Endocrinology in the time of COVID-19: Management of Cushing’s syndrome

Clinical evaluation should guide those needing immediate investigation. Strict adherence to COVID-19 protection measures is necessary. Alternative ways of consultations (telephone, video) should be used. Early discussion with regional/national experts about investigation and management of potential and existing patients is strongly encouraged. Patients with moderate or severe clinical features need urgent investigation and management. Patients with active Cushing’s syndrome, especially when severe, are immunocompromised and vigorous adherence to the principles of social isolation is recommended. In patients with mild features or in whom a diagnosis is less likely, clinical re-evaluation should be repeated at 3 and 6 months or deferred until the prevalence of SARS-CoV-2 has significantly decreased; however, those individuals should be encouraged to maintain social distancing. Diagnostic pathways may need to be very different from usual recommendations in order to reduce possible exposure to SARS-CoV-2. When extensive differential diagnostic testing and/or surgery is not feasible, it should be deferred and medical treatment should be initiated. Transsphenoidal pituitary surgery should be delayed during high SARS-CoV-2 viral prevalence. Medical management rather than surgery will be the used for most patients, since the short- to mid-term prognosis depends in most cases on hypercortisolism rather than its cause; it should be initiated promptly to minimize the risk of infection in these immunosuppressed patients. The risk/benefit ratio of these recommendations will need re-evaluation every 2–3 months from April 2020 in each country (and possibly local areas) and will depend on the local health care structure and phase of pandemic

Comorbidities in Cushing’s disease

Introduction: Cushing’s disease is a rare disorder characterized by overproduction of ACTH from a pituitary adenoma leading to hypercortisolemia that in turn leads to increased morbidity and mortality.Methods: Here we review the comorbidities associated with Cushing’s disease and their impact on quality of life and mortality.Results: Recent evidence suggests that correction of hypercortisolemia may not lead to complete resolution of comorbidities associated with this condition. In particular, increased cardiovascular risk may persist despite long-term remission of hypercortisolemia. This may be related to persistence of visceral adiposity, adverse adipokine profile, glucose intolerance, hypertension, dyslipidemia, atherosclerosis and a procoagulant phenotype. Prior prolonged exposure to glucocorticoids also may have irreversible effects on the central nervous system, leading to persistent cognitive and mood alterations. Osteoporosis and fractures, especially vertebral fractures, can further add to morbidity and a poor quality of life. Normalization of cortisol levels leads to significant improvement in comorbidities but long-term data regarding complete resolution are lacking and need further study.Conclusion: Early diagnosis and treatment of hypercortisolemia, aggressive management of comorbidities along with long-term follow-up is crucial for the optimal recovery of these patients

Cushing’s syndrome: Epidemiology and developments in disease management

Cushing’s syndrome is a rare disorder resulting from prolonged exposure to excess glucocorticoids. Early diagnosis and treatment of Cushing’s syndrome is associated with a decrease in morbidity and mortality. Clinical presentation can be highly variable, and establishing the diagnosis can often be difficult. Surgery (resection of the pituitary or ectopic source of adrenocorticotropic hormone, or unilateral or bilateral adrenalectomy) remains the optimal treatment in all forms of Cushing’s syndrome, but may not always lead to remission. Medical therapy (steroidogenesis inhibitors, agents that decrease adrenocorticotropic hormone levels or glucocorticoid receptor antagonists) and pituitary radiotherapy may be needed as an adjunct. A multidisciplinary approach, long-term follow-up, and treatment modalities customized to each individual are essential for optimal control of hypercortisolemia and management of comorbidities

Ectopic Cushing's syndrome and pulmonary carcinoid tumour identified by [111In-DTPA-D-Phe1]octreotide.

