Lymphocytic hypophysitis and hypothalamitis-case report

Lymphocytic hypophysitis is an unusual disorder that nearly exclusively affects women. We present a case of 69 year-old female patient who developed the symptoms of diabetes insipidus and partial insufficiency of the anterior pituitary gland. Magnetic resonance imaging of the brain revealed a mass involving the sella and suprasellar region. After exclusion of other causes of infiltrate in this region and due to evident reaction to glucocorticoid treatment the diagnosis of lymphocytic hypophisitis and hypothalamitis was established.     

Antipituitary antibodies in patients with lymphocytic hypophysitis.

BACKGROUND: Lymphocytic hypophysitis is one of the causes of hypopituitarism, which is considered an autoimmune reaction in the anterior pituitary. METHOD: We examined antipituitary antibodies in patients with lymphocytic hypophysitis and related diseases by immunoblotting method. RESULTS: Autoantibodies to a 22-kDa human pituitary cytosolic protein were identified in significantly higher frequencies in sera from patients with lymphocytic hypophysitis (11 of 15, 73.3%) and isolated ACTH deficiency (7 of 9, 77.8%) compared with Hashimoto thyroiditis, Basedow's disease and normal control subjects. Also, reactivity against a 49-kDa human pituitary cytosolic protein was seen in 6 of 15 patients (40%) with lymphocytic hypophysitis. N-terminal amino acid sequences of 22-kDa human and rat pituitary cytosolic protein were FPTIPLSVL and FPAMPLSSLFAN, respectively, suggesting that they are human and rat growth hormone, respectively. The pituitary dysfunction (at least one hormone dysfunction) was observed in 11 of 14 patients. Nine of them (82%) showed 22 kDa antibody but 2 of them (18%) did not. CONCLUSION: The present study demonstrated that pituitary autoantibodies could be involved in the pathogenesis of lymphocytic hypophysitis and could be a positive marker for the disease.     

Entamoeba histolytica: diffuse liver inflammation in gerbils (Meriones unguiculatus) with experimentally induced amebic liver abscess

The histopathological changes that occur in the uninfected liver lobes of gerbils with a localized amebic liver abscess (left lobe) were studied from 5 to 60 days after inoculation. Early parenchymal changes (10 days) in the right and median liver lobes showed a lymphocytic infiltrate and bile duct proliferation in the portal areas. Maximum alterations occurred at 20 to 30 days after inoculation and were characterized by a dense portal infiltrate, hepatocyte degeneration, granulocytic infiltrate and marked glycogen depletion. In drug-treated infections with metronidazole, the diffuse liver inflammation was terminated. The results of this study suggest that the diffuse liver injury was directly or indirectly induced by the presence of a proliferating amebic liver abscess and that the pathology caused by amebic liver abscess is more extensive than previously thought.     

Entamoeba histolytica: Diffuse Liver Inflammation in Gerbils (Meriones unguiculatus) with Experimentally Induced Amebic Liver Abscess

The histopathological changes that occur in the uninfected liver lobes of gerbils with a localized amebic liver abscess (left lobe) were studied from 5 to 60 days after inoculation. Early parenchymal changes (10 days) in the right and median liver lobes showed a lymphocytic infiltrate and bile duct proliferation in the portal areas. Maximum alternations occurred at 20 to 30 days after inoculation and were characterized by a dense portal infiltrate, hepatocyte degeneration, granulocytic infiltrate and marked glycogen depletion. In drug-treated infections with metronidazole, the diffuse liver inflammation was terminated. The results of this study suggest that the diffuse liver injury was directly or indirectly induced by the presence of a proliferating amebic liver abscess and that the pathology caused by amebic liver abscess is more extensive than previously thought.     

Pituitary autoantibodies in lymphocytic hypophysitis target both gamma- and alpha-Enolase - a link with pregnancy?

