Sleep disturbances in primary aldosteronism are associated to depressive symptoms - Could specific mineralocorticoidreceptors be a common pathway?

Symptoms of depression and anxiety are frequent in patients with primary aldosteronism (PA) and are supposed to be independent risk factors for cardiovascular diseases (CVD). As patients with PA have an increased cardiovascular risk compared to patients with essential hypertension, sleep disturbances, which often accompany depressive and anxiety symptoms, may be an additional contributor to the cardiometabolic consequences of PA. To clarify this possible link we investigated 132 patients with PA at baseline and after one year after initiation of treatment either by adrenalectomy (ADX) or mineralocorticoid-receptor-antagonist (MRA). Sleep disturbances and daytime sleepiness were assessed with Pittsburg sleep Inventory (PSQI) and Epworth sleepiness scale (ESS). Patients with PA showed pathological scores for sleep disturbances at baseline according to PSQI, with females being more affected (8.1 vs. 5.7 p < 0.001), which was significantly improved after initiation of specific treatment (p = 0.002). For ESS we found scores within the normal range, but higher than the general population, which significantly improved at follow-up (p < 0.001). The intensity of sleep disturbances was highly correlated with scores of anxiety and depression at baseline and follow-up. However, clinical and biochemical markers of PA (e.g. aldosterone, blood pressure) and metabolic markers did not show a consistent association with sleep changes. The degree of improvement in PSQI was significantly associated with the improvement of brief patients health questionnaire (PHQD) (p = 0.0151). Sleep disturbances seem not to be an independent risk factor for cardiovascular and metabolic problems in PA. They are strongly associated to depressive symptoms and maybe mediated by the same mineralocorticoid receptor circuits.

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)/(11ß-OH-An + 11ß-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.

Insights into diagnostic errors in endocrinology: a prospective, case-based, international study.

BACKGROUND: Diagnostic errors in internal medicine are common. While cognitive errors have previously been identified to be the most common contributor to errors, very little is known about errors in specific fields of internal medicine such as endocrinology. This prospective, multicenter study focused on better understanding the causes of diagnostic errors made by general practitioners and internal specialists in the area of endocrinology. METHODS: From August 2019 until January 2020, 24 physicians completed five endocrine cases on an online platform that simulated the diagnostic process. After each case, the participants had to state and explain why they chose their assumed diagnosis. The data gathering process as well as the participants' explanations were quantitatively and qualitatively analyzed to determine the causes of the errors. The diagnostic processes in correctly and incorrectly solved cases were compared. RESULTS: Seven different causes of diagnostic error were identified, the most frequent being misidentification (mistaking one diagnosis with a related one or with more frequent and similar diseases) in 23% of the cases. Other causes were faulty context generation (21%) and premature closure (17%). The diagnostic confidence did not differ between correctly and incorrectly solved cases (median 8 out of 10, p = 0.24). However, in incorrectly solved cases, physicians spent less time on the technical findings (such as lab results, imaging) (median 250 s versus 199 s, p < 0.049). CONCLUSIONS: The causes for errors in endocrine case scenarios are similar to the causes in other fields of internal medicine. Spending more time on technical findings might prevent misdiagnoses in everyday clinical practice.

Bayesian versus diagnostic information in physician-patient communication: Effects of direction of statistical information and presentation of visualization.

BACKGROUND: Communicating well with patients is a competence central to everyday clinical practice, and communicating statistical information, especially in Bayesian reasoning tasks, can be challenging. In Bayesian reasoning tasks, information can be communicated in two different ways (which we call directions of information): The direction of Bayesian information (e.g., proportion of people tested positive among those with the disease) and the direction of diagnostic information (e.g., the proportion of people having the disease among those tested positive). The purpose of this study was to analyze the impact of both the direction of the information presented and whether a visualization (frequency net) is presented with it on patient's ability to quantify a positive predictive value. MATERIAL AND METHODS: 109 participants completed four different medical cases (2⨯2⨯4 design) that were presented in a video; a physician communicated frequencies using different directions of information (Bayesian information vs. diagnostic information). In half of the cases for each direction, participants were given a frequency net. After watching the video, participants stated a positive predictive value. Accuracy and speed of response were analyzed. RESULTS: Communicating with Bayesian information led to participant performance of only 10% (without frequency net) and 37% (with frequency net) accuracy. The tasks communicated with diagnostic information but without a frequency net were correctly solved by 72% of participants, but accuracy rate decreased to 61% when participants were given a frequency net. Participants with correct responses in the Bayesian information version without visualization took longest to complete the tasks (median of 106 seconds; median of 13.5, 14.0, and 14.5 seconds in other versions). DISCUSSION: Communicating with diagnostic information rather than Bayesian information helps patients to understand specific information better and more quickly. Patients' understanding of the relevance of test results is strongly dependent on the way the information is presented.

