RESUMEN
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.
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Cardiomiopatía Dilatada , Gadolinio , Cardiomiopatía Dilatada/diagnóstico por imagen , Cardiomiopatía Dilatada/epidemiología , Medios de Contraste , Humanos , Imagen por Resonancia Cinemagnética , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Estudios RetrospectivosRESUMEN
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.
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Hormona Adrenocorticotrópica/sangre , COVID-19/inmunología , Hipotálamo/inmunología , Hipófisis/inmunología , Adulto , Autoanticuerpos/sangre , Autoinmunidad , COVID-19/sangre , COVID-19/metabolismo , COVID-19/virología , Estudios de Casos y Controles , Femenino , Humanos , Hidrocortisona/sangre , Hipotálamo/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Persona de Mediana Edad , Hipófisis/metabolismo , Prolactina/sangre , Estudios Prospectivos , SARS-CoV-2/fisiología , Testosterona/sangreRESUMEN
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.
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Insuficiencia Cardíaca/epidemiología , Medición de Riesgo/métodos , Volumen Sistólico/fisiología , Femenino , Salud Global , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Morbilidad/tendencias , Pronóstico , Factores de Riesgo , Factores Sexuales , Función Ventricular Izquierda/fisiologíaRESUMEN
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.
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Autoinmunidad/genética , Hormona del Crecimiento/deficiencia , Factor I del Crecimiento Similar a la Insulina/metabolismo , Enfermedades de la Hipófisis/inmunología , Hipófisis/metabolismo , Adulto , Animales , Autoinmunidad/fisiología , Niño , Enfermedades Genéticas Congénitas/inmunología , Hormona del Crecimiento/metabolismo , Humanos , Longevidad/genética , Longevidad/inmunología , Neoplasias/genética , Neoplasias/inmunología , Hipófisis/inmunología , Transducción de Señal/genética , Transducción de Señal/inmunologíaRESUMEN
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.
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Autoinmunidad/fisiología , Lesiones Traumáticas del Encéfalo/patología , Hipopituitarismo/patología , Hipófisis/patología , Animales , Lesiones Traumáticas del Encéfalo/inmunología , Humanos , Hipopituitarismo/inmunología , Hipotálamo/metabolismo , Hipotálamo/patología , Hipófisis/inmunologíaRESUMEN
BACKGROUND: Laparoscopic adrenalectomy is considered the gold standard technique for the treatment of benign small and medium size adrenal masses (<6 cm), due to low morbidity rate, short hospitalization and patient rapid recovery. The aim of our study is to analyse the feasibility and efficiency of this surgical approach in a broad spectrum of adrenal gland pathologies. METHODS: Pre-operative, intra-operative and post-operative data from 126 patients undergone laparoscopic adrenalectomy between January 2003 and December 2015 were retrospectively collected and reviewed. Diagnosis was obtained on the basis of clinical examination, laboratory values and imaging techniques. Doxazosin was preoperatively administered in case of pheochromocytoma while spironolactone and potassium were employed to treat Conn's disease. Laparoscopic adrenalectomies were all performed by the same surgeon (CG). First 30 procedures were considered as learning curve adrenalectomies. RESULTS: One hundred twenty-six patients were included in the study. Functioning tumors were diagnosed in 84 patients, 27 patients were affected by pheochromocytomas, 29 by Conn's disease, 28 by Cushing disease. Surgery mean operative time was 137.33 min (range 100-180) during the learning curve adrenalectomies and 96.5 min (range 75-110) in subsequent procedures. Mean blood loss was respectively 160.2 ml (range 60-280) and 90.5 ml (range 50-200) in the first 30 procedures and the subsequent ones. Only one conversion to open surgery occurred. No post-operative major complications were observed, while minor complications occurred in 8 patients (0,79%). In 83 out of 84 functioning neoplasms, laparoscopic adrenalectomy was effective in normalization of endocrine profile. CONCLUSIONS: Laparoscopic adrenalectomy is a safe and feasible procedure, even for functioning masses and pheochromocytomas. A multidisciplinary team including endocrinologists, endocrine surgeons and anaesthesiologists, is recommended in the management of adrenal pathology, and adrenal surgery should be performed in referral high volume centers. A thirty-procedures learning curve is recommended to improve surgical outcomes.
