Pituitary adenomas are benign tumors arising in the adenohypophysis and comprise 8%–20% of all reported primary brain tumors in the west. Transsphenoidal surgery with an aim to achieve complete tumor resection is the recommended first-line treatment for nonfunctioning as well as secretory pituitary adenoma. External beam radiation therapy (RT) has been demonstrated to be an effective treatment modality for pituitary adenoma, uncured by surgery and/or medical therapy, providing excellent long-term local control (>90%), but lower and variable rates (50%–80%) of biochemical remission in secretory tumors. The adoption of pituitary RT in the community has been limited due to concerns regarding potential late toxicity and long latency in normalization of hormonal hypersecretion. Over the years, technological advances in RT planning and delivery have resulted in progressive conformation of high doses to the target tissues while sparing adjacent neurovascular structures providing a favorable therapeutic index. The choice of RT technique should be based on size, site, and availability of infrastructure and expertise, with no significant differences between fractionated approaches and stereotactic radiosurgery (SRS). In contemporary clinical practice, the recommended dose of fractionated RT for pituitary adenoma is 45–50.4Gy in 25–28 fractions delivered over 5–6 weeks using modern high-precision techniques. The recommended dose of SRS given in a single fraction is 12–14Gy for nonfunctioning adenomas and 16–20Gy for secretory tumors. Late toxicity of pituitary RT includes hypopituitarism, neurocognitive impairment, neuropsychological dysfunction, optic neuropathy, cerebrovascular accidents, and second malignant neoplasms. Hence, RT in pituitary adenoma should be offered only to patients with residual, recurrent, progressive, or high-risk tumors with careful assessment of the benefit-risk ratio by an experienced multidisciplinary neurooncology team.

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Background: The management of hypothalamic hamartomas (HH) rests upon the type of presentation. These are rare congenital benign lesions presenting either with central precocious puberty (CPP), drug refractory epilepsy (DRE) or combination of both. We present here our experience in the management of these lesions from a neurosurgeon's perspective and review the pertinent literature. Objective: To present a series of HH presenting with CPP and DRE managed in the neurosurgery department at our center with an emphasis on the associated endocrine abnormalities. Materials and Methods: A prospective observational study over a period of five years included 16 patients of HH. All patients were evaluated with 3 Tesla Magnetic Resonance Imaging (MRI) brain, complete hormonal workup including gonadotrophins, testosterone (males) and estradiol (females), and video-electroencephalography (VEEG) as a part of epilepsy workup. All these patients were evaluated with postoperative hormonal workup and repeat MRI brain if repeat surgery was contemplated. Results: Among the 16 patients of HH, there were 11 male and 6 female children. All the patients presented with DRE with four of these had associated CPP. All the patients underwent robotic-guided radiofrequency ablation (RFA), with 75% seizure freedom following 1^st RFA surgery. Three of the four patients with CPP achieved both clinical and biochemical normalization. One patient had just a marginal reduction in the serum gonadotrophins. One patient was reoperated twice and three underwent RFA thrice. Conclusion: The management of HH should be individualized with DRE taking the precedence requiring early surgery. A multidisciplinary approach is therefore recommended for a successful outcome.

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Pituitary apoplexy (PA) is a rare, usually vision-threatening and occasionally life-threatening entity. The exact incidence of PA in large series of pituitary adenomas is variable; however, it is more common in macroadenomas and nonfunctioning adenomas though it has been reported rarely in microadenomas. There are several well-known precipitating factors for PA including the use of anticoagulants, surgery, head trauma, pregnancy, etc. The typical clinical presentation is characterized by the near universal presence of headache with or without the following: visual disturbances, extraocular palsies, altered sensorium. MRI is the imaging modality of choice. Most patients have hormonal and/or electrolyte disturbances at the time of presentation which needs to be quickly corrected. Both conservative and surgical treatment modalities have been advised for the management of this condition. However, on the basis of the evidence available in the literature, the treatment should be individualized for each patient with PA. If conservative management is chosen, close clinical monitoring is necessary for early identification of deterioration. Surgery generally is through the trans-sphenoidal route. Most patients have a good recovery in visual function and extraocular palsy. There is some evidence in the literature that surgical intervention, when necessary, should be undertaken early as it is associated with better visual outcome. The majority of the patients will have residual hormonal deficits which will require prolonged hormone replacement therapy. There is a small but significant risk of recurrent PA in patients with residual tumors, especially, in those with large tumor residues. There is also a small risk of tumor recurrence following PA and hence all patients should undergo surveillance imaging periodically to detect the possible recurrence of tumor. In recent years, the mortality from PA has decreased significantly. A high index of suspicion and prompt multidisciplinary management will often lead to an overall good outcome.

