434 research outputs found
Johns Hopkins hospital notables portrayed on philatelic material
No full textThe philatelic medium is an extensive repository of the portraits of doctors of many nations. Using an electronic matching system to identify links between the lists of alumni and faculties register of Johns Hopkins Hospital in Baltimore and that of three stamp catalogues, 14 notable persons have been identified in the philatelic record. The Johns Hopkins Hospital was established in Baltimore in 1889 and instituted the revolutionary concept of combining patient care with research and teaching. Its founder Johns Hopkins (1795-1873) and 13 among alumni and faculties have been portrayed on postage stamps and first day covers of USA, Canada, Antigua, Barbuda, Palau, Maldives, Canada and Sweden. Five of them - du Vigneaud (1901-78), Smith (b. 1931), Nathans (1928-99), Hubel (b. 1926) and Wiesel (b. 1924) - were awarded the Nobel Prize for Medicine or Physiology. By means of the philatelic medium, portraits of Hopkins scientists and doctors, including Sir William Osler (1849-1919) and Dr Virgina Apgar (1909-74), are distributed in their many tens of thousands on envelopes sent not only to recipients in the USA but to the wider world
Necrotizing infundibulo-hypophysitis: an entity too rare to be true?
No full textWe report a young woman with sudden and severe retroorbital headache, neck pain, and a large sellar mass extending to the suprasellar cistern. A presumptive diagnosis of non-secreting pituitary macroadenoma undergoing apoplexy was made and transphenoidal surgery performed. Histopathology revealed mononuclear infiltration and marked non-hemorrhagic necrosis of the anterior pituitary consistent with a diagnosis of necrotizing infundibulo-hypophysitis. The possible pathogenesis of this rare variant of hypophysitis is discussed
MON-450 Pituitary Antibodies In A Cohort Of Us Service Members With Traumatic Brain Injury
No full textTraumatic brain injury (TBI) causes pituitary dysfunction, mainly featuring GH deficiency. Several mechanisms have been proposed to explain this post-traumatic dyspituitarism, including autoimmunity. We analyzed pituitary antibodies in 100 of US Service Members chosen for a history of TBI and hearing impairment, a concurrence typically seen after blast injuries. Each soldier provided two sera, one before (-1,765 to - 66 days) and one after (10 to 177 days) TBI. All 200 sera were screened by indirect immunofluorescence for binding to a human pituitary gland collected at autopsy. Positive sera were then tested by double indirect immunofluorescence for recognition of cells expressing GH, PRL, ACTH, LH, FSH, TSH, alpha-internexin (INA), vimentin, or glial fibrillary-acidic protein (GFAP). Sera were also tested by ELISA for recognition of native GH or recombinant INA. 63 of 200 sera (31 %) contained pituitary antibodies: of them, 33 (16%) recognized the adenohypophysis, 18 (9 %) the neurohypophysis, and 12 (6%) both lobes. In the adenohypophysis, TSH-secreting cells were the most common target (26 of 45, 58%), followed by INA expressing cells (17 of 45, 37%). In the neurohypophysis, 20 of 30 sera (67 %) recognized INA, 6 (20%) vimentin, and 4 (13%) GFAP-expressing cells. There was no temporal association between pituitary antibodies and TBI: of the sera recognizing TSH-secreting cells, half had antibodies in both the pre- and post-TBI serum (13 of 26, 50%), a quarter (6 of 26, 23%) in the pre-TBI serum, and a quarter (7 of 26, 27%) in the post-TBI serum. Similarly, of the sera recognizing INA-expressing cells, 2 (11.7%) had antibodies in both the pre- and post-TBI serum, 9 (53%) only in the pre-TBI serum, and 6 (35.2%) only in the post-TBI serum. INA antibodies measured by ELISA did not differ between the pre- and post-TBI time points. On the contrary, GH antibodies tended to increase after TBI, although not reaching statistical significance (p= 0.055). The study highlights a preferential recognition of TSH- and INA-expressing cells in TBI patients, which remains to be interpreted in the context of their endocrine dysfunctions. It also suggests that the appearance of GH antibodies after TBI contributes to the GH deficiency typically seen in these patients
Primary hypophysitis: clinical-pathological correlations