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Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Laparoscopía/métodos , Feocromocitoma/cirugía , Glándulas Suprarrenales/cirugía , Adulto , Anciano , Conversión a Cirugía Abierta , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: This publication reviews the accepted knowledges and the findings still discussed on several features of autoimmune hypophysitis, including the most recently described forms, such as IgG4 and cancer immunotherapy- related hypophysitis. METHODS: The most characteristic findings and the pending controversies were derived from a literature review and previous personal experiences. A single paragraph focused on some atypical examples of the disease presenting under confounding pretences. RESULTS: Headache, visual field alterations and impaired pituitary secretion are the most frequent clinical findings of the disease. Pituitary biopsy, still considered the gold diagnostic standard, does not always receive consent from the patients. The role of magnetic resonance imaging is limited, as this disease may generate images similar to those of other diseases. The role of antipituitary and antihypothalamus antibodies is still discussed owing to methodological difficulties and also because the findings on the true pituitary antigen(s) are still debated. However, the low sensitivity and specificity of immunofluorescence, one of the more widely employed methods to detect these antibodies, may be improved, considering a predetermined cut-off titre and a particular kind of immunostaining. CONCLUSION: Autoimmune hypophysitis is a multifaceted disease, which may certainly be diagnosed by pituitary biopsy. However, the possible different clinical, laboratory and imaging features must be considered by the physician to avoid a misdiagnosis when examining a possibly affected patient. Therapeutic choice has to be made taking into account the clinical conditions and the degree of hypothalamic-pituitary involvement, but also considering that spontaneous remissions can occur.
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Hipofisitis Autoinmune/etiología , Anticuerpos Monoclonales/efectos adversos , Hipofisitis Autoinmune/diagnóstico , Hipofisitis Autoinmune/patología , Antígeno CTLA-4/inmunología , Antígenos HLA/genética , Humanos , Inmunoglobulina G , Hipófisis/patologíaRESUMEN
In the last years, especially thanks to a large diffusion of ultrasound-guided FNBs, a surprising increased incidence of differentiated thyroid cancer (DTC), "small" tumors and microcarcinomas have been reported in the international series. This led endocrinologists and surgeons to search for "tailored" and "less aggressive" therapeutic protocols avoiding risky morbidity and useless "overtreatment". Considering the most recent guidelines of referral endocrine societies, we analyzed the role of routine or so-called prophylactic central compartment lymph node dissection (RCLD), also considering its benefits and risks. Literature data showed that the debate is still open and the surgeons are divided between proponents and opponents of its use. Even if lymph node metastases are commonly observed, and in up to 90% of DTC cases micrometastases are reported, the impact of lymphatic involvement on long-term survival is subject to intensive research and the best indications of lymph node dissection are still controversial. Identification of prognostic factors for central compartment metastases could assist surgeons in determining whether to perform RLCD. Considering available evidence, a general agreement to definitely reserve RCLD to "high-risk" cases was observed. More clinical researches, in order to identify risk factors of meaningful predictive power and prospective long-term randomized trials, should be useful to validate this selective approach.
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Diferenciación Celular , Escisión del Ganglio Linfático , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Humanos , Pronóstico , Factores de Riesgo , Neoplasias de la Tiroides/patologíaRESUMEN
BACKGROUND: Hemostasis during thyroidectomy is essential; however, the safest, most efficient, and most cost-effective way to achieve this is unclear. This randomized, multicenter, single-blind, prospective study evaluated the efficacy and safety of using different hemostatic approaches in patients undergoing total thyroidectomy. METHODS: Patients aged ≥18 to 70 years were randomized to Floseal + a harmonic scalpel (HS), Floseal alone, HS alone, or standard total thyroidectomy. Primary endpoint was 24-hour drain output. Secondary endpoints included surgery duration and complications. RESULTS: Two hundred and six patients were randomized to Floseal + HS (n = 52), Floseal alone (n = 54), HS alone (n = 50), and standard total thyroidectomy (n = 50). The 24-hour drain output was lower in the Floseal + HS group compared with standard thyroidectomy. Floseal + HS also had a shorter surgery time (P < .0001) versus the other 3 treatments. CONCLUSION: Floseal + HS can be effective at reducing postsurgical drain output and provides a complementary hemostatic approach in patients undergoing total thyroidectomy.
