Aggressive pituitary neuroendocrine tumors: current practices, controversies, and perspectives, on behalf of the EANS skull base section

Acta Neurochirurgica (2021) 163:3131–3142

Aggressive pituitary neuroendocrine tumors (APT) account for 10% of pituitary tumors. Their management is a rapidly evolving field of clinical research and has led pituitary teams to shift toward a neuro-oncological-like approach.

The new terminology “Pituitary neuroendocrine tumors” (PitNet) that was recently proposed to replace “pituitary adenomas” reflects this change of paradigm. In this narrative review, we aim to provide a state of the art of actual knowledge, controversies, and recommendations in the management of APT.

We propose an overview of current prognostic markers, including the recent five-tiered clinicopathological classification. We further establish and discuss the following recommendations from a neurosurgical perspective: (i) surgery and multi-staged surgeries (without or with parasellar resection in symptomatic patients) should be discussed at each stage of the disease, because it may potentialize adjuvant medical therapies; (ii) temozolomide is effective in most patients, although 30% of patients are non-responders and the optimal timeline to initiate and interrupt this treatment remains questionable; (iii) some patients with selected clinicopathological profiles may benefit from an earlier local radiotherapy and/or chemotherapy; (iv) novel therapies such as VEGF-targeted therapies and anti-CTLA-4/anti-PD1 immunotherapies are promising and should be discussed as 2nd or 3rd line of treatment.

Finally, whether neurosurgeons have to operate on “pituitary adenomas” or “PitNets,” their role and expertise remain crucial at each stage of the disease, prompting our community to deal with evolving concepts and therapeutic resources.

Diabetes Insipidus After Endoscopic Transsphenoidal Surgery

Neurosurgery 2020 DOI:10.1093/neuros/nyaa148

Diabetes insipidus (DI) is a recognized transient or permanent complication following transsphenoidal surgery (TSS) for pituitary tumors.

OBJECTIVE: To describe significant experience with the incidence of DI after TSS, identifying predictive characteristics and describing our diagnosis and management of postoperative DI.

METHODS: A retrospective analysis was performed of 700 patients who underwent endoscopic TSS for resection of pituitary adenoma (PA), Rathke cleft cyst (RCC), or craniopharyngioma. Inclusion criteria included at least 1 wk of follow-up for diagnosis of postoperative DI. Permanent DI was defined as DI symptoms and/or need for desmopressinmore than 1 yr postoperatively. All patients with at least 1 yr of follow-up (n=345) were included in analyses of permanent DI. Multivariable logistic regression models were constructed to identify predictors of transient or permanent postoperative DI.

RESULTS: The overall rate of any postoperative DI was 14.7% (103/700). Permanent DI developed in 4.6% (16/345). The median follow-up was 10.7mo (range: 0.2-136.6). Compared to patients with PA, patients with RCC (odds ratio [OR] = 2.2, 95% CI: 1.2-3.9; P = .009) and craniopharyngioma (OR = 7.0, 95% CI: 2.9-16.9; P ≤ .001) were more likely to develop postoperative DI. Furthermore, patients with RCC (OR = 6.1, 95% CI: 1.8-20.6; P = .004) or craniopharyngioma (OR = 18.8, 95% CI: 4.9-72.6; P ≤ .001) were more likely to develop permanent DI compared to those with PA.

CONCLUSION: Although transient DI is a relatively common complication of endoscopic and microscopic TSS, permanent DI is much less frequent. The underlying pathology is an important predictor of both occurrence and permanency of postoperative DI.



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.

Comparison of outcomes between a less experienced surgeon using a fully endoscopic technique and a very experienced surgeon using a microscopic transsphenoidal technique for pituitary adenoma

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

J Neurosurg 124:596–604, 2016

The comparative efficacy of microscopic and fully endoscopic transsphenoidal surgery for pituitary adenomas has not been well studied despite the adoption of fully endoscopic surgery by many pituitary centers. The influence of surgeon experience has also not been examined in this setting. The authors therefore compared the extent of tumor resection (EOR) and the endocrine outcomes of 1 very experienced surgeon performing a microscopic transsphenoidal surgery technique with those of a less experienced surgeon using a fully endoscopic transsphenoidal surgery technique for resection of nonfunctioning pituitary adenomas in a concurrent series of patients.

