When Heart Team Really Counts: Radical Excision of Intracardiac Leiomyomatosis.

Intravenous leiomyomatosis (IVL) are rare and complex tumors, characterized by high rates of recurrences after surgical removal and the capability of multi-organ involvement including pulmonary embolization. Regarding the surgical treatment of Intracardiac Leiomiomatosis (ICL), only few articles have been published and no controlled data are available. A combined approach that involves a Team of Cardiologists, Heart Surgeons, Vascular surgeons and Radiologists seems to be successful in treating ICL.

Neuroimmunoendocrinology of SARS-CoV 2 Infection.

This review is aimed at illustrating and discussing the neuroimmune endocrinological aspects of the SARS-CoV-2 infection in light of the studies on this topic that have so far appeared in the literature. The most characteristic findings and pending controversies were derived by PubMed and Scopus databases. We included original and observational studies, reviews, meta-analysis, and case reports. The entry of the coronavirus into susceptible cells is allowed by the interaction with an ecto-enzyme located on human cells, the angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 also targets the central nervous system (CNS), including hypothalamic-pituitary structures, as their tissues express ACE2, and ACE2 mRNA expression in hypothalamus and pituitary gland cells has been confirmed in an autoptic study on patients who died of COVID 19. SARS-CoV-2 infection may cause central endocrine disorders in acute phase and in post-COVID period, particularly due to the effects of this virus at CNS level involving the hypothalamic-pituitary axis. The aggression to the hypothalamus-pituitary region may also elicit an autoimmune process involving this axis, responsible consequently for functional disorders of the satellite glands. Adrenal, thyroid and gonadal dysfunctions, as well as pituitary alterations involving GH and prolactin secretions, have so far been reported. However, the extent to which COVID-19 contributes to short- and long-term effects of infection to the endocrine system is currently being discussed and deserves further detailed research.

Assessment of Neuroendocrine Changes and Hypothalamo-Pituitary Autoimmunity in Patients with COVID-19.

SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, in particular, secondary adrenal insufficiency, using a dynamic test and the role of autoimmunity in pituitary dysfunction in patients with COVID-19. The single-center, prospective, case-control study included patients with polymerase chain reaction (PCR)-confirmed COVID-19 and healthy controls. Basal hormone levels were measured, and the adrenocorticotropic hormone (ACTH) stimulation test was performed. Antipituitary (APA) and antihypothalamic antibodies (AHA) were also determined. We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. Patients with COVID-19 had lower free T3, IGF-1, and total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. In conclusion, COVID-19 may result in adrenal insufficiency, thus routine screening of adrenal functions in these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormalities in COVID-19.

Prevalence and prognostic significance of ischemic late gadolinium enhancement pattern in non-ischemic dilated cardiomyopathy.

BACKGROUND: Typical late gadolinium enhancement (LGE) patterns in dilated cardiomyopathy (DCM) include intramyocardial and subepicardial distribution. However, the ischemic pattern of LGE (subendocardial and transmural) has also been reported in DCM without coronary artery disease (CAD), but its correlates and prognostic significance are still not known. On these bases, this study sought to describe the prevalence and prognostic significance of the ischemic LGE pattern in DCM. METHODS: A total of 611 DCM patients with available cardiac magnetic resonance were retrospectively analyzed. A composite of all-cause-death, major ventricular arrhythmias (MVAs), heart transplantation (HTx) or ventricular assist device (VAD) implantation was the primary outcome of the study. Secondary outcomes were a composite of sudden cardiac death or MVAs and a composite of death for refractory heart failure, HTx or VAD implantation. RESULTS: Ischemic LGE was found in 7% of DCM patients without significant CAD or history of myocardial infarction, most commonly inferior/inferolateral/anterolateral. Compared to patients with non-ischemic LGE, those with ischemic LGE had higher prevalence of hypertension and atrial fibrillation or flutter. Ischemic LGE was associated with worse long-term outcomes compared to non-ischemic LGE (36% vs 23% risk of primary outcome events at 5 years respectively, P = .006), and remained an independent predictor of primary outcome after adjustment for clinically and statistically significant variables (adjusted hazard ratio 2.059 [1.055-4.015], P = .034 with respect to non-ischemic LGE). CONCLUSIONS: The ischemic pattern of LGE is not uncommon among DCM patients without CAD and is independently associated with worse long-term outcomes.

