Transsphenoidal Surgery In Patients Research Articles

Predictive Factors for Delayed Hyponatremia After Endoscopic Transsphenoidal Surgery in Patients with Nonfunctioning Pituitary Tumors: A Retrospective Observational Study

Delayed hyponatremia can occur after transsphenoidal pituitary tumor surgery, resulting in unexpected readmission. Predictive factors for delayed hyponatremia after this type of surgery are not well established. In this retrospective study, predictive factors for delayed hyponatremia were investigated in patients undergoing transsphenoidal pituitary tumor surgery. Preoperative data (demographics, comorbidities, and hormonal assessment), preoperative, intraoperative, and immediate postoperative sodium concentrations, the nadir sodium concentration on postoperative day (POD) 1-2, characteristics of pituitary tumor (size, cell type, optic chiasm compression, and cavernous sinus invasion), and intraoperative data (operation time and fluid balance) were retrospectively collected from 234 patients undergoing endoscopic transsphenoidal surgery for removal of nonfunctioning pituitary tumors. Delayed hyponatremia was defined as serum sodium concentration <135 mEq/L on POD 3 or later, and after discharge, postoperative sodium concentration was measured on POD 7-10. Delayed hyponatremia was observed in 53 patients (22.6%). Of these patients, 5 (9.4%) were readmitted because of delayed hyponatremia. In binary logistic regression analysis, age >60 years (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.16-4.26; P= 0.017), the nadir sodium concentration on POD 1-2 (OR, 0.88; 95% CI, 0.77-0.99; P= 0.034), and operation time (OR, 1.01; 95% CI, 1.00-1.02; P= 0.018) were independent risk factors for delayed hyponatremia after endoscopic transsphenoidal pituitary surgery. The incidence of delayed hyponatremia in patients with nonfunctioning pituitary tumor who underwent endoscopic transsphenoidal surgery was 22.6%. Old age, low sodium concentration on POD 1-2, and long operation time were associated with the development of delayed hyponatremia in such patients.

The USP8 mutational status may predict long-term remission in patients with Cushing's disease.

Almost half of the cases of Cushing's disease (CD) tumours carry recurrent activating somatic mutations in the ubiquitin-specific protease eight gene (USP8). The USP8 mutational status could predict remission in patients with CD, so our objective was to correlate the presence of somatic USP8 mutations with the rate of recurrence after transsphenoidal surgery (TSS) retrospectively. Biochemical, radiological and clinical data were retrospectively assessed in 48 patients. USP8 mutational status was determined from corticotroph tumour samples. Association between USP8 mutational status, remission and recurrence was investigated. Patients with Cushing's disease from a single-centre cohort who underwent TSS between 1991 and 2012. Long-term remission and recurrence rate after TSS with at least 6months follow-up. Biochemical, radiological and clinical data, including sex, age at diagnosis, tumour size and pre-operative hormonal levels. USP8 mutational status. Patients with USP8 mutant corticotroph tumours (18 of 48; 37%) were diagnosed significantly earlier (mean±SD 46±10years vs 53±11years; P=0.028) and presented with higher pre-operative 24-hour urinary-free cortisol levels (median IQR μg/24hours 1174.0, 1184.5 vs 480.0, 405.3; P=0.045). The incidence of recurrence in a 10-year follow-up was significantly higher in patients with USP8 mutant tumours after the initial remission (58% vs 18% P=0.026). Recurrence appeared significantly earlier in these patients (months 70, 44-97 95% CI vs 102, 86-119 95% CI; P=0.019). Recurrence appears to be more frequent and earlier after TSS in patients with USP8 mutant corticotroph tumours.

Imaging Evaluation of the Location and Fenestration of Sellar Floor During Endonasal Transsphenoidal Surgery in Patients with Pituitary Adenomas

