The changes of standard DXA measurements and TBS depending on outcomes of neurosurgical treatment in patients with Cushing's disease

BACKGROUND: Patients with endogenous hypercortisolism have reduced bone mineral density (BMD) and trabecular bone score (TBS) that are the causes of secondary osteoporosis and low-traumatic fractures. It is well known that radical treatment (neurosurgery or radiosurgery) of Cushing’s disease leads to a decline of cortisol levels in all body fluids to normal values. However, it is still uncertain whether bone tissue structure, and particularly its microarchitecture, does recover in remission of the disease. AIMS: To evaluate an influence of hormone activity (presence or absence of remission) in patients with Cushing's disease on changes of bone structure measurements in accordance with DXA values (TBS, BMD, T- and Z-scores), as well as significance of such changes in 12 and 24 months after neurosurgical treatment. MATERIALS AND METHODS: In patients with confirmed active Cushing's disease (ACTH-producing pituitary adenoma) (n = 44) and in control group of healthy volunteers (n = 40), BMD in lumbar spine (L1-L4) and simultaneously TBS, in cut-off points before neurosurgical treatment (in both groups) and in 12 and 24 months after it (only in patients), were assessed. We diagnosed presence or absence of disease remission at cut-offs. All measurements were performed using a GE iDXA device (GE Healthcare Lunar, Madison, Wisconsin, USA). The TBS was calculated simultaneously from taken BMD scans, blinded to clinical outcome using TBS iNsight software v2.1 (Medimaps, Merignac, France). The activity of Cushing’s disease was evaluated using late-night salivary cortisol (LNSC, at 23:00). To determine the differences in DXA and TBS values before and after neurosurgical intervention depending on remission occurrence, covariate analysis (ANCOVA) was applied. RESULTS: There were found significant changes in TBS, BMD and T-score values in 12 months after neurosurgical treatment associated with presence or absence of disease remission (p = 0.039, 0.046 and 0.048, respectively). No differences in Z-score as well as in all measurements in 24 months, that might be associated with remission occurrence, were revealed. The gain in all DXA measurements (including TBS) during 24 months of observation period was statistically significant when analyzing data using Student’s paired t-test. However, the values corresponding to the age references had not been achieved for the specified time interval. CONCLUSIONS: Patients with Cushing’s disease have lower TBS values. In remission conditions TBS is getting significantly higher. The increase in BMD and TBS occurs during 24 months after achieving remission of Cushing’s disease but doesn’t lead to a full restoration of normal bone mass and microstructure throughout observation period of 24 months.

Download Full-text

Distinct Late-Night Salivary Cortisol Cut-Off Values for the Diagnosis of Hypercortisolism

Hormone and Metabolic Research ◽

10.1055/a-1608-1720 ◽

2021 ◽

Vol 53 (10) ◽

pp. 662-671

Author(s):

Lukas van Baal ◽

Marc Wichert ◽

Denise Zwanziger ◽

Henning Dralle ◽

Frank Weber ◽

...

Keyword(s):

Cushing’S Disease ◽

Salivary Cortisol ◽

Cushing's Disease ◽

Control Group ◽

High Morbidity ◽

Reference Ranges ◽

Ectopic Acth ◽

Late Night ◽

Late Night Salivary Cortisol ◽

Ectopic Acth Production

AbstractDue to high morbidity and mortality of untreated hypercortisolism, a prompt diagnosis is essential. Measurement of late-night salivary cortisol provides a simple and non-invasive method. However, thresholds and reference ranges differ among studies. The goal of this study was to define a threshold of late-night salivary cortisol for the diagnosis of hypercortisolism based on the used assay. Moreover, the influence of different aetiologies of hypercortisolism and individual comorbidities were investigated. Prospective analyses of 217 patients, including 36 patients with proven hypercortisolism were carried out. A sum of 149 patients with suspicion of hypercortisolism but negative endocrine testing and 32 patients with hypercortisolism in remission served as control group. Late-night salivary cortisol was measured using an automated chemiluminescence immunoassay. Cut-off values were calculated by ROC analysis. The calculated cut-off value for the diagnosis of hypercortisolism was 10.1 nmol/l (sensitivity 94%; specificity 84%). Only slightly lower thresholds were obtained in patients with suspected hypercortisolism due to weight gain/obesity (9.1 nmol/l), hypertension or adrenal tumours (both 9.8 nmol/l) or pituitary adenomas (9.5 nmol/l). The late-night salivary cortisol threshold to distinguish between Cushing’s disease and Cushing’s disease in remission was 9.2 nmol/l. The cut-off value for the diagnosis of ectopic ACTH-production was 109.0 nmol/l (sensitivity 50%, specificity 92%). Late-night salivary cortisol is a convenient and reliable parameter for the diagnosis of hypercortisolism. Except for ectopic ACTH-production, thresholds considering different indications for evaluation of hypercortisolism were only slightly different. Therefore, they might only be useful if late-night salivary cortisol results near the established cut-off value are present.

