Functioning pituitary adenomas (FPAs) require both cytoreduction and durable endocrinological remission (ER), which is often limited by occult invasion of the medial cavernous sinus wall. Selective medial cavernous sinus wall resection (MCSWR) has emerged as a targeted approach, but its endocrine benefits and safety profile remain incompletely understood. We synthesize syndrome-specific remission, resection, recurrence, and complication rates after MCSWR in adults with FPAs. We conducted a systematic review and meta-analysis of PubMed, Scopus, and Embase through 2025, including adults with GH-, ACTH-, and prolactin-secreting adenomas who underwent intentional medial cavernous sinus wall resection as described by the original studies and had at least one postoperative endocrine outcome. Two reviewers extracted study- and tumor-level data on resection, ER, recurrence, and complications. Pooled event rates were estimated with random-effects models. Thirteen studies (11 retrospective, 2 prospective) involving 493 patients met inclusion criteria. Among 344 patients with available endocrine follow-up, pooled ER was 85% (95% CI:77-91%), and gross total resection (GTR) was 92% (95% CI:81-97%). Recurrence occurred in 6% (95% CI:3-13%). Subgroup ER rates were 87% for acromegaly, 89% for Cushing's disease, and 78% for prolactinomas, with corresponding GTR rates of 95%, 91%, and 80%. Complications were rare: ICA injury 0%, cranial nerve III and VI palsies 3% each, and postoperative CSF leak 4%. Most studies had a serious or critical risk of bias, mainly due to confounding and single-arm designs. Follow-up ranged from 9 to 30 months in contributing cohorts, with earlier series reporting ranges up to 1-49 months. MCSWR was associated with high reported ER and GTR rates, low reported recurrence, and acceptable morbidity in carefully selected patients with FPAs, particularly somatotroph and corticotroph tumors. However, the evidence mainly comes from high-volume centers and non-comparative series with limited follow-up, highlighting the need for prospective, multicenter studies with standardized endocrine endpoints, histological confirmation, and long-term follow-up.
INTRODUCTION: Cushing's disease (CD) has traditionally been approached through a binary paradigm based on MRI findings, distinguishing MRI-positive from MRI-negative cases. However, this dichotomy incompletely reflects the heterogeneity of corticotroph tumors and complexity of intraoperative decision-making. RESEARCH QUESTION: We propose a stepwise surgical strategy that moves beyond this binary stratification by conceptualizing CD as a spectrum integrating imaging, biochemical, and intraoperative findings. METHODS: This retrospective purposefully selected illustrative case series was drawn from a prospective database of 983 patients treated for CD between 2006 and 2025. All underwent mononostril endoscopic transsphenoidal surgery by an expert pituitary surgical team. Seven cases were chosen to illustrate the CD spectrum presentations, including MRI-positive lesions with invasive features, MRI-equivocal findings, and MRI-negative disease. A stepwise algorithm integrating preoperative imaging, functional analysis, and intraoperative findings guided surgical exploration and resection. RESULTS: Seven patients were included. In MRI-visible lesions, targeted adenomectomy was performed, with extension to basal dura or cavernous sinus wall when indicated. In MRI-negative or equivocal cases, exploration was guided by repeat imaging, heterogeneous MRI signal, venous sampling, and/or FET-PET. When tumor tissue was identified, selective or enlarged adenomectomy was performed according to infiltration patterns. Early endocrine remission was achieved in 6 patients, while one patient achieved postoperative eucortisolism. Transient diabetes insipidus was the only postoperative complication. CONCLUSION: CD may be reconsidered beyond a binary MRI-based paradigm, as a spectrum of scenarios. A stepwise surgical strategy better reflects disease heterogeneity and provides a practical framework for surgical decision-making, particularly in MRI-negative or MRI-equivocal cases.
