A Relapsing Remitting Lymphocytic Hypophysitis

Lymphocytic Hypophysitis is a rare autoimmune disease of the pituitary presenting mainly with features of a mass lesion and loss of pituitary function. Its cousre is quite unpredictable and its treatment is still controversial as experience in the field remains scarce.We describe a 45 year-old woman with a history of recurrent fever and meningeal symptoms who was referred 3 years later to our department for pituitary insufficiency Hormonal studies revealed an anterior pituitary deficiency and autoimmune thyroiditis. Pituitary hypertrophy as evidenced by magnetic resonance imaging showed complete regression upon hydrocortisone substitution therapy.Two years later, fever and meningeal symptoms recurred as well as pituitary hypertrophy. Cerebrospinal fluid analysis revealed an aseptic lymphocytic meningitis. Pituitary biopsy confirmed the diagnosis of LH. The patient was started on prednisone 70 mg per day. She improved clinically and radiologically and remained free of symptoms thereafter. At a recent follow up the MRI showed an empty sella turcica. Hereby we illustrate a yet unreported pattern of LH presenting as a recurrent aseptic meningitis. We also describe one of the long-term course of the disease which is still unpredictable.     

自身免疫性垂体炎:一种易被漏诊的疾病

自身免疫性垂体炎虽相对少见,却可造成严重的健康问题,大约有一半自身免疫性垂体炎的患者被误诊为垂体腺瘤而接受了不必要的手术.提高垂体自身免疫性垂体炎的诊断率.除了需要加强对该病的认识,积累更多的诊治经验外,还需深入研究和确认垂体的致病抗原,发展血清学试验以用于垂体占位病变的鉴别诊断;其次需要建立垂体自身免疫病患者的登记数据库,为进行基础和临床创新性研究提供病例来源.     

The Risk of Autoimmunity Development following mRNA COVID-19 Vaccination

The broad spectrum of interactions between autoimmune diseases and the SARS-CoV-2 vaccination is not fully understood. This study aims to evaluate the prevalence of anti-nuclear antibodies (ANA), anti-ENA, anticardiolipin antibodies (ACL), and anti-beta-2 glycoprotein I antibodies (anti-β2GPI) before and after the SARS-CoV-2 mRNA vaccination in a real-life setting in healthcare professionals. The identification of risk factors associated with vaccine immunogenicity was evaluated. The study group consisted of employees of two hospitals (354 individuals). Samples for antibody assays were collected before vaccination and at 7–9 months after complete immunisation. There was no significant increase in the prevalence of ANA, ACL or anti-β2GPI antibodies, or autoimmune diseases in subjects who were vaccinated 7–9 months after complete immunisation. In terms of detected anti-ENA, the anti-DFS70 antibodies were found in 6 times more subjects than before vaccination at the second blood draw (in 18 and 3 subjects, respectively) (p = 0.001). There were no significant relationships between a SARS-CoV-2 infection history, humoral response, cellular response, subject category, smoking, sex, body weight, ANA, anti-ENA, ACL, or anti-β2GPI. This study revealed a possible association between the severity of vaccine adverse events (VAEs) and ANA titre. Individuals with more severe VAEs (>10 points) after the second dose of the vaccine had significantly higher ANA titre after complete immunization. When analysing the significance of time between the ANA, anti-ENA, ACL, and anti- β2GPI assays and complete immunisation antibody values, no qualitative result was statistically significant. There was correlation between the time since complete immunization and ANA after.     

Lymphocytic hypophysitis: a rare cause of hypoglycaemia in a man with type 2 diabetes mellitus

Lymphocytic hypophysitis is a primary inflammatory disorder of the pituitary gland, which may cause panhypopituitarism. The majority of cases occur in women during the peripartum period and it is rare in men. We present a case, initially presenting with recurrent hypoglycaemic episodes, in a man with previously well-controlled type 2 diabetes mellitus.     

