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

1990 ◽  
Vol 72 (3) ◽  
pp. 363-369 ◽  
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.

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

Neurosurgery ◽  
2002 ◽  
Vol 51 (1) ◽  
pp. 57-62 ◽  
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.

scholarly journals Outcomes of endoscopic transsphenoidal surgery for Cushing's disease

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.

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.

Radiosurgery for Cushing's disease after failed transsphenoidal surgery

2000 ◽  
Vol 93 (5) ◽  
pp. 738-742 ◽  
Author(s):  
Jonas M. Sheehan ◽  
Mary L. Vance ◽  
Jason P. Sheehan ◽  
Dilantha B. Ellegala ◽  
Edward R. Laws
Keyword(s):  
Gamma Knife ◽  
Cushing’S Disease ◽  
Tumor Size ◽  
Transsphenoidal Surgery ◽  
Gamma Knife Radiosurgery ◽  
Magnetic Resonance Images ◽  
Cushing's Disease ◽  
Content Type ◽  
Fine Print

Object. Although transsphenoidal surgery has become the standard of care for Cushing's disease, it is often unsuccessful in normalizing cortisol production. In this study the authors investigate the safety and efficacy of gamma knife radiosurgery (GKRS) for Cushing's disease after failed transsphenoidal surgery.Methods. The records of all patients who underwent GKRS at the authors' institution after unsuccessful transsphenoidal surgery for Cushing's disease were retrospectively reviewed. Successful treatment was considered a normal or below-normal 24-hour urinary free cortisol (UFC) level. Records were also evaluated for relapse, new-onset endocrine deficiencies, interval change in tumor size, and visual complications.Forty-three patients underwent 44 gamma knife procedures with follow up ranging from 18 to 113 months (mean 39.1, median 44 months). Normal 24-hour UFC levels were achieved in 27 patients (63%) at an average time from treatment of 12.1 months (range 3–48 months). Three patients had a recurrence of Cushing's disease at 19, 37, and 38 months, respectively, after radiosurgery. New endocrine deficiencies were noted in seven patients (16%). Follow-up magnetic resonance images obtained in 33 patients revealed a decrease in tumor size in 24, no change in nine, and an increase in size in none of the patients. One patient developed a quadrantanopsia 14 months after radiosurgery despite having received a dose of only 0.7 Gy to the optic tract.Conclusions. Gamma knife radiosurgery appears to be safe and effective for the treatment of Cushing's disease refractory to pituitary surgery. Delayed recurrences and new hormone deficiencies may occur, indicating the necessity for regular long-term follow up.

Surgical treatment of Cushing's disease

1987 ◽  
Vol 66 (2) ◽  
pp. 204-212 ◽  
Author(s):  
William F. Chandler ◽  
David E. Schteingart ◽  
Ricardo V. Lloyd ◽  
Paul E. McKeever ◽  
Gloria Ibarra-Perez
Keyword(s):  
Cushing’S Disease ◽  
Immunohistochemical Staining ◽  
Adrenocorticotropic Hormone ◽  
Cushing's Disease ◽  
Content Type ◽  
Acth Secreting ◽  
Endocrine Symptoms ◽  
Lung Carcinoid ◽  
Fine Print ◽  
Pharyngeal Pituitary

✓ The endocrinological, radiological, surgical, and pathological experience with 34 consecutive patients operated on for Cushing's disease is presented. Preoperative endocrine evaluation demonstrated that 19 patients had “typical” endocrine patterns for pituitary adrenocorticotropic hormone (ACTH)-dependent hypercortisolism and 11 had “atypical” testing. Pituitary pathology was found in 95% of the patients with typical preoperative endocrine testing but in only 55% of those with atypical testing. Eight of 34 preoperative computerized tomography scans demonstrated tumors, which correlated in all instances with the surgical findings. Microadenomas were removed from 25 patients, 22 of whom achieved postoperative remission of endocrine symptoms. Macroadenomas were found in three patients, only one of whom achieved remission after surgery. One patient had removal of an adenoma in the pharyngeal pituitary, and in another an ectopic lung carcinoid was excised; both of these patients were in postoperative remission. Four patients underwent transsphenoidal exploration but no definitive explanation was found for their hypercortisolism; these patients were not in remission. Immunohistochemical staining was performed on every specimen and all tumors showed excessive ACTH-secreting cells. A new rapid stain of the fibrovascular stroma is described.

