scholarly journals P34 Characteristics, diagnosis and management of Cushing’s disease - A systematic review and meta-analysis

BJS Open ◽  
2021 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Chan Hee Koh ◽  
Danyal Z Khan ◽  
Ronneil Digpal ◽  
Hugo Layard Horsfall ◽  
Hani J Marcus ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cushing’S Disease ◽  
Meta Analysis ◽  
A Priori ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Diagnosis And Management ◽  
Over Time

Abstract Introduction The clinical practice and research in the diagnosis and management of Cushing’s disease remains heterogeneous and challenging to this day. We sought to establish the characteristics of Cushing’s disease, and the trends in diagnosis, management and reporting in this field. Methods Searches of PubMed and Embase were conducted. Study protocol was registered a-priori. Random-effects analyses were conducted to establish numerical estimates. Results Our screening returned 159 papers. The average age of adult patients with Cushing’s disease was 39.3, and 13.6 for children. The male:female ratio was 1:3. 8% of patients had undergone previous transsphenoidal resection. The ratio of macroadenomas: microadenomas:imaging-undetectable adenomas was 18:53:29. The most commonly reported preoperative biochemical investigations were serum cortisol (average 26.4µg/dL) and ACTH (77.5pg/dL). Postoperative cortisol was most frequently used to define remission (74.8%), most commonly with threshold of 5µg/dL (44.8%). Average remission rates were 77.8% with recurrence rate of 13.9%. Median follow-up was 38 months. Majority of papers reported age (81.9%) and sex (79.4%). Only 56.6% reported whether their patients had previous pituitary surgery. 45.3% reported whether their adenomas were macroadenoma, microadenoma or undetectable. Only 24.1% reported preoperative cortisol, and this did not improve over time. 60.4% reported numerical thresholds for cortisol in defining remission, and this improved significantly over time (p = 0.004). Visual inspection of bubbleplots showed increasing preference for threshold of 5µg/dL. 70.4% reported the length of follow up. Conclusion We quantified the characteristics of Cushing’s disease, and analysed the trends in investigation and reporting. This review may help to inform future efforts in forming guidelines for research and clinical practice.

scholarly journals Prospective evaluation of transsphenoidal pituitary surgery in 108 patients with Cushing's disease

2007 ◽  
Vol 51 (8) ◽  
pp. 1355-1361 ◽  
Author(s):  
Guilherme Rollin ◽  
Nelson Pires Ferreira ◽  
Mauro A. Czepielewski
Keyword(s):  
Diabetes Insipidus ◽  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Therapeutic Choice ◽  
Remission Rates ◽  
Transsphenoidal Pituitary Surgery ◽  
Suppression Test

Transsphenoidal pituitary surgery (TSS) remains the treatment of choice for Cushing's disease (CD). Despite the widespread acceptance of this procedure as the first line treatment in CD, the indication of a second TSS in not cured or relapsed DC patients is not consensus. We report the results of TSS in 108 patients with CD (a total of 117 surgeries). The mean postoperative follow-up period was 6 years. Remission was defined as clinical and laboratorial signs of adrenal insufficiency, period of glucocorticoid dependence, serum cortisol suppression on oral 1-mg dexamethasone overnight suppression test and clinical remission of hypercortisolism. We evaluated 103 patients with CD by the time of the first TSS. Fourteen patients underwent second TSS (5 had already been operated in others centers; in 5 patients the first surgery was not curative; in 4 patients CD relapsed). Remission rates were 85.4% and 28.6% (p < 0.001) after first and second TSS, respectively. In microadenomas, remission rates were higher than macroadenomas (94.9% vs. 73.9%; p = 0.006). In patients with negative pituitary imaging remission rates were 71.4% (p = 0.003; vs. microadenomas). Postoperative complications were: transient diabetes insipidus, definitive diabetes insipidus, hypopituitarism, stroke and one death. Only hypopituitarism was more frequent after second TSS (p = 0.015). In conclusion, TSS for CD is an effective and safe treatment. The best remission rates were observed at the first surgery and in microadenomas. The low remission rates after a second TSS suggest that this approach could not be a good therapeutic choice when the first one was not curative.

