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Alzheimer’s disease (AD), a progressive dementia, is one of the world’s most dangerous and debilitating diseases. Clinical trial results of amyloid-β (Aβ) and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing. There are currently no effective strategies for slowing the progression of AD. Further understanding of the mechanisms underlying AD and the development of novel therapeutic options are critical. Neurogenesis is impaired in AD, which contributes to memory deficits. Transplanted neural stem cells (NSCs) can regenerate degraded cholinergic neurons, and new neurons derived from NSCs can form synaptic connections with neighboring neurons. In theory, employing NSCs to replace and restore damaged cholinergic neurons and brain connections may offer new treatment options for AD. However there remain barriers to surmount before NSC-based therapy can be used clinically. The objective of this article is to describe recent advances in the treatment of AD models and clinical trials involving NSCs. In addition, we discuss the challenges and prospects associated with cell transplant therapy for AD.

Background Thyrotoxicosis is a rare complication of surgery for Cushing's disease (CD). In clinical practice, given the rarity of this condition, patients may be misdiagnosed, and thus not treated appropriately. This study describes the clinical features and management of thyrotoxicosis in this context. Methods We retrospectively screened a pituitary database for CD patients who underwent surgery at Peking Union Medical College Hospital between 2010 and 2017. The electronic medical records and documentation of 732 patients were searched in order to identify instances of thyrotoxicosis. Results Fourteen patients developed postoperative thyrotoxicosis after CD remission, representing 1.9% of all the CD patients who underwent surgery and 2.5% of the CD patients who were in remission after surgery. The onset of thyrotoxicosis occurred at a median of 3.5 months after surgery. At the onset, 13 patients (92.9%) were on a maintenance dose of hydrocortisone and were managed using a higher dose of hydrocortisone. One patient had normal adrenal function and was managed by observation first, then using anti-thyroid drugs. Thyrotoxicosis was transient in all but one patient, and lasted 1.9±0.7 months (range, 1-3.2 months). Conclusions Thyrotoxicosis is a rare complication that develops during the recovery period following surgery for CD. It occurs only after the surgical resolution of hypercortisolism, and in particular alongside adrenal insufficiency during the 4 months following CD remission. Awareness of this situation should be promoted among physicians, and patients should be managed on the basis of the clinical setting and manifestation.

PurposeXanthomatous hypophysitis (XHP) is an extremely rare form of primary hypophysitis for which there is a lack of clinical experience. A comprehensive understanding of its clinical characteristics, diagnosis and treatment is needed.MethodsHere, we report a case study and conduct a systematic review of XHP. Thirty-six cases were included, and their clinical manifestations, endocrine assessment, imaging features, treatment and follow-up data were collected and analyzed.ResultsThe mean age at diagnosis was 39.1 years, and females were predominant (75.0%). The most common symptom was headache (68.6%), and 66.7% of female patients presented menstrual disorders. The most common pituitary dysfunction was growth hormone (GH) deficiency. More than half of patients exhibited central diabetes insipidus (CDI). The majority of patients had an imaging presentation of a cystic lesion with peripheral enhancement. Pituitary stalk thickening was observed in half of the patients. Total lesion resection was achieved in 57.1% of cases. The recurrence rate after partial resection and biopsy was significantly higher than that after total lesion resection (57.1% vs. 0.0%, P = 0.0147). The most common pituitary hormone abnormalities to resolve after surgery were hyperprolactinemia (100.0%) and GH deficiency (91.7%). The typical pathological feature was inflammatory infiltration of foamy histiocytes, which showed positivity for CD68.ConclusionDiagnosis of XHP is difficult when relying on clinical symptoms and imaging features. Therefore, surgical histopathology is necessary. Based on the available evidence, total lesion resection is recommended for treatment. However, the long-term prognosis for this rare disease remains unclear.

In this article, we present a 31-year-old female who presented with intermittent headache and oligomenorrhea of over 10 years’ duration. Imaging revealed a large suprasellar mass with sellar extension. The patient underwent an endoscopic endonasal trans-sphenoidal surgery to resection of the mass. Clinical, radiological, and operative findings from this patient were initially considered to be Rathke’s cleft cyst (RCC). However, postoperative histological examinations revealed a mature cystic teratoma. No radiotherapy was performed after surgery. At the most recent follow-up, approximately 1 year later, the patient is doing well with no headache and no recurrence of the teratoma.

Biochemical remission after transsphenoidal surgery is still unsatisfied in acromegaly patients with macroadenomas, especially with invasive macroadenomas. Concerning the impact of preoperative somatostatin analogues (SSAs) on surgical outcomes, previous studies with limited cases reported conflicting results. To assess current evidence of preoperative medical treatment, we performed a systematic review and meta-analysis of comparative studies. A literature search was conducted in Pubmed, Embase, and the Cochrane Library. Five randomized controlled trials (RCT) and seven non-RCT comparative studies were included. These studies mainly focused on pituitary macroadenomas though a small number of microadenoma cases were included. For safety, preoperative SSAs were not associated with elevated risks of postoperative complications. With respect to efficacy, the short-term cure rate was improved by preoperative SSAs, but the long-term cure rate showed no significant improvement. For invasive macroadenomas, the short-term cure rate was also improved, but the long-term results were not evaluable in clinical practice because adjuvant therapy was generally required. In conclusion, preoperative SSAs are safe in patients with acromegaly, and the favorable impact on surgical results is restricted to the short-term cure rate in macroadenomas and invasive macroadenomas. Further well-designed RCTs to examine long-term results are awaited to update the finding of this meta-analysis.

