Can Perfusion-Based Brain Tissue Oxygenation MRI Support the Understanding of Cerebral Abscesses In Vivo?

PURPOSE: The clinical condition of a brain abscess is a potentially life-threatening disease. The combination of MRI-based imaging, surgical therapy and microbiological analysis is critical for the treatment and convalescence of the individual patient. The aim of this study was to evaluate brain tissue oxygenation measured with dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI) in patients with brain abscess and its potential benefit for a better understanding of the environment in and around brain abscesses. METHODS: Using a local database, 34 patients (with 45 abscesses) with brain abscesses treated between January 2013 and March 2021 were retrospectively included in this study. DSC-PWI imaging and microbiological work-up were key inclusion criteria. These data were analysed regarding a correlation between DSC-PWI and microbiological result by quantifying brain tissue oxygenation in the abscess itself, the abscess capsula and the surrounding oedema and by using six different parameters (CBF, CBV, CMRO2, COV, CTH and OEF). RESULTS: Relative cerebral blood flow (0.335 [0.18-0.613] vs. 0.81 [0.49-1.08], p = 0.015), relative cerebral blood volume (0.44 [0.203-0.72] vs. 0.87 [0.67-1.2], p = 0.018) and regional cerebral metabolic rate for oxygen (0.37 [0.208-0.695] vs. 0.82 [0.55-1.19], p = 0.022) were significantly lower in the oedema around abscesses without microbiological evidence of a specific bacteria in comparison with microbiological positive lesions. CONCLUSIONS: The results of this study indicate a relationship between brain tissue oxygenation status in DSC-PWI and microbiological/inflammatory status. These results may help to better understand the in vivo environment of brain abscesses and support future therapeutic decisions.

Ultra-High-Field 7 T Magnetic Resonance Imaging Including Dynamic and Static Contrast-Enhanced T1-Weighted Imaging Improves Detection of Secreting Pituitary Microadenomas.

OBJECTIVE: A prospective preoperative evaluation of 7 T ultra-high-field magnetic resonance imaging (MRI) in patients with suspected pituitary microadenomas for both adenoma detection and intrasellar localization compared with 3 T MRI was carried out. MATERIALS AND METHODS: Patients underwent prospective preoperative standardized 3 and 7 T MRI. A distinct qualitative (lesion detection, intrasellar lesion location) and quantitative (lesion diameters, T1/T2 signal intensity ratio of the lesion to normal pituitary gland tissue) analysis was performed, along with an evaluation of image quality (IQ) regarding overall IQ, anatomical parameters, and artifacts; the findings of the qualitative analysis were compared with intraoperative findings and endocrinological outcomes. RESULTS: Sixteen patients (mean age, 43 ± 16 years; 13 women) with pituitary microadenomas were included. Using 7 T MRI allowed the detection of 15 microadenomas-3 more than 3 T MRI. In addition, 7 T MRI allowed more precise lesion localization with 93.75% (15/16) agreement with intraoperative findings, compared with 75% (12/16) agreement using 3 T MRI. Lesion diameters showed no significant difference between 3 and 7 T MRI. T1 and T2 signal intensity ratio between microadenomas and normal pituitary gland tissue were higher in 7 T MRI than in 3 T MRI. The overall IQ and the IQ of each anatomical parameter of 7 T MRI were rated higher than those of 3 T MRI. No significant differences in susceptibility or head motion artifacts were observed between 3 and 7 T MRI; however, 7 T MRI was more susceptible to pulsation artifacts. CONCLUSION: Ultra-high-field MRI surpasses 3 T MRI in pituitary microadenoma detection and enables more precise delineation with higher correlation with intraoperative findings. Thus, 7 T sellar imaging is a promising option-especially in previously magnetic resonance-negative patients with endocrinologically confirmed hormone oversecretion-and helps reduce the need for invasive diagnostics.

Clinical Evaluation of an Innovative Metal-Artifact-Reduction Algorithm in FD-CT Angiography in Cerebral Aneurysms Treated by Endovascular Coiling or Surgical Clipping.

