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Simultaneous idiopathic mediastinal and retroperitoneal fibrosis is an exceptionally rare fibro-inflammatory disorder with nonspecific clinical manifestations and challenging imaging findings. A 33-year-old man presented with acute respiratory distress and bilateral obstructive uropathy. Contrast-enhanced CT demonstrated infiltrative soft-tissue masses involving the mediastinum and retroperitoneum, encasing major vessels and the left ureter. CT-guided biopsy confirmed dense collagenous fibrosis without evidence of malignancy. Following exclusion of secondary causes, idiopathic mediastinal and retroperitoneal fibrosis was diagnosed. Corticosteroid therapy led to marked clinical improvement. This case highlights the essential contribution of multidetector computed tomography in identifying the characteristic distribution of fibro-inflammatory lesions, defining their relationship with adjacent vascular and urinary structures, guiding tissue sampling, and narrowing the differential diagnosis. Careful integration of imaging findings with histopathological and laboratory investigations is mandatory to distinguish idiopathic fibrosis from IgG4-related disease, lymphoma, metastatic malignancy, Erdheim-Chester disease, infectious fibrosing mediastinitis, and other fibro-inflammatory disorders. Contrast-enhanced CT was essential for lesion characterization, biopsy guidance, and diagnostic assessment. This rare entity should be considered in patients with simultaneous mediastinal and retroperitoneal infiltrative masses.

The hypothalamic-pituitary region can be affected by a wide and heterogeneous group of infiltrative and inflammatory disorders, including granulomatous, histiocytic, storage, infectious, non-pituitary neoplastic, and autoimmune or inflammatory conditions collectively grouped as hypophysitis. Although individually rare, these disorders are increasingly recognized due to growing awareness, wider use of pituitary imaging, and the emergence of immune checkpoint inhibitor-induced hypophysitis. They typically present with hypopituitarism (often including arginine vasopressin deficiency, which, particularly when accompanied by pituitary stalk thickening, is highly suggestive of a non-adenomatous lesion) together with mass effect symptoms and, in many cases, systemic manifestations reflecting extrapituitary organ involvement. Neuroimaging findings, while rarely pathognomonic, can narrow the differential diagnosis, particularly when pituitary stalk involvement is present: symmetric stalk/gland enlargement with homogeneous enhancement suggests lymphocytic, IgG4-related, or granulomatous hypophysitis, whereas rim enhancement, necrosis, or bone-destructive lesions point toward infectious or neoplastic causes. A structured diagnostic work-up, combining clinical history, hormonal evaluation, targeted laboratory testing, pituitary and systemic imaging, and, when necessary, histopathological confirmation, is essential to establish an accurate diagnosis before committing patients to long-term immunosuppression or unnecessary pituitary surgery. Management requires two parallel strategies: prompt hormone replacement therapy, with urgent attention to corticotroph deficiency, and disease-specific treatment tailored to the underlying etiology, ranging from glucocorticoids and immunosuppressants to antimicrobial therapy, targeted oncologic agents, or surgery. Because pituitary deficits are frequently irreversible and several of these disorders follow a relapsing course, long-term multidisciplinary follow-up is warranted. This review summarizes the pathophysiology, clinical presentation, diagnostic approach and neuroimaging features, for infiltrative and inflammatory hypothalamic-pituitary disorders, aiming to facilitate their timely recognition and appropriate management.

Chronic periaortitis is usually idiopathic but may occur secondary to malignancy or IgG4-related disease (IgG4-RD). We report a case of a 56-year-old man with dysphonia caused by recurrent laryngeal nerve compression due to periaortic soft tissue thickening. A histological examination revealed storiform fibrosis and lymphoplasmacytic infiltration, but not elevated serum IgG4 levels or abundant IgG4-positive cells. Imaging revealed progressive involvement of the left common carotid artery, and FDG-PET showed a focal uptake. Metastatic papillary thyroid carcinoma was subsequently identified in the adjacent lymph nodes. Periaortitis improved with glucocorticoids after surgery. This case highlights paraneoplastic periaortitis mimicking IgG4-RD and the need to screen for malignancy when the findings are inconclusive.

BACKGROUND: TST002 is a humanized IgG4 monoclonal antibody targeting sclerostin for osteoporosis treatment. This first-in-human study investigated its safety, tolerability, immunogenicity, pharmacokinetics (PK) and pharmacodynamics (PD) after intravenous infusion in Chinese men and postmenopausal women with low bone mineral density (BMD). RESEARCH DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled, dose-escalation trial, 32 subjects were assigned to four dose cohorts (3:1 ratio to receive single TST002 doses of 200, 400, 800, or 1200 mg or placebo) with 85 days of follow-up. PK, PD, safety, and immunogenicity were assessed. An exploratory population PK-PD model incorporating target-mediated drug disposition (TMDD) was developed. RESULTS: Among TST002 recipients (n = 24), most treatment-related adverse events were grade 1 in severity. Nonlinear PK was observed, with greater-than-dose-proportional exposure and a mean half-life of 4.38-8.06 days. Increases in serum sclerostin and lumbar spine BMD, and decreases in β-CTX were observed. An exploratory population TMDD-PD model was developed to describe the observed time courses of TST002, sclerostin, and β-CTX within the present phase I dataset. CONCLUSIONS: TST002 was well tolerated and showed preliminary PD activity. Exploratory TMDD-based PK/PD modeling provided preliminary insights into exposure-response relationships, limited by the sample size, single-dose design, and unavailable bone formation marker assessment. CLINICAL TRIAL REGISTRATION: This study was registered at Clinicaltrials.gov (NCT05391776).

A 75-year-old man presented with left eye fullness, proptosis, and bilateral lacrimal gland enlargement with elevated serum IgG4 levels, initially suggesting IgG4-related disease. However, lacrimal gland biopsy revealed MALT lymphoma. This case highlights the overlapping clinical features of IgG4-related disease and lymphoma and emphasizes the importance of histopathological confirmation before initiating treatment.