Development of New Prolactin Analogs Acting as Pure Prolactin Receptor Antagonists

Prolactin (PRL) promotes tumor growth, as recently highlighted by the spontaneous appearance of prostate hyperplasia and mammary neoplasia in PRL transgenic mice. Increasing experimental evidence argues for the involvement of autocrine PRL in this process. Human (h)PRL receptor antagonists have been developed to counteract these undesired proliferative actions of PRL. However, all PRL receptor antagonists obtained to date exhibit partial agonism, limiting their therapeutic use as full antagonists. This is the case for the first generation antagonists (the prototype of which is G129R-hPRL) that we developed ten years ago, which display antagonistic activity in some, but not all in vitro bioassays, and fail to inhibit PRL activity in transgenic mice expressing this analog. We recently developed new human PRL antagonists devoid of agonistic properties, and therefore able to act as pure antagonists. This was demonstrated using several in vitro bioassays, including assays able to detect extremely low levels of receptor activation. These new compounds also act as pure antagonists in vivo, as demonstrated by their ability to competitively inhibit PRL-triggered signaling cascades in various target tissues (liver, mammary gland and prostate). Finally, using transgenic mice specifically expressing PRL in the prostate, which have constitutively activated signaling cascades and prostate hyperplasia, these new PRL analogs are able to completely revert PRL-activated events to basal levels. These second generation antagonists are good candidates to be used as inhibitors of the growth-promoting actions of hPRL.     

Parathyroid and autoimmunity

Data in favor of chronic hypoparathyroidism as an autoimmune disease are examined. The article takes into consideration the different clinical forms, genetic patterns, histopathology, animal models, cellular immunity, circulating autoantibodies, target autoantigens, clinical manifestations, laboratory diagnosis and therapy. Furthermore, data on 71 Italian patients with chronic hypoparathyroidism are presented.     

Autoimmune comorbidity in achalasia patients

Background and Aim

Idiopathic achalasia is a rare esophageal motor disorder. The disease state manifests local and systemic inflammation, and it appears that an autoimmune component and specific autoantibodies participate in the pathogenesis. The study aims to determine the prevalence of autoimmune and chronic inflammatory diseases in patients with achalasia and compare the results with those from patients with gastroesophageal reflux disease (GERD).

Methods

It was a cross‐sectional and included 114 patients with idiopathic achalasia and 114 age‐matched and sex‐matched control patients with GERD. Data on the presence of autoimmune and inflammatory diseases, the time of presentation, and any family history of autoimmune disease were obtained from the hospital's medical records.

Results

Seventy three (64%) were female patients (mean age: 42.3 ± 15.5; median disease duration: 12 months). We identified the presence of autoimmune disease in 19 patients with achalasia (16.7%), hypothyroidism was the main diagnosis, and it was present in 52.6% of patients compared with 4.2% in controls. Thirteen of the 19 achalasia patients (68.4%) with autoimmune disease had history of familial autoimmunity. We identified 11 achalasia (9.6%) and 5 GERD patients (4.16%) with an inflammatory condition. Compared with the GERD, the achalasia group was 3.8 times more likely to have an autoimmune disease (95% CI: 1.47–9.83), 3.0 times more likely to have thyroidopathies (95% CI: 1.00–9.03), and 3.02 times more likely to suffer from any chronic inflammatory disease (95% CI: 1.65–6.20).

Conclusions

The non‐negligible number of patients with autoimmune diseases identified among the patients with idiopathic achalasia supports the hypothesis that achalasia has an autoimmune component.     