To evaluate clinical value of three-dimensional (3D) computed tomography (CT) reconstruction of the sphenoid sinus separation in localizing sellar floor during endonasal transsphenoidal surgery and determine size and location of sellar floor fenestration. There were 51 patients eligible for study inclusion. Preoperative CT scan of the paranasal sinus and CT scan and magnetic resonance imaging of the pituitary gland were obtained. Sphenoid sinus separation was reconstructed using Mimics 15.0 software, and quantity, shape, and orientation were observed and compared with intraoperative data to guide the localization of sellar floor. Anatomic variation of the sphenoid sinus and adjacent structures, tumor and sella turcica morphology, minimal distance between the cavernous segment of the internal carotid artery bilaterally, and shortest distance from the midline were measured. Based on the shape of the sphenoid sinus separation, sellar floor was accurately localized in all cases. Intraoperative sphenoid sinus separation was consistent with preoperative three-dimensional CT reconstruction images. The sellar floor was extremely small in 2 patients, and insufficient fenestration of sellar floor negatively affected tumor resection. Preoperative three-dimensional CT reconstruction is helpful for accurate and rapid localization of sellar floor. Anatomic variation of sphenoid sinus and adjacent structures, characteristics of tumor and sella, minimum distance between bilateral cavernous segment of the internal carotid artery, and shortest distance from midline are helpful for establishment of individualized sellar floor fenestration.

Cushing Disease: Are We Making Progress?

This paper comments on how we can assess the success of transsphenoidal surgery for patients with Cushing disease.

Prolactin Secreting Pituitary Microadenoma: Results of Transsphenoidal Surgery After Medical Therapy With Dopamine Agonist.

Medical therapy with dopamine agonist is very effective in controlling prolactin serum levels and it usually represents the first therapeutic choice for prolactin secreting pituitary adenomas. However, many patients present increase of prolactinemia after withdrawal of medical therapy which consequently should be taken for long time; other present intolerance to medical therapy; women with pregnancy need to withdraw dopamine agonists with consequent potential related problems: in these patients transsphenoidal surgery can be requested. The presented study concerns the efficacy of transsphenoidal surgery in patients affected by microprolactinoma after treatment with medical therapy for different periods of time. Different postsurgical results were achieved in 2 groups of 24 (group 1) and 25 (group 2) patients affected by microprolactinoma who had taken medical therapy for a period of time respectively longer or shorter than 1 year. In summary, the authors observed in group 1 a rate of hormonal remission of 33.3% and an overall prolactinemia improvement with possibility of medical therapy withdrawal in 49.9% of patients. In group 2, the authors observed a rate of hormonal remission of 84% and an overall rate of improvement with no necessity of medical therapy of 92%. Therefore, the authors' experience showed that the surgical option for the therapy of microprolactinomas should be indicated within 1 year from the beginning of medical therapy with dopamine agonist, to achieve a high rate of hormonal remission and possibility to withdraw medical therapy. The authors' protocol for microprolactinoma treatment is presented.

Bilateral inferior petrosal sinus sampling and the outcome of transsphenoidal surgery in patients with Cushing's disease: experience of a Tertiary Portuguese Hospital

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Comparison of Gross Tumor Resection Rate between Endoscopic Transsphenoidal Surgery versus Microscopic Transsphenoidal Surgery for Patients with Pituitary Adenomas: A Meta-Analysis

Comparison of Gross Tumor Resection Rate between Endoscopic Transsphenoidal Surgery versus Microscopic Transsphenoidal Surgery for Patients with Pituitary Adenomas: A Meta-Analysis

Safety of transsphenoidal microsurgical approach in patients with an ACTH-secreting pituitary adenoma.

Patients affected by Cushing's disease often have important comorbidities directly linked to hypercortisolism that might enhance the operative risk. We report the safety of transsphenoidal surgery in patients affected by Cushing's disease as compared with patients with nonfunctioning pituitary adenoma. We have retrospectively analyzed 142 patients with Cushing's disease and 299 patients with nonfunctioning pituitary adenoma who underwent transsphenoidal surgery performed by a single experienced neurosurgeon between September 2007 and December 2014. For all of them, an intraoperative computerized anesthetic record for the automatic storage of data was available. The intraoperative vital parameters and the frequency of drugs administered during anesthesia were comparable between Cushing's disease and nonfunctioning pituitary adenoma groups. The duration of surgery was similar between the two groups (41.2 ± 11.8 vs. 42.9 ± 15.6 min), while the duration of anesthesia was slightly shorter in Cushing's disease patients (97.6 ± 18.1 min) than in nonfunctioning pituitary adenoma patients (101.6 ± 20.6 min, p = 0.04). The total perioperative mortality rate was 0.2% (0% in Cushing's disease vs. 0.3% in nonfunctioning pituitary adenoma). Cushing's disease patients had surgical and medical complication rates of 3.5% each, not different from those occurring in nonfunctioning pituitary adenoma. The postoperative incidence of diabetes insipidus (10.6%) and isolated hyponatremia (10.6%) in Cushing's disease patients was significantly higher than in nonfunctioning pituitary adenoma patients (4.4 and 4.1%; p = 0.02 and p = 0.01, respectively). In a large series of unselected and consecutive patients with Cushing's disease, transsphenoidal surgery performed by one dedicated experienced neurosurgeon had a reasonably low risk of complications. In particular, despite the higher burden of comorbidities typically associated with hypercortisolism, medical complications are rare and no more frequent than in patients with nonfunctioning pituitary adenoma.