Treated cerebral aneurysms (IA) require follow-up imaging to ensure occlusion. Metal artifacts complicate radiologic assessment. Our aim was to evaluate an innovative metal-artifact-reduction (iMAR) algorithm for flat-detector computed tomography angiography (FD-CTA) regarding image quality (IQ) and detection of aneurysm residua/reperfusion in comparison to 2D digital subtraction angiography (DSA). Patients with IAs treated by endovascular coiling or clipping underwent both FD-CTA and DSA. FD-CTA datasets were postprocessed with/without iMAR algorithm (MAR+/MAR−). Evaluation of all FD-CTA and DSA datasets regarding qualitative (IQ, MAR) and quantitative (coil package diameter/CPD) parameters was performed. Aneurysm occlusion was assessed for each dataset and compared to DSA findings. In total, 40 IAs were analyzed (ncoiling = 24; nclipping = 16). All iMAR+ datasets demonstrated significantly better IQ (pIQ coiling < 0.0001; pIQ clipping < 0.0001). iMAR significantly reduced the metal-artifact burden but did not affect the CPD. iMAR significantly improved the detection of aneurysm residua/reperfusion with excellent agreement with DSA (naneurysm detection MAR+/MAR−/DSA = 22/1/26). The iMAR algorithm significantly improves IQ by effective reduction of metal artifacts in FD-CTA datasets. The proposed algorithm enables reliable detection of aneurysm residua/reperfusion with good agreement to DSA. Thus, iMAR can help to reduce the need for invasive follow-up in treated IAs.

Improved Detection of Cavernous Sinus Invasion of Pituitary Macroadenomas with Ultra-High-Field 7 T MRI.

To compare 7 T magnetic resonance imaging (MRI) of pituitary macroadenomas (PMA) with standard MRI and intraoperative findings regarding tumor detection, localization, size, and extension. Patients with suspected pituitary adenoma underwent pre-operative 1.5 T or 3 T and 7 T MRI; 14 patients with a PMA were included. A qualitative (lesion detection, location, cavernous sinus infiltration) and quantitative (lesion size, depth of cavernous sinus infiltration) analysis of 1.5 T, 3 T and 7 T MRI was performed and compared with intraoperative findings. Both 1.5/3 T and 7 T MRI enabled the detection of all PMAs; lesion size determination was equal. 7 T MRI enables more precise assessments of cavernous sinus infiltration of PMA (ncorrect 7T = 78.6%, ncorrect 1.5/3T = 64.3%). Ultra-high-field MRI is a reliable imaging modality for evaluation of PMAs providing exact information on lesion location and size. 7 T MRI yielded more accurate information on cavernous sinus infiltration with better agreement with intraoperative findings than standard MRI.

Case Report: Consecutive Adrenal Cushing's Syndrome and Cushing's Disease in a Patient With Somatic CTNNB1, USP8, and NR3C1 Mutations.

The occurrence of different subtypes of endogenous Cushing's syndrome (CS) in single individuals is extremely rare. We here present the case of a female patient who was successfully cured from adrenal CS 4 years before being diagnosed with Cushing's disease (CD). The patient was diagnosed at the age of 50 with ACTH-independent CS and a left-sided adrenal adenoma, in January 2015. After adrenalectomy and histopathological confirmation of a cortisol-producing adrenocortical adenoma, biochemical hypercortisolism and clinical symptoms significantly improved. However, starting from 2018, the patient again developed signs and symptoms of recurrent CS. Subsequent biochemical and radiological workup suggested the presence of ACTH-dependent CS along with a pituitary microadenoma. The patient underwent successful transsphenoidal adenomectomy, and both postoperative adrenal insufficiency and histopathological workup confirmed the diagnosis of CD. Exome sequencing excluded a causative germline mutation but showed somatic mutations of the ß-catenin protein gene (CTNNB1) in the adrenal adenoma, and of both the ubiquitin specific peptidase 8 (USP8) and the glucocorticoid receptor (NR3C1) genes in the pituitary adenoma. In conclusion, our case illustrates that both ACTH-independent and ACTH-dependent CS may develop in a single individual even without evidence for a common genetic background.

Tolvaptan Versus Fluid Restriction in the Treatment of Hyponatremia Resulting from SIADH Following Pituitary Surgery.

