For decades, the central skull base has been a challenge to surgeons, given its inaccessible location. Pituitary surgery or hypophysectomy has evolved over the last century from open surgery, requiring craniotomy, to a fully endoscopic endonasal procedure through the sphenoid sinuses. The transsphenoidal approach was described and popularised in 1910, by Harvey Cushing and Oskar Hirsch, utilizing sublabial and transnasal routes, respectively. Though the popularity of the transsphenoidal approach went down when Cushing abandoned it for transcranial approaches, it was preserved by Dott, Guiot, and refined by Hardy, who introduced microsurgical techniques.
Approaches to the pituitary gland can be broadly classified into transcranial and extracranial approaches. Transcranial microscopic approaches, used currently in cases where transsphenoidal approaches are contraindicated, involve anterior subfrontal approach and pterional (frontotemporal) approach. Pterional approach, which involves the removal of the sphenoid wing and minimal brain retraction, provides the shortest trajectory to the parasellar region and excellent visualization of the pituitary gland. Anterior subfrontal approach has the advantage of straight visualization of the pituitary tumor between the optic nerves. But it is less popular in comparison to the pterional approach, because of potential damage to olfactory nerves and frontal sinuses.
Extracranial approaches primarily consist of transsphenoidal microscopic approaches (transnasal or sublabial) and endoscopic transnasal transsphenoidal approach, along with modifications such as expanded endoscopic endonasal approach (EEEA) and combined transsphenoidal transmaxillary approach. Transsphenoidal microscopic approaches used the sublabial or septal incisions, followed by a wide dissection of mucoperichondrium/mucoperiosteum of the septum and floor of the nose along with partial resection of the vomer, the perpendicular plate of the ethmoid, and the sphenoid rostrum. The nasal contents are pushed laterally with a self-retaining speculum, allowing the use of an operative microscope and bimanual instrumentation. This technique was, however, associated with significant morbidities, such as facial swelling and pain, regular need for nasal packing or septal splints, etc. Sinonasal complications such as sinusitis, numbness of upper alveolus, nasal synechiae, and septal perforation were common. First described by Jankowski in 1992, endoscopic pituitary surgery uses the natural medial nasal corridor to assess the sphenoid sinus. It has gained popularity over transsphenoidal microscopic approaches due to its shorter hospital stay, panoramic view, and good mobility with angled views. Endoscopic transsphenoidal hypophysectomy has revolutionized the field of minimal access to skull base surgery and opened doors to extended anterior skull base approaches.
The pituitary gland is located in a saddle-shaped depression in the body of the sphenoid bone, sella turcica/pituitary fossa. The floor of the pituitary fossa forms the roof of sphenoid sinuses posteriorly. The anterior wall of the pituitary fossa, which ends at the tuberculum sellae, is bounded laterally by the middle clinoid processes, and the posterior boundary is a vertical projection of bone, dorsum sellae, with its posterolateral angles forming the posterior clinoid processes. Anterior to tuberculum sellae is the grooved sulcus chiasmaticus, which leads to the optic canals laterally. Optic chiasma is located posterosuperior to this sulcus and anterior to the pituitary stalk. Planum sphenoidale, the smooth roof of the sphenoid body, lies anterior to sulcus chiasmaticus. The cavernous sinuses lie lateral to the pituitary fossa.
Sphenoid sinuses are approached via passing the endoscope in a medial corridor, between the nasal septum and middle turbinate. Sphenoid ostia are located medial to superior turbinate, at the same level as the superior border of the natural ostium of the maxillary sinus. It is 1 to 1.5 cm from the choanal roof, 7 cm from the nasal sill at a 30-degree angle, and 11 mm from the skull base. The extent of sphenoid pneumatization may vary widely, commonest being sellar type, with pneumatization extending posterior to sella turcica, followed by pre-sellar and post-sellar type patterns. Sphenoid sinus can also pneumatize laterally into the pterygoid root resulting in a lateral recess, which can lead to exposure of the V2 nerve and the vidian nerve.