The first target autoantigen to have been identified in lymphocytic hypophysitis is a 49 kDa protein, identified as alpha-enolase. Pituitary autoimmunity is strongly associated with pregnancy and we have shown that pituitary autoantibodies from patients with peripartum lymphocytic hypophysitis also recognise enolase in the placenta. Enolase exists in different forms as a number of isoenzymes, which are homo- or heterodimers of three subunits, alpha, beta and gamma. alphaalpha-enolase is ubiquitous, betabeta-enolase is muscle-specific and gammagamma-enolase, which is restricted to neuronal tissue and neuroendocrine cells, is known as neuron-specific enolase (NSE). NSE is expressed in normal human pituitary and pituitary neoplasms. The current study investigated which isoforms of enolase in pituitary and placenta reacted with the sera of patients with lymphocytic hypophysitis. Immunoblotting of two-dimensional gels of human pituitary cytosolic proteins showed that autoantibodies in patient sera react with both an acidic form, and more neutral forms of enolase. Immunoblotting with a monoclonal antibody to NSE confirmed the identity of the acidic enolase isoform as the gammagamma-isoform in both pituitary and placental samples. Gamma-enolase, i.e. NSE, was detected by immunohistochemistry in term placenta in decidua, syncytiotrophoblasts, anchoring villi and terminal villi. Our study is the first to describe the cellular localisation of NSE in normal human placenta, thus establishing a direct link between pituitary and placental autoantigens. This link provides a theoretical basis for the strong prediliction of lymphocytic hypophysitis to occur during or after pregnancy.     

Echographic findings and histological feature of the thyroid: a reverse relationship between the level of echo-amplitude and lymphocytic infiltration

In 43 patients with Graves' disease, 5 patients with painless thyroiditis and 30 patients with Hashimoto-thyroiditis ultrasonographical observations and histological examinations by needle biopsy of the thyroid were carried out simultaneously. In all cases the level of echo-amplitude was well correlated with the rate of lymphocytic infiltrations and fibrosis. In cases which exhibited marked lymphocytic infiltrations in the thyroidal biopsy specimen, no apparent echoes or very low amplitude echoes were observed in the whole thyroid and in cases in which replacement with lymphocytic infiltration was observed in almost a half part of the thyroid, several sonolucent regions were observed in the thyroid and in cases in which lymphocytic infiltration or fibrosis was observed sporadically, low-amplitude and uniform echoes were observed in the whole or several regions of the thyroid. In cases with no lymphocytic infiltration in the histological specimen, diffuse high-amplitude and uniform echoes were observed throughout the whole lobe of the thyroid. In patients with painless thyroiditis, the amplitude of echo was low when the level of lymphocytic infiltration was high and the echo-amplitude showed a tendency to increase along with the decrease in the rate of lymphocytic infiltration. From these observations it is concluded that echo-amplitude is well correlated with lymphocytic infiltration and fibrosis in patients with Hashimoto-thyroiditis, Hashitoxicosis and painless thyroiditis.     

A Protracted and Affressive Variant of Lymphocytic Hypophysitis with Mammillary Body Involvement and Cognitive Dysfunction

ObjectiveOur objective was to describe the 14-year course of a patient with a protracted and aggressive variant of lymphocytic hypophysitis.MethodsThis is a case report.ResultsDespite several trials of pulse steroids, this young female patient demonstrated persistent inflammation of the pituitary gland with eventual extension into the mammillary bodies with clinical cognitive decline. To our knowledge, there is no other reported case of lymphocytic hypophysitis with autoimmune inflammation extending beyond the infundibulum.ConclusionThis case broadens the clinical spectrum of lymphocytic hypophysitis. (Endocr Pract. 2014;20:e225-e229)     

Granulomatous Adenohypophysitis after Interferon and Ribavirin Therapy

ObjectiveTo describe a case of granulomatous hypophysitis occurring after treatment with interferon alfa-2b and ribavirin for hepatitis C.MethodsClinical, radiologic, laboratory, and pathologic assessments of a woman with granulomatous hypophysitis and interferon-induced thyroiditis are presented.ResultsA 42-year-old woman with hepatitis C was treated with interferon alfa-2b and ribavirin for 5 months. She was referred after symptoms of thyrotoxicosis developed, in conjunction with laboratory and radiographic evidence of thyroiditis. During the initial evaluation, she was weak and hypotensive; biochemical evaluation showed undetectable plasma cortisol and corticotropin concentrations. Magnetic resonance imaging revealed diffuse enlargement of the pituitary gland, which encroached on but did not compress the optic chiasm. Treatment with supraphysiologic doses of prednisone resulted in clinical and radiographic improvement. Once physiologic doses of glucocorticoids were instituted, however, follow-up magnetic resonance imaging showed substantial progression of the diffuse pituitary enlargement and mild compression of the optic chiasm. Surgical debulking of the mass and histologic evaluation showed chronic, noncaseating gran-ulomatous hypophysitis. An extensive evaluation for secondary causes of granulomatous inflammation of the pituitary revealed only an elevated angiotensin-converting enzyme level; no organisms were identified. After 2 courses of high-dose glucocorticoids, she had radiographic evidence of decreased size of the pituitary lesion but continued to have multiple anterior pituitary hormone deficiencies.ConclusionGranulomatous hypophysitis and sarcoidosis of the pituitary are rare disorders. Hypophysitis should be considered in patients receiving interferon and ribavirin therapy who have symptoms consistent with pituitary dysfunction. (Endocr Pract. 2007;13:169-175)     

