Ectopic ACTH syndrome (EAS) is rare but is frequently a severe condition because of the intensity of the hypercortisolism that may be dissociated from the tumoral condition. EAS should often be considered as an endocrine emergency requiring an emergency response both in terms of diagnostic procedures and therapeutic interventions. Patient management is complex and necessitates dual skills, in the diagnosis and treatment of CS and in the specific management of neuroendocrine tumors (NET). Therefore, initial management should be performed ideally by experienced endocrinology teams in collaboration with specialized hormonal laboratory, modern imaging platforms and intensive care units. Diagnostic procedures vary according to the endocrine and tumoral contexts but should be reduced to a minimum in intense hypercortisolism. Preventive and curative treatments of cortisol-induced comorbidities, non-specific management of hypercortisolism and etiological treatments should be considered simultaneously. Therapeutic strategies vary according to (1.) the intensity of hypercortisolism, the general condition of the patient and associated comorbidities and (2.) the tumoral status, ranging from resectable ACTH secreting tumors to non-resectable metastatic endocrine tumors or occult tumors. The ideal treatment is complete excision of the ACTH-secreting tumor that can be performed rapidly or after preoperative preparation using cortisol-lowering drugs. When this is not possible, the therapeutic strategy should be discussed by a multidisciplinary experienced team in a personalized perspective and include variable combinations of pharmacological agents, bilateral adrenalectomy and non-specific tumoral interventions. Here we discuss the diagnosis and therapeutic strategies including the modern, currently available tools and emphasize on the operational effectiveness of care.

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MANAGEMENT OF ENDOCRINE DISEASE: Cushing’s syndrome due to ectopic ACTH secretion: an expert operational opinion

To review all published cases of the rare association between thrombotic thrombocytopenic purpura (TTP) and Sjogren's syndrome (SS). The authors report an additional case of this unique association. Systematic review of the literature and a case report. The database were articles published in PubMed/MEDLINE, Web of Science, LILACS, and SciELO, registered from 1966 to August 2020. The DESH terms were "Sjogren's syndrome" and "thrombotic thrombocytopenic purpura," without language limitation. Most patients were female (88%), and the age varied from 30 to 75 years old. Concerning the sequence of disease appearance, SS followed by TTP was seen in seven articles, TTP and SS in three, and simultaneous appearance of both diseases in three studies. Primary SS was observed in 16 patients, and secondary SS was detected in two cases: dermatomyositis and rheumatoid arthritis. Anemia was the most common TTP manifestation, followed by thrombocytopenia, fever, consciousness alteration, renal impairment, and schistocytes' appearance on a blood smear. Treatment involved plasmapheresis, plasma exchange, rituximab, glucocorticoid, and cyclophosphamide. A good outcome was noted in most studies; few patients died. TTP is a rare manifestation associated with SS. After the TTP diagnosis, plasmapheresis and/or plasma exchange should be immediately implemented.

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Sjögren's Syndrome Associated With Thrombotic Thrombocytopenic Purpura: A Case-Based Review.

Abstract Neoplasms that secrete ectopic adrenocorticotropin (ACTH) may cause severe, life-threatening hypercortisolism. These tumors are often difficult to localize and treat, requiring a comprehensive and systematic management plan orchestrated by a multidisciplinary team. The Mount Sinai Adrenal Center hosted an interdisciplinary retreat of experts in adrenal disorders and neuroendocrine tumors (NETs) with the aim of developing a clinical pathway for the management of Cushing syndrome due to ectopic ACTH production. The result was institutional recommendations for the diagnosis, localization, surgical approaches to intrathoracic tumors and bilateral adrenalectomy, and perioperative and postoperative medical management of hypercortisolism and its sequelae. Specific recommendations were made regarding the timing and selection of therapies based on the considerations of our team as well as a review of the current literature. Our clinical pathway can be applied by other institutions directly or serve as a guide for institution-specific management.

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The Mount Sinai Clinical Pathway for the Diagnosis and Management of Hypercortisolism due to Ectopic ACTH Syndrome

A 49-year-old female was admitted to our hospital with malaise and gross hematuria. As ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13) activity was absent and the ADAMTS13 inhibitor was detected, she was diagnosed with acquired thrombotic thrombocytopenic purpura (TTP). In addition to plasma exchange and corticosteroid therapy, she received rituximab therapy for inhibitor boosting but died suddenly of a cardiac arrest on day 9. The postmortem revealed microvascular platelet thrombi in multiple organs. In this case, the deterioration of the patient’s clinical status was considered to have been caused by inhibitor boosting-induced systemic microvascular occlusion. In particular, her sudden death may have been due to cardiovascular microthrombosis. Since inhibitor boosting can cause TTP patients to deteriorate rapidly, it is crucial to manage TTP patients who undergo inhibitor boosting appropriately. The monitoring of cardiac complications in TTP patients may also be essential, especially in the acute phase.