Outcome of Microscopic Transsphenoidal Surgery in Cushing Disease: A Case Series of 96 Patients

To analyze the results of transsphenoidal surgery in patients with Cushing disease and outcome. Retrospective analysis of the records of 96 patients with Cushing disease from 1997 to 2012. There were 73 females and 23 males, with a mean follow-up of 44 months (range, 3-13 years). The sex ratio was significantly different in children and teenagers versus adults. Magnetic resonance imaging showed microadenoma, macroadenoma, and no adenoma in 66, 18, and 12 patients, respectively. There was no surgical mortality. Early remission (normal 24-hour urinary free cortisol and basal serum cortisol <5 μg/dL) was achieved in 94.8%. Regression analysis showed that only tumor size, cavernous sinus extension, and tumor consistency influenced remission. Recurrence was seen in 21.9%. Regression analysis showed that age, preoperative basal cortisol levels, and follow-up duration influenced recurrence. Correlation analysis showed that there was a significant negative correlation between patient age and the follow-up period. After detection of recurrence, 17 patients underwent repeat transsphenoidal surgery that resulted in remission in 12 patients (70.6%). The other 5 patients were referred for gamma knife radiosurgery or bilateral adrenalectomy. Transsphenoidal surgery is a safe and highly efficient procedure in the treatment of Cushing disease. Macroadenomas, cavernous sinus invasion, and harder tumor consistencies, however, are associated with lower remission rates (higher disease persistence) and younger age, higher preoperative cortisol levels, and longer follow-up periods are associated with higher recurrence.

Significant improvement of intractable headache after transsphenoidal surgery in patients with pituitary adenomas; preoperative neuroradiological evaluation and intraoperative intrasellar pressure measurement

Headache is the most common symptom of both primary and metastatic brain tumor, and is generally considered the primary symptom in patients with large pituitary adenomas. However, patients with small pituitary adenomas rarely complain of intractable headache, and neurosurgeons are unsure whether such small adenomas actually contribute to headache. If conventional medical treatments for headache prove ineffective, surgical removal of the adenoma can be considered as an alternative management strategy. We conducted a retrospective review of 180 patients who underwent transsphenoidal surgery (TSS) for pituitary adenomas at Kanazawa University Hospital between 2006 and 2014. Patients with acute phase intratumoral hemorrhage were excluded. We identified nine patients with intractable headache as the chief complaint associated with small pituitary adenoma (diameters 15.8 ± 2.6 mm, 11-20 mm), non-functioning in eight, and prolactin-secreting in one. The preoperative neuroradiological studies and headache characteristics were assessed retrospectively, and the intrasellar pressure evaluation was performed during TSS in the last seven patients. All nine patients had complete or substantial resolution of their formerly intractable headache after TSS. Headaches consisted of ocular pain ipsilateral to the adenoma localization within the sella in four cases and bifrontal headache in five. Magnetic resonance imaging of these patients revealed small diaphragmatic foramen, which were so narrow that only the pituitary stalk could pass. Computed tomography scans showed ossification beneath the sellar floor in the sphenoid sinus, presellar type in six cases, and choncal type in three. The adenomas included cysts in seven cases. There was no cavernous sinus invasion. Intrasellar pressure measurements averaged 41.5 ± 8.5 mmHg, range 34-59, significantly higher than in control patients without headache (n = 12), namely 22.2 ± 10.6 mmHg (16-30). In this study, the authors demonstrated the validity of TSS in the treatment of intractable headache associated with pituitary adenoma. The presence of ocular pain, especially ipsilateral to the adenoma, integrity of the diaphragm sella, and ossification in the sphenoid sinus, cyst or hemorrhage and the absence of cavernous sinus invasion were the indications for TSS for patients complaining of intractable headache and having pituitary adenomas.

Therapy of endocrine disease: outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence.