scholarly journals Endoscopic transsphenoidal pituitary surgery: a good and safe primary treatment option for Cushing's disease, even in case of macroadenomas or invasive adenomas

2013 ◽  
Vol 169 (3) ◽  
pp. 329-337 ◽  
Author(s):  
M A E M Wagenmakers ◽  
H D Boogaarts ◽  
S H P P Roerink ◽  
H J L M Timmers ◽  
N M M L Stikkelbroeck ◽  
...  
Keyword(s):  
Treatment Option ◽  
Cushing’S Disease ◽  
Remission Rate ◽  
Pituitary Surgery ◽  
Primary Treatment ◽  
Endoscopic Technique ◽  
Cushing's Disease ◽  
Recurrence Rates ◽  
Transsphenoidal Pituitary Surgery

ContextAlthough the endoscopic technique of transsphenoidal pituitary surgery (TS) has been widely adopted, reports on its results in Cushing's disease (CD) are still scarce and no studies have investigated long-term recurrence rates. This is the largest endoscopic series published till now.ObjectiveTo gain insight into the role of endoscopic TS as a primary treatment option for CD, especially in patients with magnetic resonance imaging (MRI)-negative CD and (invasive) macroadenomas.DesignRetrospective cohort study.Patients and methodsThe medical records of 86 patients with CD who underwent endoscopic TS were examined. Data on preoperative and postoperative evaluation, perioperative complications, and follow-up were collected. Remission was defined as disappearance of clinical symptoms with a fasting plasma cortisol level ≤50 nmol/l either basal or after 1 mg dexamethasone.ResultsThe remission rate in different adenoma subclasses varied significantly: 60% in MRI-negative CD (n=20), 83% in microadenomas (n=35), 94% in noninvasive macroadenomas (n=16), and 40% in macroadenomas that invaded the cavernous sinus (n=15). The recurrence rate was 16% after 71±39 months of follow-up (mean±s.d., range 10–165 months).ConclusionsEndoscopic TS is a safe and effective treatment for all patients with CD. Recurrence rates after endoscopic TS are comparable with those reported for microscopic TS. Our data suggest that in patients with noninvasive and invasive macroadenomas, the endoscopic technique of TS should be the treatment of choice as remission rates seem to be higher than those reported for microscopic TS, although no comparative study has been performed.

scholarly journals Outcome of endoscopic vs microsurgical transsphenoidal resection for Cushing’s disease

2018 ◽  
Vol 7 (1) ◽  
pp. R26-R37 ◽  
Author(s):  
Nidan Qiao
Keyword(s):  
Recurrence Rate ◽  
Cushing’S Disease ◽  
Meta Analysis ◽  
Cushing's Disease ◽  
Recurrence Rates ◽  
Microscopic Surgery ◽  
Significant Difference ◽  
Comprehensive Search ◽  
Definition Of

Introduction It is unclear whether the proportions of remission and the recurrence rates differ between endoscopic transsphenoidal surgery (TS) and microscopic TS in Cushing’s disease (CD); thus, we conducted a systematic review and meta-analysis to evaluate studies of endoscopic TS and microscopic TS. Methods We conducted a comprehensive search of PubMed to identify relevant studies. Remission and recurrence were used as outcome measures following surgical treatment of CD. Results A total of 24 cohort studies involving 1670 adult patients were included in the comparison. Among these studies, 702 patients across 9 studies underwent endoscopic TS, and 968 patients across 15 studies underwent microscopic TS. Similar baseline characteristics were observed in both groups. There was no significant difference in remission between the two groups: 79.7% (95% CI: 73.1–85.0%) in the endoscopic group and 76.9% (95% CI: 71.3–81.6%) in the microscopic group (P = 0.485). It appears that patients who underwent endoscopic surgery experience recurrence less often than patients who underwent microscopic surgery, with recurrence proportions of 11.0% and 15.9%, respectively (P = 0.134). However, if follow-up time is taken into account, both groups had a recurrence rate of approximately 4% per person per year (95% CI: 3.1–5.4% and 3.6–5.1%, P = 0.651). Conclusions We found that remission proportion and recurrence rate were the same in patients who underwent endoscopic TS as in patients who underwent microscopic TS. The definition of diagnosis, remission and recurrence should always be considered in the studies assessing therapeutic efficacy in CD.