Growth and differentiation factor 15 (GDF-15) is a stress-responsive hormone secreted by various cell types in response to cellular stress. To regulate ingestive behaviour, suppress food intake, and induce nausea and vomiting during cellular stress, GDF-15 signals via a brainstem-restricted receptor, GFRAL. Elevated circulating GDF-15 levels serve as a biomarker of cellular stress and are increased in a wide range of diseases. GDF-15 has recently been established as a causal factor in cancer cachexia and GDF15-GFRAL antagonism is being pursued as a therapeutic strategy. Recent studies have highlighted a dynamic interplay between GDF-15 and the hypothalamus-pituitary-adrenal (HPA) axis, suggesting that GDF-15 acts as a sentinel hormone in stress responses. Here, we review the canonical role of GDF-15 in stress-related conditions and its potential impact on circadian regulation and HPA axis dysregulation. The review explores the potential activation of the HPA axis by GDF-15 and discuss the hypothesis that downstream glucocorticoid signalling may contribute to some of the cardiovascular, metabolic, immune, and musculoskeletal changes reported for GDF-15. Additionally, the review discusses the potential role of GDF-15 in adrenal insufficiency and its treatment and in adrenocortical carcinoma. In summary, this review aims to elucidate the role of GDF-15 in glucocorticoid homeostasis and adrenal disease in the context of the stress response.
Neurosurgery has evolved dramatically from its origins in ancient trephination to the sophisticated, technology‑driven discipline it is today. Early pioneers such as Harvey Cushing, Victor Horsley, Walter Dandy, and Geoffrey Jefferson established the foundations of modern neurosurgical practice, transforming a high‑risk field into a structured specialty. The 20th century ushered in unprecedented advances, particularly through neuroimaging, robotics, and neurostimulation, enabling greater precision, safety, and therapeutic possibilities for conditions including Parkinson's disease, epilepsy, and chronic pain. This article provides an overview of two key minimally invasive modalities-MR‑guided focused ultrasound (MRgFUS) and laser interstitial thermal therapy (LITT). By examining their procedural principles, clinical applications, and limitations, we highlighted how these complementary technologies are reshaping functional and oncological neurosurgery through effective lesioning or ablation without the need for large craniotomies.
BACKGROUND: A combination of endogenous hypercortisolism and primary hyperparathyroidism (PHPT) occurs rarely, few clinical cases are described in the literature. The causes of the development of such combination are poorly investigated. AIM: To study clinical and genetic characteristics of a combination of endogenous hypercortisolism and PHPT. MATERIALS AND METHODS: A retrospective, single-center, cross-sectional, observational study was performed. Clinical characteristics of patients with a combination of endogenous hypercortisolism and PHPT were analyzed. All patients had previously undergone genetic testing as follows: MEN1 Sanger sequencing (n=10), next-generation sequencing of a panel of genes including MEN1 and CDKN1B (n=3), whole-exome sequencing (n=8). RESULTS: 21 patients (17 females, 4 males) were included in the study: 17 with Cushing's disease (CD) and PHPT, 3 patients with Cushing's syndrome (CS) and PHPT, and one patient with ACTH-ectopic syndrome (ACTH-ES) and PHPT. Among patients with CD and PHPT ten had MEN1 mutations (multiple endocrine neoplasia type 1 syndrome (MEN1)), and seven did not have MEN1 mutations (MEN1 phenocopies). In patients with MEN1 the debut of both CD and PHPT occurred at younger age in comparison to MEN1 phenocopies (p=0,015 and p=0,0006). In 60% of MEN1 CD occured in infancy, and in all children CD was the first manifestation. In 75% of adult MEN1 patients CD was diagnosed after PHPT, whereas in all MEN1 phenocopies PHPT was diagnosed after or during investigation with regard to CD. The majority of MEN1 patients also had gastro-entero- pancreatic neuroendocrine tumors (NETs), and some had lung NETs, whereas patients with MEN1 phenocopies did not have NETs. One patient with CS (bilateral lesions) and PHPT had ARMC5 mutation. In a patient with ACTH-ES and PHPT no mutations were found. CONCLUSION: A combination of endogenous hypercortisolism and PHPT occurs more frequently in females. In children with MEN1 and in MEN1 phenocopies the first manifestation is more frequently CD, while PHPT is diagnosed accidentally during evaluation, whereas in adults with MEN1 the first manifestation is more frequently PHPT. MEN1 mutations can be the cause of a combination of these two endocrine tumor diseases, and, possibly, ARMC5 mutations in cases of CS and PHPT, though in the majority of cases the cause remains unknown. Identification of causes of endogenous hypercortisolism and PHPT co-occurrence can expand our understanding of the mechanisms of endocrine tumor development.