The differential diagnosis and management of Cushing's syndrome remain difficult, particularly for ectopic adrenocorticotropin (ACTH) syndromes resulting from small bronchial carcinoids. We report the case of a 41-year-old man with ectopic ACTH-dependent Cushing's syndrome. Two computed tomography scans of the thorax were normal and magnetic resonance imaging of the chest showed a 6-mm hyperintense T1-weighted area close to the left pulmonary hilus, interpreted as probably vascular by the radiologists. An [111In-DTPA-D-Phe1]octreotide scintigraphy scan demonstrated a positive image for somatostatin receptors in exactly the same location and surgery confirmed the presence of a small ACTH-secreting carcinoid tumour in the upper left lung lobe which was resected. Surgery cured the hypercorticism of the patient. The differential diagnosis of Cushing's syndrome and the procedure for localisation of an ACTH source are discussed

Mifepristone effects on tumor somatostatin receptor expression in two patients with Cushing's syndrome due to ectopic adrenocorticotropin secretion

Context: Two patients presented with Cushing's syndrome due to ectopic ACTH secretion. Initial localization studies included computed tomography, magnetic resonance imaging, and octreoscans (111In-pentreotide scintigraphy), which were negative in both patients. They were treated with the glucocorticoid receptor antagonist mifepristone, with improvement in their clinical symptoms. Follow-up octreoscans after, respectively, 6 and 12 months showed the unequivocal presence of a bronchial carcinoid in both patients. Objective: The objective of the study was to correlate in vivo and in vitro findings in patients with ectopic ACTH-producing syndrome. Methods: We determined the expression of somatostatin and dopamine receptors by immunohistochemistry (patients 1 and 2), quantitative PCR, and in vitro culturing of tumor cells (patient 1 only). In Vitro Results: Both tumors were strongly positive for somatostatin receptor type 2 (sst2) on immunohistochemistry, whereas one of the tumors (patient 1) was also dopamine receptor subtype 2 (D 2) positive on both immunohistochemistry and quantitative PCR. Octreotide (a sst2preferring analog) and cabergoline (D2 agonist) both decreased the ACTH levels in the cultured tumor cells of patient 1. Conclusion:Wedescribe two patients with ACTH-producing bronchial carcinoids, inwhoma direct down-regulatory effect of glucocorticoid levels on tumoral sst2 receptor expression is suggested by a remarkable change in octreoscan status after successful mifepristone therapy. Further studies will have to demonstrate whether glucocorticoid lowering or antagonizing therapy may be used to improve the diagnostic accuracy of somatostatin receptor scintigraphy in patients with ectopic ACTH production of unknown primary origin. Copyrigh

Supplementary Material for: Personalized Statin Therapy and Coronary Atherosclerotic Plaque Burden in Asymptomatic Low/Intermediate-Risk Individuals

<b><i>Background:</i></b> Current guidelines for the primary prevention of atherosclerotic cardiovascular disease are based on the estimation of a predicted 10-year cardiovascular disease risk and the average relative risk reduction estimates from statin trials. In the clinical setting, however, decision-making is better informed by the expected benefit for the individual patient, which is typically lacking. Consequently, a personalized statin benefit approach based on absolute risk reduction over 10 years (ARR₁₀ benefit threshold ≥2.3%) has been proposed as a novel approach. However, how this benefit threshold relates with coronary plaque burden in asymptomatic individuals with low/intermediate cardiovascular disease risk is unknown. <b><i>Aims:</i></b> In this study, we compared the predicted ARR₁₀ obtained in each individual with plaque burden detected by coronary computed tomography angiography. <b><i>Methods and Results:</i></b> Plaque burden (segment volume score, segment stenosis score, and segment involvement score) was assessed in prospectively recruited asymptomatic subjects (<i>n</i> = 70; 52% male; median age 56 years [interquartile range 51–64 years]) with low/intermediate Framingham risk score (< 20%). The expected ARR₁₀ with statin in the entire cohort was 2.7% (1.5–4.6%) with a corresponding number needed to treat over 10 years of 36 (22–63). In subjects with an ARR₁₀ benefit threshold ≥2.3% (vs. < 2.3%), plaque burden was significantly higher (<i>p</i> = 0.02). <b><i>Conclusion:</i></b> These findings suggest that individuals with higher coronary plaque burden are more likely to get greater benefit from statin therapy even among asymptomatic individuals with low cardiovascular risk