Outcome of transsphenoidal surgery for Cushing's disease: A high remission rate in ACTH-secreting macroadenomas

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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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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MON-LB58 The Use of 11C Methionine PET CT In Localization of ACTH Dependent Cushing’s Disease

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2273 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Shady Ibrahim ElEbrashy ◽

Ehab ElRefaay ◽

Farouq H Youssef

Keyword(s):

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Dynamic Mri ◽

Tracer Uptake ◽

Dexamethasone Suppression Test ◽

Cushing's Disease ◽

Pet Ct ◽

Suppression Test ◽

Acth Secreting ◽

Dexamethasone Suppression

Abstract Background and objective: Hypercortisolism is the hall mark of ACTH Cushing’s syndrome, which is a benign ACTH secreting tumor resulting in high morbidity and mortality. The diagnosis is based on an elevated serum ACTH, elevated 24h urinary cortisol or a non-suppressible ACTH after dexamethasone suppression test. Confirmation of ACTH hypersecretion is followed by localization of the adenoma which can be pituitary in origin or peripheral. Dynamic MRI of the pituitary gland is the gold standard for diagnosis of pituitary tumors, and contrast enhanced CT scan is the gold standard for ectopic lesions which are usually lung tumors. The localization of the lesion is often a challenge because conventional MRI fail to show pituitary lesions and sometimes requiring inferior petrosal sinus sampling to confirm pituitary origin. Transsphenoidal surgery is the treatment of choice for Cushing’s disease, even without MRI evidence of pituitary tumors, if pituitary origin is confirmed by inferior petrosal sinus sampling. This causes increase in the incidence of treatment failure and complications. Thus, the diagnosis of Cushing’s disease urges exploring new diagnostic modalities. In our study we test the sensitivity of 11C methionine PET CT together with dynamic pituitary MRI in localization of ACTH dependent Cushing’s disease. Materials and methods This is an interventional, prospective study, forty-one subjects: newly diagnosed ACTH dependent Cushing’s Syndrome (n=29). (indicated by non-suppressible ACTH on dexamethasone suppression test) or persistent hypercortisolism following transsphenoidal surgery (n=12). 11C methionine PET CT was done in all cases in addition to dynamic pituitary MRI. All patients underwent 11 C-methionine PET-CT in addition to dynamic pituitary MRI This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging.Inclusion Criteria:• Aged 18 years old or over• Patient with a diagnosed Cushing’s disease confirmed by non-suppressible ACTH on dexamethasone suppression test.• Patient with persistent ACTH dependent Cushing’s disease following transsphenoidal surgery.• Patient not enrolled in other interventional studies.Exclusion Criteria:• Contraindication to MRI• Pregnant woman, breastfeeding RESULTS: Patients with newly diagnosed ACTH dependent Cushing: 24 out of 29 of the cases showed adenoma on dynamic MRI of the pituitary; 5 out of 29 cases failed to showed any lesions on dynamic MRI of the pituitary; Inferior petrosal sampling was done and confirmed pituitary origin in 4 out of 5 and 1 out of 5 was found to have ectopic ACTH secretion. In patients with persistent hypercortisolism following transsphenoidal surgery; 3 out of 12 of the cases showed adenoma on dynamic MRI of the pituitary and 7 out of 12 cases failed to showed any lesions on dynamic MRI of the pituitary and inferior petrosal sampling was done and confirmed pituitary origin in all 12 cases. All 41 cases underwent 11C methionine PET CT scan; 39 patients showed tracer uptake on 11c methionine PET CT scan in the pituitary area, 36 of which had unilateral asymmetrical tracer uptake. All 40 subjects with suspected pituitary lesions were confirmed to be of pituitary origin by histopathological examination of biopsies taken intraoperatively. CONCLUSIONS 11C methionine PET CT has proven to be of very high sensitivity in detecting ACTH secreting adenomas, further studies should be done on a larger scale as this modality can address the pitfalls in localization of ACTH secreting lesions.

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Transsphenoidal surgery for Cushing's disease: a review of success rates, remission predictors, management of failed surgery, and Nelson's Syndrome

Neurosurgical FOCUS ◽

10.3171/foc.2007.23.3.7 ◽

2007 ◽

Vol 23 (3) ◽

pp. 1-6 ◽

Cited By ~ 67

Author(s):

Daniel F. Kelly

Keyword(s):

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Remission Rate ◽

Cushing's Disease ◽

Surgical Morbidity ◽

Nelson’S Syndrome ◽

Nelson's Syndrome ◽

Radio Therapy ◽

Transsphenoidal Adenomectomy

✓ Cushing's disease is a serious endocrinopathy that, if left untreated, is associated with significant morbidity and mortality rates. After diagnostic confirmation of Cushing's disease has been made, transsphenoidal adenomectomy is the treatment of choice. When a transsphenoidal adenomectomy is performed at experienced transsphenoidal surgery centers, long-term remission rates average 80% overall, surgical morbidity is low, and the mortality rate is typically less than 1%. In patients with well-defined noninvasive microadenomas, the long-term remission rate averages 90%. For patients in whom primary surgery fails, treatment options such as bilateral adrenalectomy, stereotactic radiotherapy or radiosurgery, total hypophysectomy, or adrenolytic medical therapy need to be carefully considered, ideally in a multidisciplinary setting. The management of Nelson's Syndrome often requires both transsphenoidal surgery and radio-therapy to gain disease control.

