Preoperative medical treatment in Cushing's syndrome : frequency of use and its impact on postoperative assessment : data from ERCUSYN

Background: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. Objective: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). Patients and methods: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). Results: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. Conclusions: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results

CLINICAL MANIFESTATIONS OF CUSHING'S DISEASE (RESULTS OF ANALYSIS OF THE CLINICAL DATABASE OF THE MOSCOW REGION)

Background: Cushing's disease (CD) is a  severe multimorbid disorder that affects primarily young people in their productive age. In most cases, the diagnosis is delayed and patients with complications of hypercorticism are seen by doctors of various specialties.Aim: To identify the most frequent clinical signs and symptoms of CD at the time of diagnosis, to assess an association between clinical manifestations of hypercorticism and main clinical and laboratory parameters.Materials and methods: We examined 44 CD patients registered in the database of CD patients of the Moscow Regional Research and Clinical Institute (MONIKI).Results: The mean age of patients was 37.9±10.5 years, with most of them (68.2%) being in the age range of 30 to 50 years. The median of disease duration was 35.5 [22; 75] months. Facial plethora, which is the most characteristic sign of hypercorticism, was seen in 97.7% of patients. Striae, thought to be most often associated with hypercorticism, were found only in 38.6% of patients. The most frequent complaints (&gt; 80%) were weight gain, fatigue, headache, and menstrual dysfunction. Some of the symptoms showed a positive correlation with cortisol levels.Conclusion: Clinical manifestations of CD are mostly non-specific. Only facial plethora was highly prevalent of all typical symptoms of hypercorticism. At least one of the "specific" symptoms was found in all patients

Clinical and morphological characteristic of ACTH producing tumors of various localization and the ectopic Cushing’s syndrome

Background: Ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome is a type hypercorticism caused by ectopic production of ACTH and/or its precursors by neuroendocrine tumors (NET) of various localization, such as lung and thymus carcinoids, less frequently those of pancreas and gastrointestinal tract, medullary thyroid cancer, pheochromocytoma, small cell lung cancer, as well as some other tumor types. The wide spectrum of tumors associated with the ectopic ACTH syndrome (EAS) makes their diagnosis and treatment a complicated issue.Materials and methods: The study was done with surgical and diagnostic biopsy samples from 60 patients who had tumors with EAS, 36 (60%) of them being bronchopulmonary carcinoids, 10 (16.7%) thymus carcinoids, 5 (8.3%) pancreatic NETs, 3 (5%) medullary thyroid cancers, 3 (5%) NETs of unknown primary localization, and NET of appendix, cecum and pheochromocytoma (one case of each, i.e. 1.7%, 1.7%, 1.7%). There were 38 female and 22 male patients (1.72:1), with their mean age of 39 ± 14 years (range, 16 to 77 years). We analyzed their clinical data, as well as the results of morphological and immunohistochemical examination of the tumors.Results: According to the World Health Organization classification (2015), typical carcinoids (TC) of the lung were found in 77.8% (28/36) of the bronchopulmonary tumors. 22.2% (8/36) of the bronchopulmonary tumors and all thymus tumors (100%, n = 10) were classified as atypical carcinoids (ATC). Four pancreatic NETs were classified as Grade 2 (G2), 1 as G3, and NETs of the cecum and appendix as G1 and G2, respectively. At present, 29 (48%) patients are living with no relapse (mean age 39 ± 13.5 years), whereas 22 (37%) of patients developed a relapse (mean age 35 ± 13 years), and 15 (25%) of them died, regardless of the age of the patients The history of the disease was not traced in 4 cases. 5-year relapse-free survival of patients with TC of the lung was 85.7% (24/28), of those with ATC 25% (2/8), with ATC of the thymus and medullary thyroid cancer 0%. Mortality from to TC of the lung for the entire follow-up period was 3.6% (1/28), to ATC 12.5% (1/8), to ATC of the thymus and for medullary thyroid cancer 62.5% and 100%, respectively. The patients with NET of the cecum, appendix and pheochromocytoma are alive without progression for 4, 5 and 6 years, respectively. Therefore, the lowest 5-year survival of patients with EAS was observed in medullary thyroid cancer, pancreatic NET and thymus carcinoids: in 100% (3/3), 75% (3/4), and 57.1% (4/7), respectively.Conclusion: The most unfavorable prognostic factors in the EAS are the localization of tumors in the thymus, pancreas and thyroid gland. This indicates the necessity of a differentiated treatment approaches to patients with this syndrome

