Suprasellar Extension Research Articles

Postoperative CSF leakages after transsphenoidal surgery for pituitary adenomas: Analysis of a series of 302 surgical procedures

IntroductionTranssphenoidal surgical removal is the preferred treatment of most pituitary adenomas. Postoperative cerebrospinal fluid (CSF) leakage is the leading cause of morbidity after this procedure, with an incidence rate that varies from 0.5 to 15% in the main published series. ObjectivesThe primary objective of this study was to establish the incidence of postoperative CSF leakage in a sample of surgeries performed at the University Hospital of La Ribera by the same surgical team. The secondary objectives were to: ascertain the distinctive features between patients with and without postoperative CSF leakage, identify risk factors for their development, evaluate the relationship between the surgical technique for closing the sella turcica and the onset of postoperative CSF leakage and evaluate different treatment regimens for this complication. MethodsThe data of 302 consecutive transsphenoidal surgical procedures for pituitary adenoma removal which were performed between 1999 and 2017 were retrospectively reviewed. Results and conclusionsThe incidence of postoperative CSF leakage in our series was 2.3% (in accordance with similar published studies). It was possible to correlate intraoperative CSF leakage with two variables: pituitary macroadenoma and tumours with suprasellar extension (p<0.005). This correlation did not exist for postoperative CSF leakage. We found a statistically significant correlation between intraoperative and postoperative CSF leakage (p<0.005). Due to the low incidence of postoperative CSF leakage in our series, it was not possible to identify risk factors for its development.

Transnasal endoscopic approach for pediatric skull base lesions: a case series.

Transnasal endoscopic transsphenoidal approaches constitute an essential technique for the resection of skull base tumors in adults. However, in the pediatric population, sellar and suprasellar lesions have historically been treated by craniotomy. Transnasal endoscopic approaches are less invasive and thus may be preferable to craniotomy, especially in children. In this case series, the authors present their institutional experience with transnasal endoscopic transsphenoidal approaches for pediatric skull base tumors. The authors retrospectively reviewed pediatric patients (age ≤ 18 years) who had undergone transnasal endoscopic transsphenoidal approaches for either biopsy or resection of sellar or suprasellar lesions between 2007 and 2016. All operations were performed jointly by a team of pediatric neurosurgeons and skull base otolaryngologists, except for 8 cases performed by one neurosurgeon. The series included 42 patients between 4 and 18 years old (average 12.5 years) who underwent 51 operations. Headache (45%), visual symptoms (69%), and symptoms related to hormonal abnormalities (71%) were the predominant presenting symptoms. Improvement in preoperative symptoms was seen in 92% of cases. Most patients had craniopharyngiomas (n = 16), followed by pituitary adenomas (n = 12), Rathke cleft cysts (n = 4), germinomas (n = 4), chordomas (n = 2), and other lesion subtypes (n = 4). Lesions ranged from 0.3 to 6.2 cm (median 2.5 cm) in their greatest dimension. Gross-total resection was primarily performed (63% of cases), with 5 subsequent recurrences. Nasoseptal flaps were used in 47% of cases, fat grafts in 37%, and lumbar drains in 47%. CSF space was entered intraoperatively in 15 cases, and postoperative CSF was observed only in lesions with suprasellar extension. There were 8 cases of new hormonal deficits and 3 cases of new cranial nerve deficits. Length of hospital stay ranged from 1 to 61 days (median 5 days). Patients were clinically followed up for a median of 46 months (range 1-120 months), accompanied by a median radiological follow-up period of 45 months (range 3.8-120 months). Most patients (76%) were offered adjuvant therapy. In this single-institution report of the transnasal endoscopic transsphenoidal approach, the authors demonstrated that this technique is generally safe and effective for different types of pediatric skull base lesions. Favorable effects of surgery were sustained during a follow-up period of 4 years. Further refinement in technology will allow for more widespread use in the pediatric population.

Recurrent Rathke's Cleft Cysts: Incidence and Surgical Management in a Tertiary Pituitary Center over 2 Decades.

Limited data exist pertaining to outcomes following surgery for recurrent Rathke's cleft cysts (RCC). To determine treatment outcomes in patients undergoing reoperation for recurrent or residual RCCs. A retrospective analysis of 112 consecutive RCC operations in 109 patients between 1995 and 2017 was conducted. Eighteen patients underwent 21 RCC reoperations with a mean follow-up of 58 mo. Patient symptoms prior to reoperation included headaches (14, 66.7%) and vision loss (12, 57.1%). Thirteen of 18 patients (72.2%) required hormone supplementation prior to reoperation including 5 with diabetes insipidus (DI). Mean RCC diameter was 16 mm and 76% had suprasellar extension. Compared to index RCC cases, intraoperative cerebrospinal fluid leak repair was more common in reoperation cases (15/21, 71% vs 43/91, 47%, P=.05). There was 1 carotid artery injury without neurological sequelae, and 2 postoperative cerebrospinal fluid (CSF) leaks (9.5%). Rates of transient hyponatremia (3/10, 30% vs 4/91, 4.4%, P=.04) and transient DI (5/10, 50% vs 17/91, 18.7%, P=.04) were higher in the reoperation vs index group. Improved headaches and vision were reported in 4/12 (33%) and 8/12 (61.5%) of RCC reoperation patients, respectively. Two patients developed new permanent DI. A higher proportion of reoperation patients had RCC squamous metaplasia (24% vs 5.4%, P=.02) or wall inflammation (42.9% vs 2.2%, P<.001) on pathological examination. Reoperation for RCCs is generally safe at tertiary pituitary centers and often results in improved vision. Hypopituitarism is less likely to improve following reoperation for recurrent RCCs. Several histopathological features may help characterize "atypical RCCs" with a higher likelihood of recurrence/progression.