Lack of sensitivity of diagnostic Cushing-scores in Germany: a multicenter validation.

OBJECTIVE: Endogenous Cushing's syndrome (CS) is a severe condition, often diagnosed at a late stage. To reduce mortality, early diagnosis plays an important role. Two screening tools for early identification of patients with CS have been developed in multicentric cohorts, but have not yet been validated in cohorts with different geographic backgrounds. DESIGN: We validated the Spanish score published by Leon-Justel et al. in 2016 and the Italian score by Parasiliti-Caprino et al. published in 2021 in our cohort. METHODS: In the multicentric German Cushing registry, patients with confirmed and expected but ruled out Cushing's syndrome are prospectively diagnosed and followed up. We validated both scores in a cohort of 458 subjects: 176 patients with confirmed CS and 282 patients with suspected, but finally excluded CS. RESULTS: Using the Spanish score, 17.5% of our patients with proven CS biochemical screening would not have been recommended. This concerned patients with pituitary CS (22%) and with adrenal CS (10%). On the contrary, only 14% of patients without CS would have received a recommendation for biochemical screening. Using the Italian score, 29% of patients with proven CS were classified into the low-risk classes not recommended for biochemical screening. This mostly affected patients with adrenal (31%) and pituitary CS (30%). About 12% of subjects without CS would have received a biochemical screening recommendation. CONCLUSIONS: Both scores had limited sensitivity and high specificity in a German validation cohort. Further research is necessary to develop a screening score, which is effective in different healthcare systems and ethnicities.

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.

Types of therapeutic errors in the management of osteoporosis made by physicians and medical students.

BACKGROUND: Clinical reasoning is of high importance in clinical practice and thus in medical education research. Regarding the clinical reasoning process, the focus has primarily been on diagnostic reasoning and diagnostic errors, but little research has been done on the subsequent management reasoning process, although the therapeutic decision-making process is at least equally important. The aim of this study was to investigate the frequency of therapeutic decision errors and the cognitive factors leading to these errors in the context of osteoporosis, as it is known to be frequently associated with inadequate treatment decisions in clinical practice worldwide. METHODS: In 2019, 19 medical students and-for comparison-23 physicians worked on ten patient cases with the medical encounter of osteoporosis. A total of 254 cases were processed. The therapeutic decision errors were quantitatively measured, and the participants' cognitive contributions to therapeutic errors and their clinical consequences were qualitatively analysed. RESULTS: In 26% of the cases, all treatment decisions were correct. In the remaining 74% cases, multiple errors occurred; on average, 3 errors occurred per case. These 644 errors were further classified regarding the cognitive contributions to the error. The most common cognitive contributions that led to errors were faulty context generation and interpretation (57% of students, 57% of physicians) and faulty knowledge (38% of students, 35% of physicians). Errors made due to faulty metacognition (5% of students, 8% of physicians) were less common. Consequences of these errors were false therapy (37% of cases), undertreatment (30% of cases) or overtreatment (2.5% of cases). CONCLUSION: The study is the first to show that errors in therapy decisions can be distinguished and classified, similar to the already known classification for errors in diagnostic reasoning. Not only the correct diagnosis, but particularly the correct therapy, is critical for the outcome of a patient.

Long-term morbidity and mortality in patients with Cushing's syndrome.

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.

Improving Diagnostic Efficiency with Frequency Double-Trees and Frequency Nets in Bayesian Reasoning.

