Headache in Patients With Pituitary Lesions

Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning pituitary adenoma

Neurosurgery 78:316–323, 2016

Headache is a presenting feature in 37% to 70% of patients with pituitary tumor. Other pituitary lesions may also present with headache, and together these lesions account for about 20% of all primary brain lesions. Although pituitary lesions have been associated with headache, the exact nature of the relationship remains undefined. It is not always clear whether the presenting headache is an unrelated primary headache, a lesion-induced aggravation of a preexisting primary headache, or a separate secondary headache related to the lesion.

OBJECTIVE: To characterize headache in patients referred to a multidisciplinary neuroendocrine clinic with suspected pituitary lesions and to assess changes in headache in those who underwent surgery.

METHODS: We used a self-administered survey of headache characteristics completed by patients upon presentation and after any pituitary surgical procedure.

RESULTS: One hundred thirty-three participants completed the preoperative questionnaire (response rate of 99%). The overall prevalence of headache was 63%. Compared to patients without headache, the group with headache was more likely to be female (P = .001), younger (P = .001), and to have had a prior headache diagnosis (P < .001). Seventy-two percent of patients reported headache localized to the anterior region of the head. Fifty-one patients with headache underwent transsphenoidal pituitary surgery. Headache was not associated with increased odds of having surgery (odds ratio, 0.90). At 3 months, 81% of surgically treated patients with headache who completed the postoperative questionnaire (21/26) reported improvement or resolution of headaches. No patient who completed the postoperative questionnaire (44/84) reported new or worsened headache.

CONCLUSION: Frequent, disabling headaches are common in patients with pituitary lesions referred for neuroendocrine consultation, especially in younger females with a preexisting headache disorder. Surgery in this group was associated with headache improvement or resolution in the majority and was not found to cause or worsen headaches. Suggestions for revision of the International Classification of Headache Disorders diagnostic criteria pertaining to pituitary disorders are supported by these findings.

Outcome of Transsphenoidal Surgery for Cushing Disease

Cushing's disease

Neurosurgery 78:216–223, 2016

Transsphenoidal surgery is the standard approach for treating Cushing disease. Evidence is needed to document effectiveness.

OBJECTIVE: To analyze results of transsphenoidal surgery in 276 consecutive patients, including 19 children.

METHODS: Medical records were reviewed for patients treated initially with surgery for Cushing disease from 1980 to 2012. Radiographic features, pathology, remissions, recurrences, and complications were recorded. Patients were categorized for statistical analysis based on tumor size (microadenomas, macroadenomas, and negative imaging) and remission type (type 1 = morning cortisol ≤3 mg/dL; type 2 = morning cortisol normal).

RESULTS: Females comprised 78% of patients and were older than men. Imaging showed 50% microadenomas, 13% macroadenomas, and 37% negative for tumor. Remission rates for microadenomas, macroadenomas, and negative imaging were 89%, 66%, and 71%, respectively. Patients with microadenomas were more likely to have type 1 remission. Pathology showed adrenocorticotropic hormone-secreting adenomas in 82% of microadenomas, in 100% of macroadenomas, and in 43% of negative imaging. The incidence of hyperplasia was 8%. The finding of hyperplasia or no tumor on pathology predicted treatment failure. The recurrence rate was 17%, with an average time to recurrence of 4.0 years. Patients with type 1 remission had a lower rate of recurrence (13% type 1 vs 50% type 2) and a longer time to recurrence. Children had similar imaging findings, remission rates, and pathology. There were no operative deaths.

CONCLUSION: Transsphenoidal surgery provides a safe and effective treatment for Cushing disease. For both adults and children, the best outcomes occurred in patients with microadenomas and/or those with type 1 remission.

Long-term Results of Endonasal Endoscopic Transsphenoidal Resection of Nonfunctioning Pituitary Macroadenomas

Results non-functioning macroadenomas

Neurosurgery 76:42–53, 2015

Several studies report early results of endoscopic endonasal transsphenoidal surgery; however, none discuss long-term outcome measures such as tumor recurrence rates and the need for additional surgical procedures.

