Abstract Introduction Central diabetes insipidus (CDI) can develop due to lymphocytic hypophysitis, IgG4-related hypophysitis, neurosarcoidosis, Langerhans cell histiocytosis, tuberculosis, syphilis, trauma, genetics, neoplastic causes, or after pituitary surgery. Among neoplastic causes, high-grade gliomas are extremely rare. In this case, we describe a diffuse midline glioma that initially presented with CDI and hypopituitarism. Clinical Case A 33-year-old man presented in 2023 with polyuria, polydipsia, and nocturia. Laboratory tests revealed low urine density, low cortisol, and ACTH levels. His thyroid and gonadal axis were normal. CDI was confirmed with a water deprivation test, and desmopressin treatment was initiated. The patient's initial pituitary MRI was reported normal. One year later, the patient was re-admitted complaining of fatigue. Secondary adrenal insufficiency, central hypothyroidism, and hypogonadism were detected. Follow-up MRI revealed new lesions involving the infundibulum, hypothalamus, anterior thalamus, and pineal gland, with no posterior pituitary bright spot. Serum ACE and IgG4 levels, autoimmune and infectious markers, and cerebrospinal fluid cytology were normal. Although neurosarcoidosis and lymphoma were initially suspected, radiologic progression and MR spectroscopy findings (elevated choline/NAA ratio of ∼4.0, lipid-lactate peaks, and low NAA) were in favor of malignant glioma. The patient underwent mass resection by neurosurgery in February 2025. Pathology reported a stage 4 diffuse midline glioma. Immunohistochemistry revealed loss of ATRX expression, GFAP and p53 positivity, and a Ki-67 index of approximately 60%. Conclusion The first point noteworthy in this case is that CDI can occur months or even years before the diagnosis of an underlying malignant disease. This reminds us that high-grade gliomas should be considered in the differential diagnosis, especially in progressive hypothalamic-pituitary lesions accompanied by hypopituitarism. While autoimmune and granulomatous diseases are more frequently considered in clinical practice, neoplastic processes should not be overlooked in the presence of progressive and aggressive radiological findings. The second important point is that in cases of new-onset CDI, a brain MRI encompassing the hypothalamic region is essential, even if the pituitary MRI appears normal. Early and comprehensive imaging, biopsy, and multidisciplinary collaboration are essential to prevent delayed diagnosis and ensure appropriate treatment.Figure 1:MRFigure 1. Coronal T2-weighted brain MRI showing an infiltrative midline lesion involving the hypothalamo-pituitary region.
Altinbezer et al. (Thu,) studied this question.