Metastatic pheochromocytoma and paraganglioma: Management of endocrine manifestations, surgery and ablative procedures, and systemic therapies Publication date: Available online 24 October 2019 Source: Best Practice & Research Clinical Endocrinology & Metabolism Author(s): Sina Jasim, Camilo Jimenez Metastatic pheochromocytomas and paragangliomas (MPPGs) are rare neuroendocrine tumors. Most patients present with advanced disease that is associated with manifestations of catecholamine release. Surgical resection of the primary tumor and ablative therapies of metastases—whenever possible—may improve clinical outcomes and, perhaps, lengthen the patient's overall survival. Significant steps in understanding the genetic alterations linked to MPPGs and scientific progress made on cancers that share a similar pathogenesis are leading to the recognition of potential systemic therapeutic options. Data derived from clinical trials evaluating targeted therapies such as tyrosine kinase inhibitors, radiopharmaceuticals, immunotherapy, and combinations of these will likely improve the outcomes of patients with advanced and progressive MPPGs. Exemplary of this success is the recent approval in the United States of the high-specific-activity iodine131 meta-iodine-benzylguanidine (MIBG) for patients with unresectable and progressive MPPGs that express the noradrenaline transporter. This review will discuss the therapeutic approaches for patients with MPPGs.

Pheochromocytoma: An approach to diagnosis Publication date: Available online 22 October 2019 Source: Best Practice & Research Clinical Endocrinology & Metabolism Author(s): Emilia Sbardella, Ashley B. Grossman Pheochromocytomas are rare neuroendocrine chromaffin-derived tumors that arise within the adrenal medulla. They are usually benign, but if not diagnosed or if left untreated, they can have devastating consequences. Clinical consideration of the diagnosis is paramount, as they may have protean manifestations, and a high index of suspicion is essential if serious consequences are to be avoided. An accurate biochemical diagnosis is crucial for the management of these patients: either plasma or urinary metanephrines are both highly sensitive and specific if correctly employed, but knowledge of pre- and post-analytic interference is essential. Diagnostic imaging with cross-sectional CT and/or MRI offers high sensitivity in their detection, but lack specificity. The introduction of PET/CT/MR has led to a dramatic improvement in the localization of both pheochromocytomas and paragangliomas, together with the increasing availability of new functional imaging radionuclides. Optimal investigation and accurate diagnosis is best achieved at ‘centers of excellence’ with expert multidisciplinary teams.

Disease monitoring of patients with pheochromocytoma or paraganglioma by biomarkers and imaging studies Publication date: Available online 21 October 2019 Source: Best Practice & Research Clinical Endocrinology & Metabolism Author(s): Florentine Schreiner, Felix Beuschlein Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors, a large proportion of which secrete catecholamines. PPGL are associated with a high cardiovascular morbidity and come with a risk of malignancy. The therapy of choice is surgical resection. Nevertheless, PPGL are associated with a lifelong risk of tumor persistence or recurrence. Currently, there are no clinical, biochemical, histopathological or imaging characteristics, which can predict or exclude malignant behavior or tumor recurrence. Therefore, long-term follow-up is recommended even after apparent complete surgical removal. Early detection of recurrence is essential to reduce cardiovascular morbidity and mortality due to catecholamine secretion, to prevent morbidity by mass effects of paraganglioma (PGL) or by metastatic spread of disease. Due to the rarity of these tumors, no prospective data on long-term surveillance exist. In fact, current recommendations are based on retrospective analyses, expert opinions and case studies. The aim of this review is to provide an overview on the current state of knowledge with regard to known factors that increase the risk of recurrence and might impact disease monitoring as well as the available possibilities for biochemical and imaging follow-up. Based on this overview, we aim to propose a practical approach for a patient-oriented follow-up after surgical removal of a PPGL.

Autoimmune polyglandular diseases Publication date: Available online 4 October 2019 Source: Best Practice & Research Clinical Endocrinology & Metabolism Author(s): George J. Kahaly, Lara Frommer Autoimmune polyglandular diseases (APD) are defined as the presence of two autoimmune –induced endocrine failures. With respect to the significant morbidity and potential mortality of APD, the diagnostic objective is to detect APD at an early stage, with the advantage of less frequent complications, effective therapy and better prognosis. This requires that patients at risk be regularly screened for subclinical endocrinopathies prior to clinical manifestation. Regarding the time interval between manifestation of first and further endocrinopathies, regular and long-term follow-up is warranted. Quality of life and psychosocial status are poor in APD patients and involved relatives. Familial clustering is high in patients with APD. Considering the high incidence of one or more endocrinopathies in first-degree relatives of patients with APD, family members should be regularly screened since they may also develop autoimmune endocrinopathies. Multidisciplinary management of these multiplex families in specialized centers is warranted.

Modern endocrine surgery – Striving for a better quality of life Publication date: Available online 28 September 2019 Source: Best Practice & Research Clinical Endocrinology & Metabolism Author(s): Henning Dralle, Frank Weber

Value of ileus-prophylactic surgery for metastatic neuroendocrine midgut tumours Publication date: Available online 25 September 2019 Source: Best Practice & Research Clinical Endocrinology & Metabolism Author(s): Frank Weber, Henning Dralle Neuroendocrine tumours of the small intestine (SINET) are a rare disease. However, a rising incidence rate and excellent long-term survival, even in the setting of metastatic disease lead to a high prevalence of SINET of up to 11/100.000. At the time of diagnosis, most patients already suffer from metastatic disease. About one third of patients demonstrate localized or regional metastatic disease at time of presentation. For those patients the indication for curative surgery is not debated and 10-year cancer specific survival of almost 90% can be achieved. Due to major limitations of existing studies actually there is no sufficient evidence in favour of ileus-prophylactic palliative surgery for metastatic SINET. Until now the available evidence favouring an ileus-prophylactic palliative small bowel resection for stage IV SI-NET must be weighed against available high-level evidence from randomized trials that showed long-term survival under systemic therapy. Importantly, there is not a single study that indicates surgery for a symptomatic patient should be postponed. Because the majority of patients are symptomatic at the time of diagnosis, the rationale for an ileus-prophylactic palliative surgery is to operate before progression of mesenteric tumour mass and desmoplasia takes place and before intestinal obstruction and ischaemia occurs. To what extent a prophylactic palliative small bowel resection will provide a survival benefit in a situation where the mesenteric tumour mass cannot be resected radically is not clearly addressed by the current level of evidence.

