藤沢 治樹

BackgroundThe relationships between thyroid hormone profiles and activities of daily living (ADLs), behavioral and psychological symptoms (BPSD), cognitive status, and physical function in patients with Alzheimer's disease (AD) remain poorly understood.ObjectiveThis study investigates the relationships among ADLs, BPSD, and cognitive and physical function relative to thyroid status in patients with AD.MethodsWe recruited 2484 outpatients diagnosed with AD aged 65 and older with serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels measured at their first memory clinic visit. The participants were divided into five groups by their serum FT4 and TSH levels: euthyroidism, hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism. Differences in dependent variables among these groups were compared using analysis of covariance. Correlations of the dependent variables with FT3, FT4, FT3/FT4, and TSH levels and the presence of non-thyroidal illness syndrome (NTIS) were examined using a multiple regression model.ResultsNo significant differences in ADLs, BPSD, and cognitive or physical performance were observed among the groups stratified by FT4 and TSH levels. Although there were slight variations according to the analytical method employed, the overall results indicated that lower FT3, higher FT4, and lower FT3/FT4 were correlated with worse ADLs, mood, and cognitive and physical function. AD patients with NTIS exhibited notably worse basic ADLs than other groups.ConclusionsThese results suggest that thyroid hormone levels are associated with ADLs, mood, and cognitive and physical function in AD patients, suggesting the need for careful monitoring of AD patients with lower FT3, higher FT4, lower FT3/FT4, and NTIS.

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.

Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia (CHN) may induce neurological manifestations, including psychological symptoms. However, the specific psychological symptoms induced by CHN, the mechanisms underlying these symptoms, and their potential reversibility remain unclear. Therefore, this study aimed to determine whether monoaminergic neurotransmission is associated with innate anxiety-like behaviors potentiated by CHN in a mouse model of CHN secondary to the syndrome of inappropriate antidiuresis. In the present study, using a mouse model of the syndrome of inappropriate antidiuresis presenting with CHN, we showed that the sustained reduction of serum sodium ion concentrations potentiated innate anxiety-like behaviors in the light/dark transition and open field tests. We also found that serotonin and dopamine levels in the amygdala were significantly lower in mice with CHN than in controls. Additionally, phosphorylation of extracellular signal-regulated kinase (ERK) in the amygdala was significantly reduced in mice with CHN. Notably, after correcting for CHN, the increased innate anxiety-like behaviors, decreased serotonin and dopamine levels, and reduced phosphorylation of ERK in the amygdala were normalized. These findings further underscore the importance of treating CHN and highlight potential therapeutic strategies for alleviating anxiety in patients with CHN, which will improve their quality of life.