Cavernous Sinus Exploration in Cushing’s Disease: Indications and Outcomes

2020 ◽  
Author(s):  
Elizabeth Hogan ◽  
Gretchen Scott ◽  
Charlampos Lysikatos-Lyssikatos ◽  
Raven McGlotten ◽  
Constantine Stratakis ◽  
...  
Heliyon ◽  
2020 ◽  
Vol 6 (10) ◽  
pp. e05299
Author(s):  
Mohammad Ghorbani ◽  
Hamideh Akbari ◽  
Christoph J. Griessenauer ◽  
Christoph Wipplinger ◽  
Alireza Dastmalchi ◽  
...  

Author(s):  
Y Meng ◽  
S Suppiah ◽  
L Gonen ◽  
G Klironomos ◽  
F Gentili ◽  
...  

Introduction: Surgical removal is the standard treatment for Cushing’s disease. Although endoscopic transsphenoidal surgical (ETS) approach has grown in popularity, its efficacy has not yet been established. Furthermore, achieving long-term remission remains challenging. Methods: We conducted a retrospective chart review of 39 consecutive patients who underwent ETS for Cushing’s disease at our institution between 2005 and 2014. Univariate analysis using Pearson’s χ2 test was carried out on variables of patient demographics, radiology, pathology, biochemical markers versus recurrence. Results: The mean age was 40, with 82% females. Average length of follow-up was 44.8 months. Based on serum cortisol level, 28 patients (71%) achieved mid to long-term remission after ETS. Of them, 25 experienced an immediate remission, and 3 achieved a delayed remission as long as 4 months postoperatively. MRI findings of (1) microadenomas or no detectable abnormality, (2) adjacency to the cavernous sinus wall were associated with significantly higher recurrence rate (p<0.05). Histologically, MIB-1 >5% was not a significant variable (p=0.55). Conclusion: We found ETS resection to be an effective and safe procedure for majority of the ACTH-secreting adenomas, with remission rates >70%. Additionally, patients with microadenomas, negative preoperative MR, and cavernous sinus adjacency were less likely to achieve remission.


Author(s):  
O. Cohen-Inbar

For patient with a recurrent or residual acromegaly or Cushing’s disease (CD) after resection, Gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow up has hampered understanding of the latent risks of hypopituitarism in patients with a Acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for Acromegaly or CD. Methods: From a prospectively created, IRB approved database, we identified all patients with a Acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow up of 60 months were included. The median follow-up is 159.5 months (60.1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement. Results: 60 patients with either Acromegaly or CD were included. Median tumor volume at time of GKRS was 1.3 cm3 (0.3-13.4), median margin dose was 25 Gy (6-30). GKRS induced new pituitary deficiency occurred in 58.3% (n=35) of patients. Growth Hormone deficiency was most common (28.3%, n=17). The actuarial overall rates of hypopituitarism at 3, 5, and 10 years were 10%, 21.7%, and 53.3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumor was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (p=0.018). Conclusions: Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS.


1999 ◽  
Vol 84 (5) ◽  
pp. 1602-1610 ◽  
Author(s):  
Kathryn E. Graham ◽  
Mary H. Samuels ◽  
Gary M. Nesbit ◽  
David M. Cook ◽  
Oisin R. O’Neill ◽  
...  

Inferior petrosal sinus sampling (IPSS) is used to distinguish pituitary Cushing’s disease from occult cases of the ectopic ACTH syndrome, but is limited in that it requires the use of ovine CRH (oCRH) and is not highly accurate at predicting the intrapituitary location of tumors. This study was designed to determine whether cavernous sinus sampling (CSS) is as safe and accurate as IPSS, whether CSS can eliminate the need for oCRH stimulation, and whether CSS can accurately predict the intrapituitary location of tumors. Ninety-three consecutive patients with ACTH-dependent Cushing’s syndrome were prospectively studied with bilateral, simultaneous CSS before and after oCRH stimulation. Prediction of a pituitary or ectopic ACTH source was based on cavernous/peripheral plasma ACTH ratios. Intrapituitary tumor location was predicted based on lateralization (side to side) ACTH ratios. These predictions were compared to surgical outcome in the 70 patients who had surgically proven pituitary (n= 65) or ectopic (n = 5) disease. CSS distinguished pituitary Cushing’s disease from the ectopic ACTH syndrome in 93% of patients with proven tumors before oCRH administration and in 100% of patients with proven tumors after oCRH. It was as safe and efficacious as published IPSS results. CSS accurately predicted the intrapituitary lateralization of the tumor in 83% of all patients and 89% of those patients with good catheter position and symmetric venous flow. CSS is as safe and accurate as IPSS for distinguishing patients with pituitary Cushing’s disease from those with the ectopic ACTH syndrome. In addition, CSS appears to be superior to IPSS for predicting intrapituitary tumor lateralization.


