Perioperative hypothalamic pituitary adrenal function in patients with silent corticotroph adenomas.

BACKGROUND: Silent corticotroph adenomas (SCAs) are characterized by strong ACTH immunostaining without clinical manifestations of hypercortisolism. Patients with SCAs often present with mechanical symptoms related to tumor growth. This study investigates the hypothalamic pituitary adrenal axis (HPA) characteristics after adenomectomy in patients with SCAs. METHODS: Biochemical parameters of HPA function were monitored frequently after surgical resection of non-functioning macroadenomas. Levels of ACTH, cortisol, DHEA and DHEA-S were measured frequently for 48 h after adenomectomy. HPA data of patients with SCAs (n = 38) were compared to others (Controls) with non-secreting, ACTH-negative immunostaining adenomas of similar age and gender distribution (n = 182) who had adenomectomy. RESULT: Plasma ACTH increased (P < 0.0001) equally in patients with SCA and controls reaching a peak at 3 h (238 ± 123 vs. 233 ± 96 ng/L, respectively) after extubation declining thereafter to baseline values 24-36 h. Similarly, serum cortisol levels increased (P < 0.0001) equally in both groups reaching a maximum at 7 h (36.8 ± 13.9 vs. 39.3 ± 13.3 ug/dL). Serum DHEA also increased (P < 0.001) equally in both groups in parallel to the rise in serum cortisol. Serum DHEA-S levels similarly increased (P < 0.001) from their respective baseline (105.9 ± 67.5 and 106.5 ± 58.7 ug/dL) reaching their peak (154.5 ± 69.5 and 153.5 ± 68.6 ug/dL; respectively) at 15 h after extubation. None of the patients acquired any hormone deficits. CONCLUSIONS: Under the maximal stimulation of the peri-operative stress, HPA function in patients with SCA behaved in an identical manner to others with ACTH-negative macroadenomas. Thus, despite the strong ACTH-positive immunostaining of these tumors, SCAs are truly non- functional.

Utilization of sinus stents as a novel approach for benign cystic lesions of the sella.

Steroid-releasing sinus stents have emerged as a safe and effective tool in endoscopic sinus surgery. In this case report, we present two patients with recurrent cystic sellar masses. Transsphenoidal approach was used to access the sella. Following resection and drainage of the cystic pathology, a Propel (Menlo Park, CA) stent was placed through the corridor of the resection site to stent the cavity open. This is the first report where a steroid-releasing sinus stent was used in the treatment of a sellar lesion. It supports that this technology is safe and effective for use in skull base surgery.

Postnatal Pancraniosynostosis in a Patient With Infantile Hypophosphatasia.

Hypophosphatasia is a rare metabolic bone disorder that predisposes patients to craniosynostosis. Typically, patients born with hypophosphatasia will exhibit fused cranial sutures at birth. This is the first reported case of delayed onset of pancraniosynostosis in a patient with infantile hypophosphatasia. The severity of onset and delayed presentation in this patient are of interest and should give pause to those care providers who treat and evaluate patients with hypophosphatasia.

Trends in central nervous system tumor incidence relative to other common cancers in adults, adolescents, and children in the United States, 2000 to 2010.

BACKGROUND: Time trends in cancer incidence rates (IR) are important to measure the changing burden of cancer on a population over time. The overall IR of cancer in the United States is declining. Although central nervous system tumors (CNST) are rare, they contribute disproportionately to mortality and morbidity. In this analysis, the authors examined trends in the incidence of the most common cancers and CNST between 2000 and 2010. METHODS: The current analysis used data from the United States Cancer Statistics publication and the Central Brain Tumor Registry of the United States. Age-adjusted IR per 100,000 population with 95% confidence intervals and the annual percent change (APC) with 95% confidence intervals were calculated for selected common cancers and CNST overall and by age, sex, race/ethnicity, selected histologies, and malignancy status. RESULTS: In adults, there were significant decreases in colon (2000-2010: APC, -3.1), breast (2000-2010: APC, -0.8), lung (2000-2010: APC, -1.1), and prostate (2000-2010: APC, -2.4) cancer as well as malignant CNST (2008-2010: APC, -3.1), but a significant increase was noted in nonmalignant CNST (2004-2010: APC, 2.7). In adolescents, there were significant increases in malignant CNST (2000-2008: APC, 1.0) and nonmalignant CNST (2004-2010: APC, 3.9). In children, there were significant increases in acute lymphocytic leukemia (2000-2010: APC, 1.0), non-Hodgkin lymphoma (2000-2010: APC, 0.6), and malignant CNST (2000-2010: APC, 0.6). CONCLUSIONS: Surveillance of IR trends is an important way to measure the changing public health and economic burden of cancer. In the current study, there were significant decreases noted in the incidence of adult cancer, whereas adolescent and childhood cancer IR were either stable or increasing.