Methods Post hoc analysis was conducted of a cohort of adult patients prospectively enrolled in a pituitary adenoma quality-of-life study between October 2011 and June 2014. Patients were followed up for 6 months after surgery. Patients were treated either by a less experienced surgeon (100 independent cases) who practices fully endoscopic surgery exclusively or by a very experienced surgeon (1800 independent cases) who practices microscopic surgery exclusively. Patient demographic characteristics, tumor characteristics, hypopituitarism, complications, and length of hospital stay were analyzed. Tumor volumes and EOR were determined by formal volumetric analysis involving manual segmentation of MR images performed before surgery and within 6 months after surgery. Logistic regression analysis was used to determine predictors of EOR.

Results Fifty-five patients underwent fully endoscopic transsphenoidal surgery, and 80 patients underwent fully microscopic transsphenoidal surgery. The baseline characteristics of the 2 treatment groups were well matched. EOR was similar between the endoscopic and microscopic groups, respectively, as estimated by gross-total resection rate (78.2% vs 81.3%, p = 0.67), percentage of tumor resected (99.2% vs 98.7%, p = 0.42), and volume of residual tumor (0.12 cm3 vs 0.20 cm3, p = 0.41). Multivariate modeling suggested that preoperative tumor volume was the most important predictor of EOR (p = 0.001). No difference was found in the development of anterior gland dysfunction (p > 0.14), but there was a higher incidence of permanent posterior gland dysfunction in the microscopic group (p = 0.04). Combined rates of major complications and unplanned readmissions were lower in the endoscopic group (p = 0.02), but individual complications were not significantly different.

Conclusions A less experienced surgeon using a fully endoscopic technique was able to achieve outcomes similar to those of a very experienced surgeon using a microscopic technique in a cohort of patients with nonfunctioning tumors smaller than 60 cm3. The study raises the provocative notion that certain advantages afforded by the fully endoscopic technique may impact the learning curve in pituitary surgery for nonfunctioning adenomas.

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.

Morphometric analysis of the medial opticocarotid recess and its anatomical relations relevant to the transsphenoidal endoscopic endonasal approaches

Morphometric analysis of the medial opticocarotid recess

Acta Neurochir (2016) 158:319–324

The medial opticocarotid recess (MOCR) is located in the posterior wall of the sphenoid sinus, medial to the junction of the optic canal (OC) and the carotid prominence (CP). There is controversy in the literature in relation to the presence of the MOCR and its constancy, which is relevant when approaching the skull base through an endoscopic route.

Methods The morphometric relations of the MOCR with the surrounding structures were studied in 18 cadaveric specimens after endoscopic endonasal approach (EEA).

Results The distance between both MOCR was 11.06± 1.14 mm; the distance between the MOCR and the lateral opticocarotid (LOCR) recess was 5.56 ± 0.85 mm; the distance between the MOCR and the suprasellar recess was 3.72±0.49 mm; the angle between the MOCR plane and the OC 13.32±2.30°; the angle between the MOCR plane and the CP 13.50±2.68° and; the angle between the OC and the CP 26.81±4.26°. All measurements showed low variability, with low standard deviation and interquartile range. No relations were found between any of the measurements.

Conclusions The MOCR may be used as a reference point for precise location of structures during EEA. Objective measurements may be especially useful in cases with distorted sphenoid bone anatomy.

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

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

J Neurosurg 121:1166–1175, 2014

The loss of anatomical landmarks, frequently invasive tumor growth, and tissue changes make transsphenoidal reoperation of nonfunctioning pituitary adenomas (NFAs) challenging. The use of intraoperative MRI (iMRI) may lead to improved results. The goal of this retrospective study was to evaluate the impact of iMRI on transsphenoidal reoperations for NFA.

Methods. Between September 2002 and July 2012, 109 patients underwent reoperations in which 111 transsphenoidal procedures were performed and are represented in this study. A 1.5-T Magnetom Sonata Maestro Class scanner (Siemens) was used for iMRI. Follow-up iMRI scans were acquired if gross-total resection (GTR) was suspected or if no further removal seemed possible.

Results. Surgery was performed for tumor persistence and regrowth in 26 (23%) and 85 (77%) patients, respectively. On the initial iMRI scans, GTR was confirmed in 19 (17%) patients. Remnants were located as follows: 65 in the cavernous sinus (71%), 35 in the suprasellar space (38%), 9 in the retrosellar space (10%). Additional resection was possible in 62 (67%) patients, resulting in a significant volume reduction and increased GTR rate (49%). The GTR rates of invasive tumors on initial iMRI and postoperative MRI (poMRI) were 7% and 25%, respectively. Additional remnant resection was possible in 64% of the patients. Noninvasive tumors were shown to be totally resected on the initial iMRI in 31% of cases. After additional resection for 69% of the procedures, the GTR rate on poMRI was 75%. Transcranial surgery to resect tumor remnants was indicated in 5 (5%), and radiotherapy was performed in 29 (27%) patients. After GTR, no recurrence was detected during a mean follow-up of 2.2 ± 2.1 years.

