Racial disparities in acromegaly and Cushing’s disease: a referral center study in 241 patients

Abstract Purpose The impact of race on presentation and postoperative outcomes in adults with acromegaly (ACM) and Cushing’s disease (CD) has not been evaluated. Methods This is a retrospective study of consecutive patients operated at a large-volume pituitary center. We evaluated: 1) racial distribution of patients residing in the metropolitan area (Metro, N=124) versus 2010 U.S. Census data, 2) presentation and postoperative outcomes in Black versus White for patients from the entire catchment area (N=241). Results For Metro area (32.4% Black population), Black patients represented 16.75% ACM (p=0.006) and 29.2% CD (p=0.56).Among 112 total ACM patients, presentations with headaches or incidentaloma were more common in Black patients (76.9% versus 31% White, p=0.01). Black patients had a higher prevalence of diabetes (54% versus 16% White, p=0.005), significantly lower IGF-1 deviation from normal (p=0.03) and borderline lower median GH levels (p=0.09). Mean tumor diameter and proportion of tumors with cavernous sinus invasion were similar. Three-month biochemical remission (46% Black, 55% White, p=0.76) and long-term IGF-1 control by multimodality therapy (92.3% Black, 80.5% White, p=0.45) were similar. Among 129 total CD patients, Black patients had more hypopituitarism (69% vs 45% White, p=0.04) and macroadenomas (33% vs 15% White, p=0.05). At 3 months, remission rate was borderline higher in White (92% vs 78% Black, p=0.08) which was attributed to macroadenomas by logistic regression. Conclusion We identified disparities regarding racial distribution, clinical and biochemical characteristics in ACM, suggesting late or missed diagnosis in Black patients. Large nationwide studies are necessary to confirm our findings.

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Outcomes of Therapy for Cushing’s Disease due to Adrenocorticotropin-Secreting Pituitary Macroadenomas1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.1.4525 ◽

1998 ◽

Vol 83 (1) ◽

pp. 63-67 ◽

Cited By ~ 1

Author(s):

Lewis S. Blevins ◽

James H. Christy ◽

Masheed Khajavi ◽

George T. Tindall

Keyword(s):

Confidence Interval ◽

Cavernous Sinus ◽

Cushing’S Disease ◽

Odds Ratio ◽

Remission Rate ◽

Cushing's Disease ◽

Tumor Diameter ◽

Cavernous Sinus Invasion ◽

Free Cortisol ◽

Acth Secreting

We reviewed our experience with 21 patients who had Cushing’s disease due to ACTH-secreting macroadenomas to clarify the natural history of this disease. All patients had typical clinical and biochemical features of ACTH-dependent hypercortisolism. Their mean maximal tumor diameter was 1.6 ± 0.1 cm, and the range was 1.0–2.7 cm. Six patients had cavernous sinus invasion, three had invasion of the floor of their sella, and nine had suprasellar extension. The observed remission rate was significantly lower in macroadenoma patients than in microadenoma patients (67% vs. 91%; χ2 = 5.7; P < 0.02). Cavernous sinus invasion (odds ratio, 35; 95% confidence interval, 2.6–475; P < 0.008) and presence of a maximum tumor diameter 2.0 cm or more (odds ratio, 12.9; 95% confidence interval, 1.4–124; P< 0.02) emerged as the only predictors of residual disease after surgery. The observed recurrence rate was significantly higher in macroadenoma patients than in microadenoma patients (36% vs. 12%; χ2 = 4.2; P< 0.05). Macroadenoma patients tended to suffer from recurrences earlier than did microadenoma patients (16 vs. 49 months). Stepwise multiple logistic regression did not identify any predictors of disease recurrence in macroadenoma patients. Eight macroadenoma patients underwent a total of nine repeat surgical procedures, but none of these resulted in clinical remissions. Only four of seven (57%) patients followed for a sufficient period of time achieved normal urinary free cortisol levels after conventional radiotherapy. Three (75%) of these four patients had re-recurrent hypercortisolism after brief periods of eucortisolism. Pharmacological agents and adrenalectomy were effective in the management of hypercortisolism in patients with residual and recurrent disease. Our results indicate that ACTH-secreting macroadenomas are more refractory to conventional treatments than are ACTH-secreting microadenomas.

