Pituitary Stalk Morphology as a Predictor of New-Onset Adrenocortical Insufficiency and Arginine Vasopressin Deficiency after Transsphenoidal Resections of Pituitary Macroadenomas: A Retrospective Single-Center Study with a Focus on iMRI.

BACKGROUND: A new-onset adrenocortical insufficiency (NAI) is the most critical postoperative endocrinological complication after transsphenoidal surgery for macroadenomas. Because of increased mortality risk, arginine vasopressin deficiency (AVP-D) is also a relevant postoperative complication. This study aimed to identify easy-to-acquire magnet resonance imaging (MRI) aspects of the pituitary stalk to predict these insufficiencies after transsphenoidal surgery. METHODS: Pituitary stalk morphology was reviewed intraoperatively and three months postoperatively in the MRIs of 48 transsphenoidal surgeries for macroadenomas. NAI was validated in endocrinological follow-up controls 10-14 months post-surgery. RESULTS: Intraoperative pituitary stalk diameters were 0.5 mm larger in patients who developed NAI and AVP-D. The odds ratio was 29 for NAI and 6 for AVP-D in binary regression analysis. A value of 2.9 mm was identified as the optimal cut-off for the minimal pituitary stalk diameter regarding NAI, with a high specificity of 89%. There was no difference in pituitary stalk diameter regarding these insufficiencies three months post-surgery. CONCLUSIONS: We identified an increased pituitary stalk diameter in intraoperative MRIs as a predictive factor of NAI and AVP-D after transsphenoidal surgery. These findings might improve the early detection of NAI and, thus, optimal management. However, validating these retrospective findings in prospective studies is obligatory.

The Benefit of Intraoperative Magnetic Resonance Imaging in Endoscopic and Microscopic Transsphenoidal Resection of Recurrent Pituitary Adenomas.

The surgical treatment of recurrent adenomas can be challenging. Intraoperative magnetic resonance imaging (iMRI) can improve the orientation and increase the safe extent of resection. We conducted a quantitative and qualitative retrospective analysis of recurrent adenomas treated by endoscopic or microscopic iMRI-assisted transsphenoidal surgery. A total number of 59 resections were selected. Detailed volumetric measurements, tumor characteristics, and MRI features of intraoperative remnants were evaluated. Intraoperative MRI increased the gross total resection (GTR) rate from 33.9% to 49.2%. Common locations of tumor remnants after iMRI were the clivus, the wall of the cavernous sinus or the perforation of the diaphragm. Increasing tumor volume and the microscopic technique were significantly associated with further resection after iMRI in the univariate analysis (p = 0.004, OR 1.6; p = 0.009, OR 4.4). Only the increasing tumor volume was an independent predictor for further resection (p = 0.007, OR 1.5). A significantly higher proportion of GTRs was achieved with the endoscopic technique (p = 0.001). Patients with a large recurrent pituitary adenoma who underwent microscopic transsphenoidal resection were the most likely to benefit from iMRI regarding the extent of resection. Occult invasions of the cavernous sinus and/or the clivus were the most common findings leading to further resection of tumor remnants after iMRI.

Characterization of tumor remnants in intraoperative MRI-assisted microscopic and endoscopic transsphenoidal resection of less invasive pituitary adenomas.

INTRODUCTION: Intraoperative magnetic resonance imaging (iMRI) improves the intraoperative detection of adenoma remnants in transsphenoidal surgery. iMRI might be redundant in endoscopic pituitary surgery in non-invasive tumors (Knosp 0-2) due to a superior visualization of anatomical structures in the periphery of the sella turcica compared to the microscopic technique. We identified the anatomical location of tumor remnants in iMRI and evaluated risk factors for secondary resection after iMRI and hereby selected patients with pituitary adenomas who may benefit from iMRI-assisted resection. METHODS: We conducted a retrospective monocenter study of patients who underwent iMRI-assisted transsphenoidal surgical resection of pituitary adenomas at our department between 2012 and 2020. A total number of 190 consecutive iMRI-assisted transsphenoidal surgeries of pituitary adenomas graded as Knosp 0-2 were selected for analysis. Exclusion criteria were missing iMRI availability or pathologies other than adenomas. Of these 190 cases, 46.3% (N = 88) were treated with microscopic, 48.4% (N = 92) with endoscopic, and 5.3% (N = 10) with endoscopic-assisted technique. Volumetric measurement of preoperative, intraoperative, and postoperative tumor extension was performed. Demographic data, tumor characteristics, and MRI features were evaluated. Additionally, analysis of adenoma remnants identified by iMRI was performed. RESULTS: An additional resection after iMRI was performed in 16.3% (N = 31). iMRI helped to reach gross total resection (GTR) in 83.9% (26/31) of these cases. False-positive resection was found in 1 patient (0.5%). Multivariable logistic analysis identified tumor volume (OR = 1.2, p = 0.007) recurrence (OR = 11.3, p = 0.002) and microscopic technique (OR = 2.8, p = 0.029) as independent risk factors for additional resection. Simultaneously, the endoscopic technique was significantly associated with GTR as evaluated by iMRI (OR = 2.8, p = 0.011) and postoperative MRI (OR = 5.8, p = 0.027). The detailed analysis of adenoma remnants on iMRI revealed the suprasellar location in a diaphragm fold, penetrating tumor above the diaphragm, or undetected invasion of cavernous sinus as well as in case of microscopic resection tumor location outside the line of sight as the main reasons for incomplete resections. CONCLUSION: Tumor volume, recurrence, and microscopic technique were identified as independent predictors for additional resection in patients with Knosp 0-2 adenomas. iMRI might increase the extent of resection (EOR) safely even after the endoscopic visualization of the sella with very low risk for false-positive findings. Remnants of tumors hidden within the diaphragmic folds, intrathecally, or behind the infiltrated wall of cavernous sinus not recognized on preoperative MRI were the most common findings in iMRI.