Pitfalls in the diagnosis and management of Cushing's syndrome.

Despite many recent advances, the management of patients with Cushing's disease continues to be challenging. Cushing's syndrome is a complex metabolic disorder that is a result of excess glucocorticoids. Excluding the exogenous causes, adrenocorticotropic hormone-secreting pituitary adenomas account for nearly 70% of all cases of Cushing's syndrome. The suspicion, diagnosis, and differential diagnosis require a logical systematic approach with attention paid to key details at each investigational step. A diagnosis of endogenous Cushing's syndrome is usually suspected in patients with clinical symptoms and confirmed by using multiple biochemical tests. Each of the biochemical tests used to establish the diagnosis has limitations that need to be considered for proper interpretation. Although some tests determine the total daily urinary excretion of cortisol, many others rely on measurements of serum cortisol at baseline and after stimulation (e.g., after corticotropin-releasing hormone) or suppression (e.g., dexamethasone) with agents that influence the hypothalamic-pituitary-adrenal axis. Other tests (e.g., measurements of late-night salivary cortisol concentration) rely on alterations in the diurnal rhythm of cortisol secretion. Because more than 90% of the cortisol in the circulation is protein bound, any alteration in the binding proteins (transcortin and albumin) will automatically influence the measured level and confound the interpretation of stimulation and suppression data, which are the basis for establishing the diagnosis of Cushing's syndrome. Although measuring late-night salivary cortisol seems to be an excellent initial test for hypercortisolism, it may be confounded by poor sampling methods and contamination. Measurements of 24-hour urinary free-cortisol excretion could be misleading in the presence of some pathological and physiological conditions. Dexamethasone suppression tests can be affected by illnesses that alter the absorption of the drug (e.g., malabsorption, celiac disease) and by the concurrent use of medications that interfere with its metabolism (e.g., inducers and inhibitors of the P450 enzyme system). In this review, the authors aim to review the pitfalls commonly encountered in the workup of patients suspected to have hypercortisolism. The optimal diagnosis and therapy for patients with Cushing's disease require the thorough and close coordination and involvement of all members of the management team.

Clinical and biochemical characteristic features of metastatic cancer to the sella turcica: an analytical review.

BACKGROUND AND OBJECTIVES: Sellar metastasis is uncommon and poorly characterized as published data include small series of subjects. This study's goal is to identify unique features that differentiate this entity from other sellar masses such as pituitary macroadenomas. METHODS: Published cases of pathologically-confirmed sellar metastasis along with our experience in such patients over a 6-years period were reviewed (total = 129). As a control group, we reviewed similar data on 55 patients with pituitary macroadenomas managed over the same time-period. Presenting symptoms, pituitary dysfunction were analyzed using univariate, multivariate and receiver operating characteristic (ROC) analyses. RESULTS: Sellar metastasis has equal gender distribution with a median patient-age of 56 years. The most common primary malignancy was breast cancer (29%) in women and lung cancer (30%) in men. Sellar metastasis was the first manifestation of cancer in over 40% of patients. Common presenting symptoms included headaches, visual field deficits, abnormal eye motility and diabetes insipidus. These symptoms were less frequent among patients with pituitary macroadenomas. Univariate regression analyses showed that headaches, abnormal eye motility, visual field deficits and diabetes insipidus were each predictive of metastatic disease. ROC analysis combining all 4 features revealed an AUC of 0.953 with a sensitivity of 0.818 and a specificity of 0.935. Using the multivariate regression, abnormal eye motility and/or diabetes insipidus independently predicted metastatic disease. CONCLUSIONS: Sellar metastasis should be suspected in patients presenting with sellar masses, abnormal eye motility and/or diabetes insipidus even those without known malignancy since pituitary metastasis can often be the first manifestation of cancer.