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Machine Learning in Preoperative Prediction of Postoperative Immediate Remission of Histology-Positive Cushing’s Disease

Frontiers in Endocrinology ◽

10.3389/fendo.2021.635795 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wentai Zhang ◽

Mengke Sun ◽

Yanghua Fan ◽

He Wang ◽

Ming Feng ◽

...

Keyword(s):

Machine Learning ◽

Cavernous Sinus ◽

Cushing’S Disease ◽

Remission Rate ◽

Tumour Size ◽

Univariate Analysis ◽

Cushing's Disease ◽

College Hospital ◽

Cavernous Sinus Invasion ◽

Preoperative Prediction

BackgroundThere are no established accurate models that use machine learning (ML) methods to preoperatively predict immediate remission after transsphenoidal surgery (TSS) in patients diagnosed with histology-positive Cushing’s disease (CD).PurposeOur current study aims to devise and assess an ML-based model to preoperatively predict immediate remission after TSS in patients with CD.MethodsA total of 1,045 participants with CD who received TSS at Peking Union Medical College Hospital in a 20-year period (between February 2000 and September 2019) were enrolled in the present study. In total nine ML classifiers were applied to construct models for the preoperative prediction of immediate remission with preoperative factors. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the performance of the models. The performance of each ML-based model was evaluated in terms of AUC.ResultsThe overall immediate remission rate was 73.3% (766/1045). First operation (p<0.001), cavernous sinus invasion on preoperative MRI(p<0.001), tumour size (p<0.001), preoperative ACTH (p=0.008), and disease duration (p=0.010) were significantly related to immediate remission on logistic univariate analysis. The AUCs of the models ranged between 0.664 and 0.743. The highest AUC, i.e., the best performance, was 0.743, which was achieved by stacking ensemble method with four factors: first operation, cavernous sinus invasion on preoperative MRI, tumour size and preoperative ACTH.ConclusionWe developed a readily available ML-based model for the preoperative prediction of immediate remission in patients with CD.

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Outcomes of endoscopic transsphenoidal surgery for Cushing's disease

BMC Endocrine Disorders ◽

10.1186/s12902-021-00679-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zarina Brady ◽

Aoife Garrahy ◽

Claire Carthy ◽

Michael W. O’Reilly ◽

Christopher J. Thompson ◽

...

Keyword(s):

Diabetes Insipidus ◽

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Remission Rate ◽

Cushing's Disease ◽

Endoscopic Transsphenoidal Surgery ◽

Endocrine Society ◽

Csf Leakage ◽

Remission Rates

Abstract Background Transsphenoidal surgery (TSS) to resect an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment for Cushing’s disease (CD), with increasing usage of endoscopic transsphenoidal (ETSS) technique. The aim of this study was to assess remission rates and postoperative complications following ETSS for CD. Methods A retrospective analysis of a prospective single-surgeon database of consecutive patients with CD who underwent ETSS between January 2012–February 2020. Post-operative remission was defined, according to Endocrine Society Guidelines, as a morning serum cortisol < 138 nmol/L within 7 days of surgery, with improvement in clinical features of hypercortisolism. A strict cut-off of < 50 nmol/L at day 3 post-op was also applied, to allow early identification of remission. Results A single surgeon (MJ) performed 43 ETSS in 39 patients. Pre-operative MRI localised an adenoma in 22 (56%) patients; 18 microadenoma and 4 macroadenoma (2 with cavernous sinus invasion). IPSS was carried out in 33 (85%) patients. The remission rates for initial surgery were 87% using standard criteria, 58% using the strict criteria (day 3 cortisol < 50 nmol/L). Three patients had an early repeat ETSS for persistent disease (day 3 cortisol 306-555 nmol/L). When the outcome of repeat early ETSS was included, the remission rate was 92% (36/39) overall. Remission rate was 94% (33/35) when patients with macroadenomas were excluded. There were no cases of CSF leakage, meningitis, vascular injury or visual deterioration. Transient and permanent diabetes insipidus occurred in 33 and 23% following first ETSS, respectively. There was one case of recurrence of CD during the follow-up period of 24 (4–79) months. Conclusion Endoscopic transsphenoidal surgery produces satisfactory remission rates for the primary treatment of CD, with higher remission rates for microadenomas. A longer follow-up period is required to assess recurrence rates. Patients should be counselled regarding risk of postoperative diabetes insipidus.