Ten years' experience with intraoperative MRI-assisted transsphenoidal pituitary surgery.

OBJECTIVE: Many innovations have been introduced into pituitary surgery in the quest to maximize the extent of tumor resection. Because of the deep and narrow surgical corridor as well as the heterogeneity of confronted pathologies, anatomical orientation and identification of the target tissue can become difficult. Intraoperative MRI (iMRI) may have the potential to increase extent of resection (EOR) in transsphenoidal pituitary surgery. Furthermore, it may simplify anatomical orientation and risk assessment in difficult cases. Here, the authors evaluated the additional value of iMRI for the resection of pituitary adenomas performed in the past 10 years in their department. METHODS: They performed a retrospective single-center analysis of patients treated for pituitary adenoma in their department after the introduction of iMRI between 2008 and 2018. Of 495 transsphenoidal approaches, 300 consecutive MRI-assisted surgeries for pituitary adenomas encompassing 294 patients were selected for further analysis. Microscopic, endoscopic, or endoscope-assisted microscopic transsphenoidal approaches were distinguished. EOR as well as additional resection following iMRI was evaluated via detailed volumetric analysis. Patients were stratified according to the Knosp adenoma classification. Furthermore, demographic data, clinical symptoms, endocrine outcome, and complications were evaluated. Univariable and multivariable Cox regression analyses of progression-free survival (PFS) were performed. RESULTS: Pituitary adenomas classified as Knosp grades 0-2 were found in 60.3% of cases (n = 181). The most common tumors were nonfunctioning adenomas (75%). Continued resection following iMRI significantly increased EOR (7.5%, p < 0.001) and the proportion of gross-total resections (GTRs) in transsphenoidal pituitary surgery (54% vs 68.3%, p < 0.001). Additional resection after iMRI was performed in 37% of cases. Only in the subgroup of patients with Knosp grades 0-2 adenomas treated with the microsurgical technique was additional resection significantly more common than in the endoscopic group (p = 0.039). Residual tumor volume, Knosp grade, and age were confirmed as independent predictors of PFS (p < 0.001, p = 0.021, and p = 0.029, respectively) in a multivariable Cox regression analysis. Improvement of visual field deficits was documented in 78.6% of patients whose optic apparatus had been affected preoperatively. Revision surgery was done in 7.3% of cases; in 5.6% of cases, it was performed for cerebrospinal fluid fistula. CONCLUSIONS: In this series, iMRI led to the detection of a resectable tumor remnant in a high proportion of patients, resulting in a greater EOR and higher proportion of GTRs after continued resection in microsurgical and endoscopic transsphenoidal resection of pituitary adenomas. The volume of residual tumor was the most important predictor of PFS. Given the study data, the authors postulated that every bit of removed tumor serves the patient and increases their chances of a favorable outcome.

Current Management and Outcome of Pregnancies in Women With Adrenal Insufficiency: Experience from a Multicenter Survey.

CONTEXT: Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment. OBJECTIVE: Multicenter survey on current clinical approaches in managing AI during pregnancy. DESIGN: Retrospective anonymized data collection from 19 international centers from 2013 to 2019. SETTING AND PATIENTS: 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%). RESULTS: Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes. CONCLUSIONS: This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.

[Hypoparathyroidism - un underestimated problem?] / Hypoparathyreoidismus ­ ein unterschätztes Problem?