The main structures encountered in a well-pneumatized sinus are optic nerve, carotid artery, and sella turcica. Once the inter-sinus septum is removed, all structures can be identified. The pituitary fossa in the midline is flanked by cavernous sinus and anterior genu of the cavernous segment of the carotid artery. The optic nerve is located at the junction of the sidewall and roof, as the carotid arteries are followed superiorly. Above the pituitary fossa is the tuberculum sella, at the junction of the anterior face of pituitary fossa and roof of the sphenoid sinus (planum sphenoidale). The lateral opticocarotid recess (OCR) is a triangular bony depression that represents the ventral surface of the optic strut. Medial OCR is a teardrop-shaped depression at the medial junction of the paraclinoid carotid and optic canal. The lateral end (tail) of medial OCR meets the medial aspect of lateral OCR, where the paraclinoid carotid artery and optic canal intersect.
The presence of various anatomical variations makes endonasal transsphenoidal access challenging. Deviation of the nasal septum or a concha bullosa (pneumatization of the middle turbinate) can narrow the nasal passage. A gross septal deviation or prior septal surgery can potentially impair the harvest of a nasoseptal flap, a common reconstructive technique in sellar surgery. Sinonasal disease or nasal polyps can obliterate the nasal passage and warrant sinus surgery. The anatomy of the sphenoid sinus and its adjacent structures need critical evaluation. Computed tomography (CT) scans need to be studied meticulously by the surgeon for the extent of pneumatization of sphenoid sinuses (including presence of lateral recesses), posterior attachment of intersinus septum and its relation to the paracavernous carotid artery, sphenoethmoidal cell/Onodi cell and dehiscence over bony walls covering optic nerve or carotid artery. The optic nerve canal is dehiscent in 4% to 8% of cases. The risk of injury to the carotid artery is around 5% in pituitary surgery and higher in para sellar surgery.
Pituitary adenomas (both micro and macroadenomas) constitute the most frequent indication for transsphenoidal hypophysectomy. Surgery is indicated for nonsecreting adenomas that cause vision disorders, hypopituitarism, pituitary apoplexy, or demonstrate the progression on serial imaging. Surgery is recommended for secreting adenomas that do not respond to medical management. Other sellar lesions can be approached in a similar fashion, such as Rathke’s cyst, craniopharyngiomas, meningiomas, chordomas, or metastatic lesions.
The transsphenoidal approach is contraindicated in sphenoid sinusitis, intrasellar vascular anomalies, ectatic midline carotid arteries, or significant lateral suprasellar extension of tumor, especially when the epicenter is lateral to the carotid artery. Relative contraindications include a poorly pneumatized sphenoid sinus, significant suprasellar adenoma extension, and constrictive diaphragma sellae.
Endoscopic transsphenoidal hypophysectomy would require the full set of instruments for sinus surgery, along with a high-speed drill and homeostatic agents like gelatin with thrombin. The microscopic approach would require a maxillofacial instrument set, with Hardy self-retaining bivalve speculum. Image guidance navigation (IGN) system is preferable in revision procedures, parasellar extension, or cases with distorted anatomy. Intraoperative MRI is of significant benefit in pituitary surgery, as it provides updated images with the change in tumor volume, of the dura, and normal pituitary.
Endoscopic surgery of pituitary tumors may require two surgeons or a four-handed technique. One surgeon holds the endoscope to provide an optimal view for the second surgeon to perform the bimanual dissection. An ideal team would include a skilled endoscopic sinus surgeon, who can provide fast and safe access to the sella, and a neurosurgeon who understands the complexities of operating in this region. Though modern-day neurosurgeons are capable of performing endonasal approaches independently, an otolaryngologist can greatly enhance the speed of surgery and provide access in cases with difficult anatomies, such as the deviated nasal septum, nasal polyps or unpneumatized sella. Usually, the otolaryngologist exposes the dura over the sella, and then the neurosurgeon opens the dura, followed by the removal of the tumor. Often, the assistance of a skilled endoscopic sinus surgeon can help tackle cases with extrasellar extensions, such as cavernous sinus and retrocarotid extension, as well as in postoperative management of complications such as nasal synechiae, atrophic rhinitis, etc. Hence, close coordination between the neurosurgeon and otolaryngologist is vital.