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Esponja de Gelatina Absorbible/uso terapéutico , Hemostáticos/uso terapéutico , Instrumentos Quirúrgicos , Tiroidectomía/instrumentación , Tiroidectomía/estadística & datos numéricos , Adulto , Femenino , Gelatina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trombina/uso terapéutico , Tiroidectomía/efectos adversos , Tiroidectomía/métodos , Resultado del TratamientoRESUMEN
UNLABELLED: Two siblings (a 15-year-old boy and an 11-year-old girl) who presented with hypocalcemic seizure at the age of 2 years and 2 months (boy) and 2 years and 4 months (girl) were diagnosed with hypoparathyroidism. At the age of 3 years, the girl developed central diabetes insipidus with good response to desmopressin acetate treatment. The family history was unremarkable, and there was no consanguinity between the parents. The father is of Iraqi/Egyptian Jewish origin and the mother is of Iranian/Romanian Jewish origin. Sequence analysis of the candidate genes for isolated hypoparathyroidism encoding calcium-sensing receptor, parathyroid hormone, and glial cells missing homolog B did not reveal any mutations. Whole-exome sequencing identified a homozygous mutation in the autoimmune regulatory gene (AIRE), c.374A>G;p.Y85C, characteristic for Jewish Iranians with autoimmune polyendocrine syndrome type 1 (APS1), which was confirmed by the Sanger sequencing. Antibodies against the adrenal, pancreatic islet cell, ovary, thyroid, pituitary, celiac, and parietal cell were negative in both siblings, while anti-diuretic hormone antibodies were positive only in the girl. No other symptoms or signs of APS1 developed during all the years of follow-up. CONCLUSION: APS1 should be part of the differential diagnosis in children presenting with isolated hypoparathyroidism or hypoparathyroidism with central diabetes insipidus (CDI). These cases show that the AIRE mutation characteristic of Iranian Jews can also be found in non-Iranian Jews.
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ADN/genética , Diabetes Insípida Neurogénica/genética , Homocigoto , Hipoparatiroidismo/genética , Mutación , Factores de Transcripción/genética , Adolescente , Niño , Análisis Mutacional de ADN , Diabetes Insípida Neurogénica/sangre , Femenino , Humanos , Hipoparatiroidismo/sangre , Masculino , Hormona Paratiroidea/sangre , Linaje , Hermanos , Factores de Transcripción/sangre , Proteína AIRERESUMEN
BACKGROUND: Minimal invasive adrenalectomy has become the procedure of choice to treat adrenal tumors with a benign appearance, ≤ 6 cm in diameter and weighing < 100 g. Authors evaluated medium- and long-term outcomes of laparoscopic adrenalectomy (LA), performed for ten years in a single endocrine surgery unit. METHODS: We retrospectively reviewed 88 consecutive patients undergone LA for lesions of adrenal glands from 2003 to 2013. The first 30 operations were considered part of the learning curve. Doxazosin was preoperatively administered in case of pheochromocytoma (PCC), while spironolactone and potassium were employed to treat Conn's disease. Perioperative cardiovascular status modifications and surgical and medium- and long-term results were analyzed. RESULTS: Forty nine (55.68%) functioning tumors, and one (1.13%) bilateral adrenal disease were identified. In 2 patients (2.27%) a supposed adrenal metastasis was postoperatively confirmed, while in no patients a diagnosis of incidental primitive malignancy was performed. There was no mortality or major post operative complication. The mean operative time was higher during the learning curve. Conversion and morbidity rates were respectively 1.13% and 5.7%. Intraoperative hypertensive crises (≥180/90 mmHg) were observed in 23.5% (4/17) of PCC patients and were treated pharmacologically with no aftermath. There was no influence of age, size and operative time on the occurrence of PCC intraoperative hypertensive episodes. Surgery determined a normalization of the endocrine profile. One single PCC persistence was observed, while in a Conn's patient, just undergone right LA, a left sparing adrenalectomy was performed for a contralateral metachronous aldosteronoma. CONCLUSIONS: LA, a safe, effective and well tolerated procedure for the treatment of adrenal neoplasms ≤ 6 cm, is feasible for larger lesions, with a similar low morbidity rate. Operative time has improved along with the increase of the experience and of the technological development. Preoperative adrenergic blockade did not prevent PCC intraoperative hypertensive crises, but facilitated the control of the hemodynamic stability.
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Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Laparoscopía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
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.
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Neoplasias Cardíacas , Leiomiomatosis , Humanos , Leiomiomatosis/diagnóstico por imagen , Leiomiomatosis/cirugía , Leiomiomatosis/patología , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/cirugía , Neoplasias Cardíacas/patología , CorazónRESUMEN
Lymphocytic hypophysitis is a rarely recognized disease that is characterized by inflammatory infiltration and destruction of the pituitary gland. The etiology of lymphocytic hypophysitis is still unclear, but an autoimmune pathogenesis has been advocated. In fact, histopathologic specimens reveal a diffuse infiltration of the hypophysis by CD3(+)CD4(+) T cells and CD20(+) plasma cells, and antipituitary antibodies are usually found in sera of affected patients. Although previous cases were found to be correlated only to pregnancy and the postpartum period, recent reports in men and women (without association with pregnancy) suggest a possibly higher prevalence of disease. We present the case of a 55-year-old woman affected by an unusually aggressive form of lymphocytic hypophysitis that infiltrated both cavernous sinuses causing bilateral internal carotid artery occlusion and acute ischemic stroke. Diagnosis was achieved with both a biopsy specimen of the pituitary gland and the detection of antipituitary antibodies. The prompt administration of steroid therapy was effective to obtain regression and stabilization of the disease, but both carotid arteries remained permanently occluded. The natural history of lymphocytic hypophysitis is unpredictable. It usually has a benign evolution, but in exceptional cases the inflammatory process may extend beyond the pituitary gland and infiltrate the surrounding structures. These extremely serious consequences highlight the importance of early diagnosis and treatment of this otherwise curable disease.