Prognostic role of global longitudinal strain by feature tracking in patients with hypertrophic cardiomyopathy: The STRAIN-HCM study.

BACKGROUND: The assessment of myocardial fiber deformation with cardiac magnetic resonance feature tracking (CMR-FT) has shown to be promising in terms of prognostic information in several structural heart diseases. However, little is known about its role in hypertrophic cardiomyopathy (HCM). Aims of the present study were: 1) to assess the prognostic role of CMR-FT derived strain parameters in patients with HCM. METHODS: CMR was performed in 130 consecutive HCM patients (93 males, mean age (54 ± 17 years) with an estimated 5-year risk of sudden cardiac death (SCD) <6% according to the HCM Risk-SCD calculator. 2D- and 3D-Global Radial (GRS), Longitudinal (GLS) and Circumferential (GCS) Strain was evaluated by FT analysis. The primary outcome of the study was a composite of major adverse cardiac events (MACE) including SCD, resuscitated cardiac arrest due to ventricular fibrillation (VF) or hemodynamically unstable ventricular tachycardia (VT), and hospitalization for heart failure. RESULTS: After a median follow-up of 51.7 (37.1-68.8) months, 4 (3%) patients died (all of them suffered from SCD) and 36 (28%) were hospitalized for heart failure. After multivariable adjustment for clinical and imaging covariates, among all strain parameters, only GLS remained a significant independent predictor of outcome events in both the model including 2D strain (HR 1.12, 95% CI 1.03-1.23, p = 0.01) and the model including 3D strain (HR 1.14, 95% CI 1.01-1.30, p = 0.04). The addition of 2D-GLS into the model with clinical and imaging predictors resulted in a significant increase in the C-statistic (from 0.48 to 0.65, p = 0.03). CONCLUSION: CMR-FT derived GLS is a powerful independent predictor of MACE in patients with HCM, incremental to common clinical and CMR risk factors including left ventricular ejection fraction and late gadolinium enhancement.

Prevalence, clinical and instrumental features of left bundle branch block-induced cardiomyopathy: the CLIMB registry.

AIMS: Although increasingly recognized as a distinct pathological entity, left bundle branch block-induced cardiomyopathy (LBBB-ICMP) is not included among the possible aetiologies of acquired dilated cardiomyopathies (DCM). While diagnostic criteria have been proposed, its recognition remains principally retrospective, in the presence of clinical and instrumental red flags. We aimed to assess the prevalence and clinical and instrumental features of LBBB-ICMP in a large cohort of patients with DCM. METHODS AND RESULTS: We analysed a cohort of 242 DCM patients from a two-centre registry. Inclusion criteria were age > 18, non-ischaemic or non-valvular DCM, and LBBB on electrocardiogram. LBBB-ICMP was defined according to previously proposed diagnostic criteria: (i) neither family history nor clinically identifiable potential causes for DCM; (ii) negative genetic testing; (iii) echocardiographic features including non-severe chamber dilation, normal absolute and relative wall thickness, marked dyssynchrony, and normal right ventricular function; and (iv) absence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). From the entire cohort, we identified 30 subjects (similar in terms of New York Heart Association class I or II in 80% vs. 75%, P = 0.56; QRS width of 150 ± 22 vs. 151 ± 24 ms, P = 0.82; and cardiac remodelling of baseline end-diastolic diameter 66 ± 8 vs. 65 ± 10 mm, P = 0.53) with a comprehensive dataset including CMR and genetic testing, required to verify the presence of the diagnostic criteria proposed for LBBB-ICMP. The main characteristics of this subgroup were 73% males, age 45 ± 13 years, left ventricular ejection fraction (LVEF) 30 ± 10%, LGE in 38% of patients, and QRS complex of 150 ± 22 ms. Patients were under guideline-directed medical therapy, and 57% of them were treated with cardiac resynchronization therapy (CRT). Two patients (6.67%, 50% males, age 53 ± 13 years) fulfilled the diagnostic criteria proposed for LBBB-ICMP. After a follow-up of 44 (12-76) months, LVEF was normal and QRS width significantly reduced (from 154 ± 25 to 116 ± 52 ms) in patients with LBBB-ICMP. Both patients were under optimal medical treatment, and one was implanted with CRT-D. Neither of the two patients experienced death, malignant ventricular arrhythmia, or heart failure hospitalization at follow-up. CONCLUSIONS: Left bundle branch block-induced cardiomyopathy emerges as a distinct pathological entity, promptly identifiable in a minority but not negligible proportion of patients with newly diagnosed DCM and LBBB, using a series of diagnostic criteria including CMR and genetic testing. Further studies are needed to better elucidate the clinical course of LBBB-ICMP.