A comprehensive history, along with a full head and neck examination, is mandatory before considering surgery. Vision examination, including visual acuity, perimetry, and gaze restriction, should be documented. Preoperative nasal endoscopy is crucial to rule out anatomical obstruction or sinonasal disease, which would need to be addressed intraoperatively or preoperatively.
An evaluation of the pituitary function and hormone status before surgery by an endocrinologist is indispensable. Inadequate pituitary reserve before surgery would increase the risk of hypopituitarism in the perioperative period. At the end of the evaluation, the interprofessional team should be aware of the following:
Measurement of growth hormone (GH), cortisol, serum prolactin, triiodothyronine, thyroxine, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are done. Thyroid and cortisol hormone levels are the most crucial preoperatively. In the case of hypocortisolemia or hypothyroidism, replacement with exogenous glucocorticoids or thyroid supplements is essential in anticipation of surgery.
Imaging, in the form of CT scan and magnetic resonance imaging (MRI) scan, is critical for any skull base surgery. T1W MRI with and without contrast, in coronal and sagittal planes, is the best method of defining sellar pathology and planning surgical approach. MRI is superior to CT scan due to its greater soft-tissue contrast, which allows the delineation of vital structures such as optic chiasm, intracavernous carotid arteries, optic nerves, and cavernous sinuses. MRI aids in understanding the exact tumor extension, tumor composition, and differentiating mass from obstructed fluid/mass. Also, it provides information on dural involvement or invasion.
Microadenomas are a diagnostic challenge. On T1W images, microadenomas are hypointense to the pituitary gland and enhance less than the normal gland. Its appearance in T2W can be variable. Microadenomas show early enhancement followed by early washout, in comparison with late and intensely enhancing pituitary gland. Macroadenomas are usually hypointense or isointense to grey matter on T1W and variable on T2W. In postcontrast images, macroadenomas enhance well, making them easy to diagnose.
Pituitary adenomas are isointense to brain parenchyma on CT without contrast. It shows intense enhancement with contrast. CT scans can demonstrate bony erosion and expansion of the sella accurately. More importantly, CT scans are vital for the planning of the surgical approach. It can help identify septal deviations, sinonasal disease or nasal polyps, the extent of pneumatization of sinuses, ease of transnasal access to the sphenoid sinus, and anatomical variations such as Onodi cell, aberrant carotid artery or bony dehiscences at the skull base.
Past Nasal Surgery
History of prior nasal surgery and, if present, its indication has to be sought. The presence of past nasal or septal surgery makes the preoperative planning and preparation more complex. If the indication for the previous surgery was a chronic disease (e.g., nasal polyps) or a tumor, then its current status needs to be evaluated in the form of nasal endoscopy and radiological imaging. Sometimes, if the previous condition is unresolved, then revision surgery may have to be undertaken before undertaking pituitary surgery. If the previous surgery was septoplasty or involving raising of the septal flap, evaluation of the septal mucosa needs to be done with preoperative nasal endoscopy. Scarred mucosa or presence of septal perforation may impede the harvest of a nasoseptal flap and warrant the use of alternate methods of reconstruction after sellar surgery. Additionally, nasal endoscopy helps to identify residual septal deviations or synechiae (post-surgery), which may be corrected at an earlier setting or concomitantly with the pituitary surgery.
Preparation and positioning
The patient is laid supine with head secured in a Mayfield head holder. Catheterization is mandatory for accurate fluid balance management, especially with the risk of diabetes insipidus. Topical vasoconstrictive agents are used to decongest both the nasal cavities. Abdomen and/or thigh is prepared as a graft donor site. In cases using the endoscopic technique, the navigation transmitter is attached to the patient’s forehead, and the patient is registered.