SAT-462 AIP Mutation-Positive Patients with Somatotropinomas End up Taller and Requiring Radiotherapy More Often Compared to AIP Mutation-Negative Patients: Data from 784 Familial and Young-Onset Cases

Introduction: Germline mutations in the aryl hydrocarbon receptor-interacting protein gene (AIP) are responsible for up to 50% of familial isolated pituitary adenoma (FIPA) kindreds affected only with somatotropinomas. AIP mutation-positive (AIPmut) somatotropinomas present earlier, more aggressively and are often more resistant to therapy. We aimed to further characterise AIPmut somatotropinomas in terms of clinical features and outcomes. Methods: We studied AIPmut somatotropinomas which presented clinically; prospectively-diagnosed AIPmut somatotropinomas (i.e. somatotropinomas diagnosed following genetic and clinical screening) were excluded from the analysis. Indications for AIP genetic testing were: i) FIPA patients, ii) sporadic pituitary GH-secreting macroadenomas with disease onset <30y, or iii) GH-secreting microadenomas with age of onset <18y. Results: Out of 784 patients with somatotropinomas included in our study, 139 had an AIP mutation (17.7%). In comparison to AIP mutation-negative somatotropinomas (AIPneg), patients with AIPmut somatotropinomas had a younger age at first symptoms (18.9±9.0 vs 26.1±11.7y; p<0.001) and at diagnosis (24.1±10.5 vs 30.1±12.4y; p<0.001), higher rates of pituitary apoplexy (9.5 vs 1.9%; p<0.001), suprasellar extension (66.1 vs 45.3%; p=0.003), extrasellar extension (81.2 vs 68.3%; p=0.032) and a higher mean number of pituitary deficiencies at diagnosis (0.4±0.9 vs 0.2±0.6, p=0.020). The clinical diagnosis of most AIPmut patients was gigantism (55.4 vs 18.4%, p<0.001). The mean final height was higher in the AIPmut somatotropinoma subgroup (187.2±18.4 vs 177.2±19.6cm; p<0.001). AIPmut male patients ended up taller than AIPneg males (193.0±17.7 vs 183.0±23.1cm; p=0.002); similarly, AIPmut female patients were taller than AIPneg ones (175.5±13.0 vs 169.2±8.6cm; p=0.007). Both AIPmut and AIPneg groups had more male patients (60.4% in AIPmut and 52.7% in AIPneg groups). The mean number of overall treatments (2.34±1.65 vs 2.32±1.45; p=0.896) or surgical operations (1.05±0.78 vs 1.07±0.63; p=0.745) did not differ significantly between AIPmut and AIPneg somatotropinomas; however, AIPmut patients were more often treated with radiotherapy (41.7 vs 28.0%; p=0.020). Conclusions:AIPmut somatotropinomas present earlier and more often with pituitary apoplexy, suprasellar and extrasellar extensions, and had a higher number of pituitary deficiencies. The remarkably higher final height in the AIPmut setting, both in males and females, likely reflects the earlier onset of disease, but also emphasizes the management challenges as suggested by the increased proportion of patients requiring radiotherapy.

SUN-425 Pituitary Apoplexy, an Unexpected Cause of Syncope: Case Report

Background Pituitary apoplexy is a rare complication in 2-12% of pituitary adenomas (1). The most common presentation is headache and visual disturbance. Syncope has been noted in 7.8 -10% of apoplexy (2) and its etiology is typically adrenal insufficiency (AI). Clinical Case A 74 year old male presented to the ER with a 3 month history of syncope and loss of peripheral vision. He had a PMH of pituitary macroadenoma with GH and testosterone deficiency for 12 years, but he declined GH and testosterone treatment. In 2017, MRI showed a slight mass increment (2.4 x 2.7 x 3.8 cm from 2.4 x 2.7 x 3.5 cm). He also had a history of primary hypothyroidism on Levothyroxine 25 mcg for 3 years. In the ER, BP was 113/66 mmHg, no orthostatic BP recorded, HR 54 bpm, RR 14 and BT 35.8 °C. Physical exam showed only bradycardia. ECG revealed sinus bradycardia. The Initial concern was a cardiogenic syncope. CT brain found enlargement of suprasellar (1.8 cm from 1.2cm). Lab showed Na 128 mmol/L (serum osmol 296 mOsm/kg, urine osmol 271 mOsm/kg, urine Na 57 mmol/L). Serum cortisol (6 AM) was 2.2 (3.0-27.0 ug/dL), IGF-1 < 10 (32-200 ng/mL), total testosterone 15 (240-950 ng/dL), prolactin 18(male <18 ng/mL), TSH 3.51 (0.34-3.0 uIU/mL) and free T4 0.7 (0.6-1.6 ng/dL). MRI brain showed enlargement of pituitary mass (2.9x3.5x4.4 cm) with suprasellar extension into the clivus and cavernous sinus with new fluid level hinting hemorrhage. Bitemporal hemianopia was confirmed by visual field exam. The patient continued with a diagnosis of partial hypopituitarism, but with the addition of a new diagnosis: AI. He was stabilized on prednisone 10 mg daily and underwent transphenoidal decompression. Syncopal episodes resolved. He was discharged with hydrocortisone 20 mg in the morning and 10 mg in the evening as well as Levothyroxine 25 mcg. On Endocrine clinic follow up, the patient had permanent AI. Bitemporal hemianopia resolved. Conclusion Our patient presented with an uncommon endocrine problem, pituitary adenoma. He then developed a rare complication, pituitary apoplexy, presenting with an atypical symptom, syncope from secondary AI. Important, is that the diagnosis was delayed because of concern for bradycardia. However, once the PMH of pituitary adenoma was recognized, lab studies demonstrated AI and evidence of apoplexy from MRI. Treatment of AI has permanently corrected syncope. Also, of interest, despite a pituitary macroadenoma, the developed primary hypothyroidism. He was on Levothyroxine for 3 years prior to presentation; it’s unlikely that replacement was responsible for precipitating AI. Reference 1. Briet C, et al. Pituitary apoplexy. Endocrinology and metabolism clinics of North America. 2015;44(1):199-209. 2. Grzywotz A, et al. Pituitary apoplexy - A single center retrospective study from the neurosurgical perspective and review of the literature. Clinical neurology and neurosurgery. 2017;163:39-45.