scholarly journals Negative surgical exploration in patients with Cushing’s disease: benefit of two-thirds gland resection on remission rate and a review of the literature

2018 ◽  
Vol 129 (5) ◽  
pp. 1260-1267 ◽  
Author(s):  
Steven B. Carr ◽  
Bette K. Kleinschmidt-DeMasters ◽  
Janice M. Kerr ◽  
Katja Kiseljak-Vassiliades ◽  
Margaret E. Wierman ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Cushing’S Disease ◽  
Remission Rate ◽  
Cushing's Disease ◽  
Entire Group ◽  
Cell Hyperplasia ◽  
Cell Adenoma ◽  
Surgical Exploration ◽  
Acth Cell

OBJECTIVEThe authors report their single-institution experience with the pathological findings, rates of remission, and complications in patients with presumed Cushing’s disease (CD) who underwent a two-thirds pituitary gland resection when no adenoma was identified at the time of transsphenoidal surgery (TSS). The authors also review the literature on patients with CD, negative surgical exploration, and histological findings.METHODSThis study is a retrospective analysis of cases found in neurosurgery and pathology department databases between 1989 and 2011. In all cases, patients had been operated on by the same neurosurgeon (K.O.L.). Twenty-two (13.6%) of 161 patients who underwent TSS for CD had no adenoma identified intraoperatively after systematic exploration of the entire gland; these patients all underwent a two-thirds pituitary gland resection. A chart review was performed to assess treatment data points as well as clinical and biochemical remission status.RESULTSOf the 22 patients who underwent two-thirds gland resection, 6 (27.3%) ultimately had lesions found on final pathology. All 6 patients were found to have a distinct adrenocorticotropic hormone (ACTH) cell adenoma. Sixteen (72.7%) of the patients had no tumor identified, with 3 of these patients suspected of having ACTH cell hyperplasia. The follow-up duration for the entire group was between 14 and 315 months (mean 98.9 months, median 77 months). Remission rates were 100% (6/6 patients) for the ACTH cell adenoma group and 75% (12/16) for the group without adenoma. Overall, 18 (81.8%) of the 22 patients had no evidence of hypercortisolism at last follow-up, and 4 patients (18%) had persistent hypercortisolism, defined as a postoperative cortisol level > 5 μg/dl. Of these 4 patients, 1 was suspected of harboring a cavernous sinus adenoma, 2 were found to have lung tumors secreting ACTH, and 1 remained with an undiagnosed etiology. Rates of postoperative complications were low.CONCLUSIONSThe diagnosis and treatment of CD can be challenging for neurosurgeons, endocrinologists, and pathologists alike. Failure to find a discrete adenoma at the time of surgery occurs in at least 10%–15% of cases, even in experienced centers. The current literature provides little guidance regarding rational intraoperative approaches in such cases. The authors’ experience with 161 patients with CD, when no intraoperative tumor was localized, demonstrates the utility of a two-thirds pituitary gland resection with a novel and effective surgical strategy, as suggested by a high initial remission rate and a low operative morbidity.

Surgical management of adrenocorticotropic hormone—secreting macroadenomas: outcome and challenges in patients with Cushing's disease or Nelson's syndrome

2005 ◽  
Vol 103 (5) ◽  
pp. 825-830 ◽  
Author(s):  
Claudio De Tommasi ◽  
Mary Lee Vance ◽  
David O. Okonkwo ◽  
Alfa Diallo ◽  
Edward R. Laws
Keyword(s):  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Signs And Symptoms ◽  
Disease Recurrence ◽  
Cushing's Disease ◽  
Nelson’S Syndrome ◽  
Content Type ◽  
Nelson's Syndrome ◽  
Acth Secreting ◽  
Fine Print

