Endocrine disturbance in multiple sclerosis (MS) is a rare condition and involvement of the hypothalamus is rarely described. 1 The hypothalamus encompasses many nuclei where demyelinating lesions are hardly detectable using conventional MRI. 2 Deficiency of antidiuretic hormone (ADH) can be encountered in inflammatory processes such as sarcoidosis, but may be idiopathic, possibly related to pathogenic antibodies. In MS, only 2 cases of ADH deficiency have been reported without overt hypothalamic lesions. 3,4 Herein, we present the case of a 28-year-old man who developed diabetes insipidus (DI) 7 years before diagnosis of MS. MRI revealed the presence of bilateral MS lesions in the supraoptic nuclei, suggesting that DI was the first manifestation of MS.Case report. A 28-year-old man was referred after discovering cerebral white matter abnormalities on an MRI prescribed to explore DI. The patient had ingested Ͼ10 L of water every day since the age of 21. He had neither familial history of DI nor personal antecedent head trauma or neurosurgery.Neurologic and general examinations were normal. The patient had no history of asthenia, fever, dyspnea, coughs, arthritis, parotitis, splenomegaly, hepatomegaly or adenopathies, erythema nodosum, or skin sarcoid. A low ADH level was found, while prolactin, growth hormone, insulin-like growth factor 1, adrenocorticotropic hormone, cortisol, and thyroid-stimulating hormone levels were within normal range. Biology revealed hypernatremia and hyponatruria, with inability to concentrate urine when deprived of water. Treatment with desmopressin (20 g nasal spray) completely suppressed polyuria/polydipsia. MRI failed to show enlargement of the pituitary stalk or gadolinium enhancement of the pituitary gland or hypothalamus. Unexpectedly, brain MRI showed periventricular and juxtacortical lesions, 2 of which were enhanced after gadolinium injection, suggesting MS. CSF analyses disclosed no white blood cells, normal CSF protein, 4 oligoclonal bands, and an increased immunoglobulin G (IgG) index. Other investigations (antinuclear antibodies, antineutrophil cytoplasmic antibodies, neuromyelitis optica IgG, HIV, human T-cell lymphotrophic virus and syphilis testing, angiotensin converting enzymes, biopsy of a minor salivary gland, millimetric chest CT scan, EKG) were normal. Two months after the first brain MRI, the patient presented with left optic neuritis. Studies on visual evoked potential showed a bilateral demyelinating pattern. Ophthalmologic examination during optic neuritis ruled out uveitis. A further brain MRI 6 months later showed new T2 hyperintensities, one of which was enhanced after gadolinium injection and confirmed the diagnosis of MS through dissemination in time. Thin (2-mm) coronal T2-weighted sections of the hypothalamus revealed the presence of lesions in both supraoptic nuclei (figure). The patient received methylprednisolone infusions (1 g/day, 3 days) and glatiramer acetate treatment was started. ADH deficiency remained unchanged.Discussion. In 85% of cases, MS ...