SUN-433 Pituitary Dysfunction Secondary to a Large Cavernous Internal Carotid Artery Aneurysm

Background: Intracranial aneurysms extending into the sellar space and leading to pituitary dysfunction are exceedingly rare. This type of vascular lesions may be responsible for less than 0.2% of cases of hypopituitarism. Herein, we present a case of hypopituitarism and hyperprolactinemia secondary to a large unruptured left cavernous internal carotid artery aneurysm with intra- and suprasellar extension. Clinical case: An 81-year-old woman with past medical history of long-standing primary hypothyroidism was noted to have a suppressed serum TSH (0.007 uU/mL [0.400 - 5.500]) on routine laboratory studies. Prior to this, she had been on a stable dose of levothyroxine replacement for several years and her TSH level had been maintained within the normal reference range. Subsequent laboratory studies showed an elevated prolactin level (173.4 ng/mL [4.5 - 26.8]), inappropriately low gonadotropin levels for a post-menopausal woman (FSH 4.4 mU/mL [20 - 100]; LH 0.8 mU/mL [>20]), normal IGF-1 (96 ng/mL [27 - 170]), and a low morning cortisol level (2.5 ug/dL (5.3 - 22.5)] with an inappropriately normal ACTH level (12 pg/mL [<47]). Her 60-minute cortisol level was <20 ug/dL during an ACTH stimulation test. The patient was started on steroid replacement and was continued on levothyroxine. A brain MRI was performed and demonstrated an area of heterogeneous unenhanced T1-weighted signal intensity and T2 signal void in the sellar space, measuring approximately 15 mm in diameter. The radiological differentials included a proteinaceous pituitary cyst or a vascular aneurysm. A brain MRA was then obtained for better characterization of the lesion, which revealed a large left cavernous internal carotid artery aneurysm (13 x 17 x 16 mm), completely filling the sellar space and extending into the suprasellar region. The patient was referred to neurosurgery and underwent a successful pipeline embolization of the aneurysm. At two months follow-up, her TSH was 0.159 uU/mL and her prolactin level was 140.3 ng/mL. Conclusion: Aneurysms with intrasellar extension should always be considered in the differential diagnosis of sellar lesions. When compared with cases of nonfunctioning pituitary macroadenomas, intrasellar aneurysms may result in comparable dysfunction in pituitary hormone production and hyperprolactinemia. Endocrine abnormalities are usually irreversible and permanent hormone replacement therapy is necessary. Long-term follow-up may elucidate pituitary function recovery after effective aneurysm treatment.

SUN-463 Tumor Shrinkage with Preoperative Relacorilant Therapy in Two Patients with Cushing Disease Due to Pituitary Macroadenomas

Background: Relacorilant (RELA, Corcept Therapeutics) is a highly selective glucocorticoid receptor antagonist (GRA) that modulates the effects of excess cortisol, while showing no significant antagonism at the progesterone, mineralocorticoid, androgen, or estrogen receptors. It is currently being investigated for the treatment of patients with endogenous Cushing syndrome (CS) of any etiology. Results from the open-label Phase 2 study (NCT02804750) indicated that treatment with RELA was generally well tolerated and significantly improved glycemic and hypertension control in patients with endogenous hypercortisolism. In this Phase 2 study, two patients with Cushing disease (CD) showed evidence of tumor shrinkage on post-treatment MRIs performed after study completion. Cases: Two patients with de novo CD due to a macroadenoma were treated for 3 months with RELA prior to previously scheduled transsphenoidal pituitary surgeries. Pituitary imaging performed after treatment with RELA revealed significant shrinkage of the tumors. Patient 1 is a 50y/o woman with a pituitary macroadenoma measuring 10 x 6.3 mm on MRI. She presented with cushingoid features (moon face, dorsal & supraclavicular fat, plethora, central obesity, easy bruising, striae) and had confirmatory biochemical tests (ACTH 12.2 pmol/L (NR 1.3-11.1 pmol/L); UFC 177.7 nmol/d (NR 11.1-138 nmol/d); DST 156 ng/mL (15.6 mcg/dL). Patient 2 is a 43y/o man with a pituitary macroadenoma measuring 22 x 25 x 26 mm with suprasellar extension, right displacement of the pituitary stalk, and invasion of the left cavernous sinus on MRI. He also had cushingoid features and confirmatory biochemical tests (ACTH 20.9 pmol/L (NR 1.3-11.1 pmol/L); UFC 356.5 nmol/d (NR 11.1-138 nmol/d); DST 247 ng/mL (24.7 mcg/dL). After completing the 3-month study, pre-operative MRIs revealed reduction in the size of their tumors. The pituitary tumor for patient 1 decreased from 10 x 6.3 mm prior to treatment to 8.0 x 5.7 mm after treatment with RELA. The pituitary tumor for patient 2, decreased from 22 x 25 x 26 mm prior to treatment to 21 x 22 x 19 mm after treatment with RELA. Conclusion: Pituitary imaging performed as part of the pre-operative standard of care revealed tumor shrinkage in two patients with macroadenomas treated for 3 months with RELA. This unexpected finding will be formally investigated in an ongoing Phase 3 study with RELA (GRACE Study, NCT03697109). A potential explanation for this finding could be tumor sensitization to endogenous (hypothalamic) somatostatin via upregulation of somatostatin receptors type 2 (SSTR2) which are downregulated in patients with hypercortisolism. If confirmed, this finding may potentially support the role of RELA as pre-operative medical treatment in patients with CD with invasive macroadenomas.

