Dealing with cognitive dissonance: an approach

Braun and Schmidmaier reflect on how one might best grapple wth the errors that Klein and McColl argue cognitive dissonance can create

Chemosensory dysfunction in Cushing's syndrome

PURPOSE Cushing's syndrome (CS) can lead to structural changes in the brain and cognitive impairment, but chemosensory function has not been investigated yet. The aim was to analyze sense of smell and taste in patients with CS and explore the effect of therapy. METHODS The study cohort comprised 20 patients with florid CS treated between 2018 and 2020 in the outpatient clinic of the LMU Munich. We compared these 20 patients with CS to 40 healthy subjects matched for age, sex, and smoking status. Patients' sense of smell and taste was examined at diagnosis and 3 months after successful therapeutic surgery leading to clinical and biochemical remission. Odor threshold, discrimination, and identification were measured with \textquotedblSniffin' Sticks\textquotedbl, taste was measured with \textquotedblTaste Strips\textquotedbl. Perceived sense of smell and taste was retrieved via a questionnaire. RESULTS Patients with florid CS had significantly reduced smell (total smell score 30.3 vs. 34.4, p < 0.0005) and taste scores (9.5 vs. 12.0, p < 0.0005) compared to controls and significantly more frequently hyposmia (55 vs. 2.5%, p < 0.0005), hypogeusia (40 vs. 0%, p < 0.0005), and self-reported chemosensory impairment (60 vs. 0%, p < 0.0005). Three months after successful surgery, CS patients showed significant improvement of odor threshold (8.1 vs. 7.0, p < 0.0005), odor discrimination (12.0 vs. 11.0, p = 0.003), total smell score (33.4 vs. 30.3, p < 0.0005), and taste (11.5 vs. 9.5, p = 0.003). CONCLUSIONS Chemosensory dysfunction is a novel and clinically relevant feature of CS

Toward a Diagnostic Score in Cushing's Syndrome

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 errors by medical students: results of a prospective qualitative study

Background: Diagnostic 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. Methods: In 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. Results: Based 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. Conclusions: Inadequate 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

Whom Should We Screen for Cushing Syndrome? The Endocrine Society Practice Guideline Recommendations 2008 Revisited

CONTEXT Cushing syndrome (CS) is a rare and serious disease with high mortality. Patients are often diagnosed late in the course of the disease. OBJECTIVE This work investigated whether defined patient populations should be screened outside the at-risk populations defined in current guidelines. METHODS As part of the prospective German Cushing registry, we studied 377 patients with suspected CS. The chief complaint for CS referral was documented. Using urinary free cortisol, late-night salivary cortisol, and the 1-mg dexamethasone suppression test as well as long-term clinical observation, CS was confirmed in 93 patients and ruled out for the remaining 284. RESULTS Patients were referred for 18 key symptoms, of which 5 were more common in patients with CS than in those in whom CS was ruled out: osteoporosis (8% vs 2%; P = .02), adrenal incidentaloma (17% vs 8%, P = 0.01), metabolic syndrome (11% vs 4%; P = .02), myopathy (10% vs 2%; P < .001), and presence of multiple symptoms (16% vs 1%; P < .001). Obesity was more common in patients in whom CS was ruled out (30% vs 4%, P < .001), but recent weight gain was prominent in those with CS. A total of 68 of 93 patients with CS (73%) had typical chief complaints, as did 106 of 284 of patients with ruled-out CS status (37%) according to the Endocrine Society practice guideline 2008. CONCLUSION The 2008 Endocrine Society Practice guideline for screening and diagnosis of CS defined at-risk populations that should undergo testing. These recommendations are still valid in 2022

Whom should we screen for Cushing syndrome? The Endocrine Society practice guideline recommendations 2008 revisited

CONTEXT: Cushing syndrome (CS) is a rare and serious disease with high mortality. Patients are often diagnosed late in the course of the disease. OBJECTIVE: This work investigated whether defined patient populations should be screened outside the at-risk populations defined in current guidelines. METHODS: As part of the prospective German Cushing registry, we studied 377 patients with suspected CS. The chief complaint for CS referral was documented. Using urinary free cortisol, late-night salivary cortisol, and the 1-mg dexamethasone suppression test as well as long-term clinical observation, CS was confirmed in 93 patients and ruled out for the remaining 284. RESULTS: Patients were referred for 18 key symptoms, of which 5 were more common in patients with CS than in those in whom CS was ruled out: osteoporosis (8% vs 2%; P = .02), adrenal incidentaloma (17% vs 8%, P = 0.01), metabolic syndrome (11% vs 4%; P = .02), myopathy (10% vs 2%; P < .001), and presence of multiple symptoms (16% vs 1%; P < .001). Obesity was more common in patients in whom CS was ruled out (30% vs 4%, P < .001), but recent weight gain was prominent in those with CS. A total of 68 of 93 patients with CS (73%) had typical chief complaints, as did 106 of 284 of patients with ruled-out CS status (37%) according to the Endocrine Society practice guideline 2008. CONCLUSION: The 2008 Endocrine Society Practice guideline for screening and diagnosis of CS defined at-risk populations that should undergo testing. These recommendations are still valid in 2022

