Management of large pituitary adenomas by transsphenoidal surgery

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Management of Large Pituitary Adenomas by Transsphenoidal Surgery Peter McL. Black, M.D., Ph.D., Nicholas T. Zervas, M.D., and Guillermo Candia, M.D. Neurosurgical Services, Brigham and Women's Hospital and the Massachusetts General Hospital, and Department of Surgery, Harvard Medical School, Boston, Massachusetts

Black PMcL, Zervas NT, Candia G. Management of large pituitary adenomas by transsphenoidal surgery. Surg Neurol 1988;29: 443-7. We evaluated the ability of transsphenoidal surgery to produce visual improvement, endocrine remission, and complete tumor removal in 113 patients with pituitary adenomas extending beyond the sella turcica. Eighty-one percent of patients with preoperative visual field defects had postoperative improvement, 19% had no change, and none deteriorated significantly. Seventy-nine percent of patients with diminished preoperative visual acuity had postoperative improvement; none deteriorated. Endocrine remission of functioning tumors was achieved in 43% of patients and complete resection by computed tomography scanning was also obtained in 43%. There were no deaths in this series and the major complication was cerebrospinal fluid leak, which occurred in 3% of patients, Comparison with transfrontal surgery suggests that these results are as good as those with transfrontal procedures and that the incidence of serious side effects is considerably lower. Transsphenoidal surgery is safe and effective in the surgical management o f large pituitary adenomas. KEY WORDS: Pituitary adenomas; Transsphenoidal surgery

Transsphenoidal surgery is now recognized as the optimum technique for resecting pituitary adenomas within the sella turcica [8,11,17,23,25,26]. At many centers, however, pituitary tumors with extrasellar extension and visual compromise are considered indications for a transfrontal approach [5,21,22]. T h e experience at the Massachusetts General Hospital with these lesions over the last 5 years suggests that transsphenoidal surgery is the safest and most effective technique for large as well as small pituitary adenomas.

Address reprint requests to: Peter McL, Black, M.D., Ph.D., Neurosurgeon-in-Chief, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115. Received September 14, 1987; accepted November 23, 1987.

© 1988by ElsevierSciencePublishingCo., Inc.

Materials and Methods Two hundred fifty-five consecutive patients with pituitary tumors undergoing surgery from j u n e 1981 to January 1984 at the Massachusetts General Hospital were classified by preoperative computed tomography (CT) scanning as having microadenomas, macroadenomas within the sella, or macroadenomas with extrasellar extension. One hundred thirteen consecutive tumors with extrasellar extension were chosen for this report. They were analyzed as to the following criteria: clinical and radiographic presentation; surgical technique, findings, and complications; pre- and postoperative endocrine results; and CT scan and neuroophthalmologic outcome within the first month after surgery. Preoperative hormone testing routinely included prolactin, thyroxine (T4), fasting blood sugar, human growth hormone, 8 a.m. cortisol, and 24-hour urinary corticosteroids. In many patients, there was also measurement o f plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Preoperative radiologic evaluation included CT scanning with contrast enhancement and either direct coronal sections or multiplanar reconstruction. On the basis o f CT scan findings, tumors were classified as having suprasellar, parasellar, retrosellar, or sphenoid extension. If the tumor was clinically "nor~functioning" and atypical of adenoma in configuration, digital subtraction angiography was done to establish that it was not an aneurysm and to delineate the vasculature around it. In a few cases metrizamide cisternography was used to establish the borders o f the tumor, but this was done less frequently as CT scanning resolution improved. Within 1 month o f surgery, CT scanning was used to evaluate residual tumor. Visual evaluation was carried out hy a neuroophthalmologist, including evaluation of fundi, visual acuity, extraocular movements, pupiUary function, and visual field testing with a Goldmann perimeter. Postoperative field testing was done within 1 month of the surgery in 56 patients with preoperative deficitS. Surgery was done with C-arm fluoroscopic monitoring and the Zeiss OP-Mi-1 microscope with the pa0090-3019/88/$3.50