Endoscopic endonasal transsphenoidal approach
Bilateral nasal cavities are decongested, and anatomical obstructions, such as a deviated nasal septum or concha bullosa, are corrected. A medial corridor between the nasal septum and middle turbinate is widened by lateralizing the latter. A pedicled septal flap, popularly known as Hadad Bassegastegay flap, based on the posterior nasal artery, can be raised if extended pituitary approaches are anticipated. The sphenoid ostium is identified and widened to lamina papyracea. The mucosa of sphenoid sinus should be elevated in a medial to lateral fashion, to leave two laterally based mucosal flaps for reconstituting the anterior wall of pituitary fossa. About 1 to 1.5 cm of the posterior edge of the septum is usually removed for ease of instrumentation.
Microscopic sublabial transsphenoidal approach
The gingival mucosa and nasal mucosa are infiltrated with local anesthetic containing a vasoconstrictor. Sublabial incision is made one canine fossa to the other, followed by subperiosteal dissection to expose the piriform aperture and the rostrum of the maxilla. Mucoperichondrium and mucoperiosteum from one side of the nasal septum and nasal floor are elevated, and the quadrangular cartilage is disarticulated from the vomer and perpendicular plate of the ethmoid. A handheld retractor is introduced, and the elevated mucosa is retracted laterally to expose the rostrum of sphenoid. Once the sphenoid ostia are identified, self-retaining Hardy bivalve speculum is introduced, allowing bimanual instrumentation henceforth. The operative microscope is employed now to improve magnification. The rostrum is resected now with rongeurs to gain access into the sphenoid sinus.
Microscopic transnasal transsphenoidal approach
This approach is through a single nostril to reach the sphenoid sinuses. An incision is made at the posterior and inferior margin of the quadrangular cartilage. After submucosal dissection, quadrangular cartilage is disarticulated at its posterior margin, and a bivalve speculum is introduced. Subsequent steps are similar to the sublabial approach. While this approach offers advantages like lesser soft tissue dissection, better cosmesis, lesser postoperative morbidity, and no upper jaw numbness, it can be a difficult approach in patients with the small nostril, necessitating an alotomy or external rhinoplasty incision, which can lead to scarring or nasal deformities.
Sphenoid sinus mucosa is stripped off to prevent postoperative mucocele formation and prevent further mucosal bleeding. Inter-sinus septations are removed carefully with a diamond drill or rongeur. Medial and lateral OCRs, anterior genu of carotid arteries and optic nerve needs to be identified, and their location limits the exposure of sella. Using diamond burr, bone over the sella is ‘egg-shelled’ and fractured. A Kerrison punch can be used to remove the bone, to expose the underlying dura from one carotid artery canal to the opposite canal and from planum sphenoidale to the clivus.
Dura is opened with a U-shaped or cruciate incision to expose the fossa. The normal pituitary gland is yellow and solid, while the tumor appears amorphous and white. An extracapsular resection of the tumor should be attempted. The tumor delivery is often facilitated by the CSF pulsations through an intact arachnoid from above. The angle between the arachnoid and the carotid artery needs to be ascertained. The arachnoid (diaphragma sella) is the limit of superior and posterior dissection. In the case of the parasellar extension, 30-degree endoscopes are used to ensure comprehensive clearance. The pituitary fossa is filled with gel foam paste, and the dura is reposited back. The mucosal flaps are placed over the dura, fixed with Surgicel, and a layer of fibrin glue.
Regardless of the reconstructive material, a multilayer closure and complete defect coverage are critical. It is essential that the edges of the defect are denuded of mucosa to prevent mucocele formation and to promote graft revascularization. Free tissue grafts are commonly used to reconstruct small to moderate skull base defects (i.e., <1 cm) and for low-flow CSF leaks. Fascia lata or collagen matrix is used as a subdural or epidural inlay graft, as the first layer of closure. A subsequent layer of onlay graft is then bolstered with free fat graft, harvested from the abdomen, or a free fascial graft. These layers are finally supported with non-absorbable gelatin sponge or the balloon of a Foley catheter.
Recent systematic reviews have shown conclusive evidence that endoscopic pituitary surgeries are safer in comparison with established complication rates of microsurgical approaches (transcranial or sublabial), though there is no difference in the efficacy between these approaches.