Peritumoral brain edema in intracranial meningiomas: the emergence of vascular endothelial growth factor-directed therapy.

Meningioma is the second most common type of adult intracranial neoplasm. A substantial subset of patients present with peritumoral brain edema (PTBE), which can cause significant morbidity via mass effect, complicate surgical management, and impact the safety of stereotactic radiosurgery. Recent studies suggest a close relationship between vascular endothelial growth factor-A (VEGF-A) expression and PTBE development in meningiomas. The authors performed a systematic review of the literature on the pathogenesis of PTBE in meningiomas, the effectiveness of steroid therapy, the role played by VEGF-A, and the current clinical evidence for antiangiogenic therapy to treat peritumoral brain edema. Mounting evidence suggests VEGF-A is secreted directly by meningioma cells to induce angiogenesis and edemagenesis of tumoral as well as peritumoral brain tissue. The VEGF-A cascade results in recruitment of cerebral-pial vessels and disruption of the tumor-brain barrier, which appear to be requisite for VEGF-A to have an edemagenic effect. Results of preliminary clinical studies suggest VEGF-directed therapy has modest activity against recurrent and progressive meningioma growth but can alleviate PTBE in some patients. A comprehensive understanding of the VEGF-A pathway and its modulators may hold the key to an effective therapeutic approach to treating PTBE associated with meningiomas. Further clinical trials with larger patient cohorts and longer follow-up periods are warranted to confirm the efficacy of VEGF-directed therapy.

Petroclival meningiomas: an update on surgical approaches, decision making, and treatment results.

OBJECT: Petroclival meningiomas remain a formidable challenge for neurosurgeons because of their location deep within the skull base and proximity to eloquent neurovascular structures. Various skull base approaches have been used in their treatment, and deciding which is the optimal one remains controversial. Attempts at achieving gross- or near-total resections are associated with an increased rate of morbidity and mortality. As adjunctive treatment options such as stereotactic radiosurgery have been developed and become widely available, there has been a trend toward accepting subtotal resections in an effort to minimize neurological morbidity. This paper reviews a recent series of patients with petroclival meningiomas and highlights current management trends and important considerations useful in surgical decision making. METHODS: The records of patients with large (> 3 cm) petroclival meningiomas surgically treated by the senior author over the past 5 years were reviewed. The clinical results are presented as examples of the surgical approaches available for approaching these tumors, and treatment options are reviewed. RESULTS: Of 196 meningiomas surgically treated during the study period, 8 lesions in 8 patients met the study criteria. Overall clinical results were excellent, with no death or major morbidity. Intracranial gross- or near-total resection (Simpson Grade 1, 2, or 3) was achieved in 5 patients (67%). New cranial nerve deficits occurred in 3 patients (37%) and were more common in patients in whom a subtotal resection was performed (2 of 3 cases). A variety of surgical approaches were used. Important considerations determining the best approach include the location of the tumor relative to the internal auditory canal, the presence of preoperative hearing loss, and the location of the tumor relative to the tentorium. CONCLUSIONS: Achieving gross- or near-total resections of large petroclival meningiomas remains achievable and should be the primary goal of surgical treatment. A retrosigmoid craniotomy remains a workhorse surgical approach for most petroclival tumors of any size. Tumors that are medial to the internal auditory canal and span both middle and posterior cranial fossae are often best treated with a combined transpetrosal approach, which is especially true if there is a preoperative hearing deficit.

Meningoencephalocele of the temporal bone: pictorial essay on transmastoid extradural-intracranial repair.

PURPOSE: A spontaneous meningoencephalocele of the temporal bone may present with effusion in the middle ear, a cerebrospinal fluid leak, hearing loss, or rarely otitic meningitis. Repair of spontaneous encephaloceles in the temporal bone has been performed using transmastoid and transcranial middle fossa approaches or a combination of the two with varied results. The authors present a technical paper on the transmastoid extradural intracranial approach for the management of temporal lobe encephaloceles. MATERIALS/METHODS: Case reports and cadaver dissections are used to provide a pictorial essay on the technique. Advantages and disadvantages compared with alternative surgical approaches are discussed. RESULTS: Traditional transmastoid approaches are less morbid compared with a transcranial repair as they avoid brain retraction. However, in the past, there has been a higher risk of graft failure and hearing loss due to downward graft migration and a potential need for ossicular disarticulation. For the appropriate lesion, the transmastoid extradural intracranial approach lesion offers a stable meningoencephalocele repair without the comorbidity of brain retraction. CONCLUSION: The authors describe a transmastoid extradural intracranial technique via case reports and cadaver dissections for the repair of spontaneous meningoencephalocele defects larger than 2 cm. This approach provides more support to the graft compared to the conventional transmastoid repair.