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

Acta Endocrinologica ◽

10.1530/eje-13-0325 ◽

2013 ◽

Vol 169 (3) ◽

pp. 329-337 ◽

Cited By ~ 48

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.

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Cushing's disease: results of transsphenoidal microsurgery with emphasis on surgical failures

Journal of Neurosurgery ◽

10.3171/jns.1990.72.3.0363 ◽

1990 ◽

Vol 72 (3) ◽

pp. 363-369 ◽

Cited By ~ 87

Author(s):

George T. Tindall ◽

Carl J. Herring ◽

Richard V. Clark ◽

David A. Adams ◽

Nelson B. Watts

Keyword(s):

Cushing’S Disease ◽

Preoperative Diagnosis ◽

Adrenocorticotropic Hormone ◽

Remission Rate ◽

Cushing's Disease ◽

Sustained Remission ◽

Original Diagnosis ◽

Content Type ◽

Transsphenoidal Microsurgery

✓ From 1977 to 1988, 56 patients with a preoperative diagnosis of Cushingαs disease were treated by transsphenoidal microsurgical exploration of the pituitary gland. In 42 patients, a discrete tumor was found and a selective adenomectomy was performed. Total hypophysectomy was performed in nine patients. In an attempt to preserve pituitary function, a technique of subtotal hypophysectomy was utilized in the remaining five patients. Regular and adequate follow-up results were obtained in 53 patients. A sustained remission was obtained in 45 of these 53 patients for a remission rate of 84.9%. Eight patients were classified as therapeutic failures. The causes for failure included: 1) invasive tumor; 2) hyperplasia mistaken for an adenoma; 3) a presumed ectopic source of adrenocorticotropic hormone; 4) misdiagnosis; 5) atypical tumor; and 6) recurrence of disease after remission. In cases of therapeutic failure, the original diagnosis of Cushing's disease must be reevaluated and treatment continued until sustained remission is achieved. Necessary measures to help avoid surgical failures and an approach for further diagnostic and therapeutic maneuvers in these cases are discussed.

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Transsphenoidal Surgery for Cushing's Disease

Journal of the Royal Society of Medicine ◽

10.1177/014107688607900504 ◽

1986 ◽

Vol 79 (5) ◽

pp. 262-269 ◽

Cited By ~ 117

Author(s):

R Fahlbusch ◽

M Buchfelder ◽

O A Müller

Keyword(s):

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Dynamic Testing ◽

Remission Rate ◽

Cushing's Syndrome ◽

Bilateral Adrenalectomy ◽

Pituitary Function ◽

Cushing's Disease ◽

Mortality And Morbidity

A series of 101 patients with Cushing's disease underwent transsphenoidal surgery. Diagnosis was fundamentally based on dynamic testing, mainly on the dosage-dependent suppression of cortisol after dexamethasone. The effect of surgery was monitored by intraoperative ACTH measurements. In 96 out of 101 patients a microadenoma of the pituitary was identified and removed selectively. In 74% of patients there was a clinical and endocrinological remission of Cushing's disease. Four ‘operative failures’ after selective adenomectomy underwent hypophysectomy in a second operation and each remitted. Thus the overall remission rate was 77%. In general, bilateral adrenalectomy was performed in patients who had failed to remit after selective adenomectomy. Although there is a considerable mortality and morbidity in patients with Cushing's syndrome, complications attributed to surgery were low. Two patients died postoperatively. In general, an improvement of disturbed pituitary function was noted after selective adenomectomy.