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Patients with pituitary masses who undergo transsphenoidal resection are at risk for a number of medical complications postoperatively. Among these are disturbances in fluid and sodium homeostasis, including diabetes insipidus (DI) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH). It is believed that these pathologic states are a result of damage to the hypothalamic–pituitary axis from surgery, as are the downstream consequences, such as the triple phase response. The triple-phase response describes the pattern of initial acute DI, subsequent rebound SIADH, and eventual chronic DI, the pathophysiology of which is described. Given the medical complexity of managing postoperative pituitary patients, it is essential to develop dedicated postoperative management protocols. Here, we describe the University of Utah's postoperative pituitary management protocol that includes immediate postoperative monitoring, treatment of DI, surveillance for the triple-phase response after discharge with outpatient serum sodium checks, and involvement of the endocrinology service for assistance with management of hypopituitarism. A complete understanding of the relevant anatomy, physiology, and development of standardized protocols for postoperative management can aid with minimizing medical complications after pituitary surgery.

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Cushing's disease is rare in the paediatric age group. The disease manifestations are similar to that seen in adults. Most of the management protocols have, therefore, been adopted from experience in adults and the therapeutic strategies employed in the latter group. Management of paediatric Cushing's disease poses significant challenges with regard to achieving an optimal growth, a proper body composition, an adequate bone health and reproductive capability as well as a good quality of life. This article reviews the special clinical, biochemical, radiological, surgical, and adjunctive therapeutic considerations in paediatric Cushing's disease.

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The classification of tumors of the pituitary gland has seen several changes in recent years. The 4^th edition of the World Health Organization Classification of Tumours of Endocrine Organs, published in 2017, saw the introduction of a classification based on cell lineage using immunohistochemistry for both pituitary specific hormones as well as pituitary specific transcription factors. The term “hormone-producing” was thus replaced by “-troph.” The other major change was that the entity of “atypical adenoma,” which was introduced in the 2004 classification, to identify tumors with a poor prognosis, was removed as it failed to identify aggressive tumors. Instead, assessment of markers of proliferation, clinical parameters, such as invasive status and histological subtypes were recommended to identify tumors with aggressive potential. The diagnostic criteria for pituitary carcinoma, however, remained unchanged and continued to be defined as a tumor of adenohypophyseal cells that metastasize craniospinally or systemically. Null cell adenomas were more clearly defined as tumors that did not show any cell-type differentiation, lacking immunoexpression of hormones as well as transcription factors. Since 2017, the classification has continued to evolve with the identification of aggressive histological variants. There is more recently a proposal to change the terminology from pituitary adenoma to pituitary neuroendocrine tumor (PitNET). This review summarizes the recent advances in the classification of pituitary adenomas.

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Pituitary adenomas are one of the common indications for gamma knife radiosurgery. Gamma knife enables one to deliver a very high radiation dose to the target in a single fraction. Due to steep radiation fall out of Gamma Knife, the adjacent visual apparatus gets minimal radiation. The aim of stereotactic radiosurgery for pituitary adenomas is to stop tumor growth, normalize hormonal hypersecretion, preserve pituitary function, and protect important surrounding structures. Surgery is the treatment modality of choice in the management of pituitary adenomas and gamma knife radiosurgery is restricted for residual or recurrent lesions only. The acceptable marginal dose for non-functional adenomas is 12 Gy. Control rates varies from 76-87% at 10 years are described in non-functional pituitary adenomas. In functional adenomas, to achieve hormonal remission a higher marginal dose up to 25 Gy is needed. However, primary gamma knife radiosurgery is needed in some situations – for instance, when the patient is unfit for surgery due to various reasons or surgical difficulties like the presence of kissing carotids.