Immune dysregulation in lichen sclerosus

Lichen sclerosus (LS) is a chronic localized lymphocyte-mediated dermatosis of genital skin with a presumed autoimmune origin. LS is characterized by localized dense lymphocytic tissue infiltrates, vasculitic processes and extensive tissue destruction. The lymphocytic infiltrate of LS biopsies contains between 1.4% and 21% of T-cells with monoclonally rearranged T-cell receptor gamma-chain gene, and the immunophenotype is dominated by B-cells, CD4-positive T-cells and antigen-presenting dendritic cells. Antigen-driven selection of T-cells and restricted T-cell receptor usage reflects prolonged exposure of the host immune system to a local (putative LS-associated) antigen. It is presently unclear at which time point in the evolution of LS the T-cell clones emerge. All investigators of LS agree on the non-neoplastic nature of the infiltrate. However, a small percentage of LS patients show serological (systemic) evidence of T-cell immune deficiencies. The lack of long-term follow up of patients with known monoclonally rearranged T-cell receptor gamma-chain gene in their LS biopsies, however, defers a final judgement on the clinical significance of our observations.     

Formalin-induced experimental sclerosing cholangitis in the rat

The few reported cases of sclerosing cholangitis following removal of an echinococcus cyst are thought to be a consequence of the chemical action of formalin used for sterilization of the residual cavity. The aim of this study was to assess this hypothesis. We injected 0.15ml of 2% buffered formalin solution into the central hepatic lobe of five rats, after a midline laparotomy. At 6, 12, 18 and 24 weeks after formalin injection all rats were reoperated upon and a sample of hepatic parenchyma from both the central and the left hepatic lobe was obtained for microscopic evaluation. Our findings, dilatation of portal tracts and bile canaliculi, thickening of the pericanalicular cytoplasm, portal and periportal inflammatory cell infiltration and fibrosis and enlargement of the perisinusoidal space of Disse, suggest that 2% formalin solution leads to the development of essential phenomena of cholestasis and sclerosing cholangitis in the rat, so thus it should be avoided in liver hydatid disease surgery.     

Distribution of Met5-enkephalin-Arg6-Gly7-Leu8-immunoreactivity in the rat and mouse pituitary gland.

The distribution of the octapeptide Met5-enkephalin-Arg6-Gly7-Leu8 (MEAGL), a proenkephalin A-derived opioid peptide, in the rat and mouse pituitary gland was studied using the indirect immunofluorescence technique and immunoelectron microscopy. The anterior lobe contained a few MEAGL-immunoreactive cells but no nerve fibers. A previously unknown enkephalin-immunoreactive nerve fiber system was revealed in the intermediate lobe. These fibers originated in a dense MEAGL-immunoreactive plexus located along the border between the intermediate and posterior lobes and were distributed throughout the lobe. In the posterior lobe, MEAGL immunoreactivity was found in a very dense network of varicose fibers that was evenly distributed over the entire lobe. These results provide a morphological correlate for previous chemical studies and together with them suggest that MEAGL-immunoreactive innervation regulates endocrine functions of the intermediate and posterior lobes directly at the pituitary level.     

Fine needle aspiration cytology and immunocytochemistry in the diagnosis of lymphoid lesions of the thyroid gland

Immunocytochemical analysis was used in conjunction with cytomorphology to evaluate fine needle aspirates from 18 patients with nodular lymphoid infiltrates of the thyroid. The smears from 13 patients had a cytomorphology that was diagnostic of chronic lymphocytic thyroiditis; immunocytochemistry showed the lymphoid population to be composed of T cells and polyclonal B cells. Three patients had high-grade malignant lymphomas by cytomorphology; immunologic evaluation showed the B-cell phenotype of the lymphoma cells and monoclonal light chain expression. Cytomorphology could not differentiate between an inflammatory and a neoplastic lymphoid infiltrate in two cases. Immunocytochemical analysis showed that the cells of B-cell phenotype were monoclonal (neoplastic) in one case and polyclonal (inflammatory) in one case.     

