32. https://doi.org/10.1055/s-0036-1571333.

Truong, Huy Q., Stefan Lieber, Edinson Najera, Joao T. Alves-Belo, Paul A. Gardner, and Juan C. Fernandez-Miranda. “The Medial Wall of the Cavernous Sinus. Part 1: Surgical Anatomy, Ligaments, and Surgical Technique for Its Mobilization and/or Resection.” Journal of Neurosurgery 131, no. 1 (July 2019): 122–30. https://doi.org/10.3171/2018.3.JNS18596.

Vaezi, Alec, Eugenio Cardenas, Carlos Pinheiro-Neto, Alessandro Paluzzi, Barton F. Branstetter, Paul A. Gardner, Carl H. Snyderman, and Juan C. Fernandez-Miranda. “Classification of Sphenoid Sinus Pneumatization: Relevance for Endoscopic Skull Base Surgery.” The Laryngoscope 125, no. 3 (March 2015): 577–81. https://doi.org/10.1002/lary.24989.

Zeinalizadeh, Mehdi, Zohreh Habibi, Juan C. Fernandez-Miranda, Paul A. Gardner, Steven P. Hodak, and Sue M. Challinor. “Discordance between Growth Hormone and Insulin-like Growth Factor-1 after Pituitary Surgery for Acromegaly: A Stepwise Approach and Management.” Pituitary 18, no. 1 (February 2015): 48–59. https://doi.org/10.1007/s11102-014-0556-y.

Zenonos, Georgios A., Eric W. Wang, and Juan Carlos Fernandez-Miranda. “Infrasellar Endoscopic Endonasal Approach for a Pituitary Adenoma Extending into the Third Ventricle, with Anterior Displacement of the Pituitary Gland.” Journal of Neurological Surgery. Part B, Skull Base 79, no. Suppl 2 (February 2018): S233–34. https://doi.org/10.1055/s-0037-1620261.

Zenonos, Georgios Andrea, Eric Wesley Wang, and Juan C. Fernandez-Miranda. “Endoscopic Endonasal Transoculomotor Triangle Approach for the Resection of a Pituitary Adenoma with Ambient Cistern Extension.” Journal of Neurological Surgery. Part B, Skull Base 79, no. Suppl 3 (April 2018): S283. https://doi.org/10.1055/s-0038-1625942.

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Pituitary Adenoma

Surgical Approach

Selective Resection of the Medial Wall of the Cavernous Sinus

Transoculomor Triangle Approach for Adenomas Invading the Roof of the Cavernous Sinus

Endoscopic Endonasal Approach for Pituitary Tumor Removal

Approach to the Patient Undergoing Pituitary Surgery

Endoscopic Endonasal Approach for Complex Macroadenoma with Subarachnoid Invasion

Endoscopic Endonasal Trans-oculomotor Triangle Approach for Invasive Pituitary Adenoma

Stanford Pituitary Center
Patient Education
Day

Innovations in Pituitary Surgery: Step-wise Anatomically-based Resection of the Medial Wall of the Cavernous Sinus

Medical Professionals

Pituitary Adenoma

Endoscopic Endonasal Approach for Pituitary Tumor Removal

Approach to the Patient Undergoing Pituitary Surgery

Endoscopic Endonasal Approach for Complex Macroadenoma with Subarachnoid Invasion

Endoscopic Endonasal Trans-oculomotor Triangle Approach for Invasive Pituitary Adenoma

Stanford Pituitary CenterPatient EducationDay

Innovations in Pituitary Surgery: Step-wise Anatomically-based Resection of the Medial Wall of the Cavernous Sinus

Stanford Pituitary Center
Patient Education
Day