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Pituitary adenomas (PA) account for approximately 15% of all intracranial neoplasms. Pituitary adenomas can be of different subtypes based on the cell of origin or associated hormone hypersecretion (non-functioning pituitary adenoma, prolactinoma, somatotropinoma, corticotropinoma, thyrotropinoma, and gonadotropinoma). Functioning PAs are associated with relatively higher morbidity and mortality because of associated hormone hypersecretion syndromes. Diagnosis of functioning PA is established by biochemical confirmation of hormone hypersecretion and demonstration of a pituitary lesion on imaging. Trans-sphenoidal surgical resection of tumor represents the first-line treatment for most tumor types, except for prolactinomas where medical therapy with dopamine agonists is preferred. Radiotherapy (RT) and medical therapy are the other options for the management of PA. It is important to individualize treatment options based on tumor type, patient's clinical condition, expertise of surgeon, affordability and patient preferences. In the first part of this series, we review the presentation and management of adrenocorticotropic hormone secreting, gonadotropin secreting and aggressive PA. Despite several recent advances, the diagnosis and management of Cushing's disease is still a challenge. Modifications in magnetic resonance imaging techniques like volume interpolated 3D spoiled gradient echo sequence have improved the sensitivity to detect microcorticotropinomas. Pituitary RT, preferably conventional RT, is a useful second-line therapy for the management of CD. Besides the conventional drugs, few drugs such as pasireotide and osilodrostat have been approved by US FDA recently, whereas several others are in pipeline which provide hope for a better outcome in CD patients. Temozolomide is a useful drug for the management of aggressive PA.

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Growth hormone (GH) hypersecretion from a pituitary adenoma results in acromegaly, an endocrinological disorder with multiple systemic manifestations that presents several unique challenges in terms of perioperative management and long term outcomes. Current guidelines provide stringent criteria for determining biochemical remission, necessitating an aggressive approach to management. Despite the development of several non-surgical therapies, transsphenoidal surgery, the endoscopic approach in particular, remains the primary line of treatment for rapid normalization of GH and Insulin-like growth factor with a low incidence of perioperative morbidity. Tumor size and invasiveness are important factors predicting surgical outcomes with better rates of postoperative remission seen in smaller and non-invasive tumors. Postoperative remission rates reported in literature with the 2020 consensus criteria vary from 30 to 85% probably reflecting varying prevalence rates of invasive tumors. Thus, a significant proportion of patients fail to achieve remission after surgery for whom treatment options for residual disease must be carefully considered. This review article discusses the surgical management of acromegaly and provides a summary of contemporary outcomes and current treatment controversies.

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Prolactinomas are a complex neuroendocrine challenge for the neurosurgeon. Management of prolactinoma patients requires centres that include neuroendocrinologists, neurosurgeons, neuroradiologists. Although dopamine agonists are the current mainstay of management of prolactinomas, surgery was often preferred management option prior to 1980, before the advent of dopamine agonists. Importantly, all patients with neurologic symptoms suspected due to the lesion, and those risk of adverse effects of medical management, treatment failure, resistance to dopamine agonists and those planning pregnancy, should be referred to a neurosurgeon at the earliest possible. When selected after meticulous evaluation, in patients with neurological deficits like acute visual loss, intolerance to medical therapy, or treatment failures, surgical intervention could come to rescue. Encouragingly, when carefully selected, surgical remission rates are high. In the current review, we review the existing literature and share the experience at our centre in the surgical management of prolactinomas.