SAT-LB082 Neurosarcoidosis Presenting as Panhypopituitarism, Diabetes Insipidus and Sellar Mass

Introduction: Granulomatous hypophysitis is a rare entity with an annual incidence of 1 in 10 million. It may be primary or secondary to tuberculosis, sarcoidosis, Wegener’s disease, syphilis or mycotic infections. It accounts for <1 % of cases of panhypopituitarism or visual field defects. Isolated Neurosarcoidosis without systemic involvement is extremely rare. It can rarely present as an isolated granuloma of the sella mimicking pituitary adenoma. Case: A 47-year-old-male was admitted with generalized weakness of 1 month and headache with loss of peripheral vision of 1 week duration. MRI brain revealed a sellar mass with suprasellar extension involving the pituitary stalk and hypothalamus representing pituitary macroadenoma. Biochemical tests were evident for central hypoadrenalism, secondary hypothyroidism and hypogonadism with mild hyperprolactinemia. He had low urine specific gravity on admission and provided history of increased thirst, polyuria and nocturia from past 3 weeks. CSF analysis showed elevated CSF protein and ACE levels. Visual field testing revealed bitemporal hemianopsia. Patient underwent transsphenoidal biopsy and partial resection of pituitary mass with significant improvement in visual field defects post operatively. Pituitary biopsy showed non-necrotizing granulomatous hypophysitis. CT chest revealed hilar and mediastinal lymphadenopathy suspicious of sarcoidosis. He had positive Quantiferon and PPD testing but hilar lymph node biopsy was negative for granuloma or malignancy. CSF analysis, pituitary and lymph node biopsy were negative for bacterial, AFB and fungal culture/stain. Tests for HIV, hepatitis, syphilis, lymphoma panel and sputum AFB culture x3 were negative. He was discharged on levothyroxine, hydrocortisone, testosterone and desmopressin. He completed treatment for latent TB and was monitored as outpatient. After 8 months, his visual field defects had completely recovered. Patient was asymptomatic with unchanged hilar and mediastinal lymphadenopathy. Repeat MRI brain showed avidly enhancing thickened pituitary stalk with complete resolution of pituitary mass lesion. He was diagnosed with probable Neurosarcoidosis and referred to rheumatology. Discussion: Hypothalamic-pituitary sarcoidosis occurs in less than 10% of patients with Neurosarcoidosis. Polyuria, polydipsia and signs and symptoms of hyperprolactinemia are the most common presenting manifestations. Earlier, the endocrine dysfunction was attributed to a destructive process affecting pituitary, but pituitary responsiveness to synthetic hypothalamic releasing factors indicates that hypothalamic insufficiency is the major cause for panhypopituitarism. Diabetes Insipidus can be masked by secondary adrenal deficiency on presentation. Clinicians should be cautious of unmasking diabetes insipidus while replacing glucocorticoids in such cases. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SAT-468 Conversion of a Non-Secreting to a Growth Hormone-Secreting Pituitary Adenoma: A Case of Rapid Development of Acromegaly