No full textObjective: Primary hypophysitis comprises of three distinct histomorphological entities: lymphocytic, granulomatous and xanthomatous. Clinical features of the three subtypes for diagnostic and treatment strategies have yet not been well characterized. Methods: Endocrine function, visual fields and acuity as well as magnetic resonance imaging characteristics were assessed before and after transphenoidal surgery in the largest series of 31 patients with primary hypophysitis (21 lymphocytic, 6 granulomatous, and 4 xanthomatous cases). Results: Only lymphocytic hypophysitis occurred during pregnancy (30%) and was associated with other autoimmune diseases (24%). Visual fields and acuity abnormalities were not seen in xanthomatous hypophysitis. Lymphocytic and granulomatous hypophysitis most often resulted in severe dysfunction of the adrenal, gonadal and thyroidal axes as well as diabetes insipidus. For patients presenting with xanthomatous hypophysitis most often, mild anterior pituitary axis failure was documented and posterior pituitary involvement was hardly found. The outcome after transphenoidal biopsy was generally favorable. Pre- or postsurgical glucocorticoid treatment was very effective in 75% of the lymphocytic form in reducing the pituitary size. In contrast, glucocorticoid therapy was less effective in granulomatous or xanthomatous hypophysitis. Conclusion: Diffuse destruction of the complete pituitary gland including the infundibulum has to be considered in lymphocytic and granulomatous hypophysitis, whereas in xanthomatous, a circumscribed anterior pituitary lesion leading to compression of the pituitary gland without alteration of the pituitary stalk and optic chiasm can be assumed
Novel autoantigens in autoimmune hypophysitis
No full textBackground Pituitary autoantibodies are found in autoimmune hypophysitis and other conditions. They are a marker of pituitary autoimmunity but currently have limited clinical value. The methods used for their detection lack adequate sensitivity and specificity, mainly because the pathogenic pituitary autoantigen(s) are not known and therefore antigen-based immunoassays have not been developed. Objectives This study aimed to identify novel pituitary autoantigens using sera as probes in proteomic assays. We also compared immunoblotting and immunofluorescence methods for their accuracy in diagnosing autoimmune hypophysitis. Study design and subjects Twenty-eight sera from autoimmune hypophysitis cases (14 histologically proven and 14 clinically suspected) were compared to 98 sera from controls, which included 14 patients with pituitary adenomas, 48 with autoimmune thyroiditis (15 Graves' disease and 33 Hashimoto's thyroiditis) and 36 healthy subjects. Methods All sera were tested against human pituitary cytosolic proteins separated by one-dimensional (1D) gel electrophoresis. The band recognition was analysed statistically to detect molecular weight regions preferentially recognized by hypophysitis sera. 2D gel immunoblotting and mass spectrometry were then used to sequence the protein spots of interest. Sera were also tested by immunofluorescence for their recognition of Macaca mulatta pituitary sections. Results A single region in the 25-27-kDa range was recognized more often by hypophysitis cases than healthy subjects (P = 0.004) or patients with pituitary adenomas (P = 0.044). This region contained two novel candidate autoantigens: chromosome 14 open reading frame 166 (C14orf166) and chorionic somatomammotrophin. Immunoblotting positivity for the 25-27-kDa region yielded greater sensitivity (64% vs. 57%) and specificity (86% vs. 76%) than immunofluorescence in predicting histologically proven hypophysitis, although the performance was still inadequate to make immunoblotting a clinically useful test. Conclusion The study reports two novel proteins that could act as autoantigens in autoimmune hypophysitis. Further studies are needed to validate their pathogenic role and diagnostic utility.NIDDK NIH HHS [DK55670
Endocrinopathies: chronic thyroiditis, addison disease, pernicious anemia, graves’ disease, diabetes, and hypophysitis
No full textChronic lymphocytic thyroiditis (CLT), also known as Hashimoto thyroiditis, is an autoimmune disease characterized by lymphocytic infiltration of the thyroid gland, with the concomitant production of autoantibodies to thyroid antigens, primarily thyroglobulin and/or thyroperoxidase (TPO), formerly known as microsomal antigen (1). Although few epidemiological data are available, the prevalence of CLT is estimated to be 1 in 1,000 people, with an incidence of 0.2
to 2% and a female-to-male ratio of about 18:1 (1). Clinical signs and symptoms manifest slowly and may involve many systems of the body (1). Accumulations of hydrophilic mucoproteins with edema, a condition called myxedema, affects skin and connective tissue and can affect the appearance of
the individual. Lethargy may ensue, with a loss of mental acuity. Systems commonly affected are the gastrointestinal tract, the hemopoietic system, the endocrine system, and the urogenital system (1). Enlargement of the thyroid gland due to lymphocyte invasion, called goiter, is a frequent manifestation,
although there is an atrophic variation. Demonstration of autoantibodies to the thyroid antigens aids in the diagnosis of CLT, distinguishing it from other causes of hypothyroidism