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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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Transsphenoidal Surgery for Cushing's Disease: Endocrinological Follow-up Monitoring of 82 Patients

Neurosurgery ◽

10.1097/00006123-200207000-00008 ◽

2002 ◽

Vol 51 (1) ◽

pp. 57-62 ◽

Cited By ~ 109

Author(s):

Ilan Shimon ◽

Zvi Ram ◽

Zvi R. Cohen ◽

Moshe Hadani

Keyword(s):

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Adrenocorticotropic Hormone ◽

Remission Rate ◽

The United States ◽

Cushing's Disease ◽

Free Cortisol ◽

Remission Rates ◽

Surgical Failure

Abstract OBJECTIVE Transsphenoidal surgery is the preferred treatment modality for adrenocorticotropic hormone-secreting pituitary adenomas. In the past 2 decades, several institutions in the United States and Europe have reported remission rates of 70 to 85% after transsphenoidal surgery for treatment of Cushing's disease. We analyzed our postoperative results for a large cohort of patients with Cushing's disease. METHODS Eighty-two patients with adrenocorticotropic hormone-secreting adenomas (79 microadenomas and 3 macroadenomas) underwent transsphenoidal surgery between 1990 and 2000. Seventy-seven patients were surgically treated for the first time, and 13 patients underwent reoperations (5 had undergone the first operation elsewhere) because of previous surgical failure (10 patients) or recurrence (3 patients). The mean postoperative follow-up period was 4.2 ± 2.8 years. Biochemical remission was defined as postoperative normalization of elevated 24-hour urinary free cortisol secretion and suppression of morning cortisol levels with 1 mg of dexamethasone. RESULTS Remission was achieved for 78% of all patients after one operation and for 62% of patients who underwent a second operation. The recurrence rate was 5%. Ten patients did not exhibit a visible tumor on magnetic resonance imaging scans, and the other patients were divided according to adenoma size (2–5 or 6–10 mm). Remission rates were similar for the three groups of patients (78–80%). Pituitary tumor stained for adrenocorticotropic hormone was detected in 78% of resected pituitary tissue specimens obtained from patients who achieved remission, compared with 53% from patients who experienced surgical failure (P = 0.06). CONCLUSION Our series demonstrates the efficacy of transsphenoidal surgery for Cushing's disease resulting from pituitary microadenomas. Microadenoma size had no effect on the remission rate. Reoperations are indicated after initial surgical failures.

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Remission rate after transsphenoidal surgery in patients with pathologically confirmed Cushing’s disease, the role of cortisol, ACTH assessment and immediate reoperation: a large single center experience

Pituitary ◽

10.1007/s11102-012-0455-z ◽

2012 ◽

Vol 16 (4) ◽

pp. 452-458 ◽

Cited By ~ 46

Author(s):

Nadia Hameed ◽

Chris G. Yedinak ◽

Jessica Brzana ◽

Sakir H. Gultekin ◽

Nicholas D. Coppa ◽

...

Keyword(s):

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Remission Rate ◽

Cushing's Disease ◽

Single Center ◽

Single Center Experience ◽

Immediate Reoperation

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Electronic Medical Records as Input to Predict Postoperative Immediate Remission of Cushing’s Disease: Application of Word Embedding

Frontiers in Oncology ◽

10.3389/fonc.2021.754882 ◽

2021 ◽

Vol 11 ◽

Author(s):

Wentai Zhang ◽

Dongfang Li ◽

Ming Feng ◽

Baotian Hu ◽

Yanghua Fan ◽

...

Keyword(s):

Electronic Medical Records ◽

Cushing’S Disease ◽

Medical Records ◽

Transsphenoidal Surgery ◽

Remission Rate ◽

Area Under The Curve ◽

Word Embedding ◽

Cushing's Disease ◽

Free Text ◽

College Hospital

BackgroundNo existing machine learning (ML)-based models use free text from electronic medical records (EMR) as input to predict immediate remission (IR) of Cushing’s disease (CD) after transsphenoidal surgery.PurposeThe aim of the present study is to develop an ML-based model that uses EMR that include both structured features and free text as input to preoperatively predict IR after transsphenoidal surgery.MethodsA total of 419 patients with CD from Peking Union Medical College Hospital were enrolled between January 2014 and August 2020. The EMR of the patients were embedded and transformed into low-dimensional dense vectors that can be included in four ML-based models together with structured features. The area under the curve (AUC) of receiver operating characteristic curves was used to evaluate the performance of the models.ResultsThe overall remission rate of the 419 patients was 75.7%. From the results of logistic multivariate analysis, operation (p < 0.001), invasion of cavernous sinus from MRI (p = 0.046), and ACTH (p = 0.024) were strongly correlated with IR. The AUC values for the four ML-based models ranged from 0.686 to 0.793. The highest AUC value (0.793) was for logistic regression when 11 structured features and “individual conclusions of the case by doctor” were included.ConclusionAn ML-based model was developed using both structured and unstructured features (after being processed using a word embedding method) as input to preoperatively predict postoperative IR.

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