Introduction: Acromegaly is known to have a slow and insidious course. As a result, the diagnosis is made very late, and at the time of diagnosis most patients have macroadenomas. The average interval from onset of symptoms of acromegaly and diagnosis is approximately 12 years. In addition, conversion of a non-functioning to a functioning pituitary adenoma is very rare. We report a case of a documented non-secreting pituitary macroadenoma turning into a growth hormone secreting one resulting in symptomatic acromegaly in less than 4 years. Clinical Case: A 28 year old African American female presented for evaluation of headaches in 2014. Her past medical history is significant for headaches and childhood epilepsy since age 9. During her workup she was found to have a 1.2 cm pituitary macroadenoma on MRI. Her review of systems showed no evidence of vision changes, galactorrhea, hand enlargement, weakness, changes in body weight or skin pigmentation. Her exam was unremarkable, in particular she did not have any acromegaloid or cushingoid features. Her pituitary hormone work-up was unremarkable, showing no evidence of hormone excess or deficiency. Her IGF-1 was found to be 251 ng/dL (Normal: 78-270). She was evaluated by neurosurgery at that time, who recommended conservative approach with serial follow-up imaging. About 3 years and 8 months later, she was admitted to the hospital for her worsening symptoms of headaches, which were noted approximately 3 times weekly. On further questioning, examination and comparison with old pictures, she was noted to have coarsening of her facial features as well as increase in her ring size. Laboratory tests showed elevated IGF-1 levels on 2 separate occasions at 570 and 551 ng/dL. On repeat imaging, the pituitary macroadenoma was noted to be increased in size to 1.8 cm with increasing suprasellar extension and abutting the anterior aspect of the optic chiasm. She underwent endoscopic excision of pituitary adenoma and reconstruction of sellar floor. The pathology came back positive for human growth hormone staining. IGF-1 level decreased to 244 ng/mL in less than 4 months after surgery. Conclusion: Conversion of non-secreting pituitary adenoma to a growth hormone secreting one can happen over a relatively short time span, resulting in symptomatic acromegaly. We had a unique opportunity to observe this since the patient had previous imaging and biochemical work-up which we could use for comparison. This is contrary to the classic description of acromegaly where the clinical picture develops very slowly over many years or even decades.

Primary tumors of the posterior pituitary: A systematic review.

In 2017, the World Health Organization established that pituicytoma, granular cell tumor (GCT), spindle cell oncocytoma (SCO) and sellar ependymomas (SE) are posterior pituitary tumors (PPT). They probably arise from the pituicytes and may constitute a unique histopathological entity. We carried out a systematic review using PubMed's database. A total of 266 patients with pathological diagnosis of PPT (135 pituicytomas, 69 GCT, 47 SCO, 8 SE and 7 mixed histology tumors) were analyzed. Gender distribution was identical and median age at diagnosis was 48 ± 21.8years. Main presentation symptoms were visual disorders (n = 142; 58.1%), headache (n = 99; 40.5%), hypopituitarism (n = 84; 34.4%), hypercortisolism (n = 10; 4.1%), polyuriapolydipsia (n = 6; 2.4%) and acromegaly features (n = 5; 2.0%). On MRI, 122 (47.6%) patients showed sellar with suprasellar extension masses, 67 (23.1%) were suprasellar and 63 (24.6%) exclusively sellar. Median tumor size was 22.0 ± 14.2mm. Two hundred sixty four patients underwent surgery, transphenoidal access was selected in 132 (64.4%) and craniotomy in 58 (28.3%). Complications were hypopituitarism (n = 70; 42.1%), diabetes insipidus (n = 55; 33.1%) and hemorrhage (n = 50; 30.1%). Tumor persisted in 93 patients (45.6%) and recurred in 13 (6.4%). Regarding comparison between main types of PPT, SCO patients were diagnosed later (60.0 vs 47.0 vs 47.0years, p = 0.023), the tumor was larger 25.0mm [10.8] vs 20.0mm [14.2] vs 2.0mm [15.0] and they were frequently sellar with suprasellar extension tumors (71.7% vs 46.2% vs 32.8%, p = 0.003) compared to pituicytoma and GCT. In conclusion, PPT are rare tumors and have been misdiagnosed mainly as non-functioning pituitary adenomas. Different types of PPT share similar epidemiology, clinical manifestations and surgical outcomes. Surgery is the only curative option but complications and subtotal resection are common.

Use of Artemis Neuro Evacuation Device in Resection of Pituitary Adenoma: Initial Technical Note

Endoscopic transsphenoidal resection has become the primary approach for resection of pituitary macroadenomas. However, challenges such as narrow sinuses, dense tumor consistency, and invasion of surrounding structures exist. We report a case in which the Artemis Neuro Evacuation device was used to endonasally remove a pituitary macroadenoma with suprasellar and parasellar extensions. The methodology and technical aspects of this device's novel use are illustrated. The long and narrow wand of the Artemis system allowed the operators to navigate through patient's narrow sinuses. Despite a dense tumor that did not come easily into a suction, the entire tumor debulking procedure lasted <10 minutes with the preservation of an intact arachnoid membrane using the Artemis. No perioperative complication was encountered, and the patient's neurologic deficits resolved. To the authors' knowledge, this represents the first reported case of the Artemis system's utility in the treatment of pituitary tumor beyond cranial hematoma and hemorrhage.

Clinical utility of routine postoperative morning cortisol monitoring in detecting new hypothalamic-pituitary-adrenal axis insufficiency following endoscopic transsphenoidal surgery for sellar lesions.