BACKGROUND: Hypoparathyroidism is a rare and disabilitating disorder characterized by hypocalcemia and low parathyroid hormone levels. Most of the cases occur as a result of the removal of parathyroid glands or damage to the glands during neck surgery. More rare causes include nonsurgical causes such as autoimmune or genetic diseases. METHOD: In this review, a panel of experts presents the current state of diagnosis and therapy of hypoparathyroidism and explains practical aspects of caring for the affected patients. RESULTS: Common signs and symptoms are abnormal sensations and increased excitability in the lower limbs, paresthesia of perioral areas and nocturnal leg cramps. Renal complications frequently occur, but also basal ganglia calcification. Treatment consists of administration of vitamin D analogs in combination with 0.5-1.0 g calcium daily. An adjunctive treatment with the in April 2017 approved recombinant human parathyroid hormone (1-84) is an option for patients whose hypoparathyroidism is difficult to control by conventional treatment alone. Initially and after dose changes follow-up controls should be performed at least every 2 weeks, in well-controlled patients or in the case of chronic progression every 3-6 months.

Intraoperative MRI in transsphenoidal resection of invasive pituitary macroadenomas.

The use of intraoperative MRI (iMRI) increases extent of resection in transsphenoidal pituitary surgery. Microsurgical and endoscopic techniques have been established as equal and standard surgical methods. The object of the current study was to evaluate the additional value of iMRI for resection of invasive pituitary adenomas. We conducted a retrospective monocenter study of all consecutive patients treated with invasive pituitary adenomas graded as Knosp III-IV at our department after the introduction of iMRI in 2008. Out of 315 transsphenoidal surgeries for pituitary adenomas, 111 met the criteria for analysis. Patients treated with endoscopic or microsurgical technique were included. iMRI was performed at surgeons' discretion, when maximal safe resection was assumed. Detailed volumetric tumor analysis using semiautomatic segmentation software (Brainlab Elements) before surgery, during surgery, and after surgery was performed. Additionally, demographic data, additional resection, endocrinological outcome as well as complications were evaluated. Postoperative tumor volume as measured in the follow-up MRI 3 months after surgery was significantly lower compared with intraoperative tumor volume (p < 0.001). The difference was statistically significant for both surgical techniques (p < 0.001). No significant difference was found between both techniques in intraoperative and postoperative tumor volume (p = 0.395 and p = 0.329 respectively). Additional tumor resection was performed in 56 cases (50.5%). We found no significant difference between microsurgical and endoscopic techniques regarding additional resection after iMRI (p = 0.512). New diagnosed permanent diabetes insipidus was found in 10 patients (10.5%, 10/95). New hypopituitarism was seen in 22.1% (21/95) cases and according to multivariate logistic regression was significantly associated with microsurgical technique (p = 0.035). Visual improvement was achieved in 76.8% (N = 53/69, p < 0.001) of patients with visual impairment before surgery. Revision surgery as the consequence of cerebrospinal fistula was performed in eight cases (7.2%). Meningitis was documented in three patients (2.7%). One patient died as a consequence of intraoperative vascular injury. Intraoperative MRI after maximal safe resection significantly improves the overall extent of resection in invasive pituitary adenomas independent of the surgical technique employed. Simultaneously, iMRI-assisted transsphenoidal surgery results in excellent visual recovery with low-risk profile for surgical complications for both endoscopic as well as microsurgical technique. Endoscopic technique might be related to the lower incidence of new hypopituitarism after surgery.

The Value of Intraoperative Magnetic Resonance Imaging in Endoscopic and Microsurgical Transsphenoidal Pituitary Adenoma Resection.

BACKGROUND: The routine use of intraoperative magnetic resonance imaging (iMRI) helps to achieve gross total resection in transsphenoidal pituitary surgery. We compared the added value of iMRI for extent of resection in endoscopic versus microsurgical transsphenoidal adenomectomy. METHODS: A total of 96 patients with pituitary adenoma were included. Twenty-eight consecutive patients underwent endoscopic transsphenoidal tumor resection. For comparison, we used a historic cohort of 68 consecutive patients treated microsurgically. We evaluated the additional resection after conducting iMRI using intraoperative and late postoperative volumetric tumor analysis 3 months after surgery. Demographic data, clinical symptoms, and complications as well as pituitary function were evaluated. RESULTS: We found significantly fewer additional resections after conducting iMRI in the endoscopic group (P = 0.042). The difference was even more profound in Knosp grade 0-2 adenomas (P = 0.029). There was no significant difference in Knosp grade 3-4 adenomas (P = 0.520). The endoscopic approach was associated with smaller intraoperative tumor volume (P = 0.023). No significant difference was found between both techniques in postoperative tumor volume (P = 0.228). Satisfactory results of pituitary function were significantly more often associated with an endoscopic approach in the multiple regression analysis (P = 0.007; odds ratio, 17.614; confidence interval 95%, 2.164-143.396). CONCLUSIONS: With the endoscopic approach, significantly more tumor volume reduction was achieved before conducting iMRI, decreasing the need for further resection. This finding was even more pronounced in adenomas graded Knosp 0-2. In the case of extensive and invasive adenomas with infiltration of cavernous sinus and suprasellar or parasellar extension, additional tumor resection and increase in the extent of resection was achieved with iMRI in both groups. The endoscopic approach seems to result in better endocrine outcomes, especially in Knosp grade 0-2 pituitary adenomas.