Background. Medical students often have problems with Bayesian reasoning situations. Representing statistical information as natural frequencies (instead of probabilities) and visualizing them (e.g., with double-trees or net diagrams) leads to higher accuracy in solving these tasks. However, double-trees and net diagrams (which already contain the correct solution of the task, so that the solution could be read of the diagrams) have not yet been studied in medical education. This study examined the influence of information format (probabilities v. frequencies) and visualization (double-tree v. net diagram) on the accuracy and speed of Bayesian judgments. Methods. A total of 142 medical students at different university medical schools (Munich, Kiel, Goettingen, Erlangen, Nuremberg, Berlin, Regensburg) in Germany predicted posterior probabilities in 4 different medical Bayesian reasoning tasks, resulting in a 3-factorial 2 × 2 × 4 design. The diagnostic efficiency for the different versions was represented as the median time divided by the percentage of correct inferences. Results. Frequency visualizations led to a significantly higher accuracy and faster judgments than did probability visualizations. Participants solved 80% of the tasks correctly in the frequency double-tree and the frequency net diagram. Visualizations with probabilities also led to relatively high performance rates: 73% in the probability double-tree and 70% in the probability net diagram. The median time for a correct inference was fastest with the frequency double tree (2:08 min) followed by the frequency net diagram and the probability double-tree (both 2:26 min) and probability net diagram (2:33 min). The type of visualization did not result in a significant difference. Discussion. Frequency double-trees and frequency net diagrams help answer Bayesian tasks more accurately and also more quickly than the respective probability visualizations. Surprisingly, the effect of information format (probabilities v. frequencies) on performance was higher in previous studies: medical students seem also quite capable of identifying the correct solution to the Bayesian task, among other probabilities in the probability visualizations. Highlights: Frequency double-trees and frequency nets help answer Bayesian tasks not only more accurately but also more quickly than the respective probability visualizations.In double-trees and net diagrams, the effect of the information format (probabilities v. natural frequencies) on performance is remarkably lower in this high-performing sample than that shown in previous studies.

Diurnal Salivary Cortisol Profiles in Patients with Cushing's Syndrome.

BACKGROUND: Quantification of salivary cortisol is one of the highly sensitive and specific screening parameters for Cushing's syndrome (CS). However, only late-night salivary cortisol is part of the standard screening procedure. In this study, we aimed to analyze salivary cortisol day profiles in patients with different types of CS to test whether specific patterns might be relevant for diagnosis and subtyping. MATERIAL AND METHODS: Among 428 patients including those with confirmed Cushing's syndrome (N=111, of those 75 with Cushing's disease, 27 patients with adrenal CS and nine patients with ectopic CS), autonomous cortisol secretion (N=39) or exclusion of CS (control group, N=278) salivary cortisol was measured five times a day. RESULTS: At each of the five time points, salivary cortisol was significantly higher in patients with CS compared to the control group (p≤0.001). Using the entire profile instead of one single salivary cortisol at 11 p.m. improved diagnostic accuracy (85 vs. 91%) slightly. Patients with ACTH-dependent CS had higher salivary cortisol levels than patients with adrenal CS. Also, morning cortisol was significantly higher in patients with ectopic CS than in patients with Cushing's disease (p=0.04). Nevertheless, there was a strong overlap between diurnal profiles, and the diagnostic yield for subtyping was low. DISCUSSION: The study results show that using diurnal salivary cortisol profiles for CS diagnosis results in a limited increase in diagnostic accuracy. With significant differences between Cushing subtypes, cortisol profiles are not useful in everyday clinical practice for subtyping of CS.

Simulated ward round training in the medical curriculum Munich.

Conducting a ward round in a structured and goal-oriented manner is one of the central competencies of a physician's work. Despite its relevance, ward round competence was only addressed in an unstructured way in the Medical Curriculum Munich (MeCuM) prior to 2011. Therefore, the project's aim was to implement an evidence-based course on medical ward round competence. This project report provides a guideline for developing such a training course. Project planning and development was guided by the steps of the "Kern cycle", beginning with needs assessment, learning objectives definition, and selection of appropriate teaching methods, and ending with implementation and evaluation.

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 "Sniffin' Sticks", taste was measured with "Taste Strips". 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.

Implementation of self-directed learning within clinical clerkships.

Background: The main aim of medical curricula is to prepare students for the first day at the work place. While teaching clinical competence is pivotal, clinical clerkships are often the last chance to close knowledge gaps with the help of clinical teachers. Self-directed learning is a dynamic field for research within medical education, though its curricular implementation is rare. This study focuses on the needs assessment of clinical clerkships using the concept of self-directed learning. Methods: The study comprised an educational experience at the Ludwig-Maximilians Universität (LMU) Munich. Medical students (n=1446, 59% female) in their second clinical year were instructed to specify learning objectives (LOs) by Doran`s SMART criteria and to gauge the probability of their fulfilment prior to the mandatory clerkship. In a second questionnaire one week later, the students rated the actual subjective fulfilment of the LOs. Data was coded with regards to the German National Catalogue of Competence-Based Learning Objectives for Undergraduate Medical Education (NKLM) and investigated qualitatively. Factors that determine goal achievement were collected and coded binary (barrier vs. enabler). Univariate analysis was used when appropriate. Results: The acquisition of "clinically practical abilities" (29%), "diagnostic methods" (21%) and "professional communication" (13%) were the LOs mentioned most. Throughout the week, subjective fulfilment diminished. Rich (vs. poor) availability to "practical exercise" (31%), "engagement of the physicians and other medical staff" (27%) and "personal initiative" (23%) resulted in higher subjective fulfilment. Conclusions: The self-chosen LOs reflect the needs of students for which the clinical teacher should be prepared. Considering these findings, it seems possible to close practical training gaps. We support the consideration of establishing curricular anchored self-directed learning in clinical clerkships. Further empirical studies would be beneficial in revealing its positive effects on the learning progress.