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is a well-documented complication of transsphenoidal craniotomy (TSC) for sellar lesions. The authors aimed to assess their multidisciplinary approach to the diagnosis and treatment of postoperative hypocortisolemia utilizing conservative screening methods. The authors performed a retrospective review of 257 patients who underwent TSC for pituitary adenoma (PA) or Rathke cleft cyst (RCC) at the University of Southern California between 2012 and 2017. Patients with preoperative adrenal insufficiency, Cushing's disease, or < 3 months of postoperative follow-up were excluded. Patient demographics, pathology, tumor characteristics, and complications were recorded. Postoperative day 1 (POD1) morning serum cortisol was assessed in all patients. Hypocortisolemia on POD1 (serum cortisol < 5 μg/dl) prompted a 7 am cortisol level measurement on POD 2 (POD2). Clinical signs and symptoms of hypocortisolemia were consistently monitored. After two serum cortisol levels < 5 μg/dl, or one serum level < 5 μg/dl plus a high clinical suspicion for HPA dysfunction, high-risk patients received glucocorticoid supplementation. Data on 165 patients were included in the analysis; there were 101 women (61.2%) and 64 men (38.7%). Preoperative diagnoses included nonfunctional adenoma (n = 97, 58.7%), growth hormone-secreting adenoma (n = 37, 22.4%), RCC (n = 18, 10.9%), prolactinoma (n = 8, 4.8%), and other (n = 5, 3.0%). One hundred thirty-eight patients (63.0%) had either suprasellar extension or cavernous sinus invasion. POD1 hypocortisolemia was diagnosed in 8 patients (4.8%). Of these patients, 2 (1.2%) were clinically asymptomatic and had normalized POD2 cortisol levels. Six patients (3.6%) had clinical symptoms and POD2 cortisol levels confirming HPA axis deficiency. Of these 6 patients treated with early glucocorticoid replacement, 2 patients recovered HPA axis function during follow-up, making the incidence of new, permanent HPA axis deficiency 2.5%. In the authors' institutional review, all patients warranting postoperative glucocorticoid replacement had both complicated surgical courses and associated clinical symptoms of hypocortisolemia. The authors' algorithm of withholding steroids until patients demonstrate clear evidence of postoperative hypocortisolemia is safe and clinically efficacious. Their data further suggest that routine postoperative cortisol screening may not be necessary following an uncomplicated operative resection, with gland preservation and the absence of clinical symptoms indicative of HPA dysfunction.

Deferred Radiotherapy After Debulking of Non-functioning Pituitary Macroadenomas: Clinical Outcomes.

Background: To describe the outcome for a cohort of patients with non-functioning pituitary macroadenomas (NFPMA), managed by debulking surgery with radiation therapy delayed until progression.Methods: Two hundred and sixty-seven patients were treated surgically for pituitary tumors at our institution between 1997 and 2005. One hundred and twenty-six patients met the inclusion criteria of NFPMA. They were followed for at least 2 years.Results: At presentation, 58% of patients had objectively decreased visual function, 66% had endocrine abnormalities, and 46% had headaches. Of the entire cohort, 75% of tumors abutted the optic chiasm and 87% had suprasellar extension. Over a median follow up of 112 months from surgery, 52% of patients had evidence of radiographic tumor progression, and 39% required additional treatment. There was a significant difference freedom from progression and in the number of patients receiving additional treatment with preoperative adenoma size of < 2 vs. ≥2 cm (p < 0.05).Conclusion: Close observation with radiation therapy delayed until the time of progression is an appropriate option for patients presenting with initial adenoma size < 2 cm, and can be considered for those with initial sizes up to 4 cm, as the majority of patients do not require further intervention for 10 or more years, thereby meaningfully postponing the risks of radiotherapy.

Predictors of Cerebrospinal Fluid Leaks in Endoscopic Surgery for Pituitary Tumors

<i>Background</i>: Cerebrospinal fluid (CSF) leak is a serious complication of endoscopic endonasal surgery for pituitary adenoma; leading to a more serious and financial burden of the surgery. Prediction of the occurrence of such sequale and proper plaining for reconstruction can reduce its prevalence and associated morbidities. <i>Purpose</i>: To determine the predictors and risk factors associated with intra/and postoperative cerebrospinal fluid (CSF) leaks in endoscopic endonasal pituitary surgery. Methods: A retrospective study included 150 patients who underwent endoscopic endonasal approach for resection of pituitary adenomas between 2015 and 2018. We analyzed the association between CSF leaks (intra/post-operative) and perioperative variables including patients’ demographic data, medical comorbidities, tumor characteristics and operative data (rates of intraoperative leak, reconstructive techniques). <i>Results</i>: 34 patients (22.6%) out of the 150 patients had an overall, CSF leak: 26 (76.5%) patients had intraoperative leaks; 5 patients out of them continued to have a postoperative leak. 8 patients (23.5%) had postoperative leak. Based on multiple logistic regression model analysis; increased body mass index (BMI), associated hydrocephalus, suprasellar extension and recurrent tumors had a significant association with intraoperative CSF leaks, while only BMI and hydrocephalus predicted postoperative CSF leaks. <i>Conclusion</i>: Elevated BMI, suprasellar extension of the tumor, recurrence or previous radiation are all important risk factors that have been proved in this study to have statistically significant association with the incidence of CSF leak. In high risk patients for CSF leakage: adequate reconstruction planis advised to avoid such morbidity.

Anterior Interhemispheric Approach in Craniopharyngiomas : Personal Experience of Operative Technique and Results

Introduction: Removal of intracranial supra-sellar masses continues to be a surgical challenge. Various approaches have been used by different authors with varying results. Anterior basal interhemispheric approach is most suitable with better results than other approaches for craniopharyngiomas&#x0D; Materials and methods: Fifteen patients with large craniopharyngiomas having third ventricular and or retro or supra-sellar extensions or reaching the interpeduncular cisterns were operated by this approach, over a period of seven years since the first use of this approach at our institute. The data of patients opearated by this approach were then retrospectively analysed. There were eleven males and four females with five patients in the pediatric age group. Follow up range was from 2 to 83 months with a mean of 21.6 months.&#x0D; Results: Total excision was achieved in seven (46.6%) and near total excision in another seven (46.6%), partial excision was done in only one (6.66%). Seven patients with total excision were disease free at mean follow up of 6.8 months. There was asymptomatic recurrence in two (13.33%) patient with near total excision at 11 and 63 months respectively and were given radiotherapy post-operatively. All patients were symptom free except one with diabetes insipidus (DI) and one mortality, and one with post operative visual deterioration.&#x0D; Conclusion: Anterior basal interhemispheric approach is a useful alternative to other transcranial approaches in the management of the craniopharyngiomas. It has the advantage of being a midline approach and displays the tumour brain interface better.

