HOW I DO IT: Cushing's disease-selective adenomectomy via an endoscopic transsphenoidal approach.

BACKGROUND: An ACTH-secreting pituitary adenoma is the most common cause of excessive endogenous glucocorticoid production resulting in Cushing's Syndrome. A multidisciplinary approach is paramount. Selective adenomectomy is the treatment of choice. METHOD: Endoscopic transnasal transsphenoidal approach to the tumour, along with techniques for resection, are demonstrated. CONCLUSION: Endoscopic transsphenoidal approaches with its magnified view of the pituitary gland allows precise microsurgical dissection during selective adenomectomy. This technique increases the possibility of proving a gross total resection, leading to clinical and biochemical cure in these patients.

Crooke Cell Adenoma Confers Poorer Endocrinological Outcomes Compared with Corticotroph Adenoma: Results of a Multicenter, International Analysis.

BACKGROUND: Crooke cell adenomas (CCAs) are a rare, aggressive subset of secretory pituitary corticotroph adenomas (sCTAs) found in 5%-10% of patients with Cushing disease. Multiple studies support worse outcomes in CCAs but are limited by small sample size and single-institution databases. We compared outcomes in CCA and sCTA using a multicenter, international retrospective database of high-volume skull base centers. METHODS: Patients surgically treated for pituitary adenoma from January 2017 through December 2020 were included. RESULTS: Among 2826 patients from 12 international centers, 20 patients with CCA and 480 patients with sCTA were identified. No difference in baseline demographics, tumor characteristics, or postoperative complications was seen. Microsurgical approaches (60% CCA vs. 62.3% sCTA) were most common. Gross total resection was higher in CCA patients (100% vs. 83%, P = 0.05). Among patients with gross total resection according to intraoperative findings, fewer CCA patients had postoperative hormone normalization of pituitary function (50% vs. 77.8%, P < 0.01) and remission of hypersecretion by 3-6 months (75% vs. 84.3%, P < 0.01). This was the case despite CCA having better local control rates (100% vs. 96%, P < 0.01) and fewer patients with remnant on magnetic resonance imaging (0% vs. 7.2%, P < 0.01). A systematic literature review of 35 studies reporting on various treatment strategies reiterated the high rate of residual tumor, persistent hypercortisolism, and tumor-related mortality in CCA patients. CONCLUSIONS: This modern, multicenter series of patients with CCA reflects their poor prognosis and reduced postsurgical hormonal normalization. Further work is necessary to better understand the pathophysiology of CCA to devise more targeted treatment approaches.

Postoperative Serum Cortisol and Cushing Disease Recurrence in Patients With Corticotroph Adenomas.

CONTEXT: In Cushing disease, the association between the rate of serum cortisol decline and recurrent disease after corticotroph adenoma removal has not been adequately characterized. OBJECTIVE: To analyze postoperative serum cortisol and recurrence rates in Cushing disease. METHODS: Patients with Cushing disease and pathology-confirmed corticotroph adenoma were retrospectively studied. Cortisol halving time was estimated using exponential decay modeling. Halving time, first postoperative cortisol, and nadir cortisol values were collected using immediate postoperative inpatient laboratory data. Recurrence and time-to-recurrence were estimated and compared among cortisol variables. RESULTS: A total of 320 patients met inclusion/exclusion criteria for final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 25 months (95% CI, 19-28 months), and 62 patients had ≥ 5 years follow-up time. Higher first postoperative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first postoperative cortisol ≥ 50 µg/dL were 4.1 times more likely to recur than those with a first postoperative cortisol < 50 µg/dL (HR 4.1, 1.8-9.2; P = .0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, P = .18). Patients with a nadir cortisol ≥2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, P < .0001). CONCLUSION: Postoperative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first postoperative cortisol and cortisol halving time, a nadir < 2 µg/dL showed the strongest association with long-term remission and typically occurs within the first 24 to 48 hours after surgery.