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Sudden Cardiac Death in a Patient with Thrombotic Thrombocytopenic Purpura: A Case Report

Introduction. Aggregatibacter are Gram-negative, facultatively anaerobic rods or coccobacilli that are infrequently encountered as pathogens causing infection.Hypothesis/Gap Statement. The range of invasive infection that Aggregatibacter cause is poorly described. The pathogenicity of species such as Aggregatibacter segnis is debated.Aim. To identify invasive infection due to Aggregatibacter species in a large healthcare organization and to characterize clinical syndromes, co-morbidities and risk factors.Methodology. All microbiological samples positive for Aggregatibacter species were identified by conventional culture or 16S rRNA PCR between October 2017 and March 2021. Electronic records for all patients with positive samples were reviewed and the infection syndrome classified for patients with invasive disease.Results. Twenty-seven patients with invasive infection were identified, with a statistically significant difference in species-specific patterns of invasive infection (P=0.02) and a statistically significant association with residence in the 30 % most deprived households in the UK by postcode (P<0.01). The three most common co-morbidities were periodontitis or recent dental work (29.6%), cardiovascular disease (25.9%) and diabetes (18.5 %).Conclusion. We describe a novel association of Aggregatibacter segnis with skin and soft tissue infection. The propensity of the Aggregatibacter species to cause invasive infection at different body sites and be associated with deprivation is reported. Aggregatibacter actinomycetemcomitans bacteraemia was associated with infective endocarditis, and Aggregatibacter aphrophilus was implicated in severe appendicitis and noted to cause brain abscess. Areas warranting future research include exploring the risk-factors required for invasive infection and those that may determine the species-specific differences in patterns of invasive disease.

Invasive Aggregatibacter infection: shedding light on a rare pathogen in a retrospective cohort analysis.

A 48-year-old man presented with a sustained fever. Abdominal computed tomography revealed multilocular liver abscesses. He underwent percutaneous needle aspiration, yielding straw-colored pus. Gram staining revealed Gram-negative coccobacilli. The organism grew only on chocolate II agar in a 7% carbon dioxide atmosphere. Identification of Aggregatibacter aphrophilus was confirmed using mass spectrometry and 16S rRNA gene sequencing. He was successfully treated with antibiotics. Liver abscess caused by A. aphrophilus is extremely rare. We herein report the first such case in Japan. Even fastidious organisms, such as A. aphrophilus, should be correctly identified using mass spectrometry or 16S rRNA gene sequencing for adequate treatment.

The First Known Case of Liver Abscess Caused by Aggregatibacter aphrophilus in Japan.

A 32-year-old woman was referred to our hospital because of severe psychosis and was found to have an ectopic ACTH-producing thymic neuroendocrine tumor. Laboratory data revealed an elevated serum cortisol and plasma ACTH level, hypokalemia, and metabolic alkalosis. Chest computed tomography (CT) revealed an anterior mediastinal mass and multiple pulmonary nodules. As the patient was unable to communicate because of her consciousness disturbance, she was managed with artificial ventilation and deep sedation. Metyrapone and potassium supplementation were administered, and steroid psychosis gradually improved. Thoracic surgery was performed and the histopathological diagnosis was thymic neuroendocrine tumor with positive anti-ACTH immunohistochemical staining. Here we present details of the case and review the literature.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1759-7714.13099

ACTH‐producing thymic neuroendocrine tumor initially presenting as psychosis: A case report and literature review

A 47-year-old man was admitted to our hospital because of thrombocytopenia and consciousness disturbance. As his laboratory data showed undetectable activity of a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) and the presence of ADAMTS13 inhibitor, he was diagnosed with acquired thrombotic thrombocytopenic purpura (TTP). Asymptomatic primary Sjogren's syndrome (SS) and primary hypothyroidism were incidentally diagnosed on screening. After initial plasma exchange therapy and pulse corticosteroid therapy, the patient received rituximab therapy for refractory TTP with "inhibitor boosting" and recovered. TTP secondary to primary SS is rare but can trigger refractory TTP. Treatment with rituximab, which is considered "inhibitor boosting," should be considered when re-exacerbation occurs.

Taiki Okumura

Papers

The First Known Case of Liver Abscess Caused by Aggregatibacter aphrophilus in Japan.

ACTH‐producing thymic neuroendocrine tumor initially presenting as psychosis: A case report and literature review

Thrombotic Thrombocytopenic Purpura Treated with Rituximab Associated with Primary Sjögren's Syndrome and Primary Hypothyroidism.