Pure Endoscopic Endonasal Surgery for Pituitary Adenomas: Technique and Early Results in Banha Neurosurgery Department

AbstractBackground: Surgery for pituitary adenomas passed though several stages of refinement during the past decades. During the past 20 years a major shift has been made by neurosurgeons towards endoscopic pituitary surgery. This has been aided by the great development in technologies of rod lens and high resolution video cameras. The panoramic view offered by the endoscope made the surgery more safe and radical in removing the tumor. Now it is widely accepted in most neurosurgical institutes that the endoscopic endonasal surgery should be the gold standard in pituitary surgery.Aim of Study: In this study we report our early results, challenges we faced and the problems we solved in applying the technique of pure endoscopic endonasal surgery for pituitary adenomas in Banha Neurosurgery Department.Study Design: This is a retrospective study case series of 35 patients with pituitary adenomas. All patients were treated surgically using the pure endoscopic endonasal technique. Patients had been followed after surgery for a period of time ranged from 4 to 36 months during the years from February 2012 to March 2015.Patients and Methods: Thirty five patients were included; twenty with nonfunctioning pituitary adenomas, (nine with suprasellar extension only and 11 with parasellar extension) and fifteen with functioning adenomas including 3 ACTH secreting, 8 GH secreting and 4 prolactinomas. Patients were endocrinologically, ophthalmologically and radiologically evaluated using CT paranasal sinus and MRI pituitary scans. Pre and post-operative scans as well as levels of pituitary hormones have been compared and evaluated for the degree of tumor resection, visual improvement and endocrinological cure.Results: Gross total resection of the tumor has been achieved in 23 patients (65.7%) while 12 patients (34.3%) had incomplete resection. Among 15 patients with pre operative visual deficits, 13 patients (86,6%) showed variable degrees of visual improvement and 2 only (13.3%) did not improve. Endocrinological cure was 75% in GH secreting adenomas, 75% in prolactinomas and 66.7% in ACTH secreting adenomas.The most common complications were transient post-operative DI and inrtaoperative CSF laek. No reported deaths, major vascular injury or worsening of vision.Conclusion: The pure endoscopic endonasal technique, although challenging, it is less traumatic, and associated with good outcome.

THE MULTIMODAL MANAGEMENT OF GROWTH HORMONE-SECRETING PITUITARY MACROADENOMA

The expansive processes of the sellar region include tumors of mesenchymal, neural or epithelial origin, along with cystic and inflammatory processes. From the epithelial sellar tumors, almost 90 % are represented by pituitary adenomata – benign tumors which develop from the adenohypophyseal cells, accounting for approximately 10–15% of all intracranial expansive processes. According to the clinical criteria, the pituitary adenomata can be classified as endocrine-inactive or non-producing adenomata, and endocrine-active or producing adenomata. The non-producing adenomata represent approximately 39–50% of all pituitary tumors; the prolactinomata represent approximately 6.1%; the growth hormone producing adenomata approximately 27.9%; the adenocorticotropic hormone producing adenomata 6%; the thyrotropic producing hormone adenomata 0.4%; and the follicle-stimulating or luteinizing producing hormone adenomata are extremely rare. The surgical approach used on a large scale today in pituitary and suprasellar tumors is the transnasal transsphenoidal approach, which is less invasive compared to the standard transcranial approach and has got excellent results so far. The purpose of this article is to illustrate the main data about pituitary tumors, based on a case report presentation. At the same time, we aim to keep track of the latest information in the specialty literature, and focus on the neurosurgical aspects. The therapeutic strategy in the case of a 24-year-old female patient diagnosed with a growth hormone-secreting pituitary macroadenoma, with a suprasellar extension and an infrasellar one in the sphenoidal sinus and with invasion in the right cavernous sinus.

A Case of Pituitary Germinoma Misdiagnosed as Lymphocytic Hypophysitis

Pituitary germinomas are difficult to be differentiated from lymphocytic hypophysitis due to similar clinical, radiological and even histological findings. However, it is of great importance to make the distinction between them because of different therapeutic approaches of the two diseases. We report a case of neurohypophysial germinoma who initially was misdiagnosed as lymphocytic hypophysitis. The patient was a 26-year-old man who first presented with central diabetes insipidus and subsequent pan-hypopituitarism. Magnetic resonance imaging (MRI) of the pituitary which first had shown mild pituitary enlargement, revealed a pituitary mass of unusual feature after 1 year. Pathological diagnosis of the lesion, biopsied through trans-sphenoidal route, was lymphocytic hypophysitis. Corticosteroid was initiated for him. Despite, intensive treatment clinical symptoms worsened and the patient developed visual field defect. Follow-up MRI revealed enlargement of the pituitary mass with suprasellar extension and involvement of optic chiasm. Surgical resection of the mass was performed, and the second histological examination confirmed the diagnosis of germinoma. Subsequently, the patient underwent radiotherapy, and complete remission was achieved; however, pan-hypopituitarism persisted. In conclusion, the possibility of neurohypophyseal germinoma should be considered in patients with the diagnosis of lymphocytic hypophysitis who do not respond to corticosteroid therapy. J Endocrinol Metab. 2018;8(5):113-118 doi: https://doi.org/10.14740/jem530w

Giant Prolactinoma in Men: Clinical Features and Therapeutic Outcomes.