Cushing syndrome caused by an ectopic ACTH-producing pituitary adenoma of the clivus region: A rare case report and literature review.

RATIONALE: Ectopic ACTH-producing pituitary adenoma (EAPA) of the clivus region is extraordinarily infrequent condition and merely a few reports have been reported to date. PATIENT CONCERNS: The patient was a 53-year-old woman who presented with Cushing-like appearances and a soft tissue mass in the clivus region. DIAGNOSES: The final diagnosis of clivus region EAPA was established by clinical, radiological and histopathological findings. INTERVENTIONS: The patient underwent gross total clivus tumor resection via transsphenoidal endoscopy. OUTCOMES: Half a year after surgery, the patient Cushing-like clinical manifestations improved significantly, and urinary free cortisol and serum adrenocorticotropin (ACTH) returned to normal. LESSONS: Given the extreme scarcity of these tumors and their unique clinical presentations, it may be possible to misdiagnose and delayed treatment. Accordingly, it is especially crucial to summarize such lesions through our present case and review the literature for their precise diagnosis and the selection of optimal treatment strategies.

Radiomics model and clinical scale for the preoperative diagnosis of silent corticotroph adenomas.

OBJECTIVE: Silent corticotroph adenomas (SCAs) are a subtype of nonfunctioning pituitary adenomas that exhibit more aggressive behavior. However, rapid and accurate preoperative diagnostic methods are currently lacking. DESIGN: The purpose of this study was to examine the differences between SCA and non-SCA features and to establish radiomics models and a clinical scale for rapid and accurate prediction. METHODS: A total of 260 patients (72 SCAs vs. 188 NSCAs) with nonfunctioning adenomas from Peking Union Medical College Hospital were enrolled in the study as the internal dataset. Thirty-five patients (6 SCAs vs. 29 NSCAs) from Fuzhou General Hospital were enrolled as the external dataset. Radiomics models and an SCA scale to preoperatively diagnose SCAs were established based on MR images and clinical features. RESULTS: There were more female patients (internal dataset: p < 0.001; external dataset: p = 0.028) and more multiple microcystic changes (internal dataset: p < 0.001; external dataset: p = 0.012) in the SCA group. MRI showed more invasiveness (higher Knosp grades, p ≤ 0.001). The radiomics model achieved AUCs of 0.931 and 0.937 in the internal and external datasets, respectively. The clinical scale achieved an AUC of 0.877 and a sensitivity of 0.952 in the internal dataset and an AUC of 0.899 and a sensitivity of 1.0 in the external dataset. CONCLUSIONS: Based on clinical information and imaging characteristics, the constructed radiomics model achieved high preoperative diagnostic ability. The SCA scale achieved the purpose of rapidity and practicality while ensuring sensitivity, which is conducive to simplifying clinical work.

Clinical presentation and recurrence of pituitary neuroendocrine tumors: results from a single referral center in Colombia.

INTRODUCTION: Pituitary neuroendocrine tumors (PitNETs) represent 15-18.2% of all intracranial tumors. Their clinical presentation can range from chronic headache, visual defects, hypopituitarism to hormone excess syndromes. PitNETS are commonly classified as functioning neuroendocrine tumors (F-PitNETs) and non-functioning neuroendocrine tumors (NF-PitNETs). At the moment, new classification has emerged based on cell lineages. Almost 50% of all patients with PitNETs require surgical intervention, and about 25% of these have residual and persistent disease that may require additional management. SUBJECTS AND METHODS: A retrospective cohort of medical records of patients with PitNETs, aiming to describe the incidence of recurrence of patients who received surgical treatment over a 12 month follow up period at San Jose Hospital (SJH) in Bogotá, Colombia, over an observation period of 10 years. Furthermore, clinical presentation, biochemical characteristics and immunohistochemistry, postoperative complications are detailed. RESULTS: Eight hundred and eighty-seven patients with pituitary tumors were included in the cohort; 83% (737/887) had a diagnosis of PitNET. Of these, 18.9% (140) received surgical management. The majority 58% (98/140) had nonfunctional-PitNETs (NF-PitNETs), followed by growth-hormone-secreting pituitary adenoma (22.1%; 33/140), adrenocorticotropic- hormone-secreting pituitary adenoma (9.3%; 13/140), and prolactinomas (9.3%; 13/140). A recurrence was found in 45.71% (64/140), subclassified as biochemical in 15.71% (22/140), controlled with medications in 20% (28/140), and remission occurred in 18.57% (26/140). CONCLUSION: Clinical presentation and incidence of recurrence in patients with PitNETs in a referral center in Colombia are similar to other surgical cohorts with low cure rates and high recurrence.