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tient's head elevated at 30 °. Either a sublabial incision or a left septal approach was used, depending upon tumor configuration and the size of the nostril. Curettes and suction were used for all procedures: in four cases the carbon dioxide laser was necessary to vaporize a tumor too firm to curette. Postoperative cerebrospinal fluid (CSF) leaks occurred in two early cases even though no CSF had been seen at surgery. These occurred when the sella had been left unpacked and led to routinely packing the sella with fat usually buttressed by bone across the sella opening. If a significant CSF leak was seen at surgery, both the sella turcica and the sphenoid sinus were packed, the latter with oxycel cotton as well as fat. The general principles of surgery were to open the sella as widely as possible and to resect tumor until the diaphragm sella could be seen prolapsed into the field, and to be willing to risk a potential CSF leak to achieve this goal. Postoperatively, patients with prolactinomas had bromocriptine therapy if a CT scan showed significant residual tumor or if the prolactin level was over 30 ng/mL. Patients with other tumors had conventional radiation therapy delivered at a rate of 180 rads/day to a total of 4000 rads to the sella; this was begun after the 1-month follow-up period included in this report. This series, therefore, represents the effect of surgery alone on tumor size and clinical manifestations. Results Of the 255 tumors in the entire series, 40.4% were microadenomas and 15.2% were macroadenomas within the sella; 113, or 44.3%, were tumors with extrasellar extension. These tumors had to have more than one-quarter of tumor mass outside the sellar to be included. Extrasellar tumors occurred equally in males (48.7%) and females (51.3%). Ages ranged from 11 to 82 years, with mean age of 45.2 -+ 1.6 years (mean -+ SEM) and median 44 years. Five patients were over age 70 and five were under age 20.

T a b l e 2. Pattern of Extension in 113 Pituitary Tumors

Growing Out of the Sdla Turcica Pattern of extension

Number

Percent

Suprasellar only Suprasellar and parasellar Suprasellar, parasellar, retrosellar Suprasellar and sphenoidal Suprasellar, parasellar, sphenoidal Suprasellar, retrosellar, sphenoidal Suprasellar, ethmoidal, sphenoidal Sphenoidal only

83 7 1 13 2 3 1 3

73 6 1 12 2 3 1 3

The majority of these tumors (61%) produced no known hormone product; men and women were represented equally in these tumors. Twenty-four (21.7 %) of the 113 extrasellar tumors were prolactinomas; the male/female ratio was 1 : 3 for prolactinomas with extrasellar extension as opposed to 1 : 50 for intrasellar prolactinomas. Twelve extrasellar tumors produced growth hormone; the male/female ratio was 3 : 11 for these, the same as that in growth hormone-producing microadenomas (4 : 11). Seven extrasellar tumors (6.2%) produced adenocorticotropic hormone (ACTH); their male/female ratio was 1 : 7, as opposed to 3 : 11 for microadenomas. One male with an extrasellar tumor produced the alpha subunit of the glycoprotein hormones and a second produced luteinizing hormone.

Pattern of Extension ExtraseUar extension was found in 24% of all prolactinomas in the series of 255 tumors, 32% of growth hormone-producing adenomas, and 18% of ACTHproducing adenomas. Table 2 presents the patterns of extension in these tumors. Suprasellar extension alone was the most common pattern, occurring in 73% of cases. Twenty-five percent of tumors had extension into suprasellar and other compartments.

Preoperative Visual Findings

Hormone Production Table 1 represents the results of clinical hormone testing in patients whose tumors had extrasellar extension. T a b l e 1. Tumor Type in 113 Patients with Extrasellar

Extension of a Pituitary Adenoma Type

Incidence (%)

"Nonfunctioning" Prolactinoma Growth hormone-producing Adrenocorticotropic hormone-producing Alpha subunit-producing Luteinizing hormone-producing

61.0 21.7 9.7 6.2 0.9 0.9

Seventy-three of 113 patients (65%) with extrasellar extension had visual field defects on examination. Seventy-nine percent of nonfunctioning tumors with extra° sellar extension had field defects, 50% of prolactinomas, 18% of growth hormone-secreting adenomas, and 14% of ACTH-producing tumors. The visual findings are presented in Table 3: bitemporal field loss was the most common pattern.