Conclusions. The use of iMRI in transsphenoidal reoperations for NFA leads to significantly higher GTR rates. It thus prevents additional operations and reduces the number of tumor remnants. The complication rates do not exceed the incidences reported in the literature for primary transsphenoidal surgery. If complete tumor resection is not possible, iMRI guidance can facilitate tumor volume reduction.

Endoscopic endonasal treatment of 103 craniopharyngiomas

Endoscopic endonasal treatment of 103 craniopharyngiomas

J Neurosurg 121:100–113, 2014

Despite their benign histological appearance, craniopharyngiomas can be considered a challenge for the neurosurgeon and a possible source of poor prognosis for the patient. With the widespread use of the endoscope in endonasal surgery, this route has been proposed over the past decade as an alternative technique for the removal of craniopharyngiomas.

Methods. The authors retrospectively analyzed data from a series of 103 patients who underwent the endoscopic endonasal approach at two institutions (Division of Neurosurgery of the Università degli Studi di Napoli Federico II, Naples, Italy, and Division of Neurosurgery of the Bellaria Hospital, Bologna, Italy), between January 1997 and December 2012, for the removal of infra- and/or supradiaphragmatic craniopharyngiomas. Twenty-nine patients (28.2%) had previously been surgically treated.

Results. The authors achieved overall gross-total removal in 68.9% of the cases: 78.9% in purely infradiaphragmatic lesions and 66.3% in lesions involving the supradiaphragmatic space. Among lesions previously treated surgically, the gross-total removal rate was 62.1%. The overall improvement rate in visual disturbances was 74.7%, whereas worsening occurred in 2.5%. No new postoperative defect was noted. Worsening of the anterior pituitary function was reported in 46.2% of patients overall, and there were 38 new cases (48.1% of 79) of postoperative diabetes insipidus. The most common complication was postoperative CSF leakage; the overall rate was 14.6%, and it diminished to 4% in the last 25 procedures, thanks to improvement in reconstruction techniques. The mortality rate was 1.9%, with a mean follow-up duration of 48 months (range 3–246 months).

Conclusions. The endoscopic endonasal approach has become a valid surgical technique for the management of craniopharyngiomas. It provides an excellent corridor to infra- and supradiaphragmatic midline craniopharyngiomas, including the management of lesions extending into the third ventricle chamber. Even though indications for this approach are rigorously lesion based, the data in this study confirm its effectiveness in a large patient series.

Transsphenoidal surgical treatment of pituitary adenomas in patients aged 80 years or older

Pituitary adenomas patients aged 80

Neurosurg Rev (2014) 37:269–277

To know the clinical characteristics of pituitary adenomas in the elderly patients aged 80 years or older who were surgically treated.

From1995 through 2012, 907 patients underwent surgery for the pituitary adenomas at Kagoshima and Hiroshima University hospitals in Japan. Ten (1.1 %) patients were aged 80 years or older. We retrospectively assessed the clinical characteristics including preoperative comorbidities, manifestations, neuroimaging findings, and endocrinologic features of these ten patients.

The subjects included eight males and two females. Their ages ranged from 80 to 86 with mean of 83.1 years. Of these, besides one case of growth hormone-producing adenoma, others were clinically nonfunctioning adenoma. Six patients had modest comorbidities such as hypertension, cardiovascular diseases, diabetes mellitus, or chronic kidney dysfunction, and all patients were classified into grade 2–3 on American Society of Anesthesiologists’ Physical Status grading. Transsphenoidal surgery was performed in all due to visual disturbance in eight, diabetes mellitus as an intercurrent illness of acromegaly in one, and for the purpose of preventing visual disturbance in one patient who had an adenoma impinging optic chiasm but still had normal visual field. The surgeries provided sufficient decompression of the optic pathways and improved visual disorder in all. In an acromegalic male, his comorbidities considerably improved. No permanent surgical morbidity ensued. More than three axes of anterior pituitary hormones were preoperatively impaired in all, which were rarely recovered.