Cerebral amyloid angiopathy-associated intracerebral hemorrhage: pathology and management.

Amyloid angiopathy-associated intracerebral hemorrhage (ICH) comprises 12%-15% of lobar ICH in the elderly. This growing population has an increasing incidence of thrombolysis-related hemorrhages, causing the management of hemorrhages associated with cerebral amyloid angiopathy (CAA) to take center stage. A concise reference assimilating the pathology and management of this clinical entity does not exist. Amyloid angiopathy-associated hemorrhages are most often solitary, but the natural history often progresses to include multifocal and recurrent hemorrhages. Compared with other causes of ICH, patients with CAA-associated hemorrhages have a lower mortality rate but an increased risk of recurrence. Unlike hypertensive arteriolar hemorrhages that occur in penetrating subcortical vessels, CAA-associated hemorrhages are superficial in location due to preferential involvement of vessels in the cerebral cortex and meninges. This feature makes CAA-associated hemorrhages easier to access surgically. In this paper, the authors discuss 3 postulates regarding the pathogenesis of amyloid hemorrhages, as well as the established clinicopathological classification of amyloid angiopathy and CAA-associated ICH. Common inheritance patterns of familial CAA with hemorrhagic strokes are discussed along with the role of genetic screening in relatives of patients with CAA. The radiological characteristics of CAA are described with specific attention to CAA-associated microhemorrhages. The detection of these microhemorrhages may have important clinical implications on the administration of anticoagulation and antiplatelet therapy in patients with probable CAA. Poor patient outcome in CAA-associated ICH is associated with dementia, increasing age, hematoma volume and location, initial Glasgow Coma Scale score, and intraventricular extension. The surgical management strategies for amyloid hemorrhages are discussed with a review of published surgical case series and their outcomes with a special attention to postoperative hemorrhage.

Activity of a Novel Anti-Inflammatory Agent F-3,6'-dithiopomalidomide as a Treatment for Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major risk factor for several neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease (AD). Neuroinflammation is a cause of later secondary cell death following TBI, has the potential to aggravate the initial impact, and provides a therapeutic target, albeit that has failed to translate into clinical trial success. Thalidomide-like compounds have neuroinflammation reduction properties across cellular and animal models of TBI and neurodegenerative disorders. They lower the generation of proinflammatory cytokines, particularly TNF-α which is pivotal in microglial cell activation. Unfortunately, thalidomide-like drugs possess adverse effects in humans before achieving anti-inflammatory drug levels. We developed F-3,6'-dithiopomalidomide (F-3,6'-DP) as a novel thalidomide-like compound to ameliorate inflammation. F-3,6'-DP binds to cereblon but does not efficiently trigger the degradation of the transcription factors (SALL4, Ikaros, and Aiolos) associated with the teratogenic and anti-proliferative responses of thalidomide-like drugs. We utilized a phenotypic drug discovery approach that employed cellular and animal models in the selection and development of F-3,6'-DP. F-3,6'-DP significantly mitigated LPS-induced inflammatory markers in RAW 264.7 cells, and lowered proinflammatory cytokine/chemokine levels in the plasma and brain of rats challenged with systemic LPS. We subsequently examined immunohistochemical, biochemical, and behavioral measures following controlled cortical impact (CCI) in mice, a model of moderate TBI known to induce inflammation. F-3,6'-DP decreased CCI-induced neuroinflammation, neuronal loss, and behavioral deficits when administered after TBI. F-3,6'-DP represents a novel class of thalidomide-like drugs that do not lower classical cereblon-associated transcription factors but retain anti-inflammatory actions and possess efficacy in the treatment of TBI and potentially longer-term neurodegenerative disorders.

3,6'- and 1,6'-Dithiopomalidomide Mitigate Ischemic Stroke in Rats and Blunt Inflammation.