Hypothalamic-Pituitary Autoimmunity in Patients Treated with Anti-PD-1 and Anti-PD-L1 Antibodies.

BACKGROUND: Autoimmune hypophysitis is a frequent immune-related adverse event (irAE) in cancer patients treated with immunecheckpoint inhibitors. Studies seeking anti-pituitary (APA) and anti-hypothalamus (AHA) antibodies in patients treated with anti-PD-1 and anti-PD-L1 are scarce. The aim of this study is to search for APA and AHA and related pituitary dysfunction in patients treated with these agents. METHODS: Cross-sectional and preliminary longitudinal studies were conducted at the Medical Oncology Unit and Endocrinology and Metabolic Diseases Unit of the University of Campania "Luigi Vanvitelli". Fifty-four cancer patients on treatments with anti-PD-1 or anti-PD-L1 (Group 1) and 50 healthy controls were enrolled for a cross-sectional study; 13 cancer patients (Group 2) were enrolled for our preliminary longitudinal study. APA/AHA titers and changes in biochemical and hormonal profile were evaluated in Group 1; in Group 2, they were evaluated before and after nine weeks from the start of immunotherapy. RESULTS: Patients of Group 1 showed a higher prevalence of APA and AHA than controls: 21 of them had APA, 16 had AHA, and 11 had both autoantibodies. In total, 7 of 13 patients in Group 2 became APA-positive and 3 became AHA-positive after nine weeks of immunotherapy, showing an increase in prolactin and a decrease in ACTH and IGF-1 levels compared with basal values. CONCLUSIONS: Anti-pituitary and anti-hypothalamus antibodies seem to play a pivotal role in hypothalamic-pituitary autoimmunity and secondary endocrine-related alterations evoked by anti-PD-1 and PD-L1 antibodies.

Hypothalamic-Pituitary Autoimmunity and Related Impairment of Hormone Secretions in Chronic Fatigue Syndrome.

CONTEXT: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe chronic illness that reduces the quality of life. A potential role of neuroendocrine autoimmune dysfunction has been hypothesized. OBJECTIVE: This work aims to investigate the occurrence of antipituitary (APA) and antihypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunctions in ME/CSF patients. METHODS: This is a case-control study conducted in a university hospital setting (Stanford, California, USA; and Naples, Italy). Thirty women with ME/CSF (group 1) diagnosed according to Fukuda, Canadian, and Institute of Medicine criteria, at Stanford University, were enrolled and compared with 25 age-matched healthy controls. APA and AHA were detected by immunofluorescence; moreover, we investigated hormonal secretions of anterior pituitary and respective target glands. APA and AHA titers both were assessed and the prevalence of pituitary hormone deficiencies was also investigated. RESULTS: Patients in group 1 showed a high prevalence of AHA (33%) and APA (56%) and significantly lower levels of adrenocorticotropin (ACTH)/cortisol, and growth hormone (GH) peak/insulin-like growth factor-1 (IGF-1) vs controls (all AHA/APA negative). Patients in group 1A (13 patients positive at high titers, ≥ 1:32) showed ACTH/cortisol and GH peak/IGF-1 levels significantly lower and more severe forms of ME/CFS with respect to patients in group 1B (7 positive at middle/low titers, 1:16-1:8) and 1C (10 antibody-negative patients). CONCLUSION: Both AHA and/or APA at high titers were associated with hypothalamic/pituitary dysfunction, suggesting that hypothalamic/pituitary autoimmunity may play an important role in the manifestations of ME/CFS, especially in its more severe forms.