Object. Adrenocorticotropic hormone (ACTH)—secreting pituitary macroadenomas are an uncommon cause of Cushing's disease (CD) and, subsequently, Nelson's syndrome (NS). They have been associated with low postoperative remission rates. The outcome of modern surgical treatment is unclear and thus was assessed in a series of 43 patients, with the goal of improving therapeutic results in patients with ACTH-secreting macroadenomas. Methods. Thirty-seven patients presented with CD and six with NS. They represented 15% of the patients surgically treated at the authors' institution for ACTH-secreting adenomas. The median patient age was 38 years (range 14–71 years), and the mean duration of follow up was 37 months (range 1–108 months). Remission occurred in 25 (67.6%) of 37 patients with CD, whereas the disease persisted in 12 (32.4%) of 37 patients. After an initial remission, three (12%) of 25 patients demonstrated signs and symptoms indicative of disease recurrence. Among patients with NS, only one (16.6%) displayed remission. Invasion of the dura mater by tumor was histologically demonstrated in 10 patients with CD and in two patients with NS. Conclusions. Comprehensive management of CD caused by ACTH-secreting macroadenomas through the appropriate use of combination therapy, including surgery, radiotherapy, radiosurgery, and adrenalectomy, can lead to outcomes similar to those for microadenomas. Disease recurrence and persistence rates are higher, often because of the invasiveness associated with macroadenomas. Remission of NS-associated macroadenomas is difficult to achieve. Strategies for the characterization and treatment of invasive macroadenomas are needed.

Delayed cure of Cushing's disease after transsphenoidal surgery of pituitary microadenomas

1978 ◽  
Vol 49 (4) ◽  
pp. 593-596 ◽  
Author(s):  
Stephen D. McDonald ◽  
Stanley E. Von Hofe ◽  
Steven G. Dorfman ◽  
Richard M. Jordan ◽  
James R. LaMorgese ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Normal Tissue ◽  
Adrenocorticotropic Hormone ◽  
Early Postoperative Period ◽  
Cushing's Disease ◽  
Content Type ◽  
Pituitary Microadenoma ◽  
Dexamethasone Suppression ◽  
Fine Print

✓ Transsphenoidal microdissection has been proposed as a preferred means of treating Cushing's disease. This procedure allows the surgeon to remove a pituitary microadenoma and at the same time to preserve normal tissue. Two cases described here were treated by this method. An interesting and important observation was that neither patient appeared to be cured for 2 to 6 weeks after surgery, as assessed by dexamethasone suppression. Later, normal suppressibility occurred and the course of each patient was compatible with cure. Patients treated by this method should not be automatically retreated because of adrenocorticotropic hormone (ACTH) non-suppressibility in the early postoperative period.

scholarly journals Duration of post-operative hypocortisolism predicts sustained remission after pituitary surgery for Cushing’s disease

2017 ◽  
Vol 6 (8) ◽  
pp. 625-636 ◽  
Author(s):  
Prachi Bansal ◽  
Anurag Lila ◽  
Manjunath Goroshi ◽  
Swati Jadhav ◽  
Nilesh Lomte ◽  
...  
Keyword(s):  
Predictive Factors ◽  
Cushing’S Disease ◽  
Tertiary Care ◽  
Cushing's Disease ◽  
Sustained Remission ◽  
Mri Findings ◽  
Recurrence Rates ◽  
Primary Treatment Modality ◽  
Remission Rates