Prolactin receptor antagonists

Most prolactin (PRL) in the circulation is produced by the pituitary. However, a wide variety of traditional target tissues of the hormone have also been shown to produce their own prolactin. The amount produced per cell is low, but may well be sufficient for autocrine/paracrine activity. Although dopamine agonists allow one to study the target tissue effects of pituitary PRL, other agents, such as PRL receptor (PRLR) antagonists, are needed to analyze autocrine/paracrine loops. With PRLR antagonists, it should be possible to dissect out the role of extrapituitary prolactin in both the normal physiology, and the pathophysiology of various tissues. In tissues where the locally produced PRL may promote disease, such antagonists have the potential to be important therapeutics. This article briefly, but critically, reviews current understanding of PRL-receptor interactions and initial signaling, and describes the development of both growth hormone (GH) and PRL antagonists within that context. In the final section, results with a very potent PRL antagonist further one theme of the article, which is whether the simple receptor dimerization model explains all signal transduction following PRLR binding.     

Prolactin and macroprolactin in patients with systemic lupus erythematosus

Aim: The aim of this study was to evaluate plasma levels of prolactin and macroprolactin in a group of systemic lupus erythematosus (SLE) patients and to determine if prolactin and macroprolactin concentrations were related to disease activity, clinical features or serological abnormalities. Methods: Ninety consecutive Iranian patients with SLE were tested for serum prolactin and macroprolactin levels. Total prolactin was measured directly in serum samples by radioimmunoassay. Free prolactin was extracted from the serum using polyethylene glycol. Clinical manifestation and SLE disease activity index (SLEDAI) were recorded. Auto antibodies were determined by standard techniques. Results: There were 90 patients (7 male, 83 female) with a mean age of 27.6 ± 9.1 (range 14–52). The mean disease duration was 27.6 ± 9.1 months. The frequency of high prolactin and macroprolactin, respectively, was 10% (9/90) and 5.6% (5/90) in patients with SLE. Macroprolactinemia was found in 55.55% (5/9) of hyperprolactinemic patients. Lupus activity was present in 63.3% (57/90) of patients without a significant difference in the frequency of high serum prolactin and macroprolactin levels when compared to inactive lupus. There were no statistically significant differences regarding demographic, clinical and laboratory characteristics between the group of patients with macroprolactinemia and the group without macroprolactinemia. Conclusion: Our results suggest that a subgroup of SLE patients have hyperprolactinemia and macroprolactinemia but they do not seem to have positive or negative correlation to clinical and laboratory features and disease activity.     

Recently characterised autoantibodies and their clinical significance

Multisystem autoimmune diseases such as systemic lupus uythcmatosus (SLE), primary Sjögrcn's syndrome (SS), sclcroderma and polymositis are characterised by the presence of antinuclear antibodies (ANAs). Immunoblotting and cDNA cloning studies reveal that the autoantigens of the multisystem autoimmune dixsucs are important proteins involved in nucleic acid metabolism, including tRNA charging, intron splicing, DNA uncoiling, and RNA polymuase co-factors.
Each spaific syndrome associates with a restricted variety of ANAs e.g. anti-La with primary SS, anti-Sm with SLE, and-synthetase enzymes with myositis, and-topoisomerase 1 (Scl 70) with scleroderma, and anti-centromere with CREST. Precise characterisation of an ANA provides valuable diagnostic and prognostic information, and should be performed when an ANA is detected.     

Positive Relationship Between the Nocturnal Concentrations of Melatonin and Prolactin, and a Stimulation of Prolactin After Melatonin Administration in Young Men

The relationship between the concentrations of melatonin and prolactin over the 24-h cycle has been investigated in a group of young men at three times in the year. Melatonin and prolactin showed a significant positive correlation (P less than 0.001) for all times during the 24-h period but with a greater contribution from concentrations during the nocturnal period, when both hormones were elevated. The positive correlation for nocturnal concentrations was evident in February and March (P less than 0.01) but was of greatest significance in June (P less than 0.001). In blood samples taken at 15-min intervals during the morning (0800-1200) and evening (2000-2400), melatonin and prolactin concentrations were not significantly correlated. Melatonin concentrations increased before prolactin during the evening and decreased before prolactin in the morning. Oral administration of 6 mg melatonin significantly stimulated prolactin release above concentrations measured after placebo administration, in both the morning (P less than 0.05) and evening (P less than 0.01) time periods; the prolactin response being greater in the evening. These results provide evidence for melatonin controlling the nocturnal increase of prolactin via its ability to stimulate prolactin release.     