Complications of Surgery There were no operative deaths within 1 month of surgery in the entire series of 255 patients with pituitary

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Table 3. Pattern of Visual Deficit in Patients with Extrasellar Extension of Pituitary Adenoma Deficit

Pattern

Incidence (%)

Bitemporal field loss

~Hemianopia ~-Quadrantanopia ~Unilateral temporal loss *-Homonymous hemianopia

64 11 15 3 4

Other field defects Eye movement weakness

adenomas. In 113 patients with extrasellar extension, three patients had CSF leaks; in two of them the leaks sealed spontaneously with 5 days of continuous lumbar drainage. One patient required reoperation and packing of the sella and sphenoid sinus. One other patient had postoperative deterioration from an intrasellar hematoma which was evacuated transsphenoidally with no sequelae. One patient had meningitis responding promptly to antibiotics, but later developed diabetes insipidus requiring long-term therapy of desmopressin acetate (dd AVP). Sinusitis occurred in one patient, again resolving with antibiotics.

A

Results on Computed Tomography Scanning Computed tomography scans were taken within 1 week of surgery in 63 patients. Although residual tissue was seen in 57% of these scans, it was not always clear whether it was tumor or normal pituitary gland seen at surgery and preserved. Figure 1 presents a typical scan taken pre- and postoperatively in a patient with suprasellar and parasellar extension; there is very satisfactory resection of both components.

Endocrine Results Endocrine improvement was found in all patients, but cure by present standards occurred in fewer than half. For prolactinomas with the initial prolactin over 200 ng/mL, 42.3% had prolactin levels less than 20 ng/mL postoperatively. For acromegaly, a growth hormone less than 10 ng/mL was achieved in 43% of patients. There were too few cases of Cushing's disease with extrasellar extension to make meaningful statements about control of the disease. Eight patients required one or more hormone axis replacements after transsphenoidal surgery which were not required preoperatively. Four of these initially presented with pituitary apoplexy.

Visual Results Visual results I month after surgery are presented in Table 4. Seventy-nine percent of patients with formal

B

Figure 1. (A) Preoperative CT scan of a large uonfunctioning pituitary adenoma with both suprasellar and parasellar extension. (B) A postoperative scan demonstrating the efficacy of tumor remoOalby the transsphenoidal approach. Both parasellar and suprasellar components have been successfully removed. The low density in the sella is the fat pad graft. There is a small amount of residual tissue posteriorly which was i!lentified as normal pituitary at surgery and left the patient with normaEpituitary function.

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Table 4. Visual Results One Month after Transsphenoidal Surgery in Patients with PreoperativeVisual Impairment Results

Visual fields Improved Unchanged Worse Visual acuity Improved Unchanged Worse

larger. Four percent of patients presented with pituitary apoplexy.

Percent

81 19 0 79 21 0

pre- and postoperative testing of visual acuity had improvement after surgery; 21.4% had normal postoperative acuity. In 21.4%, acuity was unchanged by surgery. Thirty-three percent of patients with a visual field defect preoperatively had a normal examination postoperatively, 81% of patients were improved, and 19% were unchanged. O f those who were unchanged, 71% had optic atrophy on preoperative neuroophthalmologic testing. Extraocular movement palsies occurred in 4% of tumors with extrasellar extension; they resolyed in all cases within 1 month of surgery. Discussion S i n c e its recent revitalization, transsphenoidal surgery has become a powerful technique for removing pituitary lesions confined to the sella turcica [8,11,17,23,25,26]. It has not been clear, however, whether it is appropriate for tumors with extrasellar extension. Several recent reports suggest that it is appropriate for these as well as for intrasellar neoplasms [2,3,6,12,15,16]. The present study emphasizes the safety and efficacy of transsphenoidal surgery for pituitary tumors with major suprasellar extension. The authors believe that it is the procedure of choice for such lesions because of its low morbidity and mortality, efficacy in tumor removal, and ability to produce visual improvement. Exceptions are those tumors clearly unresectable through the seUa, which in our experience as well as that of others [26] comprise about 1% of all pituitary tumors.

