Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

PurposeTo increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapyMethodsA multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline Guideline development involved a systematic review of the literature and an informal consensus process The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017ResultsThe systematic review identified 204 eligible publications Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports Due to the paucity of high-quality evidence on management

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Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline

Objective: The aim was to formulate clinical practice guidelines for acromegaly. Participants: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines. Conclusions: Using an evidence-based approach, this acromegaly guideline addresses impor...

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Acromegaly: An Endocrine Society Clinical Practice Guideline

Objective: The aim was to formulate practice guidelines for the diagnosis and treatment of hyperprolactinemia. Participants: The Task Force consisted of Endocrine Society-appointed experts, a methodologist, and a medical writer. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society, The European Society of Endocrinology, and The Pituitary Society reviewed and commented on preliminary drafts of these guidelines. Conclusions: Practice guidelines are presented for diagnosis and treatment of patients with elevated prolactin levels. These include evidence-based approaches to assessing the cause of hyperprolactinemia, treating drug-induced hyperprolactinemia, and managing prolactinomas in nonpregnant and pregnant subjects. Indications and side effects of therapeutic agents for treating prolactinomas are also presented. (J Clin Endocrinol Metab 96: 273–288, 2011)

Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline

Non-functioning pituitary adenomas (NFAs) or, as recently proposed, “non-functioning pituitary neuroendocrine tumors” are benign neoplasms that arise from the adenohypophyseal cells and are not associated with clinical evidence of hormonal hypersecretion. As lack of clinical manifestations of hormonal hypersecretion frequently results in significant diagnostic delay, they are usually detected when they are large enough to induce mass effects to surrounding structures. When treatment is indicated, surgery is the first option, combined or not with adjuvant radiotherapy and/or medical therapy (off-label for NFAs); nonetheless, an optimal followup algorithm is still unclear. Furthermore, with increased accessibility to high-quality imaging, more asymptomatic NFAs are diagnosed every year adding further burden on the health care system and anxiety to patients. The fourth edition of the World Health Organization Classification of Tumors of the Pituitary Gland adopts a classification based on cell lineage and in addition to hormone immunohistochemistry recognizes the value of other immunohistochemical markers including transcription factors. Not all NFAs have the same clinical course and robust markers predicting their future behavior and potential aggressiveness are still under discussion. Furthermore, the role of the new WHO classification in clinical practice needs to be validated. Finally, although data is scarce, long-term studies of patients with NFA suggest that mortality higher than that of the general population pointing highlighting the need for improved management strategies. Thus, this Pituitary special issue appears at an optimal time to gather current knowledge and understanding of NFAs, to highlight areas requiring further attention and to provide future perspectives in the field. Ntali and Wass provide an overview on epidemiology, clinical presentation and diagnosis. These tumors account for 14–54% of pituitary adenomas with a prevalence of 7–41.3/100,000 population. Manojlovic-Gacic, Engström and Casar-Borota offer an update based on the new WHO classification of non-functioning pituitary adenomas, * Maria Fleseriu fleseriu@ohsu.edu

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Non-functioning pituitary adenomas, not all the same and certainly not boring!

OBJECTIVE Although it is well established that overt hypercortisolism in patients with active Cushing's syndrome leads to a profound suppression of stimulated GH secretion, the role of subclinical autonomous glucocorticoid hypersecretion (SAGH), currently detected with increasing frequency in patients with adrenal incidentalomas, on GH secretory reserve has received little attention. The aim of the present study was to evaluate whether SAGH in patients presented with adrenal incidentalomas has a negative effect on GH secretory reserve. DESIGN AND PATIENTS Sixteen patients with overt Cushing's syndrome (CS) and 36 patients with adrenal incidentalomas were investigated. The latter group was further divided in 23 patients who demonstrated an adequate suppression of cortisol levels (of 70 nmol/l). The former group was defined as normocortisolaemic (NC) and the latter group as representing patients with SAGH. The combined pyridostigmine + GHRH test (PD + GHRH) was used to assess the GH secretory reserve of these patients. RESULTS Peak GH levels following PD + GHRH administration were significantly lower in CS patients compared to both the NC and SAGH group of patients with adrenal incidentalomas (2.2 +/- 0.7 vs. 18.9 +/- 2.6 and 21.5 +/- 3.6 microg/l, respectively, P < 0.05); no difference was observed in peak GH responses between the NC and SAGH group of patients. A subnormal GH response (defined as GH(max) < 12.8 microg/l) was observed in all 16 patients with CS. However, only seven NC and three SAGH patients failed to respond adequately. Correlation analysis revealed a negative correlation between peak GH response to PD + GHRH and plasma cortisol concentrations in CS patients (R =-0.6, P = 0.012), while in patients with adrenal incidentalomas such a correlation was absent. Contrary to patients with CS in whom body mass index (BMI) was not correlated to peak GH, a significant negative correlation between peak GH response to PD + GHRH and BMI was disclosed in patients with adrenal incidentalomas (R =-0.49, P = 0.003). In these patients, again contrary to CS patients, a significant negative correlation was also found between peak GH post PD + GHRH and age (R = -0.46, P = 0.002). CONCLUSIONS In conclusion, our results provide evidence that, contrary to patients with overt CS, SAGH does not affect the GH secretory response to provocative stimulation.

Evaluation of GH reserve in patients with adrenal incidentalomas and biochemical evidence of subclinical autonomous glucocorticoid hypersecretion.

Craniopharyngiomas are tumours associated with significant long-term pituitary dysfunction. The rates of anterior pituitary hormone deficits are not influenced by treatment modality and do not differ between childhood- and adult-onset disease. The apparent paradox of growth in the absence of growth hormone (GH) has been reported in children with this tumour and is not, as yet, completely understood. GH replacement therapy offers significant benefits for both children and adults (although adult patients are less likely to lose weight or body fat). Based on results of retrospective studies, GH therapy does not seem to increase the risk of tumour recurrence.

Hypopituitarism oddities: craniopharyngiomas.

Acromegaly is a rare condition of GH excess associated with significant morbidities (e.g. hypertension, glucose intolerance or diabetes mellitus, cardiac, cerebrovascular, respiratory disease and arthritis) and, when uncontrolled, high mortality. Surgery, medical treatment and radiotherapy remain our therapeutic tools. Advances in these options during the last years have offered further perspectives in the management of patients and particularly those with challenging tumours; the impact of these on the long-term morbidity and mortality remains to be assessed.

Niki Karavitaki

Papers

Non-functioning pituitary adenomas, not all the same and certainly not boring!

Evaluation of GH reserve in patients with adrenal incidentalomas and biochemical evidence of subclinical autonomous glucocorticoid hypersecretion.

Hypopituitarism oddities: craniopharyngiomas.

Recent advances in the management of acromegaly

Effectiveness of metyrapone in 195 patients with Cushing's syndrome