CONTEXT: The relevance of hyponatremia has been acknowledged by guidelines from the United States (2013) and Europe (2014). However, treatment recommendations differ due to limited evidence. OBJECTIVE: In hyponatremia following pituitary surgery-caused by the syndrome of inappropriate antidiuretic hormone (SIADH) secretion-we compared fluid restriction with the pharmacological increase of water excretion by blocking the vasopressin 2 receptors with tolvaptan at a low and a moderate dose. DESIGN: Prospective observational study. SETTING: Neurosurgical Department of a University hospital with more than 200 surgical pituitary procedures per year. PATIENTS: Patients undergoing pituitary surgery and developing serum sodium below 136 mmol/L. The diagnosis of SIADH was established by euvolemia (daily measurement of body weight and fluid balance), inappropriately concentrated urine (specific gravity), and exclusion of adrenocorticotropic and thyroid-stimulating hormone deficiency. INTERVENTION: Patients were treated with fluid restriction (n = 40) or tolvaptan at 3.75 (n = 38) or 7.5 mg (n = 48). MAIN OUTCOME MEASURES: Treatment efficacy was assessed by the duration of hyponatremia, sodium nadir, and length of hospitalization. Safety was established by a sodium increment below 10 mmol/L per day and exclusion of side effects. RESULTS: Treatment with 7.5 mg of tolvaptan resulted in a significant attenuation of hyponatremia and in a significant overcorrection of serum sodium in 30% of patients. The duration of hospitalization did not differ between treatment groups. CONCLUSIONS: Tolvaptan at a moderate dose is more effective than fluid restriction in the treatment of SIADH. Overcorrection of serum sodium may be a side effect of tolvaptan even at low doses.

Surgical treatment of aggressive pituitary adenomas and pituitary carcinomas.

Surgery of aggressive pituitary adenomas and pituitary carcinomas is part of the interdisciplinary management of these difficult to treat tumors. Invasion, giant size and unusual, asymmetric extent of these tumors frequently require modifications or extensions of the standard approaches for transsphenoidal and transcranial surgery. Frequently, only debulking procedures can be performed. In aggressive and hormone secreting adenomas, the remission rates achieved by surgery alone are relatively poor and adjuvant medical treatments or irradiation are needed. Safe resection of as much tumor as possible and symptomatic control is aimed at, rather than remission. Many procedures are required for rapid progression of lesions or recurrences, in order to extend the survival of the patients. Metastases of pituitary carcinomas within the cranial cavity or spine can be attacked. Since they can occur anywhere in the brain or spinal canal they require the entire battery of neurosurgical approaches. Unfortunately, in this group of pituitary tumors, the complication rates are higher than in primary operations of enclosed adenomas. The respective techniques with their facilities and limitations are reviewed in this article.

Skull Base Chordomas and Chondrosarcomas.

Skull base chordomas account for less than 0.2% and chondrosarcomas for less than 0.15% of all intracranial tumors. Although their clinical and imaging presentations are similar, they derive from different origins. Chordomas arise from embryonic remnants of the primitive notochord and chondrosarcomas from primitive mesenchymal cells or from the embryonic rest of the cranial cartilaginous matrix. Both entities are characterized by infiltration and destruction of the surrounding bone and soft tissue and a high locoregional recurrence rate. Chondrosarcomas, when treated with similar complex strategies, display a much better prognosis than chordomas. The overall survival is approximately 65% for chordomas and 80% for chondrosarcomas at 5 years and 30 and 50%, respectively, at 10 years. Chordomas are divided into the following 3 histological types: classical (conventional), chondroid, and dedifferentiated. Chondrosarcomas have conventional, mesenchymal, clear cell, and dedifferentiated subgroups. Both tumor entities often present with nonspecific symptoms, and headaches are the most reported initial symptom. Computed tomography and magnetic resonance imaging are required to determine the tumor localization and the extent of tumor growth. The treatment philosophy is to maximize tumor resection, minimize morbidity, and preserve function. Neurosurgical approaches commonly used for the resection of intracranial chordomas and chondrosarcomas are transsphenoidal, transbasal, cranio-orbitozygomatic, transzygomatic extended middle fossa, transcondylar, and transmaxillary approaches. Chordomas and chondrosarcomas are not sensitive to chemotherapy and there are no approved drugs for their treatment. The present treatment concept is a combination of surgical resection with a maximal excision and preserving patients' quality of life by adjuvant radiotherapy for both chordomas and chondrosarcomas.

Efficacy of Temozolomide Therapy in Patients With Aggressive Pituitary Adenomas and Carcinomas-A German Survey.

