Introduction Renewed interest in transsphenoidal surgery (TSS) as a therapeutic option for prolactinomas has emerged. This study is aimed at defining the current role of pituitary surgery in the management of prolactinomas. Materials and Methods In this retrospective, consecutive single-center study, 162 patients who underwent primary microscopic TSS for prolactinomas between 2006 and 2019 were analyzed regarding surgical indication, previous dopamine-agonist (DA) treatment, early remission rates (3 months postoperatively), surgical complications and pituitary function. Results Seventy-four microprolactinomas and 88 macroprolactinomas were operated by TSS. 62.3% of the patients had received prior DA treatment. For microprolactinomas, the predominant indication for surgery was patient’s wish (41.9%), while indications for macroprolactinomas varied. For enclosed microprolactinomas, the initial remission rate was 92.1%, while for macroprolactinomas, the rate was 70.4%. No significant difference of remission rates was found between DA-pretreated (65.3%) and non-pretreated (72.1%) patients (p=0.373).None of the patients suffered a significant complication. Re-operation for a postoperative cerebrospinal fluid leak was required in one patient (0.6%). Permanent postoperative deterioration of pituitary function was only observed in one of 158 patients with surgery for a prolactinoma (0.6%). Improvement of pituitary function was observed in 8 of 25 patients (32%) with preoperative deficits. Conclusion Transsphenoidal microsurgery is safe and efficient for treatment of prolactinomas. It is particularly suitable for enclosed prolactinomas. The patient should be well informed of the pros and cons of the treatment options, which include DA medication and TSS, and the patient’s preference should be taken into account during decision-making.
Transsphenoidal surgery (TSS) is the initial treatment modality of first choice in Cushing's disease (CD). With microscopic TSS and endoscopic TSS, two operative techniques with equally favourable remission rates and operative morbidity are available.On average, remission is achieved with primary TSS in 80% of patients with microadenomas and 60% of patients with macroadenomas. The current literature indicates that remission rates in repeat TSS for microadenomas can also exceed 70%. Experience with TSS in CD plays an important role in the success rate and centralization in Pituitary Centres of Excellence has been proposed. Microadenoma stage, imagingvisible adenoma, confirmation of ACTH-positive adenoma on histopathology and noninvasiveness are positive predictors for postoperative remission. In postoperative management, a steroid-sparing protocol with early postoperative assessment of remission status is recommended. Convincing evidence suggests that prolonged postoperative prophylactic antithrombotic measures can significantly reduce the risk of postoperative thromboembolic events in CD. Prevention or successful treatment of cortisol withdrawal syndrome remains an unsolved issue that should be a focus of future research. The further development and broad availability of functional imaging hold promise for improved preoperative detection of microadenomas. Intraoperative identification of microadenomas by specific fluorescent targeting could be a promising future avenue for the treatment of patients with negative imaging.
A wide range of vascular burden factors has been identified to impact vascular function and structure as indicated by carotid intima–media thickness (IMT). On the basis of their impact on IMT, vascular factors may be selected and clustered in a vascular burden index (VBI). Since many vascular factors increase the risk of Alzheimer’s disease (AD), a multifactorial neurodegenerative VBI may be related to early pathological processes in AD and cognitive decline in its preclinical stages. We investigated an elderly cohort at risk for neurodegeneration (TREND study, n = 1102) for the multifactorial influence of vascular burden factors on IMT measured by ultrasound. To create a VBI for this cohort, vascular factors and their definitions (considering medical history, medication, and/or blood marker data) were selected based on their statistical effects on IMT in multiple regressions including age and sex. The impact of the VBI on cognitive performance was assessed using the Trail-Making Test (TMT) and the consortium to establish a registry for Alzheimer’s disease (CERAD) neuropsychological battery. IMT was significantly predicted by age (standardized β = 0.26), sex (0.09; males > females) and the factors included in the VBI: obesity (0.18), hypertension (0.14), smoking (0.08), diabetes (0.07), and atherosclerosis (0.05), whereas other cardiovascular diseases or hypercholesterolemia were not significant. Individuals with 2 or more VBI factors compared to individuals without had an odds ratio of 3.17 regarding overly increased IMT ( ≥ 1.0 mm). The VBI showed an impact on executive control [log(TMT B−A), p = 0.047] and a trend toward decreased global cognitive function (CERAD total score, p = 0.057) independent of age, sex, and education. A VBI established on the basis of IMT may help to identify individuals with overly increased vascular burden linked to decreased cognitive function indicating neurodegenerative processes. The longitudinal study of this risk cohort will reveal the value of the VBI as prodromal marker for cognitive decline and AD.
