Significance of Crooke's Hyaline Change in Nontumorous Corticotrophs of Patients With Cushing Disease

BackgroundGlucocorticoid excess in Cushing disease (CD) leads to negative feedback suppression, resulting in Crooke's hyaline change (CC) of nontumorous pituitary corticotrophs. We aimed to determine the predictive value of CC of nontumorous corticotrophs in CD.MethodsThe retrospective chart review study included patients with clinical, biochemical, radiologic and outcome data and evaluable histopathology specimens from pituitary surgery for CD. The main outcome was remission of CD, defined by clinical features, biochemical testing, and corticosteroid dependency.ResultsOf 144 CD patients, 60 (50 women, mean age 43.6±14) had clinical follow-up, biochemical data and histopathology specimens that included evaluable nontumorous adenohypophysis. Specimens from 50 patients (83.3%) demonstrated CC in nontumorous corticotrophs, and 10 (16.7%) had no CC (including 3 with corticotroph hyperplasia). One patient with CC was lost to follow-up and one without CC had equivocal outcome results. During a mean (SD) follow-up period of 74.9 months (61.0), recurrent or persistent disease was documented in 18 patients (31.0%), while 40 (69.0%) were in remission. In patients with CC, the remission rate was 73.5% (95% CI, 59.7%-83.7%) (36/49), whereas it was 44.4% (95% CI, 18.9%-73.3%) (4/9) in patients with no CC. The combination of serum cortisol >138 nmol/L within a week of surgery coupled with absence of nontumorous CC greatly improved the prediction of recurrent or persistent disease.ConclusionsCC of nontumorous corticotrophs was observed in 83% of patients with CD, and most patients with CC experienced remission. Absence of CC in nontumorous corticotrophs may serve as a predictor of reduced remission in patients with CD.

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Outcome of using the histological pseudocapsule as a surgical capsule in Cushing disease

Journal of Neurosurgery ◽

10.3171/2008.8.jns08339 ◽

2009 ◽

Vol 111 (3) ◽

pp. 531-539 ◽

Cited By ~ 89

Author(s):

Jay Jagannathan ◽

Rene Smith ◽

Hetty L. DeVroom ◽

Alexander O. Vortmeyer ◽

Constantine A. Stratakis ◽

...

Keyword(s):

Mr Imaging ◽

Remission Rate ◽

Pituitary Surgery ◽

Anterior Lobe ◽

Accurate Identification ◽

Cushing Disease ◽

Complete Excision ◽

Imaging Results ◽

Prospective Database

Object Many patients with Cushing disease still have active or recurrent disease after pituitary surgery. The histological pseudocapsule of a pituitary adenoma is a layer of compressed normal anterior lobe that surrounds the adenoma and can be used during surgery to identify and guide removal of the tumor. In this study the authors examined the results of using the pseudocapsule as a surgical capsule in the resection of adenomas in patients with Cushing disease. Methods The authors reviewed a prospective database of data obtained in patients with Cushing disease who underwent surgery. The analysis included all cases in which a lesion was identified during surgery and in which the lesion was believed to be confined to the pituitary gland in patients with Cushing disease between January 1990 and March 2007. Since the objective was to determine the success of using the pseudocapsule as a surgical capsule, patients with invasive tumors and patients in whom no lesion was identified during surgery—challenging cases for surgical success—were excluded from analysis. Results In 261 patients an encapsulated adenoma was identified at surgery. Tumor was visible on MR imaging in 135 patients (52%); in 126 patients (48%) MR imaging detected no tumor. The range of tumor size overlapped considerably in the groups with positive and negative MR imaging results, indicating that in addition to size other features of the adenoma influence the results of MR imaging. In 252 patients hypercortisolism resolved after the first operation, whereas in 9 patients (3 with positive MR imaging and 6 with negative MR imaging) early reoperation was required. Hypercortisolism resolved in all 261 patients (256 with hypocortisolism and 5 with eucortisolism) before hospital discharge. Forty-six patients (18%) had postoperative electrolyte abnormalities (30 with hyponatremia and 16 with diabetes insipidus), but only 2 patients required treatment at discharge. The mean clinical follow-up duration was 84 months (range 12–215 months). Six patients (2%) had recurrence of hypercortisolism, all of whom were treated successfully with reoperation. Conclusions Because of their small size, adenomas can be challenging to identify in patients with Cushing disease. Use of the histological pseudocapsule of an adenoma allows accurate identification of the tumor and helps guide its complete excision. With this approach the overall remission rate is high and the rate of complications is low.