Chronothyroidology: Chronobiological Aspects in Thyroid Function and Diseases.

Chronobiology is the scientific discipline which considers biological phenomena in relation to time, which assumes itself biological identity. Many physiological processes are cyclically regulated by intrinsic clocks and many pathological events show a circadian time-related occurrence. Even the pituitary-thyroid axis is under the control of a central clock, and the hormones of the pituitary-thyroid axis exhibit circadian, ultradian and circannual rhythmicity. This review, after describing briefly the essential principles of chronobiology, will be focused on the results of personal experiences and of other studies on this issue, paying particular attention to those regarding the thyroid implications, appearing in the literature as reviews, metanalyses, original and observational studies until 28 February 2021 and acquired from two databases (Scopus and PubMed). The first input to biological rhythms is given by a central clock located in the suprachiasmatic nucleus (SCN), which dictates the timing from its hypothalamic site to satellite clocks that contribute in a hierarchical way to regulate the physiological rhythmicity. Disruption of the rhythmic organization can favor the onset of important disorders, including thyroid diseases. Several studies on the interrelationship between thyroid function and circadian rhythmicity demonstrated that thyroid dysfunctions may affect negatively circadian organization, disrupting TSH rhythm. Conversely, alterations of clock machinery may cause important perturbations at the cellular level, which may favor thyroid dysfunctions and also cancer.

COVID-19 impact on ST-elevation myocardial infarction incidence rate in a Italian STEMI network: a U-shaped curve phenomenon.

BACKGROUND: Public health emergencies such as the COVID-19 outbreak may impact on the incidence rate of ST-elevation myocardial infarction (STEMI) in severely affected areas. However, this phenomenon demands attention also in areas where media and patients were focused on the COVID-19 pandemic, but the healthcare system was not overwhelmed by the huge number of COVID-19 patients. METHODS AND RESULTS: In this observational study, we compared the incidence rate of all consecutive STEMI patients admitted at the University Hospital of Trieste, Italy, during March and April 2020 with the same 2 months of the previous 5 years (2015-2019). Patient characteristics were compared between 2020 and 2019.The incidence rate of STEMI admission in March-April 2020 was lower than those in March-April 2015-2019, 36 vs. 56 cases per 100 000 inhabitants/year [relative risk (RR) 0.65, 95% confidence interval (95% CI) 0.42-0.96, P = 0.045]. Considering that the incidence rates were constant in the past years (P = 0.24), the turnaround in 2020 is most likely due to the COVID-19 outbreak. Interestingly, this reduction was a dynamic phenomenon with a U-shaped curve during the 2-month period. System-of-care times were similar between 2020 and 2019; however in 2020, patients presented more frequently signs of heart failure compared to 2019 (Killip class ≥2 in 68% vs. 29%, P = 0.003). CONCLUSION: During the COVID-19 outbreak, we observed a marked reduction in the STEMI incidence rate. This U-shaped phenomenon demands attention because a potential cause for the decrease in STEMI incidence may include the avoidance of medical care. Public campaigns aiming to increase awareness of ischemic symptoms may be needed during community outbreak.

Hypothalamitis: A Novel Autoimmune Endocrine Disease. A Literature Review and Case Report.