Transsphenoidal surgery is safe and efficient treatment way for patients aged 80 years or older with pituitary adenomas with chiasmatic symptoms when the patients’ general condition is well preserved and pituitary hormonal deficiency is adequately replaced.

Transsphenoidal cyst cisternostomy with a keyhole dural opening for sellar arachnoid cysts

sellar cysts

Neurosurg Rev (2014) 37:261–267

A less invasive transsphenoidal approach with a keyhole dural opening for intrasellar arachnoid cysts is described. This approach was used to address seven sellar cystic lesions with suprasellar extension; they were six intrasellar arachnoid cysts (IACs) and one Rathke’s cleft cyst (RCC).

In all cases, preoperative MRI revealed cerebrospinal fluid (CSF) intensity on both T1- and T2-weighted images. On preoperative contrast-enhanced MRI, five of the six IACs manifested posterior displacement of the flattened pituitary gland toward the dorsum sellae; one of the six IACs and the RCC exhibited a flattened pituitary gland on the anterior surface of the cyst.

Wide cyst cisternostomy through a keyhole dural opening was carried out safely using a microscope with the support of a thin angled endoscope (30° and/or 70°, diameter 2.7 mm). As we aimed to avoid iatrogenic injury of the pituitary function, we found it difficult to obtain a sufficiently wide and precise opening of the cyst wall when the pituitary gland was located on the anterior surface of the cyst wall.

Our approach facilitates safe cyst cisternostomy as wide as that obtainable by transcranial manipulation. In addition, CSF leakage is prevented by dural plasty using the fascia lata and stitching with 6-0 monofilament sutures. This technique can be adapted to address various sellar cystic lesions. However, as the posterior or anterior displacement of the normal pituitary gland in the presence of IACs or RCCs, respectively, affects the width of the cyst opening, our technique is more suitable for IACs than RCCs.

Superior cerebellar artery–posterior cerebral artery bypass

Superior cerebellar artery–posterior cerebral artery bypass

J Neurosurg 118:1053–1057, 2013

Iatrogenic pseudoaneurysms are rare but serious complications of transsphenoidal surgery, and an iatrogenic pseudoaneurysm of the posterior cerebral artery (PCA) has been reported just once in the literature.

The authors encountered such a case with a new P1 segment PCA pseudoaneurysm after endoscopic transsphenoidal resection of a pituitary adenoma. The aneurysm proved ideal for a novel intracranial–intracranial bypass in which the superior cerebellar artery (SCA) was used as an in situ donor artery to revascularize the recipient P2 segment. The bypass allowed aneurysm trapping without causing ischemic stroke or neurological morbidity.

This case represents the first reported surgical treatment of an iatrogenic PCA pseudoaneurysm. Endovascular occlusion with coils was an option, but dolichoectatic morphology requires sacrifice of the P1 segment, with associated risks to the thalamoperforators and circumflex perforators. The SCA-PCA bypass was ideal because of low-flow demands. Like other in situ bypasses, it requires no dissection of extracranial arteries, no second incision for harvesting interposition grafts, and has a high likelihood of long-term patency. The SCA-PCA bypass is also applicable to fusiform SCA aneurysms requiring revascularization with trapping.

This case demonstrates a dangerous complication that results from the limited view of the posterolateral surgical field through the endoscope and the imprecision of endoscopic instruments.

Endoscopic endonasal surgery for giant pituitary adenomas: advantages and limitations

Endoscopic endonasal surgery limitations

J Neurosurg / January 4, 2013. DOI: 10.3171/2012.11.JNS121190

Giant pituitary adenomas (> 4 cm in maximum diameter) represent a significant surgical challenge. Endoscopic endonasal surgery (EES) has recently been introduced as a treatment option for these tumors. The authors present the results of EES for giant adenomas and analyze the advantages and limitations of this technique.

Methods. The authors retrospectively reviewed the medical files and imaging studies of 54 patients with giant pituitary adenomas who underwent EES and studied the factors affecting surgical outcome.

Results. Preoperative visual impairment was present in 45 patients (83%) and partial or complete pituitary deficiency in 28 cases (52%), and 7 patients (13%) presented with apoplexy. Near-total resection (> 90%) was achieved in 36 patients (66.7%). Vision was improved or normalized in 36 cases (80%) and worsened in 2 cases due to apoplexy of residual tumor. Significant factors that limited the degree of resection were a multilobular configuration of the adenoma (p = 0.002) and extension to the middle fossa (p = 0.045). Cavernous sinus invasion, tumor size, and intraventricular or posterior fossa extension did not influence the surgical outcome. Complications included apoplexy of residual adenoma (3.7%), permanent diabetes insipidus (9.6%), new pituitary insufficiency (16.7%), and CSF leak (16.7%, which was reduced to 7.4% in recent years). Fourteen patients underwent radiation therapy after EES for residual mass or, in a later stage, for recurrence, and 10 with functional pituitary adenomas received medical treatment. During a mean follow-up of 37.9 months (range 1–114 months), 7 patients were reoperated on for tumor recurrence. Three patients were lost to follow-up.