Recurrence after pituitary surgery in adult Cushing's disease: a systematic review on diagnosis and treatment

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

The Effect of Biochemical Remission on Bone Metabolism in Cushing's Syndrome: A 2‐Year Follow‐Up Study

Endogenous Cushing's syndrome (CS) is a rare cause of secondary osteoporosis. The long‐term consequences for bone metabolism after successful surgical treatment remain largely unknown. We assessed bone mineral density and fracture rates in 89 patients with confirmed Cushing's syndrome at the time of diagnosis and 2 years after successful tumor resection. We determined five bone turnover markers at the time of diagnosis, 1 and 2 years postoperatively. The bone turnover markers osteocalcin, intact procollagen‐IN‐propeptide (PINP), alkaline bone phosphatase, CTX‐I, and TrAcP 5b were measured in plasma or serum by chemiluminescent immunoassays. For comparison, 71 sex‐, age‐, and body mass index (BMI)‐matched patients in whom Cushing's syndrome had been excluded were studied. None of the patients received specific osteoanabolic treatment. At time of diagnosis, 69% of the patients had low bone mass (mean T‐score = −1.4 ± 1.1). Two years after successful surgery, the T‐score had improved in 78% of patients (mean T‐score 2 years postoperatively −1.0 ± 0.9). The bone formation markers osteocalcin and intact PINP were significantly decreased at time of diagnosis (p ≤ 0.001 and p = 0.03, respectively), and the bone resorption marker CTX‐I and TrAcP 5b increased. Postoperatively, the bone formation markers showed a three‐ to fourfold increase 1 year postoperatively, with a moderate decline thereafter. The bone resorption markers showed a similar but less pronounced course. This study shows that the phase immediately after surgical remission from endogenous CS is characterized by a high rate of bone turnover resulting in a striking net increase in bone mineral density in the majority of patients

Delineating endogenous Cushing's syndrome by GC-MS urinary steroid metabotyping

BACKGROUND Diagnosing Cushing's syndrome (CS) is highly complex. As the diagnostic potential of urinary steroid metabolome analysis by gas chromatography-mass spectrometry (GC-MS) in combination with systems biology has not yet been fully exploited, we studied a large cohort of patients with CS. METHODS We quantified daily urinary excretion rates of 36 steroid hormone metabolites. Applying cluster analysis, we investigated a control group and 168 patients: 44 with Cushing's disease (CD) (70% female), 18 with unilateral cortisol-producing adrenal adenoma (83% female), 13 with primary bilateral macronodular adrenal hyperplasia (PBMAH) (77% female), and 93 ruled-out CS (73% female). FINDINGS Cluster-Analysis delineated five urinary steroid metabotypes in CS. Metabotypes 1, 2 and 3 revealing average levels of cortisol and adrenal androgen metabolites included patients with exclusion of CS or and healthy controls. Metabotype 4 reflecting moderately elevated cortisol metabolites but decreased DHEA metabolites characterized the patients with unilateral adrenal CS and PBMAH. Metabotype 5 showing strong increases both in cortisol and DHEA metabolites, as well as overloaded enzymes of cortisol inactivation, was characteristic of CD patients. 11-oxygenated androgens were elevated in all patients with CS. The biomarkers THS, F, THF/THE, and (An + Et)/(11β-OH-An + 11β-OH-Et) correctly classified 97% of patients with CS and 95% of those without CS. An inverse relationship between 11-deoxygenated and 11-oxygenated androgens was typical for the ACTH independent (adrenal) forms of CS with an accuracy of 95%. INTERPRETATION GC-MS based urinary steroid metabotyping allows excellent identification of patients with endogenous CS and differentiation of its subtypes. FUNDING The study was funded by the Else Kröner-Fresenius-Stiftung and the Eva-Luise-und-Horst-Köhler-Stiftung