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Fully Endoscopic Transsphenoidal Resection of Pituitary Tumors: Technique and Results

American Journal of Rhinology ◽

10.2500/ajr.2007.21.3059 ◽

2007 ◽

Vol 21 (4) ◽

pp. 510-514 ◽

Cited By ~ 17

Author(s):

Brent Uren ◽

Nick Vrodos ◽

Peter-John Wormald

Keyword(s):

Remission Rate ◽

Hormone Replacement ◽

Tumor Resection ◽

Pituitary Tumors ◽

Retrospective Chart Review ◽

Pituitary Surgery ◽

Presenting Symptoms ◽

Cerebrospinal Fluid Leaks ◽

Tumor Remission

Background The aim of this study was to describe our two-surgeon fully endoscopic approach to pituitary surgery and to report results in terms of tumor remission, improvement in vision, and complications. A retrospective chart review was performed. Methods Our prospectively recorded surgical database was searched for all endoscopic transsphenoidal procedures between January 2001 and December 2005. Those patients who had surgery had their medical charts reviewed and presenting symptoms and signs, lesion characteristics, endocrine investigations, operative details, complications, and treatment outcomes recorded. Results Thirty-two patients were included in the study. Twenty-three patients had macroadenomas, five patients had microadenomas, and four patients had other pathologies. Most patients with macroadenomas had significant supra- or parasellar extension. Of the 14 patients who had visual loss at presentation, 13 had postoperative improvement. Two patients had postoperative cerebrospinal fluid leaks, which were successfully treated endoscopically. Eight patients required some form of hormone replacement after surgery. After a mean follow-up of 31 months, the overall remission rate for patients with macroadenomas was 82% and for patients with microadenomas was 100%. Conclusion The fully endoscopic transsphenoidal approach provides excellent visualization for tumor resection and results in acceptable remission rates.

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P34 Characteristics, diagnosis and management of Cushing’s disease - A systematic review and meta-analysis

BJS Open ◽

10.1093/bjsopen/zrab032.033 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

Author(s):

Chan Hee Koh ◽

Danyal Z Khan ◽

Ronneil Digpal ◽

Hugo Layard Horsfall ◽

Hani J Marcus ◽

...

Keyword(s):

Clinical Practice ◽

Cushing’S Disease ◽

Meta Analysis ◽

A Priori ◽

Pituitary Surgery ◽

Serum Cortisol ◽

Cushing's Disease ◽

Diagnosis And Management ◽

Over Time

Abstract Introduction The clinical practice and research in the diagnosis and management of Cushing’s disease remains heterogeneous and challenging to this day. We sought to establish the characteristics of Cushing’s disease, and the trends in diagnosis, management and reporting in this field. Methods Searches of PubMed and Embase were conducted. Study protocol was registered a-priori. Random-effects analyses were conducted to establish numerical estimates. Results Our screening returned 159 papers. The average age of adult patients with Cushing’s disease was 39.3, and 13.6 for children. The male:female ratio was 1:3. 8% of patients had undergone previous transsphenoidal resection. The ratio of macroadenomas: microadenomas:imaging-undetectable adenomas was 18:53:29. The most commonly reported preoperative biochemical investigations were serum cortisol (average 26.4µg/dL) and ACTH (77.5pg/dL). Postoperative cortisol was most frequently used to define remission (74.8%), most commonly with threshold of 5µg/dL (44.8%). Average remission rates were 77.8% with recurrence rate of 13.9%. Median follow-up was 38 months. Majority of papers reported age (81.9%) and sex (79.4%). Only 56.6% reported whether their patients had previous pituitary surgery. 45.3% reported whether their adenomas were macroadenoma, microadenoma or undetectable. Only 24.1% reported preoperative cortisol, and this did not improve over time. 60.4% reported numerical thresholds for cortisol in defining remission, and this improved significantly over time (p = 0.004). Visual inspection of bubbleplots showed increasing preference for threshold of 5µg/dL. 70.4% reported the length of follow up. Conclusion We quantified the characteristics of Cushing’s disease, and analysed the trends in investigation and reporting. This review may help to inform future efforts in forming guidelines for research and clinical practice.