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The authors review the anatomy of the pituitary gland on the basis of cadaver dissection studies and anatomy of dural relationships of pituitary tumors and its extensions on the basis of a 35-year-old experience of surgically treating pituitary tumors. Perfect understanding of anatomical correlates and nuances of pituitary tumor surgery is essential to achieve satisfactory surgical results. The pituitary gland is located in a specially enclosed cavity that is neither intracranial nor extracranial. It is covered strategically by meninges. Pituitary gland has a close relationship with cavernous sinuses and sphenoid air sinus. Pituitary tumors range widely in their size. Whilst microadenomas are generally associated with hormonally active tumors, large and giant sized tumors are usually hormonally non-functional. Surgical issues are unique for all sizes of pituitary tumors. Giant pituitary tumors grow in size, but a majority of them are confined to dural compartmental space. Recently proposed classification schemes have enhanced the understanding of anatomical subtleties and dural relationships of growing and giant pituitary tumors.

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The most common sellar pathology that merits neurosurgical attention is the pituitary adenoma. However, some developmental, inflammatory, and neoplastic lesions may primarily or secondarily involve the sella, mimicking pituitary tumors. Advances in imaging and endocrinological assessment have helped in the recognition of these less common sellar, supra sellar pathologies, which may occasionally create confusion in management. The most common developmental anomaly is the Rathke's cleft cyst and an increasingly recognized inflammatory pathology is the spectrum of hypophysitis. Neoplasms, viz. Craniopharyngioma, Germinoma, Langerhans's cell histiocytosis or metastasis, have more distinctive features in various age groups and are more likely to be correctly diagnosed on current imaging and managed accordingly. This review looks at mainly intraparenchymal pathologies, namely Rathke's Cleft Cyst and various hypophysitides, and will discuss their management strategies.

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CNS tumours and their treatment commonly lead to endocrinopathies in children. Advances in surgical techniques, chemotherapy and radiotherapy have improved the survival in children with CNS tumours however they have also added to the late effect burden. Since the pituitary and hypothalamus regulate many important bodily functions, loss in their function leads to major derangements in growth and hormonal milieu. This article is a review of clinical presentation, diagnosis and management of endocrinopathies encountered in common sellar and supra-sellar CNS tumours in children. The management is divided into mainly two sections: immediate (peri and post-operative) and long term.

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Cushing's disease is caused by a pituitary tumor causing increased production of adrenocorticotropic hormone, which leads to chronic hypersecretion of cortisol through adrenal cortices. Endoscopic trans-sphenoidal adenomectomy is the first choice of treatment with greatest efficiency for the treatment of the disease. However, in the absence of remission or recurrence of hypercortisolism after neurosurgical resection (adenomectomy), as well as in cases when surgical intervention cannot be carried due to medical contraindications to surgical intervention, radiation treatment is used as an alternative or adjoining therapy. In this literature review the efficiency of different radiation techniques (the conventional and the modern techniques), as well as possible complications of modern methods of radiosurgery and radiotherapy have been looked for.

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Background: Endoscopic endonasal transsphenoidal approach has become the workhorse for pituitary adenomas. The residual rates and complications continue to present as challenges for the pituitary surgeons. Objective: To review the recent developments in endoscopic pituitary surgeries for improving patient outcomes and safety rates Methodology: A search of the last ten years, on PubMed and Google Scholar was performed with the keywords “Pituitary and Neuroendoscopy”. A total of 345 articles were found (44 review, 193 original). Relevant articles were chosen. Results: Substantial improvement has taken place in the field of endoscopic pituitary surgery in the last decade. These include 3D printing, 3D endoscopes, 3D neuronavigation, multi-modal neuronavigation, ultra-high-definition endoscopes, optical fluorescence agents, intraoperative MRI, to name a few. Conclusion: The technological advancements have increased the resection rates, improved patient outcomes, and helped in the training of younger surgeons. A higher cost remains a concern.