Conclusions. Endoscopic endonasal surgery provides effective initial management of giant pituitary adenomas with favorable results compared with traditional microscopic transsphenoidal and transcranial approaches.

Pituitary Centers of Excellence

Neurosurgery 71:916–926, 2012

Pituitary tumors and associated neuroendocrine disorders pose significant challenges in diagnostic and therapeutic management. Optimal care of the “pituitary patient” is best provided in a multidisciplinary collaborative environment that includes not only experienced pituitary practitioners in neurosurgery and endocrinology, but also in otorhinolaryngological surgery, radiation oncology, medical oncology, neuro-ophthalmology, diagnostic and interventional neuroradiology, and neuropathology.

We provide the background and rationale for recognizing pituitary centers of excellence and suggest a voluntary verification process, similar to that used by the American College of Surgeons for Trauma Center verification. We propose that pituitary centers of excellence should fulfill 3 key missions: (1) provide comprehensive care and support to patients with pituitary disorders; (2) provide residency training, fellowship training, and/or continuing medical education in the management of pituitary and neuroendocrine disease; and (3) contribute to research in pituitary disorders.

As this is a preliminary proposal, we recognize several issues that warrant further consideration including center and surgeon practice volume as well as oversight of the verification process.

Results after treatment of craniopharyngiomas: further experiences with 73 patients since 1997

J Neurosurg 116:373–384, 2012. DOI: 10.3171/2011.6.JNS081451

The authors report surgical and endocrinological results of a series of 73 cases of craniopharyngioma that they treated surgically since 1997 to demonstrate their change in treatment strategy and its effect on outcome compared with a previous series and results reported in the literature.

Methods. A total of 73 patients underwent surgery for craniopharyngiomas between May 1997 and January 2005. In patients with poor clinical or neuropsychological condition, even following pretreatment, only stereotactic cyst aspiration took place (8 cases). In the remaining patients, gross-total resection (GTR) was intended and appeared to be possible. The most frequent approaches were subfrontal (27 cases) and transsphenoidal (26 cases); in some cases, a multistep approach was used. The rate of GTR, complications, and functional outcome (comparing pre- and postoperative endocrine and neuropsychological testing) were evaluated. The mean duration of follow-up was 25.2 months.

Results. Gross-total resection was achieved in 88.5% of cases in which a transsphenoidal approach was used and 79.5% of those in which a transcranial approach was used (85.2% of those in which a subfrontal approach was used and 72.7% of those in which a frontolateral approach was used). In the total series, GTR was achieved in 83.1% of cases (vs 49.3% in the authors’ former series). The complication rate was 13.8% without any mortality. New endocrine deficits were observed more frequently in patients treated with transcranial approaches over the years (16.3%– 66.7% vs 2.6%–50.0%) but were less frequent after transsphenoidal approaches (5.2%–19.2% vs 2.9%–45.7%).

Conclusions. Open surgery with intended total resection remains the treatment of choice in most patients. Initial stereotactic cyst aspiration or medical pretreatment to improve the patients’ condition and adequate choice of surgical approach(es) are essential to achieve that goal. Nevertheless, a moderate increase in endocrinological deficits has to be accepted. The authors recommend using radiotherapy only in cases in which there are tumor remnants or disease progression after surgery.

Transsphenoidal Surgery for Cushing Disease: Experience With 136 Patients

Neurosurgery 70:70–81, 2012 DOI: 10.1227/NEU.0b013e31822dda2c

This is a retrospective study of 136 patients with Cushing disease treated with transsphenoidal microsurgery.

OBJECTIVE: To evaluate factors influencing immediate postoperative results and longterm outcomes.

METHODS: Data regarding clinical presentation, endocrine evaluation, imaging studies, surgical technique, immediate postoperative biochemical remission (IPBR), and longterm results were entered into a database and analyzed statistically. IPBR was based on biochemical evidence of adrenal cortical insufficiency and clinical evidence of such insufficiency.