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Endoscopic transsphenoidal pituitary surgery: a good and safe primary treatment option for Cushing's disease, even in case of macroadenomas or invasive adenomas

Acta Endocrinologica ◽

10.1530/eje-13-0325 ◽

2013 ◽

Vol 169 (3) ◽

pp. 329-337 ◽

Cited By ~ 48

Author(s):

M A E M Wagenmakers ◽

H D Boogaarts ◽

S H P P Roerink ◽

H J L M Timmers ◽

N M M L Stikkelbroeck ◽

...

Keyword(s):

Treatment Option ◽

Cushing’S Disease ◽

Remission Rate ◽

Pituitary Surgery ◽

Primary Treatment ◽

Endoscopic Technique ◽

Cushing's Disease ◽

Recurrence Rates ◽

Transsphenoidal Pituitary Surgery

ContextAlthough the endoscopic technique of transsphenoidal pituitary surgery (TS) has been widely adopted, reports on its results in Cushing's disease (CD) are still scarce and no studies have investigated long-term recurrence rates. This is the largest endoscopic series published till now.ObjectiveTo gain insight into the role of endoscopic TS as a primary treatment option for CD, especially in patients with magnetic resonance imaging (MRI)-negative CD and (invasive) macroadenomas.DesignRetrospective cohort study.Patients and methodsThe medical records of 86 patients with CD who underwent endoscopic TS were examined. Data on preoperative and postoperative evaluation, perioperative complications, and follow-up were collected. Remission was defined as disappearance of clinical symptoms with a fasting plasma cortisol level ≤50 nmol/l either basal or after 1 mg dexamethasone.ResultsThe remission rate in different adenoma subclasses varied significantly: 60% in MRI-negative CD (n=20), 83% in microadenomas (n=35), 94% in noninvasive macroadenomas (n=16), and 40% in macroadenomas that invaded the cavernous sinus (n=15). The recurrence rate was 16% after 71±39 months of follow-up (mean±s.d., range 10–165 months).ConclusionsEndoscopic TS is a safe and effective treatment for all patients with CD. Recurrence rates after endoscopic TS are comparable with those reported for microscopic TS. Our data suggest that in patients with noninvasive and invasive macroadenomas, the endoscopic technique of TS should be the treatment of choice as remission rates seem to be higher than those reported for microscopic TS, although no comparative study has been performed.

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Surgical Revision of the Failed Obliterated Frontal Sinus

American Journal of Rhinology ◽

10.1177/194589240501900501 ◽

2005 ◽

Vol 19 (5) ◽

pp. 425-429 ◽

Cited By ~ 17

Author(s):

Peter H. Hwang ◽

Joseph K. Han ◽

Evan J. Bilstrom ◽

Todd T. Kingdom ◽

Karen J. Fong

Keyword(s):

Frontal Sinus ◽

Retrospective Chart Review ◽

Surgical Revision ◽

Fat Graft ◽

Endoscopic Management ◽

Persistent Disease ◽

Endoscopic Techniques ◽

Management Algorithm ◽

Sinus Obliteration

Background Surgical revision of failed frontal sinus obliteration, traditionally, has been limited to repeat obliteration. However, endoscopic techniques may be successful in selected cases. We review our experience in surgical revision of failed frontal obliteration and propose a management algorithm. Methods Retrospective chart review was performed over a 5-year period for patients who presented for surgical revision of a previously obliterated frontal sinus. Indications for surgery, radiological findings, and surgical approach were reviewed. Results Nineteen patients were identified, presenting an average of 9.7 years from the initial obliteration. Eighty-four percent (n = 16) were approached endoscopically and 16% (n = 3) were approached by revision obliteration. The mean follow-up was 25 months. In the endoscopic group, patients had either mucoceles in the inferomedial aspect of the frontal sinus or incomplete obliteration with persistent disease in the pneumatized frontal remnant. Eighty-one percent (13/16) were managed successfully with a single endoscopic procedure. Nineteen percent (3/16) had persistent disease requiring either a subsequent obliteration or Riedel ablation because of infected fat graft or frontal osteomyelitis. All patients who were managed successfully endoscopically remained free of disease with patent frontal sinusotomies throughout the follow-up period. The endoscopic failures required one to two additional external procedures to achieve disease resolution. In the revision obliteration group, all patients had mucoceles in either the lateral or the superior frontal sinus. All three patients had resolution of disease after a single procedure and remained free of disease throughout the follow-up period. Conclusion Selected patients undergoing revision of frontal obliteration may benefit from endoscopic approaches. If disease is localized in the frontal recess or inferomedial frontal sinus, endoscopic management may be successful in the majority of patients. Superior or lateral frontal disease appears to be best approached externally. Patients undergoing endoscopic salvage should be counseled about the possible need for revision obliteration if disease persists.