Outcomes of pituitary surgery for Cushing’s disease: a systematic review and meta-analysis

Pituitary ◽  
2020 ◽  
Vol 23 (5) ◽  
pp. 595-609
Author(s):  
Anna Stroud ◽  
Pearl Dhaliwal ◽  
Raquel Alvarado ◽  
Mark J. Winder ◽  
Benjamin P. Jonker ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cushing’S Disease ◽  
Meta Analysis ◽  
Pituitary Surgery ◽  
Cushing's Disease

scholarly journals Earlier post-operative hypocortisolemia may predict durable remission from Cushing’s disease

2018 ◽  
Vol 178 (3) ◽  
pp. 255-263 ◽  
Author(s):  
Natasha Ironside ◽  
Gregoire Chatain ◽  
David Asuzu ◽  
Sarah Benzo ◽  
Maya Lodish ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Serum Cortisol Level ◽  
Clinical Prediction ◽  
Patients At Risk ◽  
Level 2 ◽  
Clinical Prediction Tool ◽  
Durable Remission

Context Achievement of hypocortisolemia following transsphenoidal surgery (TSS) for Cushing’s disease (CD) is associated with successful adenoma resection. However, up to one-third of these patients recur. Objective We assessed whether delay in reaching post-operative cortisol nadir may delineate patients at risk of recurrence for CD following TSS. Methods A retrospective review of 257 patients who received 291 TSS procedures for CD at NIH, between 2003 and 2016. Early biochemical remission (serum cortisol nadir <5 μg/dL) was confirmed with endocrinological and clinical follow-up. Recurrence was detected by laboratory testing, clinical stigmata or medication dependence during a median follow-up of 11 months. Results Of the 268 unique admissions, remission was recorded in 241 instances. Recurrence was observed in 9% of these cases with cortisol nadir ≤5 μg/dL and 6% of cases with cortisol nadir ≤2 μg/dL. The timing of hypocortisolemia was critical in detecting late recurrences. Morning POD-1 cortisol <3.3 μg/dL was 100% sensitive in predicting durable remission and morning POD-3 cortisol ≥18.5 μg/dL was 98.6% specific in predicting remote recurrence. AUROC analysis revealed that hypocortisolemia ≤5 µg/dL before 15 h (post-operative) had 95% sensitivity and an NPV of 0.98 for durable remission. Serum cortisol level ≤2 µg/dL, when achieved before 21 h, improved sensitivity to 100%. Conclusions In our cohort, early, profound hypocortisolemia could be used as a clinical prediction tool for durable remission. Achievement of hypocortisolemia ≤2 µg/dL before 21 post-operative hours appeared to accurately predict durable remission in the intermediate term.

scholarly journals The desmopressin test as a predictive factor of outcome after pituitary surgery for Cushing's disease

2004 ◽  
pp. 727-733 ◽  
Author(s):  
R Valero ◽  
S Vallette-Kasic ◽  
B Conte-Devolx ◽  
P Jaquet ◽  
T Brue
Keyword(s):  
Cushing’S Disease ◽  
Predictive Value ◽  
Characteristic Curve ◽  
Group Discussion ◽  
Pituitary Surgery ◽  
Receiver Operator Characteristic Curve ◽  
Cushing's Disease ◽  
Long Term Study ◽  
Specificity And Sensitivity

OBJECTIVE: Taking advantage of the over-expression of V3 receptors in adenomatous corticotroph cells, we evaluated the response to the vasopressin agonist desmopressin in 22 patients operated on for Cushing's disease, with a mean follow-up of 4.5 years. SUBJECTS AND METHODS: Twenty-two patients (17 women) operated on for Cushing's disease with a follow-up >2 years (median, 48; range, 24-141 months) underwent one desmopressin test (10 mug i.v. bolus) 3-6 months postoperatively. Twelve were in remission (R group), five had immediate failure (IF) after surgery and five had late recurrence (LR). RESULTS: Both ACTH and cortisol peaks after desmopressin were significantly lower in the R group than in the LR group (P=0.003 and P=0.013 respectively). The receiver operator characteristic curve method defined an ACTH peak threshold >/=22 pg/ml or ACTH rise >/=35%; cortisol peak >/=350 nmol/l or cortisol rise >/=14%. None of twelve patients in remission had ACTH or cortisol peaks above these thresholds vs three of five patients from the LR group and five of five in the IF group. DISCUSSION: On the basis of ACTH or cortisol peaks respectively, the desmopressin test was predictive of a later recurrence with a positive predictive value of 100% or 80% respectively, and a negative predictive value of 92%. Sensitivity and specificity were 80% and 100% respectively based on ACTH peak, and 80% and 92% respectively based on cortisol peak. CONCLUSION: In this first long-term study, a marked response of ACTH or cortisol to desmopressin was predictive of a later recurrence with good specificity and sensitivity.

