Context Signs and symptoms of Cushing’s syndrome (CS) overlap with common diseases, such as the metabolic syndrome, obesity, osteoporosis, and depression. Therefore, it can take years to finally diagnose CS, although early diagnosis is important for prevention of complications. Objective The aim of this study was to assess the time span between first symptoms and diagnosis of CS in different populations to identify factors associated with an early diagnosis. Data Sources A systematic literature search via PubMed was performed to identify studies reporting on time to diagnosis in CS. In addition, unpublished data from patients of our tertiary care center and 4 other centers were included. Study Selection Clinical studies reporting on the time to diagnosis of CS were eligible. Corresponding authors were contacted to obtain additional information relevant to the research question. Data Extraction Data were extracted from the text of the retrieved articles and from additional information provided by authors contacted successfully. From initially 3326 screened studies 44 were included. Data Synthesis Mean time to diagnosis for patients with CS was 34 months (ectopic CS: 14 months; adrenal CS: 30 months; and pituitary CS: 38 months; P < .001). No difference was found for gender, age (<18 and ≥18 years), and year of diagnosis (before and after 2000). Patients with pituitary CS had a longer time to diagnosis in Germany than elsewhere. Conclusions Time to diagnosis differs for subtypes of CS but not for gender and age. Time to diagnosis remains to be long and requires to be improved.

Cushing's syndrome (CS) is a classical rare disease: it is often suspected in patients who do not have the disease; at the same time, it takes a mean of 3 years to diagnose CS in affected individuals. The main reason is the extreme rarity (1–3/million/year) in combination with the lack of a single lead symptom. CS has to be suspected when a combination of signs and symptoms is present, which together make up the characteristic phenotype of cortisol excess. Unusual fat distribution affecting the face, neck, and trunk; skin changes including plethora, acne, hirsutism, livid striae, and easy bruising; and signs of protein catabolism such as thinned and vulnerable skin, osteoporotic fractures, and proximal myopathy indicate the need for biochemical screening for CS. In contrast, common symptoms like hypertension, weight gain, or diabetes also occur quite frequently in the general population and per se do not justify biochemical testing. First-line screening tests include urinary free cortisol excretion, dexamethasone suppression testing, and late-night salivary cortisol measurements. All three tests have overall reasonable sensitivity and specificity, and first-line testing should be selected on the basis of the physiologic conditions of the patient, drug intake, and available laboratory quality control measures. Two normal test results usually exclude the presence of CS. Other tests and laboratory parameters like the high-dose dexamethasone suppression test, plasma ACTH, the CRH test, and the bilateral inferior petrosal sinus sampling are not part of the initial biochemical screening. As a general rule, biochemical screening should only be performed if the pre-test probability for CS is reasonably high. This article provides an overview about the current standard in the diagnosis of CS starting with clinical scores and screenings, the clinical signs, relevant differential diagnoses, the first-line biochemical screening, and ending with a few exceptional cases.

Diagnostic efficiency is an important outcome variable in clinical reasoning research as it corresponds to workplace challenges. Scaffolding for case representations significantly improved the diagnostic efficiency of fourth and fifth-year medical students, most likely because of a more targeted screening of the available information.

Increased multisystem morbidity and mortality in patients with Cushing's syndrome comprise clinical problems and challenges, both at the time of diagnosis and in remission. Relevant comorbidities and clinical problems include hypertension, diabetes, overweight, myopathy and a high risk for acute complications such as infections and venous thrombembolism. Although there are therapy recommendations for most of these comorbidities, there is a lack of large, prospective studies to confirm and optimise them. Mortality is especially high during active disease and within the first year after diagnosis, as a result of cardiovascular events, infections and suicide. All in all, interdisciplinary therapy management is important for reducing morbidity and mortality over the long‐term.