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Arteria Carótida Interna/patología , Estenosis Carotídea/etiología , Seno Cavernoso/patología , Linfocitos/patología , Enfermedades de la Hipófisis/complicaciones , Hipófisis/patología , Autoanticuerpos/sangre , Biopsia , Isquemia Encefálica/etiología , Estenosis Carotídea/diagnóstico , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Linfocitos/inmunología , Angiografía por Resonancia Magnética , Persona de Mediana Edad , Enfermedades de la Hipófisis/diagnóstico , Enfermedades de la Hipófisis/tratamiento farmacológico , Enfermedades de la Hipófisis/patología , Hipófisis/inmunología , Esteroides/uso terapéutico , Accidente Cerebrovascular/etiologíaRESUMEN
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.
RESUMEN
OBJECTIVE: Antipituitary (APA) but not antihypothalamus antibodies (AHA) have been investigated in patients with idiopathic hypopituitarism. This study searched for APA and AHA in some of these patients to investigate whether pituitary or hypothalamic autoimmunity could play a role in their pituitary dysfunction. DESIGN: Sixty-six patients with selective idiopathic hypopituitarism were studied: 27 with ACTH deficiency, 20 with GH deficiency and 19 with hypogonadotropic hypogonadism. Twenty patients with hypopituitarism secondary to hypophysectomy and 50 healthy subjects were enrolled as controls. MEASUREMENTS: Antipituitary and AHA were evaluated by indirect immunofluorescence in sera of patients and controls. Positive sera were retested by a four-layer double immunofluorescence to identify the cells targeted by these antibodies. RESULTS: Antipituitary were present at high titre in 4 of 27 patients with ACTH deficiency (14·8%), 4 of 20 with GH deficiency (26%) and 5 of 19 with hypogonadotropic hypogonadism (21%) and targeted, respectively, corticotrophs, somatotrophs and gonadotrophs. AHA were found at high titre only in 5 patients with ACTH deficiency (18·5%), mostly targeting corticotrophin-releasing hormone-secreting cells; none of these 5 patients resulted positive for antipituitary antibodies. Among the controls, only 1 hypophysectomized patient resulted APA positive at low titre. CONCLUSIONS: Our results suggest that in patients with selective idiopathic hypopituitarism, detection of APA or AHA could better characterize an autoimmune process involving the pituitary or hypothalamus, respectively. In particular, detection of antibodies targeting selectively ACTH-secreting or corticotrophin-releasing hormone-secreting cells may differentiate, respectively secondary from tertiary variants of autoimmune hypoadrenalism.
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Autoanticuerpos/inmunología , Hipopituitarismo/inmunología , Hipotálamo/inmunología , Hipófisis/inmunología , Hormona Adrenocorticotrópica/deficiencia , Adulto , Autoanticuerpos/sangre , Autoinmunidad/inmunología , Femenino , Técnica del Anticuerpo Fluorescente Indirecta/métodos , Hormona de Crecimiento Humana/deficiencia , Humanos , Hipofisectomía/efectos adversos , Hipopituitarismo/sangre , Hipopituitarismo/etiología , Hipotálamo/metabolismo , Masculino , Hipófisis/metabolismoRESUMEN
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.
RESUMEN
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.
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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.
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Bloqueo de Rama , Cardiomiopatías , Adulto , Anciano , Bloqueo de Rama/diagnóstico , Bloqueo de Rama/epidemiología , Bloqueo de Rama/etiología , Cardiomiopatías/diagnóstico , Cardiomiopatías/epidemiología , Cardiomiopatías/etiología , Medios de Contraste , Femenino , Gadolinio , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Sistema de Registros , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
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, ≥â 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.
Asunto(s)
Autoanticuerpos/sangre , Enfermedades Autoinmunes/epidemiología , Biomarcadores/sangre , Síndrome de Fatiga Crónica/fisiopatología , Hipotálamo/patología , Enfermedades de la Hipófisis/epidemiología , Hormona Adrenocorticotrópica/sangre , Adulto , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Hormona de Crecimiento Humana/sangre , Humanos , Hipotálamo/inmunología , Hipotálamo/metabolismo , Factor I del Crecimiento Similar a la Insulina/análisis , Enfermedades de la Hipófisis/sangre , Enfermedades de la Hipófisis/inmunología , Enfermedades de la Hipófisis/patología , Pronóstico , Estados Unidos/epidemiología , Adulto JovenRESUMEN
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.