A number of factors can influence the reported outcomes of transsphenoidal surgery (TSS) for Cushing's disease - including different remission and recurrence criteria, for which there is no consensus. Therefore, a comparative analysis of the best treatment options and patient management strategies is difficult. In this review, we investigated the clinical outcomes of initial TSS in patients with Cushing's disease based on definitions of and assessments for remission and recurrence. We systematically searched PubMed and identified 44 studies with clear definitions of remission and recurrence. When data were available, additional analyses by time of remission, tumor size, duration of follow-up, surgical experience, year of study publication and adverse events related to surgery were performed. Data from a total of 6400 patients who received microscopic TSS were extracted and analyzed. A variety of definitions of remission and recurrence of Cushing's disease after initial microscopic TSS was used, giving broad ranges of remission (42.0-96.6%; median, 77.9%) and recurrence (0-47.4%; median, 11.5%). Better remission and recurrence outcomes were achieved for microadenomas vs macroadenomas; however, no correlations were found with other parameters, other than improved safety with longer surgical experience. The variety of methodologies used in clinical evaluation of TSS for Cushing's disease strongly support the call for standardization and optimization of studies to inform clinical practice and maximize patient outcomes. Clinically significant rates of failure of initial TSS highlight the need for effective second-line treatments.

Can orale glucose tolerance testing on the 1st postoperative day predict remission and optimize the outcome after transsphenoidal surgery in patients with acromegaly?

Can orale glucose tolerance testing on the 1st postoperative day predict remission and optimize the outcome after transsphenoidal surgery in patients with acromegaly?

Complications after transsphenoidal surgery for patients with Cushing's disease and silent corticotroph adenomas.

OBJECT The purpose of this study was to describe complications associated with the endonasal, transsphenoidal approach for the treatment of adrenocorticotropic hormone (ACTH)-positive staining tumors (Cushing's disease [CD] and silent corticotroph adenomas [SCAs]) performed by 1 surgeon at a high-volume academic medical center. METHODS Medical records from Brigham and Women's Hospital were retrospectively reviewed. Selected for study were 82 patients with CD who during April 2008-April 2014 had consecutively undergone transsphenoidal resection or who had subsequent pathological confirmation of ACTH-positive tumor staining. In addition to demographic, patient, tumor, and surgery characteristics, complications were evaluated. Complications of interest included syndrome of inappropriate antidiuretic hormone secretion, diabetes insipidus (DI), CSF leakage, carotid artery injury, epistaxis, meningitis, and vision changes. RESULTS Of the 82 patients, 68 (82.9%) had CD and 14 (17.1%) had SCAs; 55 patients were female and 27 were male. Most common (n = 62 patients, 82.7%) were microadenomas, followed by macroadenomas (n = 13, 14.7%). A total of 31 (37.8%) patients underwent reoperation. Median follow-up time was 12.0 months (range 3-69 months). The most common diagnosis was ACTH-secreting (n = 68, 82.9%), followed by silent tumors/adenomas (n = 14, 17.1%). ACTH hyperplasia was found in 8 patients (9.8%). Of the 74 patients who had verified tumors, 12 (16.2%) had tumors with atypical features. The overall (CD and SCA) rate of minor complications was 35.4%; the rate of major complications was 8.5% (n = 7). All permanent morbidity was associated with DI (n = 5, 6.1%). In 16 CD patients (23.5%), transient DI developed. Transient DI was more likely to develop in CD patients who had undergone a second operation (37.9%) than in those who had undergone a first operation only (12.8%, p < 0.05). Permanent DI developed in 4 CD patients (5.9%) and 1 SCA patient (7.1%). For 1 CD patient, intraoperative carotid artery injury required endovascular sacrifice of the injured artery, but the patient remained neurologically intact. For another CD patient, aseptic meningitis developed and was treated effectively with corticosteroids. One CD patient experienced major postoperative epistaxis requiring another operative procedure to achieve hemostasis. For 2 CD patients, development of sinus mucoceles was managed conservatively. For 1 SCA patient, an abdominal wound dehisced at the fat graft site. No patients experienced postoperative CSF leakage, visual impairment, or deep vein thrombosis. CONCLUSIONS Transsphenoidal surgery is the treatment of choice for patients with CD and other ACTH-positive staining tumors. Recent advances in endoscopic technology and increasing surgeon comfort with this technology are making transsphenoidal procedures safer, faster, and more effective. Serious complications are uncommon and can be managed successfully.