COMPARATIVE ANALYSIS OF THE EFFECT OF THE RADICAL TREATMENT OF DIFFUSE TOXIC GOITER ON THE INDICES OF THE HEALTH-RELATED QUALITY OF LIFE

Background: Taking into account that many psychophysiological parameters directly depend on the severity and duration of pathological process and on the efficiency of treatment, investigations asessing remote results, health-related quality of life, and psychoemotional status of patients with a diffuse toxic goiter for a long time after radical treatment – are extremely urgent. Aim: To analyse the efficiency and safety of the radical methods of diffuse toxic goiter treatment, to compare the indices of the health-related quality of life, anxiety and depression levels depending on the kind of chosen methods of radical treatment. Materials and methods: A total of 71 patients with a diffuse toxic goiter were recruited into the study (37 patients who agreed radioiodine therapy, and 34 patients who underwent subtotal resection of the thyroid gland). Clinical examination, laboratory and instrumental analyses were carried out prior to and in 12 months after treatment. The questionnaire MOS SF-36 was used to estimate the health-related quality of life, Spillberg’s Anxiety Scale – to assess the levels of enxiety, and Beck Depression Inventory –   to assess the level of depression. Results: In the group of radioiodine therapy, the median of therapeutic activity was 12.7 [8.5; 15.2] mKi. After radioiodine therapy, the aim of treatment (hypothyroidism) was achieved in 95% of cases, and in 100% of cases – after subtotal thyroid resection. The MOS SF-36 questionnaire showed that the indices of the health-related quality of life in patients became significantly higher, and the anxiety level in 12 months after treatment – significantly lower than those before treatment (р&lt;0.05). Conclusion: The obtained results demonstrated the effectiveness of both methods used for treatment of Grave’s disease. The type of radical treatment made no difference. Compared with the initial thyrotoxicosis, compensated hypothyroidism in both cases was followed by a significantly higher quality of life and lower levels of anxiety and depression. It was also shown that people who received radical treatment, despite compensated hypothyroidism, overall, had lower quality of life, than those who did not have thyroid disease

High mortality within 90 days of diagnosis in patients with Cushing's syndrome: results from the ERCUSYN registry.

OBJECTIVE: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality. METHODS: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years. RESULTS: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment. CONCLUSION: Mortality rate was highest in patients with ectopic CS. Infectious diseases were the commonest cause of death soon after diagnosis, emphasizing the need for careful clinical vigilance at that time, especially in patients presenting with concomitant diabetes mellitus

High mortality within 90 days of diagnosis in patients with Cushing's syndrome: results from the ERCUSYN registry

To access publisher's full text version of this article click on the hyperlink belowOBJECTIVE: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality. METHODS: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years. RESULTS: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment. CONCLUSION: Mortality rate was highest in patients with ectopic CS. Infectious diseases were the commonest cause of death soon after diagnosis, emphasizing the need for careful clinical vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.European Union (EU) Novartis Ipsen European Society of Endocrinology HR

High mortality within 90 days of diagnosis in patients with Cushing's syndrome: results from the ERCUSYN registry

Objective: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality.Methods: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years.Results: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment.Conclusion: Mortality rate was highest in patients with ectopic CS. Infectious diseases the commonest cause of death soon after diagnosis, emphasizing the need for careful vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.Diabetes mellitus: pathophysiological changes and therap

Diagnostic tests for Cushing&apos;s syndrome differ from published guidelines : Data from ERCUSYN

Objective: To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing's syndrome (ERCUSYN), and to examine if their use differs from the current guidelines. Patients and methods: We analyzed data on the diagnostic tests performed in 1341 patients with Cushing's syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenaldependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS). Results: Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years (P < 0.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years (P < 0.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2 mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1 mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC (P < 0.05)