CONTEXT: Despite growing evidence that temozolomide (TMZ) therapy is effective for the treatment of aggressive pituitary tumors (APTs) or carcinomas (PCs), individual therapy decisions remain challenging. OBJECTIVE: We therefore aimed to report on clinical characteristics leading to initiation of TMZ therapy and to add evidence on TMZ long-term effectiveness. DESIGN AND SUBJECTS: Retrospective survey on TMZ treatment in patients with APTs or PCs. TMZ therapy was initiated in 47 patients (22 females) with APTs (n = 34) or PCs (n = 13). Mean age at diagnosis was 45 ± 15 years. The immunohistochemical subtypes were corticotroph (n = 20), lactotroph (n = 18), and nonfunctioning (n = 9) tumors. TMZ therapy started 8 years after initial diagnosis using a standard regimen (median 6 cycles) for the majority of patients. RESULTS: Long-term radiological response to TMZ after a median follow-up of 32 months with 4 patients still on TMZ therapy was tumor regression for 9 (20%), stable disease for 8 (17%), and tumor progression for 29 patients (63%) (outcome data available for 46 patients). Progression occurred 16 months after initiation of TMZ. Median estimated progression-free survival was 23 months. Disease stabilization and median progression-free survival did not differ between patients with APTs or PCs. Predictors of tumor response were not identified. Overall, TMZ was well tolerated. CONCLUSION: We performed a nationwide survey on TMZ therapy in patients with APTs and PCs. While early response rates to TMZ are promising, long-term outcome is less favorable. Prolonged TMZ administration should be considered. We were not able to confirm previously reported predictors of tumor response to TMZ.

Surgery for Prolactinomas to Date.

While in the past surgery for prolactinomas was a competitive option to medical treatment with dopamine agonists, to date the indications for operations are restricted to only a few specific situations. However, if a patient is intolerant to medical treatment or if the drugs are not sufficiently effective in terms of lowering prolactin levels or tumor shrinkage, surgery should always be considered. In microprolactinomas, operations can achieve excellent prolactin normalization rates. In tumors difficult to treat, the combination of surgical tumor resection and long-term medical treatment supports better control of the disease. The individual indications, results, techniques, and complications of operations for prolactinomas are briefly reviewed in this paper.

Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology.

PURPOSE: Adamantinomatous craniopharyngiomas (ACP) as benign sellar brain tumors are challenging to treat. In order to develop robust in vivo drug testing methodology, the murine orthotopic craniopharyngioma model (PDX) was characterized by magnetic resonance imaging (MRI) and histology in xenografts from three patients (ACP1-3). METHODS: In ACP PDX, multiparametric MRI was conducted to assess morphologic characteristics such as contrast-enhancing tumor volume (CETV) as well as functional parameters from dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) including area-under-the-curve (AUC), peak enhancement (PE), time-to-peak (TTP) and apparent diffusion coefficient (ADC). These MRI parameters evaluated in 27 ACP PDX were correlated to histological features and percentage of vital tumor cell content. RESULTS: Qualitative analysis of MRI and histology from PDX revealed a similar phenotype as seen in patients, although the MRI appearance in mice resulted in a more solid tumor growth than in humans. CETV were significantly higher in ACP2 xenografts relative to ACP1 and ACP3 which correspond to respective average vitality of 41%, <10% and 26% determined histologically. Importantly, CETV prove tumor growth of ACP2 PDX as it significantly increases in longitudinal follow-up of 110 days. Furthermore, xenografts from ACP2 revealed a significantly higher AUC, PE and TTP in comparison to ACP3, and significantly increased ADC relative to ACP1 and ACP3 respectively. Overall, DCE-MRI and DWI can be used to distinguish vital from non-vital grafts, when using a cut off value of 15% for vital tumor cell content. CONCLUSIONS: MRI enables the assessment of craniopharyngioma PDX vitality in vivo as validated histologically.

Rathke's Cleft Cyst as Origin of a Pediatric Papillary Craniopharyngioma.