Lower lobe pulmonary tuberculosis in immunocompetent male

We present a case of 23-year-old student misdiagnosed for two months. Radiological finding showed a pneumonial infiltrate of left lung lower lobe. Antibiotical therapy was not resulting in a radiological regression. Biopsy of the lung infiltrate by transthoracic computed tomography guided histology needle, showed granulomatous inflammation with necrosis. Bronchial aspirate received by bronchoscopy was positive in culture on Mycobacterium tuberculosis. After 6 months of antituberculotic therapy advance the complete regression of lung infiltrate. Tuberculosis of lower lung lobe is difficult to diagnose, particularly in persons who are not immunocompromised or without associated diseases. Lower lobe localization of tuberculosis is between 0.6 to 10.5% in all cases. Early diagnosis and therapy of pulmonary tuberculosis depends on bronchoscopic samples. The biopsy of the lung infiltrate by transthoracic computed tomography guided histology needle in histopathological and bacteriological diagnosis of tuberculosis was also useful.     

Problemas clínicos en micología médica: problema número 51

A 48 year-old immunocompetent woman, who had a nodular lesion in the neck and a dense infiltrate at the lower lobe of the left lung, presented at the Mycology Unit of Muñiz Hospital of Buenos Aires City. The pulmonary infiltrate disappeared spontaneously 3 months later. The histopathological study of the nodular lesion showed capsulated yeasts (mucicarmin and alcian blue positive stains) compatible with Cryptococcus. The mycological study of a new sample, obtained by a nodular puncture, allowed the isolation of yeasts, identified as Cryptococcus gattii (VGII). Latex test for Cryptococcus capsular antigen in serum was positive (1/100). CSF cultures rendered negative results. Fluconazole at a daily dose of 800 mg was given during 45 days with partial improvement; as cultures from a new clinical sample were positive for Cryptococcus, the antimycotic was changed to itraconazole 400 mg/day for 5 months, with an excellent clinical response.     

Ultrasonography assessment of hepatobiliary abnormalities in 3359 subjects with Opisthorchis viverrini infection in endemic areas of Thailand

A cross sectional study on hepatobiliary abnormalities in opisthorchiasis was performed in 8936 males and females aged from 20 to 60 years from 90 villages of Khon Kaen province, Northeast Thailand. All were stool-examined for Opisthorchis viverrini infection by standard quantitative formalin/ethyl acetate concentration technique. Of these, 3359 participants with stool egg positive underwent ultrasonography of the upper abdomen. The hepatobiliary abnormalities detected by ultrasound are described here. This study found a significantly higher frequency of advanced periductal fibrosis in persons with chronic opisthorchiasis (23.6%), particularly in males. Risks of the fibrosis included intensity of infection, and age younger than 30 years. Height of left lobe of the liver, cross-section of the gallbladder dimensions post fatty meal, sludge, and, interestingly, intrahepatic duct stones were significantly associated with the advanced periductal fibrosis. Eleven suspected cholangiocarcinoma (CCA) cases were observed. This study emphasizes the current status of high O. viverrini infection rate and the existence of hepatobiliary abnormalities including suspected CCA in opisthorchiasis endemic areas of Thailand.     

Duvelisib attenuates bleomycin-induced pulmonary fibrosis via inhibiting the PI3K/Akt/mTOR signalling pathway

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that seriously threatens the health of patients. The pathogenesis of IPF is still unclear, and there is a lack of effective therapeutic drugs. Myofibroblasts are the main effector cells of IPF, leading to excessive deposition of extracellular matrix (ECM) and promoting the progression of fibrosis. Inhibiting the excessive activation and relieving autophagy blockage of myofibroblasts is the key to treat IPF. PI3K/Akt/mTOR pathway plays a key regulatory role in promoting fibroblast activation and autophagy inhibition in lung fibrosis. Duvelisib is a PI3K inhibitor that can simultaneously inhibit the activities of PI3K-δ and PI3K-γ, and is mainly used for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma tumour (SLL). In this study, we aimed to examine the effects of Duvelisib on pulmonary fibrosis. We used a mouse model of bleomycin-induced pulmonary fibrosis to evaluate the effects of Duvelisib on pulmonary fibrosis in vivo and further explored the potential pharmacological mechanisms of Duvelisib in lung fibroblasts in vitro. The in vivo experiments showed that Duvelisib significantly alleviated bleomycin-induced collagen deposition and improved pulmonary function. In vitro and in vivo pharmacological experiments showed that Duvelisib dose-dependently suppressed lung fibroblast activation and improved autophagy inhibition by inhibiting the phosphorylation of PI3K, Akt and mTOR. Our results indicate that Duvelisib can alleviate the severity of pulmonary fibrosis and provide potential drugs for the treatment of pulmonary fibrosis.     