Ectopic invasive ACTH-secreting pituitary adenoma mimicking chordoma: a case report and literature review.

BACKGROUND: Ectopic pituitary adenoma (EPA) is defined as a special type of pituitary adenoma that originates outside of the sellar region, is extra- or intra-cranially located, and without connection to normal pituitary tissue. EPA is extremely rare, with most cases presented as case reports or small case series. Due to nonspecific symptoms and laboratory indicators, the preoperative diagnosis, treatment and management for EPA remain challenging. CASE PRESENTATION: Here, we report the imaging phenotype and pathological findings of a case of invasive EPA in a 47-year-old woman. A preoperative non-contrast CT scan revealed a 5.8 × 3.6 × 3.7 cm soft tissue mass located in the sphenoid sinus and clivus. MRI showed an ill-defined solid mass with heterogeneous signals on T1-weighted and T2-weighted images. The mass displayed infiltrative growth pattern, destroying bone of the skull base, invading adjacent muscles and encasing vessels. The patient underwent partial tumor resection via transsphenoidal endoscopic surgery. Pathological examination led to diagnosis of ectopic ACTH-secreting pituitary adenoma. Post-surgery, the patient received external beam radiotherapy. CONCLUSION: EPA with invasive growth pattern has rarely been reported. The imaging phenotype displays its relationship to the pituitary tissue and surrounding structures. Immunohistochemical examination acts as a crucial role in differentiating EPA from other skull base tumors. This case report adds to the literature on EPA by summarizing its characteristics alongside a review of the literature.

Concurrent mutations of germline GPR101 and somatic USP8 in a pediatric giant pituitary ACTH adenoma: a case report.

BACKGROUND: Cushing's disease (CD) is rare in pediatric patients. It is characterized by elevated plasma adrenocorticotropic hormone (ACTH) from pituitary adenomas, with damage to multiple systems and development. In recent years, genetic studies have shed light on the etiology and several mutations have been identified in patients with CD. CASE PRESENTATION: A girl presented at the age of 10 years and 9 months with facial plethora, hirsutism and acne. Her vision and eye movements were impaired. A quick weight gain and slow growth were also observed. Physical examination revealed central obesity, moon face, buffalo hump, supra-clavicular fat pads and bruising. Her plasma ACTH level ranged between 118 and 151 pg/ml, and sella enhanced MRI showed a giant pituitary tumor of 51.8 × 29.3 × 14.0 mm. Transsphenoidal pituitary debulk adenomectomy was performed and immunohistochemical staining confirmed an ACTH-secreting adenoma. Genetic analysis identified a novel germline GPR101 (p.G169R) and a somatic USP8 (p. S719del) mutation. They were hypothesized to impact tumor growth and function, respectively. CONCLUSIONS: We reported a rare case of pediatric giant pituitary ACTH adenoma and pointed out that unusual concurrent mutations might contribute to its early onset and large volume.

Therapeutic difficulties in an aggressive ACTH-secreting pituitary adenoma.

Not required for Clinical Vignette.

Cushing Disease: Medical and Surgical Considerations.