OBJECTIVE: To discuss the long-term outcomes after endoscopic endonasal transsphenoidal surgery for nonfunctioning pituitary macroadenomas.

METHODS: This is a retrospective study. Patients were included only if they had at least 5 years of clinical and imaging follow-up after surgery.

RESULTS: Eighty patients met the study criteria. Grossly complete resection was achieved in 71% of patients. Knosp grade 0 to 2 tumors and tumor with volumes ,10 cm3 were significantly more likely to have received a grossly complete resection. There were 7 recurrences (12%) in patients who had received grossly complete resections, with a mean time to recurrence of 53 months. Among the 23 patients who had subtotal resections, 11 (61%) progressed radiographically, and 3 (17%) had symptomatic progression. Knosp score, surgical and radiographic evidence of invasion, and preoperative visual deficits were predictive of recurrence in a univariate analysis, but Knosp grade was the only independent predictor in a multivariate analysis. Kaplan-Meier analysis projected a 10-year progression-free survival rate of 80% and 21% for patients with gross total resections and subtotal resections, respectively.

CONCLUSION: At the long-term follow-up, 12% of patients had recurrent tumors after grossly complete resection. Recurrent or residual tumors were treated with either repeat surgery or Gamma Knife radiosurgery. Rates of complete resection, postoperative surgical and endocrinological complications, and additional surgical procedures are similar to previously published reports after microscopic transsphenoidal surgery.

MicroRNAs as Biomarkers in Pituitary Tumors

MicroRNAs_as_Biomarkers_in_Pituitary_Tumors

Neurosurgery 75:181–189, 2014

The use of extracellular microRNAs (miRNAs) as circulating biomarkers is currently leading to relevant advances in the diagnosis and assessment of prognosis of several diseases.

Specific miRNAs have also been shown to play a role in the pathophysiology of many neoplastic and non-neoplastic diseases. A number of studies have demonstrated that miRNAs show differential expression in various tumors, such as in the prostate, ovary, lung, breast, brain, and pituitary.

Recent findings have built connections between miRNAs that are deregulated within the tumor and their presence in peripheral blood. MiRNAs have been shown to be stable in the blood where they are present in either free and/or uncomplexed form, as well as packed in microvesicles, exosomes, and apoptotic bodies, or bound to different proteins.

Because the pituitary is a highly vascularized organ that releases hormones into the circulation, miRNAs would be useful biomarkers for the diagnosis of pituitary tumors, as well as for predicting or detecting recurrence after surgery.

Here we review the biological significance of miRNAs in pituitary tumors and the potential value of circulating miRNAs as biomarkers.

Sphenoid sinus anatomy and suprasellar extension of pituitary tumors

Sphenoid sinus anatomy

J Neurosurg 119:669–674, 2013

As tumors enlarge, they generally grow along paths of least resistance. For pituitary macroadenomas, extrasellar extension into the suprasellar region, cavernous sinus, or sphenoid sinus may occur. The sphenoid sinus is known to have a variable anatomical configuration, and the authors hypothesize that certain anatomical factors may resist tumor expansion into the sphenoid sinus, thereby directing tumor growth into the suprasellar space. In this paper the authors’ goal was to determine if sphenoid anatomy influences pituitary tumor growth.

Methods. The authors conducted a retrospective analysis of 106 consecutive surgical cases of pituitary macroadenoma. Patient demographics, suprasellar extension, sellar width, and features of the sphenoid intersinus septum were recorded on radiographic review. The chi-square test, t-test, logistic regression, and classification and regression tree analysis were used for statistical analysis.

Results. Of the 106 patients included in the study, 71 (67%) demonstrated suprasellar extension of their tumor. Patients with suprasellar tumor extension had significantly greater intersinus septum width (width > 1.27 mm: OR = 14.32; p = 0.0012) and were significantly older (age > 54 yrs: OR = 3.33; p = 0.0176). They also tended to be male and to have two or more sphenoid partitions (OR = 6.58; p = 0.0306). While patients with suprasellar extension tended to be more likely to have a midline partition and a larger sellar width than their counterparts, these differences did not reach statistical significance.