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Current state of the art in the diagnosis and surgical treatment of Cushing disease: early experience with a purely endoscopic endonasal technique

Neurosurgical FOCUS ◽

10.3171/foc.2007.23.3.11 ◽

2007 ◽

Vol 23 (3) ◽

pp. 1-8 ◽

Cited By ~ 42

Author(s):

Amir R. Dehdashti ◽

Fred Gentili

Keyword(s):

Surgical Treatment ◽

Cavernous Sinus ◽

Pituitary Surgery ◽

Magnetic Resonance Images ◽

Primary Therapy ◽

Cushing Disease ◽

Endoscopic Endonasal ◽

Number Of Patients ◽

Free Cortisol

Object Transsphenoidal pituitary surgery is the primary therapy for Cushing disease because of its potential to produce lasting remission without the need for long-term drug or hormone replacement therapy. The authors evaluated the current role of pure endoscopic endonasal pituitary surgery in the treatment of Cushing disease. Methods Twenty-five patients underwent pure endoscopic surgery for confirmed Cushing disease. Thirteen patients had microadenomas and seven had macroadenomas; magnetic resonance images obtained in five patients were only suspicious or nondiagnostic, and thus they underwent inferior petrosal sinus sampling. Two patients had evidence of cavernous sinus involvement. Final histological results were consistent with adrenocorticotropin hormone (ACTH)–secreting adenoma in 20 patients. Results Twenty patients (80%) had clinical remission and laboratory confirmation of hypocortisolemia (serum cortisol < 100 nmol/L requiring substitution therapy), suppression to low-dose dexamethasone, and normal 24-hour urinary free cortisol. The median follow-up period was 17 months (range 3–32 months). There was no recurrence at the time of the last follow-up. Three patients presented with new anterior pituitary deficiency, but no one had permanent diabetes insipidus. In one patient a cerebrospinal fluid leak developed but later resolved following lumbar drainage. Treatment failure was attributable to involvement of the cavernous sinus in two patients, incomplete tumor removal in one, negative exploration in one, and nodular corticotroph hyperplasia of the pituitary gland in one. Conclusions Early results indicated that endoscopic endonasal surgery is a safe and effective treatment for ACTH-producing adenomas. The rate of remission in this study is comparable to those in previous series, and the rate of major postoperative complications is extremely low. Further studies with a larger number of patients and longer follow-ups are required to determine whether this more minimally invasive pure endoscopic approach should become the standard of care for the surgical treatment of Cushing disease.

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Impact of Technique on Cushing Disease Outcome Using Strict Remission Criteria

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s031716710001427x ◽

2013 ◽

Vol 40 (3) ◽

pp. 334-341 ◽

Cited By ~ 17

Author(s):

Hussein Alahmadi ◽

Michael D. Cusimano ◽

Kenneth Woo ◽

Ameen A. Mohammed ◽

Jeannette Goguen ◽

...

Keyword(s):

Remission Rate ◽

Serum Cortisol ◽

P Value ◽

Cushing Disease ◽

Repeat Surgery ◽

Free Cortisol ◽

Significant Difference ◽

Morning Serum Cortisol ◽

Remission Criteria

Background:Cushing disease (CD) constitutes a challenging condition for the pituitary surgeon. Given the variety of factors affecting outcomes in CD, it is uncertain whether the newer endoscopic technique improves the results of surgery.Methods:A review was conducted of CD cases at our institution between 2000 and 2010. Analysis was done to: determine if surgical technique had an effect on outcome, identify the predictors of outcome and provide details of failed cases. Remission was defined as normal postoperative 24-hour urinary free cortisol (24-h UFC), suppression of morning serum cortisol to <50 nmol/L after 1mg of dexamethasone or being dependent on steroid replacement.Results:Forty-two patients met our inclusion criteria. Average follow-up period was 33 months. There were 15 macroadenomas and 27 microadenomas. Seventeen patients had an endoscopic transsphenoidal surgery and twenty-five patients had a microscopic transsphenoidal procedure. Long-term overall remission was achieved in 26 (62%) patients. There was no significant difference in remission rates between the two techniques (p value 0.757). Patient's subjective symptomatic improvement and drop of morning serum cortisol in the postoperative period to less than 100 nmol/L correlated with long-term remission (p value 0.0031and 0.0101, respectively) while repeat surgery was the only predictor of the lack of postoperative remission (p value 0.0008).Conclusions:Revision surgery predicted poor remission rate for CD. Within the power of our study size, there was no difference in outcome between the endoscopic and microscopic approaches. Surgical outcomes should be reviewed in association with remission criteria used in a study.