Cushing disease is a disorder of hypercortisolemia caused by hypersecretion of adrenocorticotropic hormone by a pituitary adenoma and is a rare diagnosis. Cushing disease presents with characteristic clinical signs and symptoms associated with excess cortisol, but diagnosis is difficult and often relies on repeated and varied endocrinologic assays and neuroradiologic investigations. Gold standard treatment is surgical resection of adrenocorticotropic hormone-secreting pituitary adenoma, which is curative. Patients require close endocrinologic follow-up for maintenance of associated neuroendocrine deficiencies and surveillance for potential recurrence. Medications, radiation therapy, and bilateral adrenalectomy are alternative treatments for residual or recurrent disease.

Clinical Course and Unique Features of Silent Corticotroph Adenomas.

OBJECTIVE: Silent corticotroph adenomas (SCAs) behave more aggressively than other non-functioning adenomas (NFAs). This study aims to expand the body of knowledge of the behavior of SCAs. METHODS: Retrospective analysis of 196 non-corticotroph NFAs and 20 SCAs from 2012-2017 was completed. Demographics, clinical presentation, imaging, and biochemical data were gathered. The primary endpoint was to identify features of SCAs versus other NFAs that suggest aggressive disease, including pre-surgical comorbidities, postoperative complications, extent of tumor, and recurrence. Golden-angle radial sparse parallel (GRASP) magnetic resonance images were obtained from a subset of SCAs and NFAs. Permeability data were obtained to compare signal-to-time curve variation between the 2 groups. RESULTS: With multivariate regression analysis, SCAs showed higher rates of hemorrhage on preoperative imaging than NFAs (P = 0.017). SCAs presented more frequently with headache (P = 0.012), vision changes (P = 0.041), and fatigue (P = 0.028). SCAs exhibited greater extent of tumor burden with increased occurrence of stalk deviation (P = 0.008), suprasellar invasion (P = 0.021), optic chiasm compression (P = 0.022), and cavernous sinus invasion (P = 0.015). On GRASP imaging, SCAs had significantly lower permeability of contrast than NFAs (P = 0.001). Thirty percent of SCAs were noted to recur with a 14% recurrence rate in other NFAs, though this difference was not of statistical significance (P = 0.220). CONCLUSIONS: SCAs exhibit features of more aggressive disease. Interestingly, a significant increase in recurrence was not seen despite these features. The results of this study support the growing body of evidence that SCAs behave more aggressively than other NFPAs and was able to provide some insight into factors that may contribute to recurrence.

Functioning Crooke Cell Adenomas: Case Series and Literature Review.

BACKGROUND: Crooke cell adenomas (CCAs) are rare, potentially aggressive pituitary adenomas. Data regarding prevalence and clinical course are sparse. METHODS: We performed a retrospective review of 59 consecutive functioning corticotroph adenomas operated on between October 2017 and November 2020 and a literature review of CCA publications since 1991. RESULTS: The prevalence of CCAs among functioning corticotroph adenomas at our institution was 8.5% (5/59). In the 4 other surgical case series, prevalence of CCAs was 0%-6.8%. Our patients (4 women and 1 man, mean age 46 ± 11 years) presented with hypercortisolism (3/5), with vision loss (1/5), and incidentally (1/5). All patients had elevated adrenocorticotropic hormone (151 ± 54 pg/mL) and urinary free cortisol (830 ± 796.5 µg/day). Radiologically, 3 tumors were macroadenomas and 2 had cavernous sinus invasion. All patients achieved biochemical remission at 3 months postoperatively. One patient with a giant pituitary adenoma underwent fractionated radiation for residual tumor. During follow-up (range, 3.1-31.0 months), no patients had evidence of radiological or biochemical recurrence. The literature review identified 22 functioning corticotroph adenomas with outcome data. Additional treatments included reoperation (50%), radiation (59%), bilateral adrenalectomy (23%), and temozolomide (36%). CONCLUSIONS: We found a higher CCA prevalence among functioning adrenocorticotropic hormone adenomas after implementation of the 2017 World Health Organization classification. In our series and the literature, most CCAs were macroadenomas with high adrenocorticotropic hormone levels. Postoperative outcomes were excellent in our series, while some cases from the literature were refractory to standard treatments. Larger clinical and molecular studies are needed to identify patients at risk.

