Long Term Results of Transsphenoidal Adenomectomy in Patients with Cushing's Disease

Abstract As part of an ongoing series, 100 patients with Cushing's disease underwent transsphenoidal operations. Pituitary adenomas were confirmed in 93 patients, and initial remission was achieved in 86 (92%) of them. Hypercortisolemia was not corrected in 7 patients, and in 4 this was due to invasive adenomas. These patients were subjected to irradiation, medical treatment, or both after operation. Only 7 of the 100 patients had no pituitary adenoma found at operation, and they obtained no clinical remission even after partial or subtotal hypophysectomy. Follow-up review, with an emphasis on endocrinological studies, was performed on these patients for a mean period of 38 months. Seventy-eight patients were in long term remission after operation and had restoration of noncorticotropic hormone secretion as well as pituitary-adrenal function. Recurrence was noted in 8 patients after 19 to 82 months in remission. In all of these patients, pituitary adenomas were verified by reoperation and no case of corticotrophic cell hyperplasia was noted. We conclude that late recurrence of Cushing's disease may occur after adenoma removal and is due to the regrowth of adenoma cells left behind in the peritumoral tissue at the first operation. In view of the overall remission rate, transsphenoidal adenomectomy is considered a highly effective treatment for Cushing's disease.

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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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Comparison of Long Term Results Between Prolactin Secreting Adenomas and ACTH Secreting Adenomas

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100030080 ◽

1990 ◽

Vol 17 (1) ◽

pp. 74-77 ◽

Cited By ~ 17

Author(s):

Kalmon D. Post ◽

Jo-Ellen Habas

Keyword(s):

Cushing’S Disease ◽

Late Recurrence ◽

Long Term Results ◽

Cushing's Disease ◽

Late Relapse ◽

Entire Group ◽

Cure Rate ◽

Recurrence Rates ◽

Hypothalamic Regulation

ABSTRACT:A series of 100 prolactin secreting pituitary adenomas was reviewed and demonstrated an early cure rate of 85.2% with a cure rate of 89% if prolactin was less than 200 ng/ml. For macroadenomas the cure rate was 50% giving an overall cure rate of 71% for the entire group. When long term (> 5 years) followup was obtained a 17% incidence of recurrence was noted for the microadenoma group with a 20% recurrence rate for the macroadenoma group. Secretory dynamic studies were done shortly after surgery and then after a delay. Many showed a return to normal prolactin secretory dynamics suggesting that the underlying hypothalamic regulation is normal in most patients. Abnormal secretory dynamics at 6 weeks post operative testing were not predictive of which patients would relapse as many patients who had abnormal dynamics early did not relapse even during prolonged followup. Conversely a normal response to provocative testing did not preclude late relapse. A similar series of 40 consecutive patients with Cushing's disease was reviewed. Tumor was found in all but three cases. 84% of patients were cured and thus far only one patient (2.5%) has shown late recurrence with this occurring at 62/3 years following surgery with normal stimulatory dynamics present for five years. The implication is that hypothalamic regulation is normal in Cushing's disease as well. The differences in recurrence rates may be reflective of the aggressiveness with which one disease is treated, with the acceptance of a higher incidence of hypopituitarism as a consequence of more radical surgery for Cushing's disease.

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Pituitary Cushing's disease without adenoma

Acta Endocrinologica ◽

10.1530/acta.0.0940297 ◽

1980 ◽

Vol 94 (3) ◽

pp. 297-303 ◽

Cited By ~ 40

Author(s):

Adrian M. Schnall ◽

Kalman Kovacs ◽

Jerald S. Brodkey ◽

Olof H. Pearson

Keyword(s):