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Cushing disease: use of perioperative serum cortisol measurements in early determination of success following pituitary surgery

Neurosurgical FOCUS ◽

10.3171/foc.2007.23.3.8 ◽

2007 ◽

Vol 23 (3) ◽

pp. 1-8 ◽

Cited By ~ 21

Author(s):

Armand Krikorian ◽

Dima Abdelmannan ◽

Warren R Selman ◽

Baha M Arafah

Keyword(s):

Sella Turcica ◽

Pituitary Surgery ◽

Serum Cortisol ◽

Serum Cortisol Level ◽

Current Recommendation ◽

Cushing Disease ◽

Acth Deficiency ◽

Cortisol Levels ◽

Acth Secreting

✓Despite many recent advances, management of cases of Cushing disease continues to be challenging. After complete resection of ACTH-secreting adenomas, patients develop transient ACTH deficiency requiring glucocorticoid replacement for several months. The current recommendation by many centers, including ours, for patients with ACTH-secreting adenomas is to withhold glucocorticoid therapy during and immediately after adenomectomy until there is clinical or biochemical evidence of ACTH deficiency. A serum cortisol level of less than 2 μg/dl within the first 48 hours after adenomectomy is a reliable biochemical marker of ACTH deficiency and is associated with clinical remission of Cushing disease. Higher serum cortisol levels in the immediate postoperative period should be interpreted with caution. The decision to immediately reexplore the sella turcica should be individualized, taking into account the findings at surgery, the histopathological findings, and the changes in serum cortisol levels as well as the patient's wishes and concerns. Optimal diagnosis and therapy for patients with Cushing disease require thorough and close coordination and involvement of all members of the management team.

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Outcomes of Isolated Neutropenia Referred to Pediatric Hematology Oncology Clinic

Blood ◽

10.1182/blood-2019-126274 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5858-5858

Author(s):

Vishnu Nagalapuram ◽

David McCall ◽

Prasannalaxmi Palabindela ◽

Christina Bemrich Stolz ◽

Thomas H. Howard ◽

...

Keyword(s):

Pediatric Patients ◽

Retrospective Chart Review ◽

Outcome Data ◽

Severe Neutropenia ◽

Admission Diagnosis ◽

Drug Induced ◽

Pediatric Hematology ◽

Black Patients ◽

Immunosuppressant Medications

Introduction: Patients with absolute neutrophil count (ANC) <1500 x10^9/L are frequently referred to Pediatric Hematology Oncology. Scant literature exists on outcomes and interventions for isolated neutropenia. We hypothesize that most patients will have resolved neutropenia without the need for an intervention from Pediatric Hematology Oncology. Methods: We performed a five-year IRB-approved, retrospective chart review of patients referred to a Pediatric Hematology-Oncology clinic for isolated neutropenia. Patients were excluded if they also had anemia or thrombocytopenia at the time of the referral. Degree of neutropenia was categorized: 1) at the time of referral, 2) at the lowest value, and 3) at the current ANC as Mild: 1.001-1.500 x109/L, Moderate: 0.501-1.000 x109/L, Severe: 0.201-0.5 x109/L, or Very Severe ≤0.2 x109/L. Descriptive statistics and odds ratios were performed. Results: Among 154 patients referred with isolated neutropenia over five years, 45 (29%) had mild neutropenia, 65 (42%) had moderate neutropenia, 29 (19%) had severe neutropenia, and 15 (10%) had very severe neutropenia. Only 29 (19%) patients progressed to a lower ANC category than their referral ANC category. At a median follow-up of 12 months, 101 (66%) patients had resolved neutropenia, 40 (26%) patients had mild, ten (6%) patients had moderate, three patients had severe, and one patient had very severe neutropenia. Most patients (54%) were not identified with a specific diagnosis. The most common diagnoses included viral suppression (16%), autoimmune neutropenia (14%) and drug induced neutropenia (8%). The most common medications reported as responsible for neutropenia were either anti-epileptic medications or immunosuppressant medications. No patients were diagnosed with a malignancy. Black patients had a 3.5 times higher odds of having persistent, mild, undiagnosed neutropenia which, for some patients, may be benign ethnic neutropenia. Seven (4.5%) patients received G-CSF therapy. Five patients were either managed by a Rheumatologist or an Immunologist. Finally, there were 16 hospitalizations that occurred in 10 patients for a prevalence of one admission for every 21 patient years. The most common admission diagnosis was febrile neutropenia without subsequent bacteremia (n=13). Conclusion: Most pediatric patients referred for isolated neutropenia do not progress, develop leukemia, or require sub-specialty interventions. Hospitalization of patients referred for isolated neutropenia is rare as is bacteremia. This study provides important outcome data that can improve our counseling of pediatric patients identified with isolated neutropenia. Disclosures Howard: Novartis: Consultancy. Lebensburger:Novartis: Consultancy; Pfizer: Research Funding.