CONTEXT: The relationship between the endocrine system and autoimmunity has been recognized for a long time and one of the best examples of autoimmune endocrine disease is autoimmune hypophysitis. A better understanding of autoimmune mechanisms and radiological, biochemical, and immunological developments has given rise to the definition of new autoimmune disorders including autoimmunity-related hypothalamic-pituitary disorders. However, whether hypothalamitis may occur as a distinct entity is still a matter of debate. EVIDENCE ACQUISITION: Here we describe a 35-year-old woman with growing suprasellar mass, partial empty sella, central diabetes insipidus, hypopituitarism, and hyperprolactinemia. EVIDENCE SYNTHESIS: Histopathologic examination of surgically removed suprasellar mass revealed lymphocytic infiltrate suggestive of an autoimmune disease with hypothalamic involvement. The presence of antihypothalamus antibodies to arginine vasopressin (AVP)-secreting cells (AVPcAb) at high titers and the absence of antipituitary antibodies suggested the diagnosis of isolated hypothalamitis. Some similar conditions have sometimes been reported in the literature but the simultaneous double finding of lymphocytic infiltrate and the presence of AVPcAb so far has never been reported. CONCLUSIONS: We think that the hypothalamitis can be considered a new isolated autoimmune disease affecting the hypothalamus while the lymphocytic infundibuloneurohypophysitis can be a consequence of hypothalamitis with subsequent autoimmune involvement of the pituitary. To our knowledge this is the first observation of autoimmune hypothalamic involvement with central diabetes insipidus, partial empty sella, antihypothalamic antibodies and hypopituitarism.

Patients with adrenal insufficiency have cardiovascular features associated with hypovolemia.

CONTEXT: Patients with adrenal insufficiency (AI) have excess mortality and morbidity, mainly due to cardiovascular (CV) diseases. The mechanisms for this is unclear. OBJECTIVE: To assess CV structure and function in AI patients on conventional replacement therapy and after switching to once-daily, modified-release hydrocortisone (OD-HC) in comparison with healthy matched controls. METHODS: This was a retrospective analysis of 17 adult AI patients (11 with primary AI, 6 with secondary AI) on stable replacement with cortisone acetate [median (minimum, maximum) 33.5 (12.5-50) mg] and, if needed, fludrocortisone [0.1 (0.05-0.2) mg], and 17 healthy matched controls. Ten patients were switched to an equivalent dose of OD-HC. Data from echocardiography, 24 h Holter-ECG and 24 h blood pressure monitoring were collected at baseline and 6 months after the switch to OD-HC. RESULTS: At baseline, AI patients had smaller left ventricular diastolic diameter (47.1 ± 4.2 vs. 51.6 ± 2.3 mm; P = 0.001) and left atrial diameter (34.9 ± 4.7 vs. 38.2 ± 2.6 cm; P = 0.018), and a higher ejection fraction (62.5 ± 6.9% vs. 56.0 ± 4.7%; P = 0.003) than controls. AI patients had lower nocturnal systolic and diastolic blood pressure than controls (108 ± 15 mmHg vs. 117 ± 8 mmHg; P = 0.038 and 65 ± 9 mmHg vs. 73 ± 7 mmHg; P = 0.008, respectively). After the switch to OD-HC, nocturnal diastolic blood pressure normalised. No significant changes were observed in echocardiographic and Holter-ECG parameters following the switch. CONCLUSIONS: AI patients on conventional treatment display cardiovascular abnormalities that could be related to hypovolemia. Switch to OD-HC seems to have beneficial effect on blood pressure profile, but no effect on cardiovascular structure and function.

Remission of Pituitary Autoimmunity Induced by Gluten-Free Diet in Patients With Celiac Disease.