scholarly journals Low immediate postoperative serum-cortisol nadir predicts the short-term, but not long-term, remission after pituitary surgery for Cushing’s disease

2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Jon Ramm-Pettersen ◽  
Helene Halvorsen ◽  
Johan Arild Evang ◽  
Pål Rønning ◽  
Per Kristian Hol ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Short Term ◽  
Postoperative Serum

scholarly journals High Prevalence of Adrenal Remnant Tissue in Patients Undergoing Bilateral Adrenalectomy for Cushing’s Disease

2020 ◽  
Author(s):  
Julian B. Wilson ◽  
Mohan Zopey ◽  
Jaimie Augustine ◽  
Randolph Schaffer ◽  
Manfred Chiang ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Signs And Symptoms ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Bilateral Adrenalectomy ◽  
Cushing's Disease ◽  
Adrenal Tissue ◽  
Number Of Patients ◽  
Free Cortisol ◽  
Endogenous Cortisol

AbstractBilateral adrenalectomy (BLA) is a treatment option for patients with Cushing’s Disease (CD) if transsphenoidal pituitary surgery fails or is not a therapeutic option. For most patients, BLA eliminates endogenous glucocorticoid and mineralocorticoid production, but for a small number of patients, endogenous secretion of adrenal hormones from adrenal tissue continues or recurs, leading to signs and symptoms of hypercortisolism. If adrenal tissue is confined to the adrenal bed, it is considered adrenal remnant tissue, while if it is outside the adrenal bed, it is considered adrenal rest tissue. We retrospectively evaluated morning serum cortisol, nighttime serum cortisol, nighttime salivary cortisol, and 24-h urine free cortisol on at least three occasions in 10 patients suspected of having endogenous cortisol production. Imaging of adrenal remnant tissue was also reviewed. Ten of 51 patients who underwent BLA during this time period had adrenal remnant/rest tissue marked by detectable endogenous glucocorticoid production; 9 of the 10 patients had signs and symptoms of hypercortisolism. Localization and treatment proved difficult. We conclude that the incidence of adrenal remnant/rest tissue in those undergoing BLA following unsuccessful pituitary surgery was 12% although there may have been a selection bias affecting this prevalence. The first indication of remnant tissue occurrence is a reduction in glucocorticoid replacement with symptoms of hypercortisolism. If this occurs, endogenous cortisol production should be tested for by cortisol measurements using a highly specific cortisol assay while the patient is taking dexamethasone or no glucocorticoid replacement. Endocrinologists need to monitor the development of both adrenal remnant tissue and Nelson’s syndrome following BLA.

scholarly journals Delayed Remission after Transsphenoidal Surgery in Patients with Cushing’s Disease

2010 ◽  
Vol 95 (2) ◽  
pp. 601-610 ◽  
Author(s):  
Elena Valassi ◽  
Beverly M. K. Biller ◽  
Brooke Swearingen ◽  
Francesca Pecori Giraldi ◽  
Marco Losa ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Tertiary Care ◽  
Case Series ◽  
Expectant Management ◽  
Pituitary Surgery ◽  
Cushing's Disease ◽  
Optimal Timing ◽  
Retrospective Case