(1) Background: An important concomitant of stroke is neuroinflammation. Pomalidomide, a clinically available immunomodulatory imide drug (IMiD) used in cancer therapy, lowers TNF-α generation and thus has potent anti-inflammatory actions. Well-tolerated analogs may provide a stroke treatment and allow evaluation of the role of neuroinflammation in the ischemic brain. (2) Methods: Two novel pomalidomide derivatives, 3,6'-dithiopomalidomide (3,6'-DP) and 1,6'-dithiopomalidomide (1,6'-DP), were evaluated alongside pomalidomide in a rat middle cerebral artery occlusion (MCAo) stroke model, and their anti-inflammatory actions were characterized. (3) Results: Post-MCAo administration of all drugs lowered pro-inflammatory TNF-α and IL1-ß levels, and reduced stroke-induced postural asymmetry and infarct size. Whereas 3,6'- and 1,6'-DP, like pomalidomide, potently bound to cereblon in cellular studies, 3,6'-DP did not lower Ikaros, Aiolos or SALL4 levels-critical intermediates mediating the anticancer/teratogenic actions of pomalidomide and IMiDs. 3,6'-DP and 1,6'-DP lacked activity in mammalian chromosome aberration, AMES and hERG channel assays -critical FDA regulatory tests. Finally, 3,6'- and 1,6'-DP mitigated inflammation across rat primary dopaminergic neuron and microglia mixed cultures challenged with α-synuclein and mouse LPS-challenged RAW 264.7 cells. (4) Conclusion: Neuroinflammation mediated via TNF-α plays a key role in stroke outcome, and 3,6'-DP and 1,6'-DP may prove valuable as stroke therapies and thus warrant further preclinical development.

Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors.

BACKGROUND: DNA methylation abnormalities are pervasive in pituitary neuroendocrine tumors (PitNETs). The feasibility to detect methylome alterations in circulating cell-free DNA (cfDNA) has been reported for several central nervous system (CNS) tumors but not across PitNETs. The aim of the study was to use the liquid biopsy (LB) approach to detect PitNET-specific methylation signatures to differentiate these tumors from other sellar diseases. METHODS: We profiled the cfDNA methylome (EPIC array) of 59 serum and 41 plasma LB specimens from patients with PitNETs and other CNS diseases (sellar tumors and other pituitary non-neoplastic diseases, lower-grade gliomas, and skull-base meningiomas) or nontumor conditions, grouped as non-PitNET. RESULTS: Our results indicated that despite quantitative and qualitative differences between serum and plasma cfDNA composition, both sources of LB showed that patients with PitNETs presented a distinct methylome landscape compared to non-PitNETs. In addition, LB methylomes captured epigenetic features reported in PitNET tissue and provided information about cell-type composition. Using LB-derived PitNETs-specific signatures as input to develop machine-learning predictive models, we generated scores that distinguished PitNETs from non-PitNETs conditions, including sellar tumor and non-neoplastic pituitary diseases, with accuracies above ~93% in independent cohort sets. CONCLUSIONS: Our results underpin the potential application of methylation-based LB profiling as a noninvasive approach to identify clinically relevant epigenetic markers to diagnose and potentially impact the prognostication and management of patients with PitNETs.

Neurosurgery residency and fellowship education in the United States: 2 decades of system development by the One Neurosurgery Summit organizations.

The purpose of this report is to chronicle a 2-decade period of educational innovation and improvement, as well as governance reform, across the specialty of neurological surgery. Neurological surgery educational and professional governance systems have evolved substantially over the past 2 decades with the goal of improving training outcomes, patient safety, and the quality of US neurosurgical care. Innovations during this period have included the following: creating a consensus national curriculum; standardizing the length and structure of neurosurgical training; introducing educational outcomes milestones and required case minimums; establishing national skills, safety, and professionalism courses; systematically accrediting subspecialty fellowships; expanding professional development for educators; promoting training in research; and coordinating policy and strategy through the cooperation of national stakeholder organizations. A series of education summits held between 2007 and 2009 restructured some aspects of neurosurgical residency training. Since 2010, ongoing meetings of the One Neurosurgery Summit have provided strategic coordination for specialty definition, neurosurgical education, public policy, and governance. The Summit now includes leadership representatives from the Society of Neurological Surgeons, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, the American Board of Neurological Surgery, the Review Committee for Neurological Surgery of the Accreditation Council for Graduate Medical Education, the American Academy of Neurological Surgery, and the AANS/CNS Joint Washington Committee. Together, these organizations have increased the effectiveness and efficiency of the specialty of neurosurgery in advancing educational best practices, aligning policymaking, and coordinating strategic planning in order to meet the highest standards of professionalism and promote public health.