Natural frequency trees improve diagnostic efficiency in Bayesian reasoning.

When physicians are asked to determine the positive predictive value from the a priori probability of a disease and the sensitivity and false positive rate of a medical test (Bayesian reasoning), it often comes to misjudgments with serious consequences. In daily clinical practice, however, it is not only important that doctors receive a tool with which they can correctly judge-the speed of these judgments is also a crucial factor. In this study, we analyzed accuracy and efficiency in medical Bayesian inferences. In an empirical study we varied information format (probabilities vs. natural frequencies) and visualization (text only vs. tree only) for four contexts. 111 medical students participated in this study by working on four Bayesian tasks with common medical problems. The correctness of their answers was coded and the time spent on task was recorded. The median time for a correct Bayesian inference is fastest in the version with a frequency tree (2:55 min) compared to the version with a probability tree (5:47 min) or to the text only versions based on natural frequencies (4:13 min) or probabilities (9:59 min).The score diagnostic efficiency (calculated by: median time divided by percentage of correct inferences) is best in the version with a frequency tree (4:53 min). Frequency trees allow more accurate and faster judgments. Improving correctness and efficiency in Bayesian tasks might help to decrease overdiagnosis in daily clinical practice, which on the one hand cause cost and on the other hand might endanger patients' safety.

Persisting Muscle Dysfunction in Cushing's Syndrome Despite Biochemical Remission.

CONTEXT: Glucocorticoid-induced myopathy is a characteristic symptom of endogenous Cushing's syndrome (CS). Its long-term outcome is largely unknown. OBJECTIVE: To evaluate long-term muscle function following the remission of endogenous CS. STUDY DESIGN: Observational longitudinal cohort study. SETTING: Tertiary care hospitals and a specialized outpatient clinic. PATIENTS: As part of the prospective multicenter German Cushing's Registry, we assessed muscle strength in patients with overt endogenous CS. 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 4 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 the 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 with 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 hemoglobin A1c at baseline. Furthermore, muscle strength during follow-up was strongly correlated with quality of life. CONCLUSION: This study shows that CS-associated myopathy does not spontaneously resolve during remission. This calls for action to identify effective interventions to improve muscle dysfunction in this setting.

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.

Spironolactone reduces biochemical markers of bone turnover in postmenopausal women with primary aldosteronism.

CONTEXT: Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Besides its deleterious impact on cardiovascular target organ damage, PA is considered to cause osteoporosis. PATIENTS AND METHODS: We assessed bone turnover in a subset of 36 postmenopausal women with PA. 18 patients had unilateral PA and were treated by adrenalectomy, whereas 18 patients had bilateral PA and received mineralocorticoid receptor antagonist (MRA) therapy respectively. 18 age- and BMI-matched females served as controls. To estimate bone remodeling, we measured the bone turnover markers intact procollagen 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin and tartrate resistant acid phosphatase 5b in plasma by chemiluminescent immunoassays at time of diagnosis and one year after initiation of treatment. STUDY DESIGN: Observational longitudinal cohort study. SETTING: Tertiary care hospital. RESULTS: Compared with controls, patients with PA had mildly elevated osteocalcin at baseline (p = 0.013), while the other bone markers were comparable between both groups. There were no differences between the unilateral and the bilateral PA subgroup. One year after initiation of MRA treatment with spironolactone bone resorption and bone formation markers had significantly decreased in patients with bilateral PA. In contrast, patients adrenalectomized because of unilateral PA showed no significant change of bone turnover markers. CONCLUSION: This study shows that aldosterone excess in postmenopausal women with PA is not associated with a relevant increase of bone turnover markers at baseline. However, we observed a significant decrease of bone markers in patients treated with spironolactone, but not in patients treated by adrenalectomy.