Perioperative Tranexamic Acid for ACTH-Secreting Pituitary Adenomas: Implementation Protocol Results and Trial Prospectus.

OBJECTIVE: Primary resection of adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma has become a front-line standard-of-care treatment for Cushing disease. However, surgical intervention can be challenging because of elevated blood pressure, as well as direct cortisol impacts on endothelial cells, vascular permeability, and tissue friability-potentially resulting in increased intraoperative bleeding. Tranexamic acid (TXA) is a well-studied, widely used intravenous hemostatic; however, the potential benefit during resection of ACTH-secreting pituitary adenoma is unstudied. The purpose of this study was to define an institutional protocol for perioperative administration of TXA in patients undergoing endoscopic endonasal approach for resection of ACTH-secreting pituitary adenoma, and to study the implementation of our novel protocol in a prospective fashion. METHODS: Criteria for preoperative TXA were defined by age, medical history, and risk factors. Descriptive statistics were reported for all patients receiving perioperative TXA. RESULTS: Thirty patients met inclusion criteria and underwent perioperative administration of TXA, using a standardized dosing protocol of a 10 mg/kg bolus in 30 minutes prior to incision, followed by maintenance infusion of 2 mg/kg/hour for the duration of the procedure. No incidence of myocardial infarction or postoperative thromboembolic events were noted. Subjective assessments indicated satisfaction with the patient selection protocol, and meaningful reduction in the extent of intraoperative bleeding. CONCLUSIONS: Perioperative TXA represents a potentially efficacious approach for control of intraoperative bleeding during endonasal resection of ACTH-secreting tumors. Careful preoperative patient selection is emphasized, given the potential for thromboembolic complications; however, initial experience with our institutional protocol suggests a favorable risk/benefit profile when this treatment is applied judiciously.

Clinical, Biological, Radiological Pathological and Immediate Post-Operative Remission of Sparsely and Densely Granulated Corticotroph Pituitary Tumors: A Retrospective Study of a Cohort of 277 Patients With Cushing's Disease.

Purpose: Cushing's disease is the most common cause of endogenous hypercortisolemia due to a corticotroph pituitary tumor. Up-to-date there is no reliable biomarker of invasiveness among corticotroph tumors, while it is well established in the literature that sparsely granulated somatotroph tumors are characterized by poorer prognosis. The aim of the study was to correlate multiple data including clinical, biochemical, radiological, and pathological findings (including granulation pattern) as well as immediate post-operative remission status among patients operated on due to corticotroph tumors. Methods: We enrolled all patients consecutively operated on for planned transsphenoidal neurosurgery due to corticotroph PitNETs in years 2010-2018. We excluded from analysis silent corticotroph tumors, plurihormonal PitNETs, and the Crooke's cell adenomas. Results: We recorded 348 hormonally active corticotroph PitNETs. The results of the analysis showed the female predominance 79.88% (n = 278), with the mean age of Cushing's disease occurrence 43.27 years of age. The mean time from the first signs and symptoms to the operation was 2 years. The women were diagnosed earlier (20-40 years of age vs. 50-60 years of age among men). We performed a detailed analysis of 277 cases classified by granularity pattern as DG or SG corticotroph PitNETs. Densely granulated tumors (DG) occurred four times more frequently than sparsely granulated (SG) (n = 225 vs. n = 52), at similar age (mean 42.94; median 40 vs. mean 45.46; median 45.5; p = 0.3896), but were characterized by lower Knosp's scale grades (p = 0.0147*), smaller preoperative tumors' volumes measured at MRI, and more commonly exhibited lower Ki-67 labeling index (<3%) (p = 0.0168*). What is more, DG adenomas more frequently achieved an immediate remission status (measured as postoperative cortisol concentration <2 µg/dl; p = 0.0180*), and the mean postoperative cortisol concentration in DG group was lower than in SG group (mean 5.375 µg/dl vs. 10.47 µg/dl; median 2.49 µg/dl vs. 6.52 µg/dl; p = 0.0028**). Conclusions: Our study indicates that DG corticotroph adenomas occurred at younger age, more commonly were microadenomas as compared to SG tumors, less frequently had invasive features in comparison to SG corticotroph adenomas (p = 0.0019**), and more commonly achieved an immediate postsurgical hormonal remission (p = 0.0180*). We highlight the need for an accurate differentiation of DG and SG subtypes in the pathomorphological diagnosis of corticotropic tumors, especially in invasive PitNETs.