A 6-year old patient presented with an intra and suprasellar cystic lesion accompanied with impairment of the hypothalamic-pituitary axis and partial hypopituitarism. The most likely cause of sellar lesions in this age group are adamantinomatous craniopharyngioma (adaCP) or Rathke´s cleft cysts (RCCs). AdaCP are characterized by CTNNB1 mutations accompanied with aberrant nuclear beta-catenin expression. RCC show neither nuclear beta-catenin expression nor BRAF mutation. The latter is a hallmark of papillary craniopharyngiomas (papCP) that exhibit remarkable histological similarity with metaplasia of RCC. Diagnosis of the patient was elucidated by CTNNB1 and BRAF mutation screening, utilizing different approaches, as well as histological examination of markers, e.g., beta-catenin, claudin-1, EpCAM and the mutated BRAFV600E protein, which are known to be differentially expressed in sellar lesions. The case presented reveals extraordinary aspects for two reasons. Firstly, the lesion appeared clinically, on MRI, intraoperatively and histologically as RCC with prominent squamous metaplasia, but showing an expression pattern of markers also found in papCP, whilst exhibiting a hitherto undescribed BRAFV600E mutation. This important result documents a supposable transition of RCC metaplasia into a papillary craniopharyngioma (papCP). Secondly, this intriguing case shows unexpectedly that although papCP usually occurs almost exclusively in adults, it can also arise in childhood.

The surgical treatment of acromegaly.

PURPOSE: Surgical extraction of as much tumour mass as possible is considered the first step of treatment in acromegaly in many centers. In this article the potential benefits, disadvantages and limitations of operative acromegaly treatment are reviewed. METHODS: Pertinent literature was selected to provide a review covering current indications, techniques and results of operations for acromegaly. RESULTS: The rapid reduction of tumour volume is an asset of surgery. To date, in almost all patients, minimally invasive, transsphenoidal microscopic or endoscopic approaches are employed. Whether a curative approach is feasible or a debulking procedure is planned, can be anticipated on the basis of preoperative magnetic resonance imaging. The radicality of adenoma resection essentially depends on localization, size and invasive character of the tumour. The normalization rates of growth hormone and IGF-1 secretion, respectively, depend on tumour-related factors such as size, extension, the presence or absence of invasion and the magnitude of IGF-1 and growth hormone oversecretion. However, also surgeon-related factors such as experience and patient load of the centers have been shown to strongly affect surgical results and the rate of complications. As compared to most medical treatments, surgery is relatively cheap since the costs occur only once and not repeatedly. There are several new technical gadgets which aid in the surgical procedure: navigation and variants of intraoperative imaging. CONCLUSIONS: For the mentioned reasons, current algorithms of acromegaly management suggest an initial operation, unless the patients are unfit for surgery, refuse an operation or only an unsatisfactory resection is anticipated. A few suggestions are made when a re-operation could be considered.

Predictors for occlusion of cerebral AVMs following radiation therapy : Radiation dose and prior embolization, but not Spetzler-Martin grade.

BACKGROUND: Intracranial arteriovenous malformations (AVMs) may show a harmful development. AVMs are treated by surgery, embolization, or radiation therapy. OBJECTIVE: This study investigated obliteration rates and side effects in patients with AVMs treated by radiation therapy. METHODS: A total of 40 cases treated between 2005 and 2013 were analyzed. Single-dose stereotactic radiosurgery (SRS) was received by 13 patients and 27 received hypofractionated stereotactic radiation therapy (HSRT). In 20 patients, endovascular embolization had been performed prior to irradiation and 24 patients (60 %) had a history of previous intracranial hemorrhage. RESULTS: Treatment resulted in complete obliteration (CO) in 23/40 cases and partial obliteration in 8/40. CO was achieved in 85 % of patients receiving SRS compared to 44 % of those receiving HSRT. In the HSRT group, a first indication of an influence of AVM volume on obliteration rate was found. Equivalent 2 Gy fraction doses (EQD2) >70 Gy showed an obliteration rate of 50 %. Prior embolization was significantly associated with a higher portion of CO (p = 0.032). Median latency period (24.2 vs. 26 months) until CO was similar in both groups (SRS vs. HSRT). The rate of intracranial hemorrhage in patients with no prior bleeding events was 0 %. CONCLUSION: Excellent obliteration rates were achieved by SRS. Consistent with the literature, this data analysis suggests that the results of HSRT are volume-dependent. Furthermore, regimens with EQD2 doses >70 Gy appear more likely to achieve obliteration than schemes with lower doses. The findings indicate that radiation therapy does not increase the risk of bleeding. Prior embolization may have a good prognostic impact.

Intraoperative Magnetic Resonance Imaging for Pituitary Adenomas.