Silent corticotroph adenomas (SCAs) can be redefined according to the 2017 World Health Organization pituitary classification system with the introduction of T‑PIT, a transcription factor. We studied the clinical features of these redefined SCAs.We compared 112 patients with SCAs and 198 patients with silent gonadotroph adenomas (SGAs) who underwent surgery from January 2019 to May 2020.The prevalence of SCAs increased from 21.3 to 30.2% under the new classification rules. T-PIT-positive, adrenocorticotropic hormone-negative SCAs and T-PIT-positive, adrenocorticotropic hormone-positive SCAs exhibited similar clinical features. SCAs exhibited significant female preponderance (90.2% vs. 29.8%, P 0.0001); more frequent invasion (36.6% vs. 7.6%, P 0.0001), especially multiple-site invasion (P 0.0001); and marked cystic changes on imaging compared with SGAs (54.5% vs. 19.2%, P 0.0001). SCAs had a softer tumor consistency (89.2% vs. 61.1%, P 0.0001). Gross total resection was achieved in 66.1% of SCAs and 66.2% of SGAs (P 0.9999). The overall recurrence/progression rates of SCAs and SGAs were 9.8% and 6.6% at 14.1 and 13.5 months of follow-up, respectively (P = 0.3765). The proportion of patients with more than two recurrences requiring multiple surgeries and radiation was similar between SCAs and SGAs (7.1% vs. 3.0%, P = 0.1514). However, multiple recurrences of SCAs affected younger patients than SGAs (39.0 vs. 53.5 years, P = 0.0433).The prevalence of SCAs increased with the introduction of T-PIT. SCAs and SGAs exhibited comparable size and recurrence/progression rates, but SCAs showed increased invasion and more marked cystic change. Aggressive SCAs tended to affect younger patients. Close long-term monitoring for SCA recurrence/progression is required.

Simple Summary The 2017 World Health Organization classification of endocrine tumors defines pituitary adenomas based on their cell lineages. T-PIT can serve as a complimentary tool for further identification of silent corticotroph adenomas (SCAs). Unlike functioning corticotroph adenomas in patients with Cushing’s disease, SCAs present no clinical and biochemical features of Cushing’s syndrome. SCAs have been shown to exhibit a more aggressive course characterized by a higher probability of recurrence and resistance to conventional treatment due to their intrinsic histological features. The aim of our review is to offer an update on the diagnosis, mechanisms, clinical features and management of SCAs. Studies of the molecular mechanisms of SCA pathogenesis will provide new directions for the diagnosis and management of SCAs. Abstract With the introduction of 2017 World Health Organization (WHO) classification of endocrine tumors, T-PIT can serve as a complementary tool for identification of silent corticotroph adenomas (SCAs) in some cases if the tumor is not classifiable by pituitary hormone expression in pathological tissue samples. An increase of the proportion of SCAs among the non-functioning pituitary adenomas (NFPAs) has been witnessed under the new rule with the detection of T-PIT-positive ACTH-negative SCAs. Studies of molecular mechanisms related to SCA pathogenesis will provide new directions for the diagnosis and management of SCAs. A precise pathological diagnosis can help clinicians better identify SCAs. Understanding clinical features in the context of the pathophysiology of SCAs is critical for optimal management. It could provide information on appropriate follow-up time and aid in early recognition and treatment of potentially aggressive forms. Management approaches include surgical, radiation, and/or medical therapies.

Background: Prediction of radiotherapeutic response before radiotherapy could help determine individual treatment strategies for patients with acromegaly. Objective: To develop and validate a machine-learning-based multiparametric MRI radiomics model to non-invasively predict radiotherapeutic response in patients with acromegaly. Methods: This retrospective study included 57 acromegaly patients who underwent postoperative radiotherapy between January 2008 and January 2016. Manual lesion segmentation and radiomics analysis were performed on each pituitary adenoma, and 1561 radiomics features were extracted from each sequence. A radiomics signature was built with a support vector machine using leave-one-out cross-validation for feature selection. Multivariable logistic regression analysis was used to select appropriate clinicopathological features to construct a clinical model, which was then combined with the radiomics signature to construct a radiomics model. The performance of this radiomic model was assessed using receiver operating characteristics (ROC) analysis and its calibration, discriminating ability, clinical usefulness. Results: At 3-years after radiotherapy, 25 patients had achieved remission and 32 patients had not. The clinical model incorporating seven clinical features had an area under the ROC (AUC) of 0.86 for predicting radiotherapeutic response, and performed better than any single clinical feature. The radiomics signature constructed with six radiomics features had a significantly higher AUC of 0.92. The radiomics model showed good discrimination abilities and calibration, with an AUC of 0.96. Decision curve analysis confirmed the clinical utility of the radiomics model. Conclusion: Using pre-radiotherapy clinical and MRI data, we developed a radiomics model with favorable performance for individualized non-invasive prediction of radiotherapeutic response, which may help in identifying acromegaly patients who are likely to benefit from radiotherapy.