Cons: endoscopic endonasal transsphenoidal pituitary surgery is not superior to microscopic transsphenoidal surgery for pituitary adenomas.

The introduction of the endoscope to transsphenoidal pituitary surgery is not new and it has been abandoned in the past. Now, after some technological advances has been proposed again as an advancement in this field. However, there is still a debate on this topic and some authors consider endoscopic surgery a form of developing surgery in an evolution step. The use of the endoscope to visualize the sella has been suggested to offer a better visualization as well as an improved range of motion compared to the operating microscope. However, the real advantage in terms of efficacy and safety is still matter of debate. The conversion to microsurgery has been reported in a significant number of cases, particularly in recurrences, where the difficulties of reoperation require more skill. There is evidence in recent studies that the endonasal and bleeding complications are significantly higher in endoscopic approaches than in microscopic ones. In particular, patient discomfort, smell, and taste impairment are higher with the endoscopic method compared with microscopic approaches. At present pure endoscopic transsphenoidal surgery is not a cost effective technology. In fact, the operative time is longer than in microscopic approaches and the number of surgeons required for the procedure is usually double compared to microscopic approaches. This paper will outline on the basis of the data available in literature the reasons why, at present, the pure endoscopic endonasal transsphenoidal surgery should not be yet considered the standard technique for transsphenoidal surgery in patients with pituitary adenomas.

Improvement of insulin resistance following transsphenoidal surgery in patients with acromegaly: correlation with serum IGF-I levels.

The aim of this study was to determine the correlation between the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis and glucose intolerance in acromegaly during the early postoperative period. The study included 20 patients with acromegaly caused by GH-secreting pituitary adenoma who received transsphenoidal surgery in our hospital. Glucose tolerance was evaluated with oral glucose tolerance tests (OGTTs) performed during pre- and early postoperative periods (9 [7-18] days after surgery). Homeostasis model assessment of insulin resistance (HOMA-IR) and insulinogenic index (IGI) were calculated, and correlation analyses were performed between these values and the GH-IGF-I axis. Patients were divided according to postoperative changes of the axis, and glucose tolerance was compared between the groups. In preoperative OGTTs, nine patients had impaired glucose tolerance and two had diabetes mellitus patterns. Postoperatively, significant reduction was observed both in fasting plasma glucose levels (p<0.01) and in HOMA-IR (p<0.01), whereas IGI showed no significant change. HOMA-IR was significantly correlated with serum IGF-I levels both before (r=0.83, p<0.01) and after (r=0.57, p<0.01) surgery, although it was not correlated with serum GH levels. Patients who achieved more than 50% postoperative reduction in serum IGF-I levels showed significant improvement in OGTTs results (p<0.05). In patients with acromegaly, serum IGF-I levels, but not GH levels, were significantly correlated with insulin resistance. Early postoperative improvement of glucose tolerance is observed in patients who achieved postoperative reduction in serum IGF-I levels.

Fusiform dilatation of the cavernous carotid artery in acromegalic patients

Surgeons undertaking transsphenoidal surgery in patients with acromegaly confront multiple unique challenges secondary to the anatomic alterations caused by growth hormone-secreting tumors. The senior author has noted a fusiform dilatation of the cavernous carotid artery in many acromegalic patients. The authors aim to quantify this dilatation and correlate it with potential contributing factors. Clinical and radiographic data were retrospectively assessed in acromegalic patients undergoing transsphenoidal surgery from 2000 through 2011. Randomly selected patients with nonsecreting pituitary adenomas were used as the control cohort. Demographic information, comorbidities, and preoperative growth hormone and insulin-like growth factor-1 levels were recorded. Magnetic resonance (MR) imaging variables included tumor size, diameters of the petrous, cavernous, and supraclinoid segments of the carotid artery, and extent and location of cavernous sinus invasion. Independent correlations between acromegaly and each variable were assessed with multivariate regression analysis. Forty randomly selected patients with growth hormone-secreting adenomas who underwent surgery and had MR imaging with thin coronal slices of the pituitary region were enlisted in our study cohort. The mean age was 45.7 years. Forty-two males (52.5 %) were included in the study. Mean carotid artery diameter measurements for acromegalic and control patients, respectively, were 4.2 vs. 3.8 mm (petrous carotid), 5.0 vs. 4.0 mm (cavernous carotid), and 3.3 vs. 2.9 mm (supraclinoid carotid). Multivariate analysis showed only age and cavernous carotid diameter were statistically significant independent variables (p = 0.02, p < 0.001, respectively). Age, tumor size, growth-hormone or insulin-like growth factor-1 levels, and cavernous sinus invasion did not correlate with cavernous carotid artery diameter. In patients with acromegaly, there is a fusiform dilatation of the cavernous carotid artery that must be considered when planning transsphenoidal surgery.