Complications can occur at every stage of operation, though they are infrequent. Complications that may occur during the nasal stage of the approach are orbital injury, saddle nose deformity, anosmia, cribriform plate injury with CSF leak, and bleeding from injury to sphenopalatine artery and its branches. Complications arising in the sphenoid sinus are sinusitis, injury to the carotid artery or optic nerve, and mucoceles. Complications encountered during tumor removal include CSF leak, diabetes insipidus, hypopituitarism, meningitis, postoperative hematoma, injury to the carotid artery or optic nerve, vasospasm, ophthalmoplegia, subarachnoid hemorrhage, and tension pneumocephalus.
Immediate postoperative complications
The most common complications are CSF leak, sinusitis, and meningitis. CSF leaks, occurring in 6 in every 100 cases, is usually prevented by a multilayer closure at the end of surgery. In the occurrence of a leak in the postoperative period, the patient is advised bed rest, and a lumbar drain is placed. If the leak does not improve in 24 hours, exploration and closure of the defect are to be done. Worsening of vision as a result of bleeding or manipulation and arterial hemorrhage are other immediate complications. A detailed study of preoperative imaging is essential to avoid catastrophes like optic nerve and carotid artery injury. The presence of anatomical variations such as sphenoethmoidal cell or Onodi cell places the optic nerve at risk. Suspected injury to the optic nerve would entail a full gamut of measures, from observation, intravenous high dose steroids to optic nerve decompression, depending on the degree of suspicion, time since the injury, and loss/ progressive deterioration of vision. Attachment of inter sinus septa laterally onto the carotid artery wall or the medial location of the carotid artery needs to be carefully identified. Carotid artery injury is undoubtedly the most challenging surgical field in endoscopic endonasal surgery. The control of such arterial bleeding can be achieved using muscle patches or direct vascular repair using endovascular clamps and clip appliers. In situations where intraoperative hemostasis could not be achieved, immediate transfer for endovascular interventions such as stenting, balloon occlusion or coiling, is critical.
Long term complications
Nasal congestion and mild nasal bleeding are anticipated in the immediate first 1 to 2 weeks after surgery. Other anticipated complications include pain over the nasomaxillary region, nasal crusting, mucosal scarring, periorbital edema, and numbness of the upper incisors. These complications, though transient, are more common in the sublabial approach in comparison to transnasal approaches and arise due to the extensive dissection involved and injury to the infraorbital nerve and its branches. The presence of nasal splints or packs often compounds the postoperative morbidity. Mucosal damage can impair ciliary function and lead to sinusitis. Some patients also report hyposmia. Long term complications include nasal synechiae (treated with radiofrequency ablation, nasal isolation, corticosteroids, and nasal irrigation) and septal perforation, which may warrant endoscopic repair operation using mucoperiosteal pedicle flap of the floor of the nasal cavity if the patient is symptomatic. Atrophic rhinitis may need regular nasal endoscopic cavity cleaning, soothing nasal drops, and nasal irrigation.
The most common endocrine complication in the early postoperative period is abnormalities of antidiuretic hormone (ADH) secretion, which includes diabetes insipidus (DI) and inappropriate secretion of antidiuretic hormone (SIADH). DI is the most common endocrine complication after sellar surgery, with the postoperative incidence of DI ranging between 5% and 35%. Postoperative DI is often characterized by a triphasic response: polyuria and polydipsia occurring in the first 48 hours and last a few days. Following this, a period of antidiuresis and hyponatremia develops, commonly after 1 week of surgery. This is followed by the polyuric phase, ending in permanent DI. In most cases, DI resolves spontaneously without any specific therapy within 24 hours. Lesions located in the pituitary stalk or above the median eminence are prone for permanent DI. Mild DI, with urine output less than 4 to 6 liters/day and serum sodium less than 150 MEq/L, is managed conservatively. Initial management includes oral fluid replacement. However, in the event of unresolved DI, therapy is stepped up, ranging from fluid replacement with 5% dextrose to the administration of synthetic ADH analog, desmopressin. Intranasal desmopressin is the drug of choice for chronic cases of DI.