The aim of the study was to evaluate the clinical features and long-term therapeutic outcome of giant prolactinoma (gPRLoma) in men and to compare them with those of a group of male patients with non-gPRL macroprolactinomas (non-gPRLomas). A retrospective and multicenter study of gPRLomas in men diagnosed in a 20-year period was performed. Clinical data and treatment outcome were registered. The diagnosis of gPRLoma was established when the maximal tumor diameter was ≥40 mm or the tumor had ≥20 mm of suprasellar extension associated to hyperprolactinemia (PRL>1000 ng/ml). Non-gPRLoma was considered when tumor diameter was ≥ 10 mm and<40 mm associated to hyperprolactinemia (PRL≥200 ng/ml). Twenty-three patients with gPRLoma (age 38.3±13.5 years) followed for at least 3 months (follow-up 87.1±60.5 months, range 3-211 months) were evaluated. A group of 42 patients with non-gPRLoma (age 42±16.6 years; NS; follow-up 89±65.9 months, range 3-222 months; NS) served as a control group. More than half (56.5%) of the gPRLoma patients were younger than 40 years at diagnosis. Visual disturbances were significantly more common in gPRLoma than in non-gPRLoma patients (65.2 vs. 25.6%; p=0.004). Prevalence of hypopituitarism was similar in both groups of patients (73.9% vs. 80.9%; gPRLoma vs non-gPRLoma; NS). Serum PRL concentrations were significantly higher in gPRLoma than in non-gPRLoma patients [median (IR), 3978 ng/ml (1179-9012) vs. 907 ng/ml (428-3119); p<0.001]. Maximum tumor diameter in gPRLomas was 4.8±0.8 cm and 2.4±0.7 cm in non-gPRLoma (p<0.001). All patients were treated with dopamine agonists (DA). Twelve (52.2%) gPRLoma patients and 32 (73.8%) non-gPRLoma patients were treated with DA as monotherapy (p=0.045). Surgery was used in 12 (52.2%) gPRLoma patients and in 12 (28.6%) non-gPRLoma patients (p=0.054). Lastly, radiotherapy was used in 5 (21.7%) gPRLoma patients and in 6 (14.2%) non-gPRLoma patients (NS). At last visit, PRL was similar in both groups of patients [16 ng/ml (4-30) vs. 11 ng/ml (4-25); gPRLomas vs. non-gPRLomas; ns] and tumor size decreased significantly (p<0.001) in both groups of patients. Clinical cure (maintained normoprolactinemia without therapy for>1 year and no radiological evidence of pituitary tumor) was achieved in 2 (8.7%) gPRLoma patients and in 2 (4.8%) non-gPRLoma patients (NS). gPRLomas in men are usually diagnosed at a mean age of 40 years, an age similar to that of non-gPRLomas. The only clinical difference with non-gPRLomas is their greater prevalence of visual disturbances. The therapeutic approaches and tumor outcomes were similar to those obtained in patients with non-gPRLomas. Complete cure in gPRLoma is rare, but similar to that achieved in non-gPRLomas, reached in less than 10% of patients.

Endocrine Remission after Pituitary Stereotactic Radiosurgery: Differences in Rates of Response for Matched Cohorts of Cushing’s Disease and Acromegaly Patients

To compare and describe the time to endocrine remission and new hypopituitarism among patients with growth hormone (GH) and adrenocorticotropic hormone (ACTH) secreting pituitary adenomas after radiosurgery after controlling for several known prognostic factors. An institutional review board approved, institutional retrospective analysis of patients with GH- and ACTH-secreting pituitary adenomas was performed, with matching based on patient gender, age at radiosurgery, time interval between the last resection and radiosurgery, use of previous radiotherapy, whole sella treatment, suprasellar extension, cavernous sinus invasion, and margin dose. Endocrine remission was defined, off of suppressive medications, as a normal serum IGF-1 (GH-secreting) or a normal 24-hour urine free-cortisol (ACTH-secreting). Endocrine remission and the incidence of new hypopituitarism after single fraction radiosurgery were described and compared between groups. Two-hundred and forty-two (242) patients were evaluated, 121 with GH-secreting tumors and 121 with ACTH-secreting tumors. A total of 75% of patients had cavernous sinus invasion and 10% had suprasellar extension at the time of radiosurgery. The median radiosurgical marginal dose was 25 Gy to the 50% isodose line between each group. After multivariable adjustment, factors associated with increased time to endocrine remission included patient age (HR 1.016, p = 0.023), cavernous sinus invasion (HR 1.793, p = 0.004), and patients with acromegaly (HR 2.912, p < 0.001). The incidence of a new hypopituitarism developing after SRS was 29% and did not appreciably differ by adenoma subtype (p = 0.180). After radiosurgery, patients with ACTH-secreting tumors achieve endocrine remission sooner than those with GH-secreting tumors. These results provide insight into the relative tumor biology and post-radiosurgical disease course that will serve to further improve clinical outcomes and patient management in the future.