Download Full-text

Comparative analysis of the hormonal, MRI and morphological characteristics of patients with Cushing's disease remission and no remission after neurosurgical treatment

Endocrine Abstracts ◽

10.1530/endoabs.32.p706 ◽

2013 ◽

Author(s):

Eugenia Marova ◽

Svetlana Arapova ◽

Galina Kolesnikova ◽

Anastasiya Lapshina ◽

Ludmila Rozhinskaya

Keyword(s):

Comparative Analysis ◽

Cushing’S Disease ◽

Morphological Characteristics ◽

Cushing's Disease ◽

Disease Remission ◽

Neurosurgical Treatment

Download Full-text

Bone Mineral Density at Diagnosis and Following Successful Treatment of Pediatric Cushing's Disease

Yearbook of Endocrinology ◽

10.1016/s0084-3741(08)70428-1 ◽

2006 ◽

Vol 2006 ◽

pp. 366-367

Author(s):

D.E. Schteingart

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Successful Treatment ◽

Cushing’S Disease ◽

Cushing's Disease ◽

Mineral Density

Download Full-text

Preoperative predictors of Cushing's disease remission after transsphenoidal endoscopic surgery

Endocrine Abstracts ◽

10.1530/endoabs.63.p675 ◽

2019 ◽

Author(s):

Natalia Kuritsyna ◽

Uliana Tsoy ◽

Vladislav Cherebillo ◽

Artem Paltsev ◽

Anna Dalmatova ◽

...

Keyword(s):

Endoscopic Surgery ◽

Cushing’S Disease ◽

Cushing's Disease ◽

Disease Remission ◽

Transsphenoidal Endoscopic Surgery ◽

Preoperative Predictors

Download Full-text

Neural network for predicting recurrence of the Cushing's disease within three years after neurosurgical treatment

Endocrine Abstracts ◽

10.1530/endoabs.63.p259 ◽

2019 ◽

Author(s):

Elena Nadezhdina ◽

Olga Rebrova ◽

Andrey Grigoriev

Keyword(s):

Neural Network ◽

Cushing’S Disease ◽

Cushing's Disease ◽

Neurosurgical Treatment

Download Full-text

Pitfalls in the diagnosis and management of Cushing's syndrome

Neurosurgical FOCUS ◽

10.3171/2014.11.focus14704 ◽

2015 ◽

Vol 38 (2) ◽

pp. E4 ◽

Cited By ~ 34

Author(s):

Vivek Bansal ◽

Nadine El Asmar ◽

Warren R. Selman ◽

Baha M. Arafah

Keyword(s):

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Salivary Cortisol ◽

Clinical Symptoms ◽

Cushing's Syndrome ◽

Cushing's Disease ◽

Biochemical Tests ◽

Late Night ◽

Late Night Salivary Cortisol ◽

Free Cortisol

Despite many recent advances, the management of patients with Cushing's disease continues to be challenging. Cushing's syndrome is a complex metabolic disorder that is a result of excess glucocorticoids. Excluding the exogenous causes, adrenocorticotropic hormone–secreting pituitary adenomas account for nearly 70% of all cases of Cushing's syndrome. The suspicion, diagnosis, and differential diagnosis require a logical systematic approach with attention paid to key details at each investigational step. A diagnosis of endogenous Cushing's syndrome is usually suspected in patients with clinical symptoms and confirmed by using multiple biochemical tests. Each of the biochemical tests used to establish the diagnosis has limitations that need to be considered for proper interpretation. Although some tests determine the total daily urinary excretion of cortisol, many others rely on measurements of serum cortisol at baseline and after stimulation (e.g., after corticotropin-releasing hormone) or suppression (e.g., dexamethasone) with agents that influence the hypothalamic-pituitary-adrenal axis. Other tests (e.g., measurements of late-night salivary cortisol concentration) rely on alterations in the diurnal rhythm of cortisol secretion. Because more than 90% of the cortisol in the circulation is protein bound, any alteration in the binding proteins (transcortin and albumin) will automatically influence the measured level and confound the interpretation of stimulation and suppression data, which are the basis for establishing the diagnosis of Cushing's syndrome. Although measuring late-night salivary cortisol seems to be an excellent initial test for hypercortisolism, it may be confounded by poor sampling methods and contamination. Measurements of 24-hour urinary free-cortisol excretion could be misleading in the presence of some pathological and physiological conditions. Dexamethasone suppression tests can be affected by illnesses that alter the absorption of the drug (e.g., malabsorption, celiac disease) and by the concurrent use of medications that interfere with its metabolism (e.g., inducers and inhibitors of the P450 enzyme system). In this review, the authors aim to review the pitfalls commonly encountered in the workup of patients suspected to have hypercortisolism. The optimal diagnosis and therapy for patients with Cushing's disease require the thorough and close coordination and involvement of all members of the management team.

