Two Cases of anti-PIT-1 Hypophysitis Exhibited as a Form of Paraneoplastic Syndrome not Associated With Thymoma.

Anti-pituitary-specific transcription factor 1 (PIT-1) hypophysitis (anti-PIT-1 antibody syndrome) is a thymoma-associated autoimmune disease characterized by acquired growth hormone (GH), prolactin (PRL), and thyrotropin (TSH) deficiencies due to autoimmunity against PIT-1. Ectopic expression of PIT-1 in the thymoma plays a causal role in development of the disease. Here, we report 2 cases of anti-PIT-1 hypophysitis exhibiting as a form of paraneoplastic syndrome with conditions other than thymoma. A 79-year-old woman (case 1) and an 86-year-old man (case 2) were referred with a suspicion of anti-PIT-1 hypophysitis because of acquired GH, PRL, and TSH deficiencies. Case 1 was complicated by diffuse large B-cell lymphoma (DLBCL) of the bladder and case 2 was diagnosed with malignancy with multiple metastases of unknown origin. Because circulating anti-PIT-1 antibody was detected, both patients were diagnosed with anti-PIT-1 hypophysitis. Circulating PIT-1-reactive T cells were detected in case 1 via enzyme-linked immunospot (ELISPOT) assay. Interestingly, the PIT-1 protein was ectopically expressed in the DLBCL cells of case 1, whereas DLBCL tissues derived from patients without anti-PIT-1 hypophysitis were negative for PIT-1. In case 2, the materials were not available because of best supportive care was under way. These data show that anti-PIT-1 hypophysitis is associated not only with thymoma but also with other malignancies. Additionally, the ectopic expression of PIT-1 in the DLBCL tissues and presence of PIT-1-reactive T cells suggested that the underlying mechanisms were similar to those observed in thymoma. Thus, anti-PIT-1 hypophysitis is defined as a form of paraneoplastic syndrome.

Diffusion-weighted magnetic resonance imaging in autoimmune pancreatitis.

PURPOSE: The aim of this study was to investigate the usefulness of diffusion-weighted magnetic resonance imaging (DWI MRI) for the diagnosis and evaluation of autoimmune pancreatitis (AIP). MATERIALS AND METHODS: A total of 4 consecutive patients with AIP, 5 patients with chronic alcoholic pancreatitis (CP), and 13 patients without pancreatic disease (controls) were studied. DWI was performed in the axial plane with spin-echo echo-planar imaging single-shot sequence. Apparent diffusion coefficients (ADCs) were measured in circular regions of interest in the pancreas. In AIP patients, abdominal MRI was performed before, and 2-4 weeks after steroid treatment. Follow-up study was performed chronologically for up to 11 months in two patients. The correlation between ADCs of the pancreas and the immunoglobulin G4 (IgG4) index (serum IgG4 value/serum IgG4 value before steroid treatment) was evaluated. RESULTS: In the AIP patients, DWI of the pancreas showed high signal intensity, and the ADCs of the pancreas (mean +/- SD: 0.97 +/- 0.18 x 10(-3) mm(2)/s) were significantly lower than those in patients with CP (1.45 +/- 0.10 x 10(-3) mm(2)/s) or the controls (1.45 +/- 0.16 x 10(-3) mm(2)/s) (Mann-Whitney U-test, P < 0.05). In one AIP patient with focal swelling of the pancreas head that appeared to be a mass, DWI showed high signal intensity throughout the pancreas, indicating diffuse involvement. The ADCs of the pancreas and IgG4 index were significantly inversely correlated (Spearman's rank correlation coefficient, r (s) = -0.80, P < 0.05). CONCLUSION: Autoimmune pancreatitis showed high signal intensity on DWI, which improved after steroid treatment. ADCs reflected disease activity. Thus, diffusion-weighted MRI might be useful for diagnosing AIP, determining the affected area, and evaluating the effect of treatment.

Circulating naïve and CD4+CD25high regulatory T cells in patients with autoimmune pancreatitis.