2002 ◽  
Vol 110 (07) ◽  
pp. 329-335 ◽  
Author(s):  
J. Flitsch ◽  
D. Lüdecke ◽  
U. Knappe ◽  
U. Grzyska

Neuropeptides ◽  
1998 ◽  
Vol 32 (2) ◽  
pp. 119-123 ◽  
Author(s):  
H Watanobe ◽  
T Tamura ◽  
S Habu ◽  
Y Kakizaki ◽  
A Kohsaka ◽  
...  

1998 ◽  
Vol 83 (1) ◽  
pp. 63-67 ◽  
Author(s):  
Lewis S. Blevins ◽  
James H. Christy ◽  
Masheed Khajavi ◽  
George T. Tindall

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 &lt; 0.02). Cavernous sinus invasion (odds ratio, 35; 95% confidence interval, 2.6–475; P &lt; 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&lt; 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&lt; 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.


2003 ◽  
pp. 195-200 ◽  
Author(s):  
S Cannavo ◽  
B Almoto ◽  
C Dall'Asta ◽  
S Corsello ◽  
RM Lovicu ◽  
...  

OBJECTIVE: Since Cushing's disease due to large pituitary tumors is rare, we evaluated biochemical characteristics at entry and the results of first surgical approach and of adjuvant therapeutic strategies during a long-term follow-up period. DESIGN: We studied 26 patients (nine male, 17 female; 42.5+/-12.7 years, mean+/-s.e.) with ACTH-secreting pituitary macroadenoma (tumor diameter: 11-40 mm). METHODS: At entry, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were measured in all patients, a high-dose dexamethasone (dexa) suppression test was evaluated in 22 cases and a corticotrophin releasing hormone (CRH) test in 20 cases. Patients were re-evaluated after operation and, when not cured, they underwent second surgery, radiotherapy and/or ketoconazole treatment. The follow-up period was 78+/-10 months. RESULTS: Before surgery, dexa decreased ACTH (>50% of baseline) in only 14/22 patients. The CRH-stimulated ACTH/cortisol response was normal in six patients, impaired in six patients and exaggerated in eight patients. After operation eight patients were cured, nine had normalized cortisol levels and nine were not cured. Pre-surgery, mean ACTH values were significantly higher in the not cured patients than in those normalized (P<0.05) and cured (P<0.01); the ACTH response to CRH was impaired in only six patients of the not cured group. The tumour diameter was significantly less in cured patients (P<0.02) and in normalized patients (P<0.05) than in the not cured ones. Magnetic resonance imaging (MRI) showed invasion of the cavernous sinus in 2/9 normalized, and in 6/9 not cured patients. After surgery, ACTH, cortisol and UFC were significantly lower than at entry in cured and in normalized patients, but not in not cured patients. In the cured group, the disease recurred in one patient who was unsuccessfully treated with ketoconazole. In the normalized group, a relapse occurred in eight patients: radiotherapy and ketoconazole induced cortisol normalization in one case, hypoadrenalism in one case and were ineffective in another one, while five patients were lost at follow-up. In the not cured group, eight patients underwent second surgery, radiotherapy and/or ketoconazole, while one patient was lost at follow-up. These therapies induced cortisol normalization in two patients and hypoadrenalism in one. CONCLUSIONS: (i) A sub-set of patients with ACTH-secreting pituitary macroadenoma showed low sensitivity to high doses of dexamethasone and to CRH, (ii) pituitary surgery cured Cushing's disease in a minority of patients, (iii) high baseline ACTH levels, impaired ACTH response to CRH, increased tumor size or invasion of the cavernous sinus were unfavourable prognostic factors for surgical therapy, and (iv) second surgery, radiotherapy and/or ketaconazole cured or normalized hypercortisolism in half of the patients with recurrence or not cured.


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