Conclusions. Certain aspects of the sphenoid sinus anatomy may function to resist pituitary tumor growth into the sphenoid sinus. Progressive enlargement of pituitary macroadenomas may extend in a suprasellar direction, in part, as a consequence of the sphenoid sinus anatomy.

Intraoperative computed tomography registration and electromagnetic neuronavigation for transsphenoidal pituitary surgery: accuracy and time effectiveness

J Neurosurg 114:329–335, 2011. (DOI: 10.3171/2010.5.JNS091821)

The authors assessed the feasibility, anatomical accuracy, and cost effectiveness of frameless electromagnetic (EM) neuronavigation in conjunction with portable intraoperative CT (iCT) registration for transsphenoidal adenomectomy (TSA).

Methods. A prospective database was established for data obtained in 208 consecutive patients who underwent TSA in which the iCT/EM navigation technique was used. Data were compared with those acquired in a retrospective cohort of 65 consecutive patients in whom fluoroscope-assisted TSA had been performed by the same surgeon. All patients in both groups underwent transnasal removal of pituitary adenomas or neuroepithelial cysts, using identical surgical techniques with an operating microscope. In the iCT/EM technique–treated cases, a portable iCT scan was obtained immediately prior to surgery for registration to the EM navigation system, which did not require rigid head fixation. Preexisting (nonnavigation protocol) MR imaging studies were fused with the iCT scans to enable 3D navigation based on MR imaging data. The accuracy of the navigation system was determined in the first 50 iCT/EM cases by visual concordance of the navigation probe location to 5 preselected bony landmarks. For all patients in both cohorts, total operating room time, incision-to-closure time, and relative costs of imaging and surgical procedures were determined from hospital records.

Results. In every case, iCT registration was successful and preoperative MR images were fused to iCT scans without affecting navigation accuracy. There was 100% concordance between probe tip location and predetermined bony loci in the first 50 cases involving the iCT/EM technique. Total operating room time was significantly less in the iCT/EM cases (mean 108.9 ± 24.3 minutes [208 patients]) compared with the fluoroscopy group (mean 121.1 ± 30.7 minutes [65 patients]; p < 0.001). Similarly, incision-to-closure time was significantly less for the iCT/EM cases (mean 61.3 ± 18.2 minutes) than for the fluoroscopy cases (mean 71.75 ± 19.0 minutes; p < 0.001). Relative overall costs for iCT/EM technique and intraoperative C-arm fluoroscopy were comparable; increased costs for navigation equipment were offset by savings in operating room costs for shorter procedures.

Conclusions. The use of iCT/MR imaging–guided neuronavigation for transsphenoidal surgery is a time-effective, cost-efficient, safe, and technically beneficial technique.

Intrasellar Ultrasound in Transsphenoidal Surgery: A Novel Technique

Neurosurgery 66:173-186, 2010. doi: 10.1227/01.NEU.0000360571.11582.4F

OBJECTIVE: Residual tumor masses are common after transsphenoidal surgery. The risk of a residual mass increases with tumor size and parasellar or suprasellar growth. Transsphenoidal surgery is usually performed without image guidance. We aimed to investigate a new technical solution developed for intraoperative ultrasound imaging during transsphenoidal surgery, with respect to potential clinical use and the ability to identify neuroanatomy and tumor.

METHODS: In 9 patients with pituitary macroadenomas, intrasphenoidal and intrasellar ultrasound was assessed during transsphenoidal operations. Ultrasound B-mode, power-Doppler and color-Doppler images were acquired using a small prototype linear array, side-looking probe. The long probe tip measures only 3 × 4 mm. We present images and discuss the potential of intrasphenoidal and intrasellar and ultrasound in transsphenoidal surgery.

RESULTS: We present 2-dimensional, high-resolution ultrasound images. A small side-looking, high-frequency ultrasound probe can be used to ensure orientation in the midline for the surgical approach to identify important neurovascular structures to be avoided during surgery and for resection control and identification of normal pituitary tissue. The image resolution is far better than what can be achieved with current clinical magnetic resonance imaging technology.

CONCLUSION: We believe that the concept of intrasellar ultrasound can be further developed to become a flexible and useful tool in transsphenoidal surgery.