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Cushing’s Syndrome: A Historic Review of the Treatment Strategies and Corresponding Outcomes in a Single Tertiary Center over the Past Half-Century

Hormone and Metabolic Research ◽

10.1055/a-0580-0460 ◽

2018 ◽

Vol 50 (04) ◽

pp. 280-289 ◽

Cited By ~ 2

Author(s):

Anelia Nankova ◽

Maria Yaneva ◽

Atanaska Elenkova ◽

Dimitar Tcharaktchiev ◽

Marin Marinov ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Remission Rate ◽

Treatment Strategies ◽

Cushing's Syndrome ◽

New Drugs ◽

Cushing's Disease ◽

Treatment Modalities ◽

Tertiary Center

AbstractCushing’s syndrome (CS) is associated with serious comorbidities and an increased mortality rate that could be reduced only if strict biochemical control is achieved. The aim of this study was to show the 50-year experience of a single tertiary center in the management of CS patients – the different treatment modalities used over the years and the corresponding outcomes. It was a retrospective study of a large cohort of patients from the Bulgarian CS database: 613 patients (374 with ACTH-dependent and 239 with ACTH-independent CS). Pituitary surgery was applied to 242 patients with Cushing’s disease (CD) with initial remission rate of 74% of which 10% relapsed. Approximately 36% manifested with active disease during the long-term follow-up (26% with persistent disease, 10% relapses) most of which were subjected to a secondary treatment (13.6% to pituitary resurgery, 14% to pituitary radiotherapy, and 5.4% to bilateral adrenalectomy). A total of 294 CD patients received medical therapy with overall remission rates for the most commonly used drugs: dopamine agonists 20%, pasireotide 30%, and ketoconazole 63%. Significant improvement of results was achieved by combining drugs with different mechanisms of action. Regardless of the progress in the neurosurgery and radiotherapy techniques and new drugs discovery, the management of patients with CS remains a real challenge for physicians. Not only patients with adrenal carcinoma but also significant percentage of subjects with persistent and recurrent Cushing’s disease often require a polymodal approach and the efforts of a multidisciplinary highly qualified, experienced, and motivated team in order to achieve a long-term remission.

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Lipid Abnormalities in Patients With Cushing’s Disease and Its Relationship With Impaired Glucose Metabolism

Frontiers in Endocrinology ◽

10.3389/fendo.2020.600323 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaolin Sun ◽

Ming Feng ◽

Lin Lu ◽

Zixuan Zhao ◽

Xinjie Bao ◽

...

Keyword(s):

Cardiovascular Risk ◽

Glucose Metabolism ◽

Cushing’S Disease ◽

Cushing's Disease ◽

Impaired Glucose Metabolism ◽

Post Surgery ◽

Morning Cortisol ◽

Independent Risk Factors ◽

Lipid Abnormalities ◽

The Impact

PurposeDyslipidemia has been frequently reported and associated with increased cardiovascular risk in patients with Cushing’s disease (CD). Few studies are available regarding the relationships between lipid abnormalities and other preoperative metabolic comorbidities in CD, and the data on alterations of the lipid profile after surgery is quite variable. We aimed to investigate the associations between hyperlipidemia and other baseline metabolic and hormonal parameters and the impact of surgical remission on lipid metabolism in patients with CD.MethodsThis retrospective study included 104 patients diagnosed with CD. Baseline hormonal and metabolic parameters were compared between the hyperlipidemia (HLP) group and non-hyperlipidemia (NLP) group, and their relationships with hyperlipidemia at diagnosis were evaluated. Alterations in lipid profiles after surgical remission of CD were evaluated in 65 patients with available follow-up data.ResultsUpon baseline, logistic regression analysis showed that impaired glucose metabolism (IGM) (OR=4.68, 95%CI:1.38–15.91) and morning cortisol levels (per 10 μg/dl change) (OR=1.81, 95%CI:1.11–2.95) are both independent risk factors of preoperative occurrence of hyperlipidemia in patients with CD. The baseline triglyceride (TG) level was positively correlated with systolic blood pressure (SBP) (r=0.297, p=0.003). Lipid abnormalities had improvement but may persist after surgical remission, and the persisted hyperlipidemia is associated with higher baseline total cholesterol (TC) levels (r=0.505, p=0.033).ConclusionsPersistence of post-surgery hyperlipidemia is associated with severe baseline lipid abnormalities. Surgical remission with concomitant control of impaired glucose metabolism at diagnosis may have significant implications for controlling hyperlipidemia and reducing cardiovascular risk in CD.

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