CONTEXT: An improvement of some autoimmune diseases associated with celiac disease (CD) has been observed after a gluten-free diet (GFD). OBJECTIVE: The aim of this longitudinal study was to evaluate the effect of a GFD on autoimmune pituitary impairment in patients with CD and potential/subclinical lymphocytic hypophysitis (LYH). DESIGN: Five-year longitudinal observational study. SETTING: Tertiary referral center for immunoendocrinology at the University of Campania "Luigi Vanvitelli". PATIENTS: Ninety-three newly diagnosed LYH patients (high titer of antipituitary antibodies [APA] and normal or subclinically impaired pituitary function) were enrolled from 2000 to 2013 and grouped as follows: group 1, consisting of 43 patients with LYH + CD, and group 2, consisting of 50 patients with isolated LYH only. INTERVENTION: A GFD was started in patients in group 1 after the diagnosis of CD. MAIN OUTCOME MEASURES: APA titers and pituitary function were evaluated at the beginning of the study and then yearly for 5 years in both groups. Patients progressing to a clinically overt LYH were excluded from the follow-up. RESULTS: Complete remission of LYH (disappearance of APA and recovery of pituitary function in patients with previous subclinical hypopituitarism) occurred in 15 patients in group 1 after a GFD (34%) and spontaneously in only 1 patient in group 2 (2%) (P < .001). Two patients in group 1 and 25 in group 2 progressed to a clinically overt hypopituitarism and dropped out from the study to receive an appropriate replacement therapy. The presence of CD was the only independent predictor of pituitary function recovery (hazard ratio [HR] 0.059, 95% confidence interval [CI] 0.01-0.54, P = .012). CONCLUSION: In patients with LYH and CD, a GFD may be able to induce remission of subclinical LYH, or prevent the progression to clinical stage of this disease.

Different Formulations of Levothyroxine for Treating Hypothyroidism: A Real-Life Study.

OBJECTIVE: Hypothyroid patients are treated by sodium levothyroxine (LT4). Tablet is the mostly used LT4 formulation, and the fasting regimen is required for the absorption of active principle. Also, gastrointestinal diseases and drugs may impair the LT4 bioavailability when tablet is used. Nonsolid LT4 formulations (i.e., liquid solution (LS) and soft gel (SG) capsule) were manufactured to overcome the limitations of LT4 tablet. This study was conceived to evaluate the performance of nonsolid LT4 formulations in a real-life scenario. METHODS: Two institutions participated in the study that was conducted in two phases (i.e., enrollment and re-evaluation). Adults with autoimmune or postsurgical hypothyroidism and on LT4 from a few months were selected. A nonparametric statistical analysis for paired or unpaired data was performed. RESULTS: 121 consecutive cases were included. At the enrollment phase, a 52% of patients took the therapy at least 30 min before breakfast with no difference between tablet and SG/LS users. TSH was 1.65 mIU/L (0.86-2.70) in patients on LT4 tablet and 1.70 mIU/L (1.10-2.17) in those on SG/LS (p=0.66). At the re-evaluation phase, among the patients using correct LT4 assumption, the TSH value was stable in the tablet group (p=0.66). At the re-evaluation phase, among the patients using correct LT4 assumption, the TSH value was stable in the tablet group (p=0.66). At the re-evaluation phase, among the patients using correct LT4 assumption, the TSH value was stable in the tablet group (p=0.66). At the re-evaluation phase, among the patients using correct LT4 assumption, the TSH value was stable in the tablet group (p=0.66). At the re-evaluation phase, among the patients using correct LT4 assumption, the TSH value was stable in the tablet group (. CONCLUSION: The performance of nonsolid LT4 formulations is not influenced by correct or incorrect use of therapy. On the contrary, LT4 tablet does not guarantee euthyroidism when it is ingested without waiting for at least 30 minutes before breakfast. These new data, obtained in a real-life scenario, suggest that LT4 SG/LS should be regarded as first-line therapy for treating adults with newly diagnosed hypothyroidism.

Antibodies Against Hypothalamus and Pituitary Gland in Childhood-Onset Brain Tumors and Pituitary Dysfunction.