Clinical Presentation of Pituitary Adenomas with Extrasellar Extension Most pituitary adenomas with extrasellar extension come to medical attention because of visual loss; hypersecretion is a second presentation [10,12,13,24,28]. The male/female ratio for patients with acromegaly and Cushing's disease is the same in microadenomas as it is in adenomas with extrasellar extensions; for prolactinomas the ratio becomes more equalized as tumors get

Complications of Transfrontal vs. Transsphenoidal Surgery The transfrontal route has traditionally been used for the resection of large adenomas. Mortality has been 2 % - 4 % [4,9]. Frequent sequelae of the transfrontal approach include unilateral or bilateral anosmia, with total anosmia in 30% of the series of Ray and Patterson [18] and panhypopituitarism in virtually all cases from section of the pituitary stalk [ 1,5,7,17,18,19,27 ]. These are debilitating but expected outcomes. The risk of seizure disorder is thought to be 3 % - 4 % [17]. In about 3% of cases CSF leak occurs [21]. Long-term diabetes insipidus occurs in 12% of patients and transient diabetes insipidus in 21% [27]. Disturbances of consciousness lasting 1-3 weeks occurred in 9% of cases in one recent microsurgical series [14]. A definite incidence of visual worsening occurs in most series of transfrontal resections, although Symon and Jakubowski reported no cases of postoperative visual deterioration in 101 cases [21]. The rate of worsened postoperative vision in other series ranges from 2% to 7.5% [5,18,20,27]. Transsphenoidal surgery has significantly lower morbidity and mortality than transfrontal surgery. There were no deaths in the present series or those of Cohen [3] and Ciric [2] and their colleagues. Three percent of our patients had CSF leak; the reported incidence varies from 0.% to 4% [2,3,16,26]. No patient had long-term visual deterioration in the present series, nor in that of Ciric et al [2].

Operative Results in Transsphenoidal Surgery Morphologic Results. Ciric et al reported complete removal of adenoma morphologically in 41% of patients [2]; this is very similar to the present series, with complete removal by CT scan in 43% of patients.

Endocrine Results. Endocrinologically, Zervas' survey suggested that about 30% of patients with macroadenomas were cured [29]. In the series of Ciric et al, 27% of patients with prolactin-secreting tumors and 20% of those with growth hormone-secreting macroadenomas were "cured" by contemporary criteria [2]. In the present series, a slightly larger percentage of tumors was put into endocrine remission, ranging from 42.3% to 43%. The authors believe, however, that cure is a concept that may be overly optimistic for this group; long-term follow-up after radiation therapy will be necessary to establish the true remission rate.

Transsphenoidal Surgery for Large Pituitary Adenomas

Visual Results. Using transfrontal surgical techniques, Ray and Patterson reported improvement of vision in 80% of patients and eventual return to normal in 50%; 2% of patients had worsened vision [18]. Nakane et al found 57.7% of patients improved and 4.8% worsened [14]; Bakay noted improvement in 40.7% and worsening in 26.2% [1]; Svien et al improvement in 63.4% and normalization in 21.2% of patients [20]. Symon and Jakubowski noted normalization at six months in 57% and improvement in another 37% [21]; this included the effect of radiation therapy as well, an effect which in the present series would be expected to improve the eventual visual result. Using transsphenoidal techniques in the present series, 81% of patients with pre- and postoperative visual field testing were improved shortly after surgery and none were made permanently worse; in 33% the vision was normalized. Acuity improved in 79%. These data are consistent with those from other authors: Cohen et al found an improvement in acuity or fields in 79% of patients [3], Pasztor et al in 75% [16], Ciric et al in 90% [2], Findlay et al in 85% [6], Nicola in 90% [15], and Nakane et al in 91% [14]. Our improvement was measured within a short period after surgery; continued improvement over the course of a year is found in many patients [21]. In the series of Ciric et al, recovery was usually rapid and did not depend on tumor size, direction of growth, invasion into surrounding structures, or tumor consistency [2]. Summary These data suggest that transsphenoidal surgery is at least as effective as transfrontal surgery for resection of large pituitary adenomas in terms of endocrine remission and visual improvement; it is associated with substantially fewer complications, including visual deterioration. Its use provides an effective technique for the management of large as well as small pituitary adenomas.

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