Factors influencing the outcome of microsurgical transsphenoidal surgery for pituitary adenomas: A study on 184 patients

Evaluation of factors influencing the outcome of microsurgical transsphenoidal surgery in patients harbouring pituitary adenomas as well as of the efficacy and safety of this procedure. A total of 184 consecutive patients with pituitary adenomas, undergoing microsurgical transsphenoidal resection of their lesions from March 2004 to June 2011, were prospectively studied. Extent of tumour resection and disease remission were defined according to recently established radiological and hormonal consensus criteria. The study included 97 nonfunctioning and 87 functioning adenomas. A gross-total removal, as documented on postoperative imaging, was achieved in 67.4% of all patients. Residual tumour after surgery was detected in 37.1% of patients with nonfunctioning adenomas. The remission rates for patients with functioning adenomas, as documented by the last endocrinological evaluation, were 54.9% for growth hormone-secreting, 69.5% for adrenocorticotropin hormone-secreting, 72.7% for prolactin-secreting and 100% for thyroid-stimulating hormone-secreting, with two recurrences in patients with Cushing's disease. Multivariate analysis showed that factors influencing surgical outcome were cavernous sinus invasion, large tumour diameter (≥25 mm) and reoperation for the nonfunctioning adenomas, and cavernous sinus invasion as well as large tumour diameter (≥25 mm) for the functioning adenomas. In the latter cohort, predictors for endocrinological remission were maximum tumour diameter (≤20 mm) and reoperation. Postoperative complications were present in 3.3% of the cases. One patient developed epistaxis, two hemorrhage at the surgical field, one postoperative rhinorrhea, one postoperative permanent diabetes insipidus and one postoperative panhypopituitarism. Microsurgical transsphenoidal surgery is an effective and safe treatment in all patients with pituitary adenomas, except for prolactinomas responsive to medical therapy.

Remission rate after transsphenoidal surgery in patients with pathologically confirmed Cushing’s disease, the role of cortisol, ACTH assessment and immediate reoperation: a large single center experience

Postoperative serum cortisol is used as an indicator of Cushing's disease (CD) remission following transsphenoidal surgery (TSS) and guides (controversially) the need for immediate adjuvant treatment for CD. We investigated postoperative cortisol and adrenocorticotropic hormone (ACTH) levels as predictors of remission/recurrence in CD in a large retrospective cohort of patients with pathologically confirmed CD, over 6 years at a single institution. Midnight and morning cortisol, and ACTH at 24-48 h postoperatively (>24 h after last hydrocortisone dose) were measured. Remission was defined as normal 24-h urine free cortisol, normal midnight salivary cortisol, a normal dexamethasone-corticotropin releasing hormone (CRH) test or continued need for hydrocortisone, assessed periodically. Statistical analysis was performed using PASW 18. Follow up data was available for 52 patients (38 females and 14 males), median follow up was 16.5 month (range 2-143 months), median age was 45 years (range 21-72 years), 28 tumors were microadenomas and 16 were macroadenomas, and in eight cases no tumor was observed on magnetic resonance imaging. No patient with postoperative cortisol levels >10 mcg/dl were found to be in remission. Ten of the 52 patients with cortisol >10 mcg/dl by postoperative day 1-2 underwent a second TSS within 7 days. Forty-three patients (82.7%) achieved CD remission (36 after one TSS and 7 after a second early TSS) and six patients suffered disease recurrence (mean 39.2 ± 52.4 months). An immediate second TSS induced additional hormonal deficiencies (diabetes insipidus) in three patients with no surgical complications. Persistent disease was noted in nine patients despite three patients having an immediate second TSS. Positive predictive value for remission of cortisol <2 mcg/dl and ACTH <5 pg/ml was 100%. Cortisol and ACTH levels (at all postoperative time points and at 2 months) were correlated (r = 0.37, P < 0.001). Nadir serum cortisol of ≤2 mcg/dl and ACTH <5 pg/ml predicted remission (P < 0.005), but no level predicted lack of recurrence. Immediate postoperative ACTH/cortisol did not predict length of remission. No patients with postoperative cortisol >10 mcg/dl were observed to have delayed remission; all required additional treatment. There was no significant difference in age, body mass index, tumor size and length of follow-up between postoperative cortisol groups: cortisol ≤2 mcg/dl, cortisol >5 mcg/dl and cortisol >10 mcg/dl. Immediate postoperative cortisol levels should routinely be obtained in CD patients post TSS, until better tools to identify early remission are available. Immediate repeat TSS could be beneficial in patients with cortisol >10 mcg/dl and positive CD pathology: our combined (micro- and macroadenomas) remission rate with this approach was 82.7%. ACTH measurements correlate well with cortisol. However, because no single cortisol or ACTH cutoff value excludes all recurrences, patients require long-term clinical and biochemical follow-up. Further research is needed in this area.