Download Full-text

Assessment of Vitamin D Metabolism in Patients with Cushing’s Disease in Response to 150,000 IU Cholecalciferol Treatment

Nutrients ◽

10.3390/nu13124329 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4329

Author(s):

Alexandra Povaliaeva ◽

Viktor Bogdanov ◽

Ekaterina Pigarova ◽

Artem Zhukov ◽

Larisa Dzeranova ◽

...

Keyword(s):

Vitamin D ◽

Cushing’S Disease ◽

Serum Vitamin ◽

Urinary Free Cortisol ◽

Cushing's Disease ◽

Control Group ◽

Vitamin D Metabolites ◽

Vitamin D Metabolism ◽

Serum Vitamin D ◽

Free Cortisol

In this study we aimed to assess vitamin D metabolism in patients with Cushing’s disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D3 levels (p > 0.05) and higher 25(OH)D3/24,25(OH)2D3 ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D3/24,25(OH)2D3 ratio (r = 0.36, p < 0.05). The increase in 25(OH)D3 after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently lower 25(OH)D3/24,25(OH)2D3 ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.

Download Full-text

Cushing’s Disease: Assessment of Early Cardiovascular Hemodynamic Dysfunction With Impedance Cardiography

Frontiers in Endocrinology ◽

10.3389/fendo.2021.751743 ◽

2021 ◽

Vol 12 ◽

Author(s):

Agnieszka Jurek ◽

Paweł Krzesiński ◽

Grzegorz Gielerak ◽

Przemysław Witek ◽

Grzegorz Zieliński ◽

...

Keyword(s):

Blood Pressure ◽

Arterial Hypertension ◽

Cushing’S Disease ◽

Impedance Cardiography ◽

Left Ventricular ◽

Cushing's Disease ◽

Control Group ◽

Stroke Index ◽

Disease Group ◽

Hemodynamic Assessment

BackgroundCushing’s disease is a rare condition associated with a high cardiovascular risk and hypercortisolemia-related hemodynamic dysfunction, the extent of which can be assessed with a noninvasive method, called impedance cardiography. The standard methods for hemodynamic assessment, such as echocardiography or ambulatory blood pressure monitoring may be insufficient to fully evaluate patients with Cushing’s disease; therefore, impedance cardiography is being currently considered a new modality for assessing early hemodynamic dysfunction in this patient population. The use of impedance cardiography for diagnosis and treatment of Cushing’s disease may serve as personalized noninvasive hemodynamic status assessment and provide a better insight into the pathophysiology of Cushing’s disease. The purpose of this study was to assess the hemodynamic profile of Cushing’s disease patients and compare it with that in the control group.Material and MethodsThis observational prospective clinical study aimed to compare 54 patients with Cushing’s disease (mean age 41 years; with 64.8% of this population affected with arterial hypertension) and a matched 54-person control group (mean age 45 years; with 74.1% of this population affected with arterial hypertension). The hemodynamic parameters assessed with impedance cardiography included the stroke index (SI), cardiac index (CI), systemic vascular resistance index (SVRI), velocity index (VI), (ACI), Heather index (HI), and thoracic fluid content (TFC).ResultsThe Cushing’s disease group was characterized by a higher diastolic blood pressure and a younger age than the control group (82.9 vs. 79.1 mmHg, p=0.045; and 41.1 vs. 44.9 years, p=0.035, respectively). Impedance cardiography parameters in the Cushing’s disease group showed: lower values of SI (42.1 vs. 52.8 ml/m2; p ≤ 0.0001), CI (2.99 vs. 3.64 l/min/m2; p ≤ 0,0001), VI (42.9 vs. 52.1 1/1000/s; p=0.001), ACI (68.7 vs. 80.5 1/100/s2; p=0,037), HI (13.1 vs. 15.2 Ohm/s2; p=0.033), and TFC (25.5 vs. 27.7 1/kOhm; p=0.006) and a higher SVRI (2,515 vs. 1,893 dyn*s*cm-5*m2; p ≤ 0.0001) than those in the control group.ConclusionsCushing’s disease is associated with significantly greater vasoconstriction and left ventricular systolic dysfunction. An individual assessment with impedance cardiography may be useful in Cushing’s disease patients in order to identify subclinical cardiovascular complications of chronic hypercortisolemia as potential therapeutic targets.

Download Full-text