Pituitary macroadenomas can generally be divided into non-functional tumors and functional tumors with consequent hypersecretion syndromes and endocrinopathies. Irrespective of the tumor’s secretory activity, macroadenomas can create regional mass effect by virtue of their size. Mass effect exerted within the sella can lead to pituitary gland dysfunction while vertical extension into the suprasellar cistern can compress the optic apparatus.

Tumors can also extend horizontally with invasion into the cavernous sinus making complete resection less likely. While lateral extension into the cavernous sinus can make resection difficult and may not always be indicated, suprasellar components must be removed to relieve the optic chiasm compression. Outcome from surgical removal and likelihood of recurrence is directly proportional to the degree of resection. The impact of the degree of resection is especially important in the case of functional tumors since hypersecretion syndrome and endocrinopathy can persist when a small residual focus of tumor is left behind.

Traditional surgical approaches to pituitary tumors have relied on microseptal transphenoidal access to the sella. Larger tumors often required a craniotomy for optimal removal and decompression. The advent of the endoscopic endonasal approach has provided for superior visualization of both the sellar and suprasellar component of these tumors. This approach avoids anterior transeptal dissection associated with traditional approaches, thus, minimizing patient discomfort and postoperative pain. Furthermore, the endoscopic technique by virtue of angled lenses allows for inspection of all components of the regional anatomy and removal of tumor under direct visualization. Opening of the diaphragma sella is possible thus allowing for decompression of the optic apparatus under direct visualization.

At UPMC Presbyterian, the endoscopic approach, when combined with image guidance neuronavigation technology has obviated the need for craniotomy even in exceptionally large tumors. This approach allows for less traumatic access into the cavernous sinus for further tumor removal. The availability of Gamma Knife radiosurgery particularly for functional tumors invading the cavernous sinus has made such cavernous sinus exploration less necessary.

In this review, we examined our experience with the endoscopic endonasal approach used for the resection of pituitary macroadenomas. A retrospective review of 64 macroadenomas was undertaken. This consisted of review of the pre and postoperative MRI images and measurements of the tumor in three dimensions for volumetric analysis by a neuroradiologist. Optic nerve function was assessed in terms of visual fields, visual acuity and color saturation. Tumors were divided into functional and non-functional categories.

There were approximately twice as many patients with non-functioning tumors (n=46) as there were with functioning tumors (n=18). The most common presenting features were visual compromise (64%), pituitary hypersecretion syndromes (37.5%) and pituitary insufficiency (31%). Patients with endocrinopathy presented at an earlier age (41.2 years-old. ± 13.1 years) than did those without non-functioning tumors (59.9 years-old ± 10.9 years). This is not surprising as the former developed symptoms from excessive hormone secretion, rather than, the insidious onsetof visual compromise, which is easier to accommodate to.

Degree of Resection

Thirty patients had adequate imaging available. Endocrine active tumors presented at a smaller size (median = 4.5ml) than non-functional tumors (9.15ml). The degree of resection is more complete in the case of functional tumors. This can be explained by two facts: (1) there is a greater need to be aggressive with functional tumors in order to resolve the endocrinopathy, whereas for non-functional tumors the primary goal is adequate optic decompression; (2) non-functioning tumors are generally larger at presentation often with lateral extension into the cavernous sinus, removal of which may not be indicated if adequate optic decompression has already been achieved.

Visual Function

Visual function was assessed by considering pre and postoperative visual fields, acuity and color saturation. Preoperative visual function was categorized as normal or impaired. Postoperative function was categorized as improved, stable or deteriorated. Forty-seven of the 64 patients had adequate data for review. Overall 35/47 patients (74%) presented with impaired visual function of which 31(89%) recovered visual function. The four patients with impaired visual function that did not improve maintained their preoperative status. All four of these patients had longstanding compromise associated with optic atrophy. No patient experienced a deterioration in visual function following surgery. There were five patients that presented with opthalmopalegia (4 with III nerve palsy, 1 with VI nerve palsy). All five patients recovered completely.

Neuroendocrine Outcomes

Each hormonal axis was examined individually to assess anterior pituitary gland function. Within the non-functioning group two patients did not have adequate data for review. Of the remaining 44 patients, three (6.8%) developed a new anterior gland insufficiency (one adrenal, one adrenal and thyroid, and one panhypopituitarism). The Functional group was expanded in this analysis to include an additional five hormonally active microadenomas along with the eighteen macroadenomas. Two patients (8.6%) with functional tumors developed a new anterior gland hormonal axis dysfunction (one thyroid and the other thyroid and adrenal) while 12% of the entire group recovered pituitary function following surgery likely from relief of mass effect.

The incidence of Diabetes Insipidus in the entire series including the giant and invasive tumors was 7% transient and 5% permanent. All cases of endoncrinopathy and hypersecretion were resolved with either endoscopic surgery alone or the addition of radiosurgery for the cavernous component.

Aggressive decompression and resection of pituitary macro-adenomas is an important goal. The endoscopic approach enables radical resection of these tumors with direct visualization of the optic apparatus and confirmation of decompression. Eighty-nine percent of patients enjoyed a recovery of visual function while the rest remained stable. The degree of resection is even more paramount in the case of functional tumors as the indication for surgery is not only optic decompression but also resolution of endocrinopathy. All cases of endocrinopathy were resolved even with cavernous sinus extension when adjuvant Gamma Knife radiosurgery was added to the treatment.

We suggest that the endonasal endoscopic approach is a safe and effective means of removal of even very large tumors with 95.6% and 93.6% median volume reduction for functional and non-functional tumors respectively. This is done without the need for craniotomy even in the case of very large and invasive tumors. Not only is this minimally invasive approach more effective, but it is also better tolerated by patients in comparison to the more traditional approaches.

Case Illustration

In the case of 50 year-old male with an invasive prolactinoma (figure 1 below), despite six months of dopamine agonist therapy the patient continued to have profoundly elevated and climbing prolactin levels. While the initial bromocriptine therapy resulted in some improvement of visual function, persistent severe deficits were noted.

A decision was made to undertake surgical debulking with the goal of cytoreductive surgery (complete decompression of the optic apparatus and removal of the suprasellar portion). Removal of the intrasellar content and the component that has eroded the upper and middle third of the clivus was achieved (figures 2 and 3 below). The patient did not have pre-operative ophthalmoplegia, and therefore, an upfront decision was made to leave the tumor within the cavernous sinus to be treated with postoperative Gamma Knife radiosurgery. With this combination therapy, the patient completely recovered the preoperative visual loss and retained normal pituitary function.

Figure 1. Preop image of an invasive prolactinoma that has failed medical management. Note the significant suprasellar extension with complete distortion and profound compression of the optic apparatus. Erosion of adjacent bony structures is visible. Anteriorly the planum sphenoidale has been destroyed. Posteriorly the upper and middle third of the clivus have been eroded with the tumor encroaching on the basilar artery with a rim of dura intervening. Figure 2 and 3. Postoperative image of the same case. Note the complete removal of the vertical extent of the tumor. The suprasellar portion and anterior portion eroding the planum has been completely resected. The optic apparatus and infundibulum can now be seen. The posterior portion eroding the clivus has been removed and normal CSF space in the prepontine cistern has returned. There is some postoperative packing in the sphenoid sinus that was used to achieve hemostasis that can be seen. On the coronal image note the relatively small residual component left within the cavernous sinus representing the lateral extension of the tumor. Postoperatively the patient retained preoperative level of normal pituitary function while the prolactin level normalized and a complete recovery of visual function was achieved.