Pituitary tumor apoplexy in patients with Cushing’s disease: endocrinologic and visual outcomes after transsphenoidal surgery

Pituitary apoplexy in patients with adrenocorticotropic hormone (ACTH) producing tumors is a rare occurrence. We report four patients with Cushing's disease harboring ACTH-secreting macroadenomas who presented with pituitary apoplexy. We report the endocrinologic and visual outcomes of these patients after emergent transsphenoidal surgery. A retrospective chart review was performed in 4 patients who presented with pituitary apoplexy from hemorrhage into an ACTH-secreting pituitary adenoma. The patient charts were reviewed for clinical presentation, neuroimaging findings, intraoperative surgical findings, pathologic findings, and postoperative endocrinologic and visual outcomes. All patients presented with acute headaches, nausea, vomiting, and visual loss from optic compression. MR imaging demonstrated a hemorrhagic macroadenoma that was confirmed at surgery. All patients underwent emergent transsphenoidal decompression (within 24 h of presentation). One of these underwent an additional craniotomy to resect residual tumor. Postoperatively, all patients showed significant improvement in visual acuity and visual fields with biochemical remission confirmed on laboratory testing. Significant weight loss as well as resolution of diabetes and hypertension was noted in all cases. All four patients remained in biochemical remission at their most recent follow-up visit (mean 40 months, range: 24-72 months). Excellent endocrine and visual outcomes can be achieved after emergent transsphenoidal surgery in patients with Cushing's disease presenting with pituitary apoplexy. Although the cure rates of non-apoplectic ACTH macroadenomas are generally poor, higher rates of remission can be achieved in cases of pituitary apoplexy. This may be partly due to the effects of tumor infarction.

Low Incidence of Adrenal Insufficiency after Transsphenoidal Surgery in Patients with Acromegaly: A Long-Term Follow-Up Study

The long-term prevalence of adrenal insufficiency after transsphenoidal surgery for GH-secreting pituitary adenomas is unknown. However, recently a single study reported a high prevalence of adrenal insufficiency in acromegalic patients after surgical and/or medical treatment without postoperative radiotherapy. The objective of the study was to assess the prevalence and incidence rates of adrenal insufficiency in consecutive patients during long-term follow-up after successful transsphenoidal surgery for acromegaly. In 91 consecutive patients in remission after transsphenoidal surgery only, we retrospectively reviewed insulin tolerance tests, CRH stimulation tests, metyrapone tests, and ACTH stimulation tests used to assess corticotrope function. Early postoperatively, insufficient adrenal function was observed in 16 patients (18%), which was transient in eight and irreversible in eight other patients in the first year of postoperative follow-up. Therefore, after the first year, the prevalence of adrenal insufficiency was 9%. Late, new-onset adrenal insufficiency developed in only three patients 13, 18, and 24 yr after surgery. The incidence rate of late adrenal insufficiency after successful surgery was 2/1000 person-years. After long-term follow-up, a median of 8.1 (1-31 yr), the prevalence of secondary adrenal insufficiency was 12% in patients in remission after surgery for acromegaly. The prevalence of adrenal insufficiency 1 yr after surgery was 9%, whereas during prolonged follow-up, the incidence rate of adrenal insufficiency was only 2/1000 person-years in patients in remission after surgery. Therefore, development of late-onset adrenal insufficiency is a very infrequent complication in patients with acromegaly in remission after transsphenoidal surgery only.