Surgery for pituitary adenomas attempts the optimally possible amount of tumor resection, which ideally is total excision. However, there are limitations in the resectability and in the intraoperative assessment of the radicality of an adenomectomy. Postoperative imaging is usually performed with a few months delay after tumor resection. Intraoperative magnetic resonance imaging (MRI) is used to depict the extent of tumor removal already achieved in the operating theater during surgery. To date, there are different low- and high-field intraoperative MRI systems available. Decompression of optic pathways, preservation of the pituitary and residual tumor can be largely predicted from the intraoperative images. Several studies convincingly show that intraoperative depiction of residual tumor allows targeted attack of the remnant. Not only is the amount of tumor resected increased, but also the percentage of total tumor excisions. Intraoperative MRI provides an immediate feedback to the surgeon and is thus a valuable quality control for pituitary surgery. It also allows the acquisition of data sets for precise intraoperative navigation. However, the MRI scanners are heavy and expensive and some systems even require extensive modification of the operating theater. Imaging slightly prolongs the operation but is not associated with an increased complication rate. There are also potential artifacts which must be considered.

Anatomical location of the vocal cords in relation to cervical vertebrae: A new predictor of difficult laryngoscopy?

BACKGROUND: Several anatomical factors, such as prognathism, sex, short thyromental distance and others are known to make direct laryngoscopy difficult. OBJECTIVE: We investigated the hypothesis that the anatomical position of the vocal cords in relation to the cervical vertebrae correlates with difficult laryngoscopy. Existing MRI was used to identify the position of the vocal cords relative to the cervical spine in patients with and without difficult laryngoscopy. DESIGN: Observational study with adaptive enrichment. SETTING: University hospital. PATIENTS: A total of 142 adult patients, 91 with easy (Cormack-Lehane class 1 or 2) and 51 with difficult (Cormack-Lehane class 3 or 4) laryngoscopy. MAIN OUTCOME MEASURES: Position of the vocal cords relative to cervical vertebrae in patients with easy vs. difficult laryngoscopy. RESULTS: In patients with difficult laryngoscopy, we found a higher incidence of cranial position of the vocal cords in relation to the cervical spine compared with patients with easy laryngoscopy (P < 0.001). CONCLUSION: Anaesthesiologists should take advantage of existing imaging of the cervical spine when assessing the patient's airway.

Novel Techniques in the Surgical Treatment of Acromegaly: Applications and Efficacy.

Since the establishment of transsphenoidal microsurgery as the operative treatment of choice in most patients with acromegaly 40 years ago, a few novel technical developments have evolved. Their application, utility and efficacy will be briefly discussed in this review article, based on an analysis of published results and the authors' personal experience. The endoscope was additionally used to search for residual tumours in locations which could not be visualised with the operating microscope. In many centres it has by now fully replaced the operating microscope. Extended endoscopic operations hardly have limits in respect to accessible pathology. Overall, the results and complications reported from microsurgical and endoscopic series are comparable. Intraoperative magnetic resonance imaging allows depicting the completeness of a tumour resection. While in many patients additional tumour resections are performed on the basis of intraoperative imaging, the improvements in hormonal remission rates reported are less impressive. Neuronavigation uses imaging data to improve the surgeon's orientation, and it is certainly a major asset to the inexperienced. In high-caseload centres it is mainly appreciated in anatomical variants and reoperations. While the Doppler probe is a valuable and easily affordable gadget to avoid vascular arterial injury, intraoperative ultrasound imaging of tumour extension has a much poorer resolution than magnetic resonance imaging and is thus not widely implemented. The clinical value of intraoperative growth hormone measurements is controversially discussed. In summary, the application of modern technology has only led to a minor improvement of results, but it has widened the spectrum of accessible pathologies and increased the safety of the procedures for the patient. It is expected that outcomes will continue to improve as novel techniques and concepts are being developed.

Diagnosis of Primary Hypophysitis in Germany.