Clinical profiles of silent corticotroph adenomas compared with silent gonadotroph adenomas after adopting the 2017 WHO pituitary classification system.

PURPOSE: Silent corticotroph adenomas (SCAs) can be redefined according to the 2017 World Health Organization pituitary classification system with the introduction of T­PIT, a transcription factor. We studied the clinical features of these redefined SCAs. METHODS: We compared 112 patients with SCAs and 198 patients with silent gonadotroph adenomas (SGAs) who underwent surgery from January 2019 to May 2020. RESULTS: The prevalence of SCAs increased from 21.3 to 30.2% under the new classification rules. T-PIT-positive, adrenocorticotropic hormone-negative SCAs and T-PIT-positive, adrenocorticotropic hormone-positive SCAs exhibited similar clinical features. SCAs exhibited significant female preponderance (90.2% vs. 29.8%, P < 0.0001); more frequent invasion (36.6% vs. 7.6%, P < 0.0001), especially multiple-site invasion (P < 0.0001); and marked cystic changes on imaging compared with SGAs (54.5% vs. 19.2%, P < 0.0001). SCAs had a softer tumor consistency (89.2% vs. 61.1%, P < 0.0001). Gross total resection was achieved in 66.1% of SCAs and 66.2% of SGAs (P > 0.9999). The overall recurrence/progression rates of SCAs and SGAs were 9.8% and 6.6% at 14.1 and 13.5 months of follow-up, respectively (P = 0.3765). The proportion of patients with more than two recurrences requiring multiple surgeries and radiation was similar between SCAs and SGAs (7.1% vs. 3.0%, P = 0.1514). However, multiple recurrences of SCAs affected younger patients than SGAs (39.0 vs. 53.5 years, P = 0.0433). CONCLUSIONS: The prevalence of SCAs increased with the introduction of T-PIT. SCAs and SGAs exhibited comparable size and recurrence/progression rates, but SCAs showed increased invasion and more marked cystic change. Aggressive SCAs tended to affect younger patients. Close long-term monitoring for SCA recurrence/progression is required.

A challenging case of Cushing's disease complicated with multiple thrombotic phenomena following trans-sphenoidal surgery; a case report.

BACKGROUND: Cushing's syndrome occurs due to overproduction of cortisol from adrenal glands. Endogenous hypercortisolemia can occur secondary to adrenocorticotropic hormone (ACTH) dependent as well as independent causes. The presence of non-specific symptoms and signs contributes to a delay in diagnosis. Early identification and prompt definitive management is crucial. It is important to be alert about the post-operative complications including multiple thrombotic phenomena, which can add to the mortality. We report a case of Cushing's disease in a young female managed with trans-sphenoidal surgery, followed by a challenging post-operative period complicated with multiple thrombotic phenomena, ultimately succumbed. CASE PRESENTATION: A 32-year-old Sri Lankan female presented with overt features of Cushing's syndrome and diagnosed to have ACTH dependent Cushing's disease with pituitary microadenoma. She underwent trans-sphenoidal surgery, following which she developed fatal multiple complications including diverticular rupture and ischemic colitis, needing hemicolectomy, followed by a parieto-occipital infarction. CONCLUSION: This case highlights important and aggressive complications associated with Cushing's syndrome giving rise to a challenging post-operative course. Diverticular rupture had been described in association with hypercortisolemia and this case adds to the existing literature. Post-operative ischemic colitis and stroke which contributed to the death of this patient could have been due to the procoagulant state associated with Cushing's syndrome, with a high risk during the immediate post-operative period. This emphasizes the need to consider post-operative thromboprophylaxis in patients undergoing surgery for Cushing's syndrome.