Pregnancy, postpartum autoimmune thyroiditis, and autoimmune hypophysitis: Intimate relationships
No full textAutoimmune diseases comprise a group of about 85 heterogeneous conditions that can affect virtually any organ and tissue in the body. Many autoimmune diseases change significantly during pregnancy: some ameliorate, some worsen, and others are unaffected. Two autoimmune diseases present prominently in relation to pregnancy: postpartum autoimmune thyroiditis and autoimmune hypophysitis. This article will review the current state of knowledge of the immunological changes that occur during normal pregnancy, and will explore the striking temporal association with pregnancy observed in thyroiditis and hypophysitis. (C) 2009 Elsevier B.V. All rights reserved
Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis
No full textIntroduction: Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. Objective: To identify clinical and radiological findings associated with response to glucocorticoids. Design and methods: 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). Results: MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis (n = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis (n = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients (P = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced (P = 0.008) but diabetes insipidus persisted in all. Conclusions: Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids
From Pituitary Expansion to Empty Sella: Disease Progression in a Mouse Model of Autoimmune Hypophysitis
No full textLymphocytic hypophysitis has a variable clinical course, where a swelling of the pituitary gland at presentation is thought to be followed by pituitary atrophy and empty sella. Data in patients, however, are scanty and contradictory. To better define the course of hypophysitis, we used an experimental model based on the injection of pituitary proteins into SJL mice. A cohort of 33 mice was divided into three groups: 18 cases were immunized with pituitary proteins emulsified in complete Freund's adjuvant; six controls were injected with adjuvant only; and nine controls were left untreated. Mice were followed by cranial magnetic resonance imaging (MRI) for up to 300 d, for a total of 106 MRI scans, and killed at different time points to correlate radiological and pathological findings. Empty sella was defined as a reduction in pituitary volume greater than 2 SD below the mean volume. All immunized mice showed by MRI a significant expansion of pituitary volume during the early phases of the disease. The volume then decreased gradually in the majority of cases (14 of 18, 78%), reaching empty sella values by d 300 after immunization. In a minority of cases (four of 18, 22%), the decrease was so rapid and marked to induce a central area of necrosis accompanied by hemorrhages, mimicking the condition known in patients as pituitary apoplexy. No radiological or pathological changes were observed in controls. Overall, these findings indicate that the evolution of hypophysitis is complex but can lead, through different routes, to the development of empty sella. (Endocrinology 152: 4190-4198, 2011
Hypophysitis Secondary to Cytotoxic T-Lymphocyte-Associated Protein 4 Blockade: Insights into Pathogenesis from an Autopsy Series
No full textHypophysitis that develops in cancer patients treated with monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4; an inhibitory molecule classically expressed on T cells) is now reported at an incidence of approximately 10%. Its pathogenesis is unknown, in part because no pathological examination of the pituitary gland has been reported to date. We analyzed at autopsy the pituitary glands of six cancer patients treated with CTLA-4 blockade, one with clinical and pathological evidence of hypophysitis, one with mild lymphocytic infiltration in the pituitary gland but no clinical signs of hypophysitis, and four with normal pituitary structure and function. CTLA-4 antigen was expressed by pituitary endocrine cells in all patients but at different levels. The highest levels were found in the patient who had clinical and pathological evidence of severe hypophysitis. This high pituitary CTLA-4 expression was associated with T-cell infiltration and IgG-dependent complement fixation and phagocytosis, immune reactions that induced an extensive destruction of the adenohypophyseal architecture. Pituitary CTLA-4 expression was confirmed in a validation group of 37 surgical pituitary adenomas and 11 normal pituitary glands. The study suggests that administration of CTLA-4 blocking antibodies to patients who express high levels of CTLA-4 antigen in the pituitary can cause an aggressive (necrotizing) form of hypophysitis through type IV (T-cell dependent) and type II (IgG dependent) immune mechanisms
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