Yoshihisa Sugimura

Lymphocytic infundibuloneurohypophysitis (LINH) is a disease with an etiology involving an autoimmune mechanism, characterized by lymphocytic inflammation of the posterior pituitary and infundibular stalk, resulting in arginine vasopressin deficiency. It is difficult to distinguish from pituitary neoplasm or infiltrative diseases, and biopsy is necessary for a definitive diagnosis, but this is highly invasive. In children, it is especially important to distinguish LINH from tumors such as germ cell tumors. Recently, the usefulness of anti-rabphilin-3A antibody as a serum marker for LINH has been reported. To date, only a limited number of pediatric cases have been reported. We present a 4-year-old boy with arginine vasopressin deficiency. Magnetic resonance imaging of the head showed thickening of the pituitary stalk without a posterior pituitary bright spot, and anti-rabphilin-3A antibody was positive. Consequently, pituitary biopsy was not performed because of the strong suspicion of LINH. Five months after symptom onset, the pituitary stalk thickening had resolved. This case represents the first report of probable or definitive LINH with anti-rabphilin-3A antibody positivity in a 4-year-old child, making it the youngest positive case reported to date. Our case highlights the importance of noninvasive approaches and careful follow-up to avoid invasive interventions for children with LINH.

OBJECTIVES: Phosphate (Pi) induces differentiation of arterial smooth muscle cells to the osteoblastic phenotype by inducing the type III Na-dependent Pi transporter Pit-1/solute carrier family member 1. This induction can contribute to arterial calcification, but precisely how Pi stress acts on the vascular wall remains unclear. We investigated the role of extracellular Pi in inducing microstructural changes in the arterial wall. METHODS: Aortae of Pit-1-overexpressing transgenic (TG) rats and their wild-type (WT) littermates were obtained at 8 weeks after birth. The thoracic descending aorta from WT and TG rats was used for the measurement of wall thickness and uniaxial tensile testing. Structural and ultrastructural analyses were performed using light microscopy and transmission electron microscopy. Gene expression of connective tissue components in the aorta was quantified by quantitative real-time polymerase chain reaction. RESULTS: Aortic wall thickness in TG rats was the same as that in WT rats. Uniaxial tensile testing showed that the circumferential breaking stress in TG rats was significantly lower than that in WT rats (p<0.05), although the longitudinal breaking stress, breaking strain, and elastic moduli in both directions in TG rats were unchanged. Transmission electron microscopy analysis of the aorta from TG rats showed damaged formation of elastic fibers in the aortic wall. Fibrillin-1 gene expression levels in the aorta were significantly lower in TG rats than in WT rats (p<0.05). CONCLUSIONS: Pi overload acting via the arterial wall Pit-1 transporter weakens circumferential strength by causing elastic fiber malformation, probably via decreased fibrillin-1 expression.