Retinal vein occlusion as the presenting feature of Cushing's syndrome.

A 53-year-old man presented to his optician with blurring of vision in the right eye and was diagnosed to have branch retinal vein occlusion. Over the following 3 months, he had further progressive visual impairment due to right central retinal vein occlusion (CRVO) and then left CRVO. Soon thereafter, during a hospital admission for infected submandibular gland, he was noted to have secondary hypothyroidism and persistent hypokalaemia which led to the diagnosis of Cushing's syndrome. This case was unusual as the patient did not manifest any classical features of Cushing's syndrome at the time of presentation with bilateral CRVO, and only 3 months later had dramatic weight loss, muscle weakness and acute psychosis. He received intravenous etomidate and underwent emergency transsphenoidal hypophysectomy with dramatic clinical and biochemical improvement and complete visual recovery in the left eye but unfortunately vision in the right eye remained limited to hand movements.

Comprehensive Diagnosis and Surgical Management of Cushing Disease: Two-Dimensional Angiographic and Operative Video.

Cushing disease (CD), or hypercortisolemia secondary to an adrenocorticotropic hormone-secreting (ACTH-secreting) pituitary adenoma, is the most common etiology of noniatrogenic Cushing syndrome.1 The diagnostic algorithm employed in the patient with suspected CD is complex and includes consideration for inferior petrosal sinus sampling (IPSS).2,3 When workup is consistent with CD, extracapsular resection of the ACTH-secreting pituitary adenoma through the endonasal corridor is the preferred operative strategy.4 In this publication, we discuss the case of a 26-year-old woman who presented with 9 months of weight gain (Video 1). Initial labs, including low- and high-dose dexamethasone suppression tests, were consistent with CD. Findings on dynamic magnetic resonance imaging were suggestive of a left 2-mm microadenoma. IPSS confirmed central origin of hypercortisolemia and was indicative of a left-sided focus. The patient was taken to the operating room for endoscopic endonasal approach for extracapsular resection of left-sided, ACTH-secreting microadenoma. Following surgery, the patient required glucocorticoid supplementation after her cortisol levels decreased to 2 ug/dL the evening of surgery. Subsequent laboratory analysis has been consistent with hormonal cure.5,6 The accompanying video manuscript describes 1) preoperative diagnostic evaluation of the patient with suspected CD, 2) indications for and techniques of IPSS, 3) nuances of endoscopic transsphenoidal surgical management, and 4) relevant considerations in postoperative care. Of note, full patient consent for photography and/or recording of other forms of video/imaging was obtained in the preoperative period.7-10.

The definition of remission and recurrence of Cushing's disease.

Accurate classification of postsurgical remission, and early recognition of recurrence are crucial to timely treat and prevent excess mortality in Cushing's Disease, yet the criteria used to define remission are variable and there is no consensus to define recurrence. Remission is defined as postsurgical hypocortisolemia, but delayed remission may occur. Recurrence is the return of clinical manifestations with biochemical evidence of hypercortisolism. The proper combination of tests and their timing are controversial. Reliable predicting tools may lead to earlier diagnosis upon recurrence. Many factors have been studied independently for prediction with variable performance. Novel artificial intelligence approaches seek to integrate these variables into risk calculators and machine-learning algorithms with an acceptable short-term predictive performance but lack longer-term accuracy. Prospective studies using these approaches are needed. This review summarizes the evidence behind the definitions of remission and recurrence and provide an overview of the available tools to predict and/or diagnose them.