Calvarial lesions are rare and can present as a variety of different diseases. The lesions can be palpable on the skin and cause local pain and paraesthesia and, depending on the location, neurological deficits can also occur. This research aims to present an overview of typical imaging features as well as neurosurgical management. We examined the charts of patients who underwent surgery on a calvarial lesion in our department between 2004 and 2017 (n=133). Retrospectively, the pre-, intra-, and postoperative data were analyzed with morphological and histological findings and compared with each other. Pain, swelling, cosmetically disturbing, and neurological deficits were the main complaints. Seventy-seven lesions were limited to the bone, while another 56 lesions showed an infiltrating growth in the adjacent tissue. Depending on the clinical signs and suspected diagnosis, a biopsy, a partial removal, or a complete resection was performed. Histiocytosis (n=20), meningiomas (n=20), metastases (n=19), and osteomas (n=16) were the most common lesions. Fibrous dysplasia (n=6) and intraosseous hemangioma (n=9) were less common; other lesions were present only in isolated cases. Imaging features may suggest the lesion to be benign or malignant, but the diagnosis can be only confirmed by histological examination. The surgical strategy depends on the complaints, location of the lesion, and suspected diagnosis. Adjuvant treatment should be initiated according to the histological findings.
ObjectiveTo evaluate diagnostic accuracy of the corticotropin-releasing hormone (CRH) stimulation test and the overnight 8 mg dexamethasone suppression test (DST) for the differentiation of Cushing’s disease (CD) and ectopic Cushing’s syndrome (ECS).MethodsRetrospective study in 6 European centers. Inclusion criteria: patients with a) overt adrenocorticotropin (ACTH)-dependent Cushing’s syndrome at the time of dynamic testing, b) histopathological confirmed tumors and/or c) postoperative biochemical remission and/or adrenal insufficiency. Optimal cut-offs were calculated via receiver operating characteristic (ROC) analysis using CD as reference.Results469 patients were analyzed [78% females; median age 43 years (IQR 19)]. CRH test and overnight 8 mg DST were performed in 420 [CD, n=394 (94%); ECS, n=26 (6%)] and 237 patients [228 CD (96%), 9 ECS (4%)]. Both tests were performed in 205 patients (44%). The post-CRH %-increase at 30 minutes of both ACTH (cut-off ≥31%, sensitivity 83%, specificity 85%, AUC 0.81) and cortisol (cut-off ≥12%, sensitivity 82%, specificity 89%, AUC 0.86) discriminated best between CD and ECS. A test duration of >60 minutes did not improve diagnostic performance of the CRH test. The optimal cortisol cut-off for the %-suppression during the 8 mg DST was ≥55% (sensitivity 80%, specificity 78%, AUC 0.75).ConclusionThe CRH test has equivalent sensitivity but higher specificity than the 8 mg DST and is therefore the test of first choice. The diagnostic outcome of ACTH and cortisol is well comparable, however, sampling beyond 60 minutes post-CRH does not provide diagnostic benefits.
Corticotroph macroadenomas are rare but difficult to manage intracranial neoplasms. Mutations in the two Cushing’s disease mutational hotspots USP8 and USP48 are less frequent in corticotroph macroadenomas and invasive tumors. There is evidence that TP53 mutations are not as rare as previously thought in these tumors. The aim of this study was to determine the prevalence of TP53 mutations in corticotroph tumors, with emphasis on macroadenomas, and their possible association with clinical and tumor characteristics. To this end, the entire TP53 coding region was sequenced in 86 functional corticotroph tumors (61 USP8 wild type; 66 macroadenomas) and the clinical characteristics of patients with TP53 mutant tumors were compared with TP53/USP8 wild type and USP8 mutant tumors. We found pathogenic TP53 variants in 9 corticotroph tumors (all macroadenomas and USP8 wild type). TP53 mutant tumors represented 14% of all functional corticotroph macroadenomas and 24% of all invasive tumors, were significantly larger and invasive, and had higher Ki67 indices and Knosp grades compared to wild type tumors. Patients with TP53 mutant tumors had undergone more therapeutic interventions, including radiation and bilateral adrenalectomy. In conclusion, pathogenic TP53 variants are more frequent than expected, representing a relevant amount of functional corticotroph macroadenomas and invasive tumors. TP53 mutations associated with more aggressive tumor features and difficult to manage disease.
Objective In Cushing's disease (CD), detection of an adenoma by magnetic resonance imaging (MRI) is challenging. The aim of this study is to compare real-life MRI in the initial diagnostic work-up of CD with high-quality MRI performed in a tertiary center for pituitary diseases. Design and Methods We retrospectively analyzed 139 patients with CD who underwent primary transsphenoidal surgery (TSS) in our department and had both an MRI conducted at a different institution (external MRI; extMRI) and an MRI conducted at our institution (internal MRI; intMRI). Preoperative interpretation of MRI was performed independently by an external radiologist (extRAD), an internal neuroradiologist (intRAD) and a pituitary surgeon (SURG). Intraoperative detection of an adenoma and endocrinological remission provided proof of the true adenoma localisation in 105 patients. Results Interpretation of extMRI by extRAD and SURG was concordant in only 64% (89/139) of cases, while 74.1% (103/139) concordance was observed for interpretation of intMRI by intRAD and SURG. Based on extMRI, the true localisation of the adenoma was correctly predicted in only 46.7% of the patients by extRAD and in 65.7% by SURG. In contrast, the sensitivity to correctly identify the adenoma on intMRI was 80.0% for intRAD and 94.3% for SURG. Conclusion Both the quality of MRI and the reader’s experience are paramount for detection of microadenomas in CD. Every effort should be made to perform high-quality initial MRI according to current standards and to ensure rating by an expert in pituitary imaging.
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