Thyroid antigen-antibody nephritis: possible involvement of fucosyl-GM1 as the antigen

Hyperthyroidism, microscopic hematuria, and proteinuria developed in an 11-year-old girl. Proteinuria decreased during treatment of hyperthyroidism with an antithyroid drug. On admission, serum anti-thyroglobulin antibody, antimicrosomal antibody, and immune complex were present. The thyrotropin binding inhibitory immunoglobulin (TBII) level was low. On the other hand, an antibody to the ganglioside component (fucosyl-GM1) was detected by an enzyme linked immunosolvent assay (ELISA). A thyroid biopsy specimen showed massive lymphocytic infiltration and interstitial fibrosis. A renal biopsy specimen showed marked proliferation of mesangial cells and increased mesangial matrix with focal segmental capillary wall abnormality. Electron microscopec studies demonstrated mild paramesangial dense deposits. By indirect immunofluorescence, granular glomerular basement membrane and mesangial staining were not detected with rabbit antibody to thyroglobulin, but were detected with rabbit antibody to fucosyl GM1. Fucosyl GM1 was also seen along the basilar aspect of the thyroid follicular epithelial cells. These observation suggests the development of glomerulonephritis mediated by thyroid antigen, particularly ganglioside component.     

Diagnosis of unexpected acute myeloid leukemia and chronic lymphocytic leukemia: a case report demonstrating the perils of restricted panels in flow cytometric immunophenotyping

We report on the flow cytometric identification of concomitant acute myeloid leukemia and chronic lymphocytic leukemia in cytology specimens submitted with minimal clinical information. A 64-year-old man presented with fever and progressive dyspnea on exertion. Chest X-ray and computed tomography scan showed a left upper lobe pulmonary mass. Pulmonary capillary pullback specimens were collected to determine infectious verses neoplastic etiology. The pulmonary capillary pullback specimens showed atypical mononuclear cells with enlarged, slightly irregular nuclei; visible nucleoli; and basophilic cytoplasm. Flow cytometric analysis of the specimen for lymphoma was requested. Flow cytometric immunophenotypic studies showed that 78% of the cells were CD34 positive, CD45 dim positive and CD11c positive, consistent with acute myeloid leukemia. About 0. 75% of the cells expressed CD5 as well as dim CD20 and were monoclonal for kappa light chains: consistent with chronic lymphocytic leukemia/small lymphocytic lymphoma. At this time the clinician communicated a history of myelodysplastic syndrome of refractory anemia subtype. Peripheral blood was obtained for further immunophenotyping and the patient was immediately treated for his acute myeloid leukemia. This case demonstrates that a diagnostic antibody panel should allow evaluation of all cell types as per the U.S./Canadian consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry (Stewart et al.: Cytometry 30:231-235, 1997). Published 2000 Wiley-Liss, Inc.     

Induction of an organ-specific autoimmune disease, lymphocytic hypophysitis, in hamsters by recombinant rubella virus glycoprotein and prevention of disease by neonatal thymectomy.

Glycosylated, membrane-associated E1 (58-kDa) and E2 (47- to 49-kDa) rubella virus proteins and unglycosylated nucleoprotein C (33 kDa), from separately expressed vaccinia virus recombinants, were injected into golden Syrian hamsters. Rubella virus E1 and E2 glycoproteins consistently induced an organ-specific autoimmune disease, autoimmune lymphocytic hypophysitis, which was evidenced by the induction of autoantibodies against pituitary cells and by lymphocytic infiltration of the pituitary. Neonatal thymectomy prevented the disease. In contrast, rubella virus nucleoprotein C did not induce either autoantibodies against pituitary cells or lymphocytic infiltration of the pituitary. This finding raises the possibility that virus-specific protein itself can induce an organ-specific autoimmune disease in certain circumstances.