Context Glucocorticoid-induced myopathy is a characteristic symptom of endogenous Cushing’s syndrome. Its long-term outcome is largely unknown Objective To evaluate long-term muscle function following remission of endogenous Cushing’s syndrome Study design Observational longitudinal cohort study Setting Tertiary care hospitals and specialized outpatient clinic Patients As part of the prospective multicenter German Cushing’s Registry we assessed muscle strength in patients with overt endogenous Cushing’s syndrome. We studied the patients at the time of diagnosis (n=88), after 6 months (n=69) and thereafter annually following surgical remission over a period of up to four years (1 year: n=55; 2 years: n=34; 3 years: n=29; 4 years: n=22). Muscle function was evaluated by hand grip strength and by chair rising test Results Grip strength was decreased to 83 % of normal controls (100 %) at time of diagnosis. It further decreased to 71 % after 6 months in remission (p≤0.001) and showed no improvement during further follow-up compared to baseline. Chair rising test performance improved initially (8 seconds at baseline vs 7 seconds after 6 months, p=0.004) but remained at this reduced level thereafter (7 seconds after 3 years vs 5 seconds in controls, p=0.038). In multivariate analysis we identified as predictors for long-term muscle dysfunction age, waist-to-hip-ratio and HbA1c at baseline. Furthermore, muscle strength during follow-up was strongly correlated with quality of life Conclusion This study shows that Cushing’s syndrome associated myopathy does not spontaneously resolve during remission. This calls for action to identify effective interventions to improve muscle dysfunction in this setting

BiliCheck provides a convenient, non-invasive possibility for bilirubin estimation in preterm infants. However, there are limitations: the method gives reliable results only in newborns older than 30 wk gestation, without PT and artificial ventilation.

BackgroundDiagnostic errors occur frequently in daily clinical practice and put patients’ safety at risk. There is an urgent need to improve education on clinical reasoning to reduce diagnostic errors. However, little is known about diagnostic errors of medical students. In this study, the nature of the causes of diagnostic errors made by medical students was analyzed.MethodsIn June 2016, 88 medical students worked on eight cases with the chief complaint dyspnea in a laboratory setting using an electronic learning platform, in summary 704 processed cases. The diagnostic steps of the students were tracked and analyzed. Furthermore, after each case the participants stated their presumed diagnosis and explained why they came to their diagnostic conclusion. The content of these explanations was analyzed qualitatively.ResultsBased on the diagnostic data gathering process and the students’ explanations, eight different causes could be identified of which the lack of diagnostic skills (24%) and inadequate knowledge base (16%) were the most common. Other causes that often contributed to a diagnostic error were faulty context generation (15%) and premature closure (10%). The causes of misdiagnosis varied per case.ConclusionsInadequate skills/knowledge and faulty context generation are the major problems in students’ clinical reasoning process. These findings are valuable for improving medical education and thus reducing the frequency of diagnostic errors in students’ later everyday clinical practice.

Purpose Recurrence after pituitary surgery in Cushing’s disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery, respectively. In this review, we give an overview of the current literature regarding prevalence, diagnosis, and therapeutic options of recurrent CD. Methods We systematically screened the literature regarding recurrent and persistent Cushing’s disease using the MESH term Cushing’s disease and recurrence. Of 717 results in PubMed, all manuscripts in English and German published between 1980 and April 2020 were screened. Case reports, comments, publications focusing on pediatric CD or CD in veterinary disciplines or studies with very small sample size (patient number < 10) were excluded. Also, papers on CD in pregnancy were not included in this review. Results and conclusions Because of the high incidence of recurrence in CD, annual clinical and biochemical follow-up is paramount. 50% of recurrences occur during the first 50 months after first surgery. In case of recurrence, treatment options include second surgery, pituitary radiation, targeted medical therapy to control hypercortisolism, and bilateral adrenalectomy. Success rates of all these treatment options vary between 25 (some of the medical therapy) and 100% (bilateral adrenalectomy). All treatment options have specific advantages, limitations, and side effects. Therefore, treatment decisions have to be individualized according to the specific needs of the patient.