Purpose: To detect the presence of antipituitary (APA) and antihypothalamus antibodies (AHA) in subjects treated for brain cancers, and to evaluate their potential association with pituitary dysfunction. Methods: We evaluated 63 patients with craniopharyngioma, glioma, and germinoma treated with surgery and/or radiotherapy and/or chemotherapy at a median age of 13 years. Forty-one had multiple pituitary hormone deficiencies (MPHD), six had a single pituitary defect. GH was the most common defect (65.1%), followed by AVP (61.9%), TSH (57.1%), ACTH (49.2%), and gonadotropin (38.1%). APA and AHA were evaluated by simple indirect immunofluorescence method indirect immunofluorescence in patients and in 50 healthy controls. Results: Circulating APA and/or AHA were found in 31 subjects (49.2%) and in none of the healthy controls. In particular, 25 subjects out of 31 were APA (80.6%), 26 were AHA (83.90%), and 20 were both APA and AHA (64.5%). Nine patients APA and/or AHA have craniopharyngioma (29%), seven (22.6%) have glioma, and 15 (48.4%) have germinoma. Patients with craniopharyngioma were positive for at least one antibody in 39.1% compared to 33.3% of patients with glioma and to 78.9% of those with germinoma with an analogous distribution for APA and AHA between the three tumors. The presence of APA or AHA and of both APA and AHA was significantly increased in patients with germinoma. The presence of APA (P = 0.001) and their titers (P = 0.001) was significantly associated with the type of tumor in the following order: germinomas, craniopharyngiomas, and gliomas; an analogous distribution was observed for the presence of AHA (P = 0.002) and their titers (P = 0.012). In addition, we found a significant association between radiotherapy and APA (P = 0.03). Conclusions: Brain tumors especially germinoma are associated with the development of hypothalamic-pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.

Impact of Pituitary Autoimmunity and Genetic Disorders on Growth Hormone Deficiency in Children and Adults.

Growth hormone (GH), mostly through its peripheral mediator, the insulin-like growth factor 1(IGF1), in addition to carrying out its fundamental action to promote linear bone growth, plays an important role throughout life in the regulation of intermediate metabolism, trophism and function of various organs, especially the cardiovascular, muscular and skeletal systems. Therefore, if a prepubertal GH secretory deficiency (GHD) is responsible for short stature, then a deficiency in adulthood identifies a nosographic picture classified as adult GHD syndrome, which is characterized by heart, muscle, bone, metabolic and psychic abnormalities. A GHD may occur in patients with pituitary autoimmunity; moreover, GHD may also be one of the features of some genetic syndromes in association with other neurological, somatic and immune alterations. This review will discuss the impact of pituitary autoimmunity on GHD and the occurrence of GHD in the context of some genetic disorders. Moreover, we will discuss some genetic alterations that cause GH and IGF-1 insensitivity and the arguments in favor and against the influence of GH/IGF-1 on longevity and cancer in the light of the papers on these issues that so far appear in the literature.

Gender-related differences in heart failure: beyond the "one-size-fits-all" paradigm.

Cardiovascular diseases show many sex-related differences in prevalence, etiology, phenotype expression, and outcomes. Complex molecular mechanisms underlie this diverse pathological manifestation, from sex-determined differential gene expression to sex hormones interaction with their specific receptors in different tissues. More recently, differential non-coding RNAs regulation also turned out to be an involved mechanism. This review focuses on sex impact on the various heart failure syndromes, including coronary artery disease, heart failure with preserved ejection fraction and with reduced ejection fraction, with particular attention to dilated cardiomyopathy. Despite similar genetic predisposition in terms of identified causative mutations, other causes, such as cardiotoxic drugs exposure or stress-induced cardiomyopathy, are more prevalent in women. Beyond this, differences in disease presentation and natural history reveal a more severe clinical onset with otherwise better long-term outcomes in women compared to men. Understanding the varying characteristics of disease manifestation and outcomes is warranted for a prompt and tailored treatment for both men and women. This is a mandatory step in the road to the personalized medicine. Moreover, despite a higher enrollment in the last years, the under-representation of females in clinical trials is the first obstacle to overcome in the long way to develop appropriate sex-based therapy approach.