Insights into the autoimmune aspect of premature ovarian insufficiency Publication date: Available online 16 September 2019 Source: Best Practice & Research Clinical Endocrinology & Metabolism Author(s): Kassem Sharif, Abdulla Watad, Charlie Bridgewood, Darja Kanduc, Howard Amital, Yehuda Shoenfeld Premature ovarian insufficiency (POI) refers to a continuum of decreasing ovarian function in women before the age of 40. To date, the cause of POI in the majority of cases remain unresolved. Many cases has been linked to genetic, toxic, infections, enzymatic and iatrogenic causes. A key function of the immune system is to identify and differentiate “self” and “non self” i.e. tolerance. Loss of self-tolerance results in an immune response against self-tissues and thus autoimmunity. Various investigations have highlighted the role of autoimmunity and its pertinence to POI. Several potential immune antigenic targets in the ovary have been reported to be involved in autoantibody induced autoimmune attack. The presence of lymphocytic oöphorits in ovarian samples of patients with POI provides histopathological evidence of autoimmune ovarian involvement. Finally, POI is strongly associated with other autoimmune conditions including for instance Addison disease, autoimmune polyglandular syndrome (APS) −1, APS-4, hypothyroidism, and diabetes mellitus among other autoimmune diseases. Taken together, these lines of evidence provide strong basis that support the role of autoimmunity as a potential cause of disease etiopathogenesis. Continuing research is increasingly providing more insight into the complex disease process. The aim of this review is to summarize the current literature related to the autoimmune nature of POI.

Exacerbations of autoimmune diseases during pregnancy and postpartum Publication date: Available online 11 September 2019 Source: Best Practice & Research Clinical Endocrinology & Metabolism Author(s): Vânia Vieira Borba, Gisele Zandman-Goddard, Yehuda Shoenfeld Autoimmune diseases represent a complex heterogeneous group of disorders that occur as a results of immune homeostasis dysregulation and loss of self-tolerance. Interestingly, more than 80% of the cases are found among women at reproductive age. Normal pregnancy is associated with remarkable changes in the immune and endocrine signaling required to tolerate and support the development and survival of the placenta and the semi-allogenic fetus in the hostile maternal immune system environment. Gravidity and postpartum represent an extremely challenge period, and likewise the general population, women suffering from autoimmune disorders attempt pregnancy. Effective preconception counseling and subsequent gestation and postpartum follow-up are crucial for improving mother and child outcomes. This comprehensive review provides information about the different pathways modulating autoimmune diseases activity and severity, such as the influence hormones, microbiome, infections, vaccines, among others, as well as updated recommendations were needed, in order to offer those women better medical care and life quality.

Autoimmune diseases and pregnancy Publication date: Available online 11 September 2019 Source: Best Practice & Research Clinical Endocrinology & Metabolism Author(s): Angela Tincani, Cecilia Nalli, Jamilya Khizroeva, Victoria Bitsadze, Andrea Lojacono, Laura Andreoli, Yehuda Shoenfeld, Alexander Makatsariya Pregnancy in autoimmune diseases remains an argument of debate. In last years great improvements were done and with the correct medical support women with disease such as Systemic Lupus Erythematosus or Antiphospholipid Syndrome can afford a pregnancy and have healthy babies. The starting point is a good counselling. Women should be informed about risks that can occur taking some medications while pregnant and, on the other hand, that there are medications that can be safety assumed during pregnancy. Furthermore, there are known maternal risks factor such as the presence of antiphospholipid antibodies or anti-Ro/SSA antibodies that must be carefully manage by both rheumatologists and obstetrics. In addition, also disease activity during pregnancy can represent an issue. For all these reason, a multidisciplinary approach is mandatory in order to give our patients an optimal medical support, before, during and after pregnancy.

Prolactin and autoimmunity: The hormone as an inflammatory cytokine Publication date: Available online 11 September 2019 Source: Best Practice & Research Clinical Endocrinology & Metabolism Author(s): Vânia Vieira Borba, Gisele Zandman-Goddard, Yehuda Shoenfeld Nowadays, more than 80 autoimmune disorders are recognized, in which an aberrant immune response against different organs and tissues plays a crucial role. Hormonal homeostasis has great influence in achieving competent and healthy immune system function. Prolactin has a bioactive function acting as a hormone and a cytokine. It influences the immune system modulation, mainly inhibiting the negative selection of autoreactive B lymphocytes. Hyperprolactinemia has been detected in many patients with different autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, multiple sclerosis, autoimmune thyroid disease, systemic sclerosis, among others, and its believed to play a crucial role in disease pathogenesis. A direct correlation between prolactin levels and disease activity was not clear. Genetic factors may have a role in humans as in animal models. Dopamine agonists have proven to offer clinical benefits among autoimmune patients and represent a promising therapy to be explored. In this review, the authors attempt to provide a critical overview on the role of prolactin in the immune system, exploring its contribution to the development of autoimmune diseases.