Autoimmunity in hepatitis C and D virus infection

SUMMARY. A large number of viruses are capable of inducing acute or chronic hepatitis. The syndrome of chronic hepatitis encompasses not only viral but also autoimmune liver diseases. The hepatitis C virus, and recently also the hepatitis D virus have been found to be associated with an array of autoimmune syndromes, diseases and markers of autoimmunity. The relationship of hepatotropic virus infection and the immune system leading to virus-associated autoimmunity, and its distinction from genuine autoimmune disease represents a fascinating field of research. Clinically, the differentiation between autoimmune liver diseases, virus infection and virus-associated autoimmunity is difficult and epidemiological evaluations have not come up with universally applicable and valid classification criteria. However, both autoimmune liver diseases and viral hepatitis can readily be diagnosed and distinguished through precise and molecularly determined immunological testing systems. The overlap of both, virus-associated autoimmunity, is still at the centre of research activities aimed at establishing diagnostic and risk-assessment criteria. Studies of molecular autoantigens and autoepitopes have begun to define the differences of the B-cell response in autoimmune disease and virus-associated autoimmunity. This provides data that may contribute to the safe application of therapeutic strategies as different as immunosuppression and interferon-α (IFN-α). The present review focuses on the clinical, epidemilogical and molecular aspects of these disease entities.     

Idiopathic Chronic Urticaria and Celiac Disease

Idiopathic chronic urticaria (ICU) is a chronic relapsing cutaneous disease. Some case reports or studies on small series of celiac disease (CD) patients have suggested a possible association between CD and ICU. The aim of this study was to assess the prevalence of CD in a population of adults ICU patients with respect to healthy controls. We consecutively enrolled 80 patients affected by ICU and 264 blood donors as the control population without a history of ICU. Serum anti-transglutaminase IgG and anti-endomysium IgA antibodies were evaluated in all subjects. In the case of positivity to serology, diagnosis was confirmed by duodenal biopsy. One of 80 (1.25%) ICU patients were positive to both anti-transglutaminase and anti-endomysium antibodies. Duodenal biopsy showed partial villous atrophy. One control of 264 (0.38%) had CD. No statistical difference was found in the prevalence of CD between the two groups. ICU patients do not seem to bear a greater risk for CD compared to the general population.     

Melatonin Effects on Prolactin Secretion in Pituitary-Grafted Male Rats

Melatonin influences prolactin (PRL) secretion through unknown mechanisms. This work was undertaken to study the effects of melatonin administration on PRL secretion in pituitary-grafted male rats. Melatonin administration 5 hours before dark resulted in a marked decrease of previously high basal plasma PRL levels in pituitary-grafted rats, whereas a marked increase was detected in sham-operated animals. Vehicle treatment did not modify basal PRL values in grafted or sham-operated animals. Luteinizing hormone-releasing hormone (LHRH) administration resulted in a marked decrease of plasma PRL levels in vehicle-treated, sham-operated or grafted rats, as well as in melatonin-treated sham-operated rats. An increase in PRL levels was shown in grafted rats treated with melatonin. Estradiol benzoate (EB) administration resulted in an increase in plasma PRL levels both in sham-operated and grafted vehicle-treated rats. No PRL response could be detected in sham-operated, melatonin-treated animals after EB administration. In pituitary-grafted animals given melatonin, PRL response to EB administration was slight and delayed. From these data, melatonin appears to modify PRL secretion through multiple complex mechanisms that may depend on the physiological status (hormonal and neurotransmitter) of the animals. A direct effect at the pituitary level altering lactotroph sensitivity seems to be one plausible explanation for the current findings, although an hypothalamic site of action cannot be excluded.