OBJECTIVE: Autoimmune pancreatitis (AIP) is a new clinical entity of pancreatic disorder. There are several immunologic and histological abnormalities specific for the disease, including increased levels of serum IgG4 and infiltration of lymphocytes and IgG4-positive plasmacytes. The role of IgG4 is unclear. Recently, regulatory T cells (Tregs) have been reported to be involved in the development of various autoimmune diseases as well as B cell shifting to IgG4-producing plasmacytes. To clarify the role of Tregs in the pathophysiology of AIP, we analyzed circulating Tregs in AIP. METHODS: We recruited 27 patients with AIP for this study. For comparison, we also recruited 23 patients with other pancreatic disease and 32 healthy subjects as controls. We analyzed Tregs as CD4+CD25high and CD4+CD25+CD45RA+ (naïve) from peripheral blood by flow cytometry. RESULTS: In peripheral blood, CD4+CD25high Tregs were significantly increased in AIP patients (3.01% T 1.77%) compared with alcoholic chronic pancreatitis (CP) (1.65% T 0.58%), idiopathic CP (1.53% T0.56%), and healthy control (1.72% T 0.81%, P G 0.05). Naïve Tregs significantly decreased in AIP (0.32% T 0.22%) compared with healthy control (0.83% T 0.65%) and CP group (alcoholic and idiopathic CP; 0.52% T 0.40%, P G 0.05). In untreated AIP patients,the number of CD4+CD25high Tregs and IgG4 are correlated (R =0.53, P G 0.05). CONCLUSIONS: Increased numbers of CD4+CD25high Tregs may influence IgG4 production in AIP, whereas decreased numbers of naïve Tregs may be involved in the pathogenesis of AIP.

Subclinical hypercortisolism in hospitalized patients with type 2 diabetes mellitus.

Pre(sub)clinical Cushing's disease is a recently described entity defined by the autonomous secretion of ACTH and the absence of a cushingoid appearance. We screened 77 hospitalized patients with diabetes mellitus for subclinical hypercortisolism and detected pre(sub)clinical Cushing's disease in 2 (2.6%) of them. In both patients, transsphenoidal surgery was performed and a microadenoma was removed. Their metabolic clearance rate of glucose measured by a glucose clamp study, an index of insulin sensitivity, significantly improved after surgery. Our results indicate that screening for subclinical hypercortisolism in diabetic patients might be useful, as surgery improves glucose tolerance and insulin sensitivity.

A case of suspected lymphocytic hypophysitis and organizing pneumonia during maintenance therapy for autoimmune pancreatitis associated with autoimmune thrombocytopenia.

A 75-year-old man with a medical history of autoimmune pancreatitis associated with autoimmune thrombocytopenia was emergently admitted to our hospital because of anorexia, vomiting, and transient loss of consciousness. Serum sodium was 115 mEq/l and the endocrinologic data indicated impaired secretion of ACTH, TSH, and gonadotropin, a preserved GH response, and increased PRL. Dynamic magnetic resonance imaging revealed marked swelling of the pituitary gland and stalk, with enhancement on early phase. The findings were consistent with lymphocytic hypophysitis according to the diagnostic criteria. Chest computed tomography revealed consolidation adjacent to the pleura in the right upper lobe, lower lobe, and left lower lobe. Because lymphocytic hypophysitis and associated organizing pneumonia were suggested, 50 mg of prednisolone was started and the dose was tapered. Swelling of the pituitary gland, lung lesion, and the LH and FSH response on the stimulation test were all markedly improved. Autoimmune pancreatitis, pituitary lesion, and organizing pneumonia might all be components of a systemic autoimmune fibrosclerosing disease in our case, although further studies are required to confirm this hypothesis.

High prevalence of autoantibodies against carbonic anhydrase II and lactoferrin in type 1 diabetes: concept of autoimmune exocrinopathy and endocrinopathy of the pancreas.

INTRODUCTION: Dysfunction of the exocrine as well as the endocrine pancreas has been reported in type 1 diabetes. Lymphocytic infiltration of the exocrine pancreas is observed in approximately half of Japanese type 1 diabetic patients. AIMS: To investigate the involvement of autoimmunity against the exocrine pancreas in type 1 diabetes. METHODOLOGY: We examined autoantibodies against human carbonic anhydrase II (ACA) and lactoferrin (ALF), antigens in the pancreatic duct cells and the pancreatic acinus, respectively, in 43 type 1 diabetic patients and 20 type 2 diabetic patients using the enzyme-linked immunosorbent assay method. RESULTS: Of 43 type 1 diabetic patients, ACA was detected in 28 patients (65%) and ALF was detected in 29 patients (67%). One or both of the antibodies were detected in 33 type 1 diabetic patients (77%). In contrast, neither ACA nor ALF were detected in type 2 diabetic patients. CONCLUSIONS: The high prevalence of both ACA and ALF strongly suggests the involvement of autoimmunity against the exocrine pancreas as well as the endocrine pancreas in some type 1 diabetic patients. We propose that these conditions be referred to as autoimmune exocrinopathy and endocrinopathy of the pancreas.