Purpose Transsphenoidal surgery (TSS) is the primary treatment modality for Cushing’s disease (CD). However, the predictors of post-operative remission and recurrence remain debatable. Thus, we studied the post-operative remission and long-term recurrence rates, as well as their respective predictive factors. Methods A retrospective analysis of case records of 230 CD patients who underwent primary microscopic TSS at our tertiary care referral centre between 1987 and 2015 was undertaken. Demographic features, pre- and post-operative hormonal values, MRI findings, histopathological features and follow-up data were recorded. Remission and recurrence rates as well as their respective predictive factors were studied. Results Overall, the post-operative remission rate was 65.6% (early remission 46%; delayed remission 19.6%), while the recurrence rate was 41% at mean follow-up of 74 ± 61.1 months (12–270 months). Significantly higher early remission rates were observed in patients with microadenoma vs macroadenoma (51.7% vs 30.6%, P = 0.005) and those with unequivocal vs equivocal MRI for microadenoma (55.8% vs 38.5%, P = 0.007). Patients with invasive macroadenoma had poorer (4.5% vs 45%, P = 0.001) remission rates. Recurrence rates were higher in patients with delayed remission than those with early remission (61.5% vs 30.8%, P = 0.001). Duration of post-operative hypocortisolemia ≥13 months predicted sustained remission with 100% specificity and 46.4% sensitivity. Recurrence could be detected significantly earlier (27.7 vs 69.2 months, P < 0.001) in patients with available serial follow-up biochemistry as compared to those with infrequent follow-up after remission. Conclusion In our study, remission and recurrence rates were similar to that of reported literature, but proportion of delayed remission was relatively higher. Negative/equivocal MRI findings and presence of macroadenoma, especially those with cavernous sinus invasion were predictors of poor remission rates. In addition to early remission, longer duration of post-operative hypocortisolism is an important predictor of sustained remission. Regular biochemical surveillance may help in identifying recurrence early.

Early repeat surgery for persistent Cushing's disease

1994 ◽  
Vol 80 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Zvi Ram ◽  
Lynnette K. Nieman ◽  
Gordon B. Cutler ◽  
George P. Chrousos ◽  
John L. Doppman ◽  
...  
Keyword(s):  
Cortisol Level ◽  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Cushing's Disease ◽  
Sustained Remission ◽  
Repeat Surgery ◽  
Content Type ◽  
Initial Surgery ◽  
Early Reoperation ◽  
Fine Print

✓ The potential efficacy of early repeat transsphenoidal surgery for persistent Cushing's disease has not previously been examined. On 222 patients with no prior pituitary treatment and a preoperative diagnosis of Cushing's disease, 29 (13%) remained hypercortisolemic after an initial transsphenoidal pituitary exploration. Seventeen of these 29 patients underwent further surgery 7 to 46 days after the initial transsphenoidal approach in order to completely excise suspected residual tumor. Patients were followed for 4 to 84 months (mean ± standard deviation, 34 ± 25 months) to document sustained remission or recurrence of Cushing's disease (a urine free cortisol level > 90 µg/day was considered evidence of recurrence). Of the 17 patients with repeat surgery, 12 (71%) had resolution of hypercortisolism (morning plasma cortisol level < 5 µg/dl); however, in three of these 12, hypercortisolism recurred 5, 12, and 24 months later. In 14 patients a lesion that appeared to be a tumor was identified during the initial procedure or on histological examination. Of these, 12 had immediate resolution of hypercortisolism and nine are still in remission. Three patients, in whom no adenoma could be identified during the initial surgery or an examination of the partial hypophysectomy specimen from the initial surgery, had persistent Cushing's syndrome after the second operation. Seven (41%) of the 17 patients developed hypopituitarism requiring treatment with thyroid hormone, gonadal steroid, or vasopressin replacement. The low incidence of identification of an adenoma on computerized tomography or magnetic resonance images (three of 17 patients), the failure to find a corticotrophic adenoma during the initial surgery (10 of 17 patients), and the failure of these 17 patients to respond to the initial transsphenoidal surgery suggest that they may comprise a subset of patients who are more difficult to treat successfully with surgery than most patients with Cushing's disease. Despite that, early reoperation induced immediate remission of hypercortisolism in 71% of cases, but did so at the expense of a high risk of hypopituitarism. However, since the alternative treatments (such as radiation therapy, long-term drug therapy, or bilateral adrenalectomy) also have potential adverse effects, early reoperation deserves consideration for the management of persistent Cushing's disease, especially when an adrenocorticotrophic hormone-secreting adenoma was partially excised during the first surgery.

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