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Transsphenoidal Surgery of Invasive Corticotroph Adenomas: Results in A Series of 86 Consecutive Patients

10.21203/rs.3.rs-810471/v1 ◽

2021 ◽

Author(s):

Congxin Dai ◽

Ming Feng ◽

Lin Lu ◽

Bowen Sun ◽

Yanghua Fan ◽

...

Keyword(s):

Transsphenoidal Surgery ◽

Remission Rate ◽

Partial Resection ◽

Gross Total Resection ◽

Subtotal Resection ◽

Total Resection ◽

Persistent Disease ◽

Biochemical Remission ◽

Corticotroph Adenomas

Abstract Objective: Surgery is first-line treatment for corticotroph adenomas. Although most of corticotroph adenomas are noninvasive microadenomas that show expansive growth to surrounding tissues, a small subset of them is locally invasive and difficult to manage. The aim of this study was to evaluate surgical outcome of invasive corticotroph adenomas from a single-center. Patients and Methods: The clinical features and outcomes of CD patients who underwent transsphenoidal surgery (TSS) between January 2000 and September 2019 at Peking Union Medical College Hospital were collected from medical records. The clinical, endocrinological, radiological, histopathological, surgical outcomes and a minimum 12-month follow-up of 86 consecutive CD patients with invasive corticotroph adenomas were retrospectively reviewed. Results: Eighty-six patients with invasive corticotroph adenomas were included in the study. The average age at TSS was 37.7 years (range, 12 to 67 years), with a female-to-male ratio of 3.1:1 (65/21). The median duration of symptoms was 52.6 months (range, 1.0 to 264 months). The average of maximum diameter of tumor was 17.6 mm (range, 4.5–70 mm). All 86 patients with invasive corticotroph adenomas were performed TSS by microscopic or endoscopic approach. Gross-total resection was achieved in 63 patients (73.3%), subtotal resection in 18 (20.9%), and partial resection in 5 (5.8%). After surgery, the overall postoperative immediate remission rate was 48.8% (42/86), 51.2 % (44/86) of patients maintained persistent hypercortisolism. In 42 patients with initial remission, 16.7 % (7/42) of them experienced a recurrence. In these patients with persistent disease and recurrent CD, data about further treatment was available for 30 patients. The radiotherapy was used for 15 patients, and 4 (26.7%) of them achieved biochemical remission. Repeat TSS was performed in 5 patients, and none achieved remission. Medication was administrated in 4 patients, and one of them obtained disease control. Adrenalectomy was performed in 6 patients, and 5 (83.3 %) achieved biochemical remission. At last follow-up, (33.3%) 10 of 30 patients were in remission, and 20 patients still had persistent disease. The remission rate in patients with invasive corticotroph adenomas who underwent gross-total resection and first TSS were significantly higher than that in patients undergoing subtotal resection, partial resection, and a second TSS (all P＜0.05). However, there was no significant difference in the remission rate between patient with different tumor size, Knosp Grade and surgical approaches (P＞0.05).Conclusion: The management of invasive corticotroph adenomas remain a therapeutic challenge due to incomplete resection of invasive and/or a large adenoma. With application of multiple techniques assistance, approximately half of the patients could achieve gross-total resection and biochemical remission via TSS by experienced neurosurgeons. The extent of tumor resection and number of operations were associated with surgical remission rate in invasive corticotroph adenomas. If the remission was not achieved by surgery, other treatments including radiotherapy, medical therapy, and even bilateral adrenalectomy are required.

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