CONTEXT: Representative data on diagnostic findings in primary hypophysitis (PrHy) are scarce. OBJECTIVE: The objective of the study was to collate consistent data on clinical features in a large series of patients with PrHy. Another objective was to gain information on current practice in a diagnostic work-up. DESIGN: The Pituitary Working Group of the German Society of Endocrinology conducted a nationwide retrospective cross-sectional cohort study in Germany. PATIENTS: Seventy-six patients with PrHy were identified. MAIN OUTCOME MEASURES: Clinical and endocrinological features were assessed. RESULTS: Headache (50%) and increase in body mass (18%) were the most frequent nonendocrine symptoms. Hypophysitis was associated with pregnancy in only 11% of the female patients. Diabetes insipidus was found in 54% of the patients at presentation. Hypogonadotropic hypogonadism was the most frequent endocrine failure (62%), whereas GH deficiency was the least frequent (37%). With 86%, thickening of the pituitary stalk was the prevailing neuroradiological sign. Compared with surgical cases, the cases without histological confirmation presented more often with suprasellar lesions and had less severe nonendocrine symptoms. Granulomatous hypophysitis was associated with more severe clinical symptoms than lymphocytic hypophysitis. Examination of cerebrospinal fluid was predominantly performed in participating neurosurgical centers, whereas thyroid antibodies were almost exclusively assessed in endocrinological centers. CONCLUSION: In contrast to the literature, hypogonadism was found to be the most frequent endocrine failure in PrHy. Weight gain was identified as a clinical sign of PrHy. In the majority of patients, PrHy can be reliably identified by characteristic clinical signs and symptoms, obviating histological confirmation. The diagnostic approach should be standardized in PrHy.

Treatment of Primary Hypophysitis in Germany.

CONTEXT: The best treatment of primary hypophysitis (PrHy) is a matter of debate. OBJECTIVE: Our main objective was to analyze the treatment practice for PrHy in Germany and to compare the outcome of the main treatment options. DESIGN: The Pituitary Working Group of the German Society of Endocrinology conducted a nationwide retrospective cross-sectional cohort study. PATIENTS: Seventy-six patients with PrHy were eligible for the study. MAIN OUTCOME MEASURES: Clinical and endocrinological outcomes, side effects and complications of therapy, initial response, and recurrence rates were assessed. Outcome depending on the treatment modality was evaluated. RESULTS: For mere observation, regression of space-occupying lesions was observed in 46%, unchanged size in 27%, and progression reported in 27%. Pituitary function improved in 27% of patients during observation. Deterioration of pituitary function was only found in patients with progressive lesions. The initial response to glucocorticoid pulse therapy was most favorable, with early failure in only 3%. However, the overall failure and recurrence rate was 41%. Recurrence rate was not related to duration of steroid administration. Side effects of steroids occurred in 63%. The surgical approach was transsphenoidal in 94%. The histological subtype was lymphocytic hypophysitis in 70% and granulomatous hypophysitis in 30%. Progression or recurrence was observed in 25% after surgical treatment. CONCLUSION: Glucocorticoid pulse therapy is associated with a high recurrence rate. Evidence suggests that surgery is not able to prevent recurrence. Considering the favorable results of observation, conservative management is recommended in PrHy unless symptoms are severe or progressive.

Insights into the infiltrative behavior of adamantinomatous craniopharyngioma in a new xenotransplant mouse model.

Adamantinomatous craniopharyngiomas (adaCP) cause hypothalamic pituitary dysfunction. Elucidation of pathomechanisms underlying tumor progression is essential for the development of targeted chemotherapeutic treatment options. In order to study the mechanisms of tumor outgrowth, we implanted human primary adaCP tissue from three different surgical specimens stereotactically into the brain of immunodeficient mice (n = 20). Three months after tumor inoculation, magnetic resonance imaging and histology confirmed tumor engraftment in all 20 mice (100%) that obtained tissue transplants. The lesions invaded adjoining brain tissue with micro finger-shaped protrusions. Immunohistochemical comparison of the primary tumor and xenotransplants revealed a similar amount of proliferation (Mib-1) and cytokeratin expression pattern (KL-1). Whole tumor reconstruction using serial sections confirmed whirl-like cell clusters with nuclear ß-catenin accumulations at the tumor brain border. These whirls were surrounded by a belt of Claudin-1 expressing cells, showed an activated epidermal growth factor receptor (EGFR) and distinct CD133 as well as p21(WAF1/Cip1) positivity, indicating a tumor stem cell phenotype. Consistent with our previous in vitro studies, intracranial xenotransplants of adaCP confirmed cells with nuclear ß-catenin and activated EGFR being the driving force of tumor outgrowth. This model provides the possibility to study in vivo tumor cell migration and to test novel treatment regimens targeting this tumor stem cell niche.