The role of autoimmunity in pituitary dysfunction due to traumatic brain injury.

PURPOSE: Traumatic brain injury (TBI) is one of the most common causes of mortality and long-term disability and it is associated with an increased prevalence of neuroendocrine dysfunctions. Post-traumatic hypopituitarism (PTHP) results in major physical, psychological and social consequences leading to impaired quality of life. PTHP can occur at any time after traumatic event, evolving through various ways and degrees of deficit, requiring appropriate screening for early detection and treatment. Although the PTHP pathophysiology remains to be elucitated, on the basis of proposed hypotheses it seems to be the result of combined pathological processes, with a possible role played by hypothalamic-pituitary autoimmunity (HPA). This review is aimed at focusing on this possible role in the development of PTHP and its potential clinical consequences, on the basis of the data so far appeared in the literature and of some results of personal studies on this issue. METHODS: Scrutinizing the data so far appeared in literature on this topic, we have found only few studies evaluating the autoimmune pattern in affected patients, searching in particular for antipituitary and antihypothalamus autoantibodies (APA and AHA, respectively) by simple indirect immunofluorescence. RESULTS: The presence of APA and/or AHA at high titers was associated with an increased risk of onset/persistence of PTHP. CONCLUSIONS: HPA seems to contribute to TBI-induced pituitary damage and related PTHP. However, further prospective studies in a larger cohort of patients are needed to define etiopathogenic and diagnostic role of APA/AHA in development of post-traumatic hypothalamic/pituitary dysfunctions after a TBI.

Management of cardiovascular complications in Klinefelter syndrome patients.

INTRODUCTION: Klinefelter syndrome (KS), also known as 47, XXY, shows increased mortality when compared with mortality rates among the general population. Cardiovascular, hemostatic, metabolic diseases are implicated. Moreover, cardiac congenital anomalies in KS can contribute to the increase in mortality. AREAS COVERED: In this study, we have systematically reviewed the relationships between KS and the cardiovascular system and the management of cardiovascular complication. In summary, patients with KS display increased cardiovascular risk profile, characterized by increased prevalence of metabolic alterations including dyslipidemia, diabetes mellitus (DM), and abnormalities in biomarkers of cardiovascular disease. KS subjects are characterized by subclinical abnormalities in endothelial function and in left ventricular (LV) systolic and diastolic function, which - when associated with chronotropic incompetence - may negatively influence cardiopulmonary performance. Moreover, KS patients appear to be at a higher risk for cardiovascular disease, due to thromboembolic events with high prevalence of recurrent venous ulcers, venous insufficiency, recurrent venous and arterial thromboembolism leading to deep venous thrombosis or pulmonary embolism. EXPERT OPINION: Considering the unequivocal finding of increased mortality of KS patients, we suggest a periodic cardiovascular follow up in specialized centers with multidisciplinary care teams that comprise endocrinologists and cardiologists dedicated to KS syndrome.

Autoimmune pituitary involvement in Prader-Willi syndrome: new perspective for further research.

The role of antipituitary antibodies in the pathophysiology of pituitary hormone deficiency has been increasingly elucidated over the last decade. Prader-Willi syndrome is a genetic disorder which includes hypothalamic/pituitary dysfunction as one of its main features. We looked for autoimmune pituitary involvement in 55 adults with Prader-Willi syndrome, discovering that about 30% of them have a positive titer of antipituitary antibodies. Although the presence of these autoantibodies could only be an "epiphenomenon", our results suggest that autoimmune mechanisms might contribute, at least in part, to the pituitary impairment of Prader-Willi syndrome, and in addition to genetically determined dysfunction of the central nervous system. This paper provides a new perspective on pituitary impairment in these patients, suggesting that the search for hypophisitis could be a reasonable and interesting field for further research.