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Functioning pituitary tumors contribute to significant morbidity and mortality. Proper diagnostic approach and management is essential for optimal outcomes. Prolactinomas, the commonest of these, are the only tumors which can be managed medically. Acromegaly, apart from acral enlargement, can have multiple comorbidities like diabetes, hypertension, and obstructive sleep apnea. The primary treatment is surgical and it can be supplemented by radiotherapy and medications such as somatostatin analogs, growth hormone receptor blockers, or cabergoline. Thyrotropin-secreting tumors are rare and present with hyperthyroidism. Optimal preoperative management followed by surgical resection often leads to cure.

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Introduction: Endoscopic endonasal approach (EEA) has become the preferred surgical approach for resection of pituitary adenomas in most centers. This technique has a number of advantages such as improved visualization and maneuverability, when compared to microscopic transsphenoidal approach. However, the long-term results of this approach are still scarce. Ten years ago, we published our initial series of patients having undergone an endoscopic removal of their pituitary adenomas reporting favorable short-term results. This project aims to revisit the results of that series, addressing the long-term results regarding recurrence of pituitary adenomas. Methods: A retrospective analysis of consecutive, endoscopically managed pituitary adenomas in a single center from 2004-2007. Only patients with >5 years of follow up (FU) and complete follow up data were included in this study. Recurrences were defined as evidence of any new tumor growth or enlargement of previously noted residual adenoma and/or biochemical recurrence of disease activity, in cases of functioning adenomas. Results: A total of 98 patients matched the inclusion criteria for this study. The median follow-up period was 144 months. Nonfunctioning adenoma was the most common subtype (n = 66, 67.3%), followed by GH-secreting tumors (n = 19, 19.4%), ACTH-secreting tumors (n = 7, 7.1%), prolactinomas (n = 4, 4.1%) and TSH-secreting adenomas (n = 2, 2%). Age ranges from 23 to 82 years, with median age of 53 years. Preoperative visual deficits were observed in 46 patients (46.9%) and hormonal deficits were identified in 31% of cases. 22.4% of patients had undergone a previous pituitary adenomas resection prior to treatment in our center. Surgery achieved gross total resection (GTR) and near total resection (NTR) in 89 cases (90.8%) (56.1% and 34.7%, respectively). A total of 37 cases had recurrences during FU (mean recurrence free survival: 80 months). Recurrences were observed in 34% of patients who had had GTR while recurrences were observed in 39.5% of cases that underwent subtotal resection. Most recurrences occurred after 5 years of FU and univariate analysis demonstrated previous surgery (P = 0.005), cavernous sinus invasion (P = 0.05) and Ki-67 >5% (P = 0.01) to be factors associated with higher chance of recurrence. Multivariate Cox-regression analysis demonstrate that previous surgery and Ki-67 >5% are factors associated with recurrences. Surgery and/or radiation were utilized for management of recurrences in 29/37 cases. Conclusion: Long-term FU analysis demonstrates that progression/recurrence of previously resected adenomas is observed in a significant number of patients, especially in those with previous/multiple surgical resections, elevated ki-67 and cavernous sinus invasion. Short-term FU may shadow real tumor control rates achieved after EEA and underscores the importance of long-term FU in these patients. Therefore, long-term FU should be pursued in all cases.

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Endoscopic endonasal surgery for pituitary tumors can be performed safely with a good outcome. Complications are uncommon and relate most often to nearby structures at risk. The authors detail the nuances, tips and tricks useful in avoiding complications and their early detection and management.

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The aim of the present paper is to provide essential knowledge of neuroendocrinology. This article is based on the daily experience and frequent confrontation with endocrinological problems interdisciplinary cooperation since the early time when determination of pituitary hormones became available.

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Pituitary tumors may well be the most common brain tumors with a mean incidence of 16.7%. Even small tumors become symptomatic when they arise from functioning cells and produce devastating effects on the body. The nonfunctioning tumors may become quite large before producing symptoms due to raised intracranial pressure or mass effect on the surrounding structures, most commonly, the optic apparatus. Many of them remain asymptomatic through life. Evolution of pituitary surgery is testimony to the advances in diagnostic and surgical techniques in neurosurgery and improved understanding of 360° of surgical skullbase anatomy as well as the need to provide not only immediate good postoperative results but also a long-lasting relief. Despite considerable advances in medical treatment as well as focussed radiation techniques, surgery remains the primary treatment in many of these tumors. Visual improvement, hormonal cure, avoidance of hypopituitarism, and neurological deficit remain immediate goals of surgery. Long-term cure or remission may require a multidisciplinary approach.