Evidence-based review of primary and secondary ischemic stroke prevention in adults: a neurosurgical perspective.

In this paper, the authors' aim is to provide an evidence-based review of primary and secondary ischemic stroke prevention guidelines covering most of the common risk factors and stroke etiologies for the practicing neurosurgeon. The key to stroke prevention is in the identification and treatment of the major risk factors for stroke. These include hypertension, heart disease, diabetes mellitus, dyslipidemia, and tobacco smoking. An updated approach to secondary prevention of stroke in the setting of intracranial and extracranial large vessel atherosclerosis and cardioembolism is provided along with a brief overview of pertinent clinical trials. Novel pharmacological options for prevention of cardioembolic strokes, such as new alternatives to warfarin, are addressed with recommendations for interruption of therapy for elective surgical procedures. In addition, the authors have reviewed the anticoagulation guidelines and the risk of thromboembolic complications of such therapies in the perioperative period, which is an invaluable piece of information for neurosurgeons. Less common etiologies such as arterial dissections and patent foramen ovale are also briefly discussed. Finally, the authors have outlined the quality measures in the Medicare Physician Quality Reporting System and essential guidelines for Primary Stroke Center certification, which have implications for day-to-day neurosurgical practice.

Drug Repurposing in the Treatment of Traumatic Brain Injury.

Traumatic brain injury (TBI) is the most common cause of morbidity among trauma patients; however, an effective pharmacological treatment has not yet been approved. Individuals with TBI are at greater risk of developing neurological illnesses such as Alzheimer's disease (AD) and Parkinson's disease (PD). The approval process for treatments can be accelerated by repurposing known drugs to treat the growing number of patients with TBI. This review focuses on the repurposing of N-acetyl cysteine (NAC), a drug currently approved to treat hepatotoxic overdose of acetaminophen. NAC also has antioxidant and anti-inflammatory properties that may be suitable for use in therapeutic treatments for TBI. Minocycline (MINO), a tetracycline antibiotic, has been shown to be effective in combination with NAC in preventing oligodendrocyte damage. (-)-phenserine (PHEN), an anti-acetylcholinesterase agent with additional non-cholinergic neuroprotective/neurotrophic properties initially developed to treat AD, has demonstrated efficacy in treating TBI. Recent literature indicates that NAC, MINO, and PHEN may serve as worthwhile repositioned therapeutics in treating TBI.

Peri-operative management of Cushing's disease.

Management of patients with ACTH producing pituitary adenoma remains to be challenging. Removal of the pituitary adenoma through transsphenoidal surgery is the main stay of treatment. Complete resection of the adenoma is followed by the development of ACTH deficiency since the normal corticotrophs are suppressed by the pre-existing hypercortisolemia. The concern for ACTH deficiency has led many centers to advocate the use glucocorticoids before, during and after surgery. We provide evidence that such coverage with glucocorticoids is unnecessary until clinical or biochemical documentation of need is established. Given that patients are closely monitored, they are immediately treated with glucocorticoids once they exhibit any clinical and/or biochemical evidence of adrenal insufficiency. Defining remission in the immediate postoperative period has been rather difficult despite using different biochemical markers. Serum cortisol continues to be the best determinant of disease activity after surgical adenomectomy. However it needs to be interpreted with caution as a biochemical marker of remission in patients given glucocorticoids during and after surgery. Other biochemical markers are also used in the peri-operative period to determine the possibility of remission. These include the dexamethasone suppression test, CRH stimulation without dexamethasone, urinary free cortisol measurements, desmopressin stimulation test, the determination of salivary cortisol and / or plasma ACTH concentrations. Each test has its own advantages and limitations. The simplest and most informative approach is to measure serum cortisol levels repeatedly after surgery without the administration of exogenous glucocorticoids. Low serum cortisol levels (less than 2 µg/dL) in the peri-operative period are highly indicative of surgical success and a high likelihood for clinical remission. Higher serum cortisol levels require careful interpretation and further planning and discussions between the patient and the management team.