To describe a rare case of pituitary metastasis arising from mandibular squamous cell carcinoma (SCC), in which pituitary-related symptoms represented the first clinical evidence of distant metastatic disease. Case report and targeted literature review. A patient with previously treated mandibular SCC presented with new-onset visual disturbance and endocrine dysfunction. Imaging, endocrine evaluation, and histopathologic confirmation were performed. Published reports of pituitary metastases from head and neck SCC were reviewed. Magnetic resonance imaging demonstrated an enhancing sellar mass with suprasellar extension and infundibular thickening concerning for metastatic disease. Endoscopic endonasal biopsy confirmed metastatic keratinizing SCC consistent with the primary mandibular tumor. No other distant metastases were identified on staging imaging. Visual field deficits and partial hypopituitarism were the sole presenting manifestations of metastatic spread. Pituitary metastasis from mandibular SCC is exceptionally rare and may present as the earliest sign of distant disease.

SOX3 is a single-exon gene located on the X chromosome (Xq27.1), encoding a transcription factor critical for early central nervous system and pituitary development, as well as gonadal function. A growing body of literature reports a diverse array of phenotypes associated with different classes of SOX3 variants, including single nucleotide variants, indels, polyalanine tract changes, copy number variants, and structural rearrangements. These variants have been implicated in conditions ranging from pan-hypopituitarism or isolated growth hormone deficiency to neural tube defects, disorders/differences in sex development, and complex syndromes involving craniofacial and intellectual disability. In this review, we comprehensively summarize all known variants involving SOX3 reported to date, highlighting the different pathogenetic mechanisms that have been reported or hypothesized (e.g., gene dosage, transcriptional regulation) and the phenotypes to which these variants are associated to. Special emphasis is placed on established genotype-phenotype correlations and the challenges in interpretation relevant to clinical diagnostics. This review aims to provide a reference framework for clinicians, researchers, and geneticists working with SOX3-related disorders.

Background and Clinical Significance: Neurosarcoidosis (NS) is a rare manifestation of systemic sarcoidosis involving the central nervous system, with highly variable neurological and endocrine presentations. Among these, anterior pituitary dysfunction is particularly uncommon and diagnostically challenging. Case Presentation: We report the case of a 37-year-old woman with a 4-year history of secondary amenorrhoea and an initially suspected pituitary microadenoma, who was ultimately diagnosed with probable NS presenting with multiaxial anterior pituitary insufficiency. Early magnetic resonance imaging (MRI) revealed a small pituitary lesion and isolated pituitary stalk thickening, without other central nervous system abnormalities. Subsequent imaging demonstrated contrast-enhancing lesions involving the meninges and cranial nerves, along with progression of pituitary stalk involvement and loss of the posterior pituitary bright spot. Further evaluation confirmed systemic sarcoidosis. High-dose corticosteroid therapy led to partial clinical and radiological improvement; however, relapse necessitated methotrexate, and persistent pituitary hormone deficiencies required long-term hormonal replacement. Conclusions: This case highlights the diagnostic complexity of NS presenting with isolated endocrine dysfunction and subtle imaging findings. It underscores the need to consider systemic sarcoidosis in patients with unexplained hypopituitarism.

Myostatin (GDF-8), a TGF-β family myokine, regulates skeletal muscle growth and systemic metabolism and influences pituitary development and hormone secretion. This review summarizes experimental, translational, and clinical data linking myostatin to pituitary biology, including recent mouse evidence identifying muscle-derived myostatin as an endocrine driver of FSH synthesis via activin-type II/TGFBR1 signaling, with human confirmation pending. We analyze how pituitary disorders - growth hormone deficiency, acromegaly, hypercortisolism, central thyroid disease, central hypogonadism, and hypopituitarism - modify myostatin signaling, contributing to sarcopenia, anabolic resistance, and metabolic dysfunction. Across these conditions, human evidence remains limited and confounded by assay heterogeneity and comorbidities, as circulating myostatin often fails to mirror intramuscular changes. We propose an evidence framework emphasizing standardized assays (mature vs latent forms), longitudinal clinical cohorts, and integration of hormonal and functional endpoints. Myostatin remains a promising yet unvalidated biomarker and therapeutic target in endocrine-related muscle disease.