RESULTS: IPBR for the entire series was 83.4%. In microadenomas, IPBR was 89.8% with a mean immediate postoperative plasma cortisol (IPPC) of 2.1 mg/dL (range, ,0.5-5.3). Positive magnetic resonance imaging (MRI) was associated with 18 times greater odds of finding microadenoma at surgery (P < .001) and with 4.1 times greater odds of IPBR (P = .07). In patients with a negative MRI, a positive inferior petrosal sinus sampling (IPSS) test was associated with 93% of IPBR (P = .004). IPBR in macroadenomas was 30.7%. Of patients followed for 12 months or longer, 34.8% required glucocorticoid replacement for the duration of follow-up. The mean follow-up in microadenomas was 68.4 months with a 9.67% incidence of recurrences. The estimated actuarial incidence of recurrences increased with the passage of time and IPPC of greater than 2 mg/dL was associated with higher incidence of recurrences, although without statistical significance (P = .08).

CONCLUSION: In microadenomas, a positive MRI and positive IPSS test were associated with a higher incidence of IPBR. Recurrences increased with the passage of time, and an IPPC of greater than 2 mg/dL may be associated with higher incidence of recurrences.

Suprasellar Rathke Cleft Cysts: Clinical Presentation and Treatment Outcomes

Neurosurgery 69:1058–1069, 2011 DOI: 10.1227/NEU.0b013e318228bcea

Rathke cleft cysts (RCCs), benign remnants of the Rathke pouch typically arising in the sella, sometimes have suprasellar extension. Purely suprasellar RCCs are rarely reported.

OBJECTIVE: To compare the presentations, surgical outcomes, and pathology of purely suprasellar RCCs and sellar-based RCCs.

METHODS: We retrospectively reviewed records, magnetic resonance images, laboratory results, and pathology of 151 RCC patients surgically managed at our institution from 1989 to 2009. The RCCs were classified as purely sellar (type I, n = 76), sellar with suprasellar extension (type II, n = 56), or purely suprasellar (type III, n = 19).

RESULTS: The RCCs with a suprasellar component (types II and III) more commonly presented with visual dysfunction (P < .001). Complete cyst drainage occurred in 89%, 55%, and 38% of type I, II, and III RCCs, respectively (P < .001). Vision improved in 100%, 55%, and 33% and headache improved in 74%, 64%, and 29% of type I, II, and III patients, respectively (P = .02). Temporary or permanent postoperative diabetes insipidus occurred in 5%, 16%, and 21% of type I, II, and III patients, respectively. (P < .001). In a multivariate analysis, RCC type was the only factor predicting recurrence. Kaplan-Meier 3-year recurrence/progression rates were 0%, 16%, and 29% for type I, II, and III RCCs, respectively (P , .001, type I vs II, type I vs III; P = .5 type II vs III).

CONCLUSION: The RCCs with a suprasellar component are neurosurgically challenging because of their proximity to the optic chiasm and infundibulum. Compared with sellar-based RCCs, RCCs with a suprasellar component more frequently present with visual dysfunction, are more difficult to completely eliminate, recur more frequently, and are associated with higher postoperative endocrine morbidity, and their preoperative visual dysfunction and headache less frequently improve with surgery. These factors must be considered during the treatment of RCCs with a suprasellar component.

Pituitary apoplexy: an overview of 186 cases published during the last century

Acta Neurochir (2010) 152:749–761.DOI 10.1007/s00701-009-0595-8

Pituitary apoplexy is a rare and life-threatening complication occurring in 0.6–10.5% of all cases of pituitary adenomas. Although the association between pituitary apoplexy and visual dysfunction has been recognized for a long time, the optimal management of this problem still remains controversial. The purpose of this overview was to present the surgical experience by analyzing the literature on the management of pituitary apoplexy for better treatment of these cases.

Materials and method To establish a new guideline for the surgical treatment of this entity, publications reported during the last century and databases containing medical literature were analyzed. In addition, an illustrative case with pituitary apoplexy presenting with complaints of sudden onset severe headache associated with nausea, vomiting, and a sudden loss of vision was described. In fact, the experience in our complicated patient prompted us to review the available literature on the management of pituitary apoplexy to date.

Conclusions Based on an overview of 186 cases of apoplectic pituitary adenoma presenting with monocular or binocular blindness, we highlight the importance of correct diagnosis and an early, but not necessarily emergency, surgery within the first week of admission to optimize visual outcome of such patients. The illustrative case further exemplifies the value of close interaction between members of the management team for optimal outcome.