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Objective and Aims: To study hormonal axis (HA) dysfunction pre-operatively and at three months after surgery in patients with large (>3 cms) (Hardy's grade C) and giant (>4 cms) nonfunctioning pituitary adenomas (NFPA). Methods: One hundred thirty nine patients operated between 2006 and 2017, with 3 months post-operative hormonal evaluation, were included in this retrospective study. HA damage was categorized as 0 to 3 based on number of axes (thyrotroph, corticotroph and gonadotroph) that were affected. Risk factors studied for HA dysfunction before and after surgery included duration of symptoms, size of tumor, diabetes mellitus, hypertension and extent of resection. Results: Preoperatively 45 (32.3%) had no axis involvement, 34 (24.4%), 36 (25.8%) and 24 (17.2%) had one, two and three axes involvement respectively. Thyrotroph axis was affected in most patients. Tumor volume had significant correlation with preoperative pituitary dysfunction (P < 0.000). Post-operatively HA function remained same in 100 (72%), improved in only 7 (5%) and worsened in 32 (23%) of the patients. Of the 3 HA, corticotroph function worsened in most patients. None of the patients who had dysfunction in all three axes had improvement after surgery. No significant risk factors were associated with post-operative pituitary function outcomes. Persistent diabetes insipidus was noted in six (4.3%) patients. Conclusion: Pre-operatively anterior pituitary dysfunction is noted in nearly two-thirds of patients with large and giant NFA. Tumor volume >15 cc had significant correlation with pre-operative panhypopituitarism. Post-operatively, pituitary function remains the same in nearly three quarters of the patients. No significant risk factors were found for post-operative hormonal outcomes.

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Background: The COVID-19 pandemic is currently an evolving situation. Operating rooms (OR) are high-risk areas for the transmission of any respiratory infection with multiple personnel involved, in close proximity. Of concern to neurosurgeons, is the high-risk of aerosol generating procedures (AGPs) like transsphenoidal and endonasal surgery. Endonasal AGPs theoretically present a higher risk of viral exposure due to the longer duration of exposure and aggressive disruption of potentially virus-containing mucosa. Objective: The current review discusses potential strategies to neuro-surgeons to avoid transmission of COVID 19 during endo-nasal and trans-sphenoidal surgeries. Materials and Methods: We searched PubMed using the search terms “COVID-19”, “SARS-CoV-2”, “coronavirus” in combination with “neurosurgery”, and identified 13 relevant articles. A pre-surgical risk assessment score is proposed based on the risk of transmission. A flow chart of patient selection and care has been formulated. Conclusion: In all emergency patients, it is preferable to consider transcranial surgery or a sub-labial approach avoiding exposure to mucosa. Due to laboratory constraints routine swabs is not always available. Therefore, routine preoperative screening computed tomography (CT) chest is performed in all patients. Based on risk of transmission of infection to others, we propose a classification of patients for skull-based surgery into low, high and very high risk groups and suggest suitable personal protective equipment. Additionally, we discuss avoiding use of powered drills in or any AGP. However, cold procedures involving shavers and microdebriders generate lesser amounts of aerosol. Post-operatively, the length of stay could be reduced with a multidisciplinary approach.

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Even in ideal circumstances, the performance of safe and effective endoscopic transsphenoidal pituitary surgery requires complicated orchestration of care amongst multiple medical and surgical teams in the preoperative, intraoperative, and postoperative settings. The current COVID-19 pandemic further complicates this highly orchestrated effort. Healthcare systems around the globe are working to adapt to the rapidly changing healthcare landscape as information about the SARS-CoV-2 virus is discovered and disseminated. The nature of the transsphenoidal corridor exposes the pituitary surgery team to increased risk of virus exposure.

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