Rathke's cleft cysts are benign epithelial-lined sellar and suprasellar lesions that are often incidental findings but can cause visual deficits, hypopituitarism, and headaches when they enlarge and compress adjacent structures. Recurrence after surgical treatment remains challenging despite various surgical approaches. Marsupialization has emerged as an alternative technique for complex recurrent cases, establishing permanent communication between the cyst and the nasal cavity while minimizing surgical risk. We present a case of a 76-year-old man with type 2 diabetes mellitus, a history of meningeal tuberculosis, and panhypopituitarism who experienced progressive visual decline following multiple failed Rathke's cleft cyst surgeries. Ophthalmological evaluation revealed right temporal hemianopsia and reduced visual acuity, and magnetic resonance imaging confirmed a recurrent sellar-suprasellar lesion compressing the optic chiasm. Revision endoscopic endonasal surgery was performed using the marsupialization technique, including a type III sphenoidotomy, cyst aperture, dural membrane eversion toward the nasal cavity, and nasoseptal flap placement on the cyst floor. Surgery was completed without complications. At eight-month follow-up, the patient demonstrated complete resolution of hemianopsia, improved visual acuity, and stable postoperative changes without cyst reaccumulation on imaging. Endoscopic transnasal marsupialization represents a safe and effective therapeutic option for recurrent Rathke's cleft cysts, particularly following multiple failed interventions, providing permanent drainage while minimizing manipulation of delicate neurovascular structures. It may also potentially reduce recurrence rates and improve functional outcomes in complex cases.

The chemokine network in the microenvironment of pituitary neuroendocrine tumours (PitNETs) may modulate tumour biology, aggressiveness, and treatment responses. We aimed to study the role of various chemokines and chemokine receptors in defining PitNET phenotype and clinical outcomes. We included 96 patients (51 females) with available snap-frozen PitNET tissue from surgery between 2014 and 2020. Chemokine and chemokine receptors were studied by RT-qPCR. Fold difference in mRNA expression was calculated using the ΔΔCt method; chemokine and receptor expression levels were normalised to the expression of the control gene TBP, and expressed relative to a reference sample. Ten chemokines and receptors were studied (CCL2, CCL3, CCL4, CXCL8, CX3CL1, CCR2, CCR4, CCR5, CXCR1, CXCR2), and their expression correlated with clinico-pathological and outcome data, as well as other available microenvironment-related data. We found strong positive correlations between all chemokines and chemokine receptors. Higher chemokine and receptor expression levels were seen in patients who had pituitary apoplexy (CCR2, CXCR1), hypopituitarism at diagnosis (CCL2, CCR4), Ki-67 >3% (CCL4, CXCR2), as well as in patients who required re-operation (CCL3, CXCL8, CXCR2), multimodal therapy (CCL2), and had active disease at last-follow-up (CCL2). There was a positive correlation between the number of pituitary surgeries and expression levels of CCL3, CXCL8, CX3CL1, CXCR1, and CXCR2. Compared to nonfunctioning-PitNETs, somatotropinomas had higher expression of CCL2, CCL4, and CCR2, and lower expression of CX3CL1 and CCR4. Expression of CDH1 (encoding E-cadherin) correlated negatively with CCL2, CCL4, CCR2, CCR4, and CXCR2, while the expression of ZEB1 (mesenchymal marker) positively correlated with CCL3, CCL4, and CX3CL1. PitNETs expressing higher levels of CCL4, CX3CL1, CCR4, CCR5, and CXCR1 had more and bigger vessels. Somatotropinomas treated pre-operatively with somatostatin analogues were associated with higher expression of CCL2, CCR4, CXCR1, and CXCR2, while nonfunctioning-PitNETs pre-surgically treated with dopamine agonists were associated with lower expression of CCL3, CCL4, CX3CL1, CCR5, CXCR1, and CXCR2. Our data suggests that chemokines and chemokine receptors may be involved in the modulation of different tumorigenic mechanisms in PitNETs, including tumour proliferation, epithelial-to-mesenchymal transition, and angiogenesis, and may be associated with more aggressive and difficult-to-treat disease.

Primary hypothalamic involvement in primary central nervous system lymphoma is rare and can present with nonspecific neurological and endocrine manifestations, resulting in significant diagnostic delays. We report the case of an immunocompetent 29-year-old female who presented with intermittent fever, seizures, progressive behavioral changes, central diabetes insipidus, and hypopituitarism. She was initially treated empirically for encephalitis with anti-epileptics and corticosteroids. Neuroimaging subsequently demonstrated a homogeneously enhancing lesion along the chiasmatic-hypothalamic axis. Initial biopsy was nondiagnostic due to corticosteroid pretreatment, necessitating repeat biopsy via craniotomy, which confirmed diffuse large B-cell lymphoma. This case illustrates the importance of recognizing endocrine red flags in hypothalamic lesions, emphasizes the negative impact of prebiopsy steroid exposure on diagnostic yield, obscuring histopathology even in the absence of radiological regression.