SIADH is the most common cause of hyponatremia after pituitary surgery and occurs in 9% to 30 % of patients undergoing transsphenoidal approach. Most patients with SIADH are asymptomatic, and are diagnosis is detected on the serum electrolyte panel done on postoperative day 7. Postoperative SIADH is treated based on the degree of hyponatremia, presence of symptoms, and comorbid conditions. Fluid restriction and, occasionally, salt administration are the mainstay of therapy. Most patients can be managed on an outpatient basis with serial sodium and fluid output monitoring. Correction of sodium levels may take up to 5 days. Symptomatic patients are hospitalized and managed with intravenous 3% saline. Hyponatremia is the most frequent cause of unplanned readmission after pituitary surgery, due to SIADH, usually presenting after postoperative day 5.
Acute management of postoperative hypopituitarism involves adequate glucocorticoid replenishment with fluid and electrolyte replacement. The doses of glucocorticoid are tailored in the perioperative period according to the preoperative hormone levels and stress levels and subsequently tapered to preoperative doses. The key principle is to provide adequate glucocorticoid coverage before and 24 hours after surgery.
In the immediate postoperative period, patients are monitored in an intensive care unit with monitoring for neurological deterioration, epistaxis, visual dysfunction, diabetes insipidus (DI), and hypotension secondary to acute hypocortisolism. Desmopressin and/or steroid replacement need to be continued postoperatively if the patient was already on it, along with strict electrolyte surveillance. If the preoperative pituitary function was normal, serum cortisol and prolactin levels are measured on the morning after the procedure. In the case of a secretory tumor, nonstimulatory hormone levels (cortisol, prolactin, or GH) are obtained on postoperative days 1 and 2. Serum sodium and urine output are serially monitored for the next 48 hours. If the cortisol levels are low, then steroid replacement is initiated. If new onset DI is suspected, oral fluid management with water may suffice if the patient is awake and stable. If desmopressin is started, then it requires close monitoring by an endocrinologist. Usually, patients are discharged by postoperative day 2 or 3.
The need for nasal packs is dependent on the type of reconstructive technique and the surgeon's choice (used only in a minority of cases). The nasal pack is removed on postoperative day 1. Septal splints are warranted in traditional sublabial-transeptal-transsphenoidal approaches and removed on postoperative day 5 to 7. The first follow up visit is 1 week after the procedure, where postoperative day 7 serum sodium levels are reviewed to rule out occult hyponatremia. Serial nasal endoscopies are done for debridement and to assess healing. The frequency of follow-up visits is determined by nasal crusting and maintenance of nasal hygiene with irrigation. Routine early postoperative imaging is not done in most patients. The majority of patients undergo MRI after three months of the procedure.
Transsphenoidal hypophysectomy is an effective surgical technique for the removal of pituitary and other intrasellar tumors with minimal morbidity and hospital stay. In addition to improvement in endocrine function (if deranged), it also reverses the pressure effects on the pituitary gland and adjacent structures such as optic nerves.
Pituitary tumors are complex disease processes with serious implications on multiple endocrine systems as well as vision. Optimal management of such tumors warrants an interprofessional approach, with the involvement of endocrinologists, ophthalmologists, neurosurgeons, and otolaryngologists.
These tumors are often incidentally detected on imaging studies by radiologists and referred to neurosurgeons for surgical management. Nonfunctioning tumors are monitored with serial imaging, to identify an increase in the size of tumor or complications associated with it. Functioning tumors, such as a prolactinoma, requires rigorous medical management by an endocrinologist. Tumors refractory to medical management are referred to the neurosurgeons.
Ophthalmologists play a vital role in the early recognition of visual abnormalities in the pre- and postoperative period.
Surgical management involves a team, including a neurosurgeon and an otolaryngologist, neuro anesthetists as well as nurses specialized in such complex cases. Otolaryngologist provides access to the tumor via the nasal cavities, and neurosurgeon performs the resection of the tumor. Postoperative management is crucial, with close coordination between critical care specialists, nurses, and endocrinologists required. Hence for improved patient care, expert interprofessional team performance is vital. [Level 5]
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