Yoshihisa Sugimura

Lymphocytic infundibulo-neurohypophysitis (LINH) presents with arginine vasopressin deficiency (AVP-D), also known as central diabetes insipidus, caused by autoimmune mechanisms in the infundibulum and posterior pituitary. A 32-year-old man developed polydipsia and polyuria two months after influenza infection. A hypertonic saline test revealed no AVP responses. Magnetic resonance imaging demonstrated the loss of posterior pituitary hyperintensity. The patient tested positive for serum anti-rabphilin-3A antibodies, a diagnostic marker for LINH. This is the first report of a case of probable LINH with anti-rabphilin-3A antibody positivity following an influenza infection, thus providing novel clinical insight into the diagnostic evaluation of post-infectious AVP-D.

Lymphocytic hypophysitis (LYH) is a rare autoimmune disorder characterized by lymphocytic infiltration of the pituitary gland, leading to central diabetes insipidus (CDI) and hypopituitarism. Although distinguishing LYH from other diseases presenting with pituitary enlargement is challenging, the use of anti-rabphilin-3A antibody (RPH3A-Ab) in the diagnosis of LYH has been recently reported. Case reports of LYH following coronavirus disease 2019 (COVID-19) infection in adult and adolescent patients have been accumulated. Here, we present the first case confirming the presence of RPH3A-Abs in pediatric CDI following COVID-19. A 4-yr-old girl developed CDI one week after COVID-19, and anterior hypopituitarism was confirmed 14 mo later. Head magnetic resonance imaging (MRI) revealed progressive pituitary stalk thickening, which subsequently improved. Although other disease-specific markers did not increase, serological testing confirmed the presence of RPH3A-Ab, supporting the clinical diagnosis of LYH. It has previously reported that RPH3A-Ab demonstrate high sensitivity and specificity in differential diagnosis of LYH, and RPH3A-Ab are also identified as positive in pediatric cases of LYH with a biopsy. Additionally, this is the first documented prepubertal case of LYH following COVID-19. Our case study indicates that LYH can occur in children after COVID-19, and RPH3A-Ab may be useful in its diagnosis.

BACKGROUND: Lymphocytic panhypophysitis (LPH) is a rare inflammatory disorder that primarily affects the pituitary gland. Extension into the cavernous sinus has been described, but clival involvement is exceedingly rare. To date, no cases of isolated clival extension have been documented. Anti-rabphilin-3A antibodies have been identified as diagnostic markers that may facilitate the diagnosis of this challenging condition. OBSERVATIONS: An 81-year-old man presented with headache, anorexia, and fatigue. Evaluation demonstrated panhypopituitarism followed by central diabetes insipidus. MRI revealed homogeneous pituitary enlargement with isolated clival extension. Endoscopic evaluation during transsphenoidal biopsy demonstrated thickened dura mater extending from the pituitary gland to the clivus. Histopathological analysis revealed lymphoplasmacytic infiltration with a predominance of CD20-positive B cells over CD3-positive T cells and inflammatory infiltration between the clival bone trabeculae, confirming direct invasion. The serum anti-rabphilin-3A antibody test was positive. Hormone replacement therapy resulted in clinical improvement, and follow-up MRI at 3 and 6 months showed marked resolution. LESSONS: This appears to be the first reported case of LPH with isolated clival extension. Intraoperative dural thickening and histological evidence of trabecular bone infiltration suggest a potential pathway for extrapituitary extension. Anti-rabphilin-3A antibody testing can support diagnosis, particularly in such atypical presentations. https://thejns.org/doi/10.3171/CASE25737.