Pituitary Adenoma ◽

Cushing’S Disease ◽

Pituitary Adenomas ◽

Great Majority ◽

Serum Levels ◽

Cushing's Disease ◽

Serial Sections ◽

Cell Hyperplasia ◽

Biochemical Remission ◽

Lower Limits

Abstract. Recent reports of patients with Cushing's disease who have been explored via the transsphenoidal route indicate that the great majority has pituitary adenomas. We report a patient with biochemically documented pituitary-based hypercortisolism who had a clinical and biochemical remission following hypophysectomy. Serial sections of the pituitary tissue removed showed hyperplasia of corticotroph cells but no adenoma. Hypophysectomy was complete as documented by serum levels of FSH, LH, TSH, prolactin, hGH and ACTH at the lower limits of the respective assays, with no response to appropriate stimuli. This case demonstrates that a minority of patients with Cushing's disease has corticotroph cell hyperplasia without a pituitary adenoma.

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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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Long-Term Results of Stereotactic Radiosurgery in Secretory Pituitary Adenomas

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2008-2772 ◽

2009 ◽

Vol 94 (9) ◽

pp. 3400-3407 ◽

Cited By ~ 118

Author(s):

Frederic Castinetti ◽

Mariko Nagai ◽

Isabelle Morange ◽

Henry Dufour ◽

Philippe Caron ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Gamma Knife ◽

Pituitary Adenomas ◽

Univariate Analysis ◽

Late Recurrence ◽

Long Term Results ◽

Free Cortisol ◽

Mean Time

Context: To date, no study reported long-term follow-up results of gamma knife stereotactic radiosurgery (SR). Objective: The aim of the study was to determine long-term efficacy and adverse effects of SR in secreting pituitary adenomas. Design: We conducted a retrospective study of patients treated by SR in the center of Marseille, France, with a follow-up of at least 60 months. Patients: A total of 76 patients were treated by SR for acromegaly (n = 43), Cushing’s disease (CD; n = 18), or prolactinoma (n = 15) as a primary (n = 27) or adjunctive postsurgical treatment (n = 49). Main Outcome Measures: After withdrawal of antisecretory drugs, patients were considered in remission if they had mean GH levels below 2 ng/ml and normal IGF-I (acromegaly), normal 24-h urinary free cortisol, and cortisol less than 50 nmol/liter after low-dose dexamethasone test (CD) or two consecutive normal samplings of prolactin levels (prolactinoma). Results: After a mean follow-up of 96 months, 44.7% of the patients were in remission. Mean time to remission was 42.6 months. Twelve patients presented late remission at least 48 months after SR. Two patients with CD presented late recurrence 72 and 96 months after SR. Forty percent of patients treated primarily with SR were in remission. Target volume and initial hormone levels were significant predictive factors of remission in univariate analysis. Radiation-induced hypopituitarism was observed in 23% patients; in half of them, hypopituitarism was observed after a mean time of 48 to 96 months. Twenty-four patients were followed for more than 120 months; rates of remission and hypopituitarism were similar to the whole cohort. Conclusions: SR is an effective and safe primary or adjunctive treatment in selected patients with secreting pituitary adenomas. Long-term results of Gamma Knife radiosurgery draw attention to the possibility of late recurrence, late remission, and low risk of hypopituitarism.

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Long-term results of treatment in patients with ACTH-secreting pituitary macroadenomas

Acta Endocrinologica ◽

10.1530/eje.0.1490195 ◽

2003 ◽

pp. 195-200 ◽

Cited By ~ 56

Author(s):

S Cannavo ◽

B Almoto ◽

C Dall'Asta ◽

S Corsello ◽

RM Lovicu ◽

...

Keyword(s):

Cavernous Sinus ◽

Cushing’S Disease ◽

Long Term Results ◽

Cushing's Disease ◽

Tumor Diameter ◽

Pituitary Macroadenoma ◽

Second Surgery ◽

Acth Secreting

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

Journal of Neurosurgery ◽

10.3171/2017.5.jns162901 ◽

2018 ◽

Vol 129 (5) ◽

pp. 1260-1267 ◽

Cited By ~ 3

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.

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