Abstract Background: Transsphenoidal surgery (TSS) is the treatment of choice for Cushing’s disease (CD). Postoperative hypercortisolemia mandates further therapy. Objective: The aim of the study was to characterize patients without immediate postoperative remission who have a delayed decrease to normal or low cortisol levels without further therapy. Design and Setting: A retrospective case series was conducted at three tertiary care centers. Patients and Intervention: We reviewed the records of 620 patients (512 females, 108 males; mean age, 38 ± 13 yr) who underwent transsphenoidal pituitary surgery for CD between 1982 and 2007. Results: Outcomes were classified into the following three groups based upon the postoperative pattern of cortisol testing: group IC (immediate control) included 437 of the 620 patients (70.5%) with hypocortisolism and/or cortisol normalization throughout the postoperative follow-up; group NC (no control) included 148 of 620 patients (23.9%) with persistent hypercortisolism; and group DC (delayed control) included 35 of 620 patients (5.6%) who had early elevated or normal UFC levels and developed a delayed and persistent cortisol decrease after an average of 38 ± 50 postoperative days. The total rate of recurrence was 13% at a median follow-up time of 66 months after TSS; the cumulative rate of recurrence at 4.5 yr was significantly higher in group DC vs. group IC (43 vs. 14%; P = 0.02). Conclusions: Hormonal assessment in the immediate postoperative period after TSS for CD may be misleading because delayed remission can occur in a subset of patients. Expectant management and retesting may spare some patients from unnecessary further treatment. Optimal timing to determine the need for further therapy after TSS remains to be determined.

scholarly journals Mortality and Morbidity in Cushing's Disease over 50 Years in Stoke-on-Trent, UK: Audit and Meta-Analysis of Literature

2011 ◽  
Vol 96 (3) ◽  
pp. 632-642 ◽  
Author(s):  
R. N. Clayton ◽  
D. Raskauskiene ◽  
R. C. Reulen ◽  
P. W. Jones
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
General Population ◽  
Cushing’S Disease ◽  
Meta Analysis ◽  
Age At Diagnosis ◽  
Cushing's Disease ◽  
Persistent Disease ◽  
Overall Mortality

Context: Pituitary ACTH-dependent Cushing's disease (CD) is uncommon, and there are very limited data on long-term mortality. Objective: The aim was to summarize what is known about mortality in ACTH-dependent CD, to report on our own data, and to provide a meta-analysis of six other reports that addressed mortality of CD. Design and Methods: Vital status of 60 CD patients was recorded as of December 31, 2009, and the standardized mortality ratio (SMR) was calculated and compared with the general population of England and Wales, United Kingdom. A meta-analysis of SMRs from seven studies (including ours) was performed for overall mortality in CD. Where reported (four studies), a similar meta-analysis was performed for those patients whose hypercortisolism was in remission after treatment compared to those patients from the same center with persistent disease. Results: 1. From Stoke-on-Trent, 51 of 60 patients were female, median age at diagnosis was in the range of 36–46 yr, and median follow-up was 15 yr. There were 13 deaths, nine due to cardiovascular disease. Overall SMR for the whole cohort was 4.8 (95% confidence interval, 2.8–8.3) (P &lt; 0001). SMR for vascular disease was 13.8 (7.2–36.5) (P &lt; 0001). For persistent disease (n = 6), SMR was 16 (6.7–38.4) vs. remission (n = 54) SMR of 3.3 (1.7–6.7); after adjustment for age and sex, relative risk of death for persistent disease was 10.7 (2.3–48.6) (P = 0.002). Hypertension and diabetes mellitus were associated with significantly worse survival. 2. Using a random effects model meta-analysis revealed an overall (remission plus persistent disease) SMR of 2.2 (1.45–3.41) (P &lt; 0.001). Pooled SMR was 1.2 (0.45–3.2) (P = not significant) for patients in remission and 5.5 (2.7–11.3) (P = 0.001) for patients with persistent disease. Persistence of disease, older age at diagnosis, and presence of hypertension and diabetes are the main determinants of mortality. Conclusions: Overall mortality in CD is double that of the general population. However, patients with CD in remission fare much better than those with persistence of hypercortisolism, and they appear not to have an increased mortality rate. Hypertension and diabetes mellitus are risk factors for worse outcome. Because diagnosis and treatment of patients are at a young age, much longer follow-up of patients in remission is required before one can be confident that their mortality outcome is no different from that of the general population, especially because cardiovascular risk factors may persist after successful biochemical control of the disease.

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