scholarly journals Update on the management of recurrent Cushing's disease

2015 ◽  
Vol 38 (2) ◽  
pp. E16 ◽  
Author(s):  
Martin J. Rutkowski ◽  
Patrick M. Flanigan ◽  
Manish K. Aghi
Keyword(s):  
Patient Outcomes ◽  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Bilateral Adrenalectomy ◽  
Cushing's Disease ◽  
Tumor Control ◽  
Repeat Resection ◽  
Risks And Benefits ◽  
Acth Secreting

After transsphenoidal surgery, Cushing's disease (CD) shows excellent long-term remission rates, but it may recur and pose a therapeutic challenge. Findings in recent published reports on the treatment of recurrent adrenocorticotropic hormone (ACTH)–secreting tumors suggest that repeat resection, radiation-based therapies such as Gamma Knife surgery and proton-beam radiosurgery, pharmacotherapy, and bilateral adrenalectomy all have important roles in the treatment of recurrent CD. Each of these interventions has inherent risks and benefits that should be presented to the patient during counseling on retreatment options. Radiation-based therapies increasingly appear to have efficacies similar to those of repeat resection in achieving biochemical remission and tumor control. In addition, an expanding retinue of medication-based therapies, several of which are currently being evaluated in clinical trials, has shown some promise as tertiary adjunctive therapies. Lastly, bilateral adrenalectomy may offer durable control of refractory recurrent CD. An increasing number of published studies with long-term patient outcomes highlight the evolving treatment patterns in the management of recurrent CD.

Favorable long-term outcome of bilateral adrenalectomy in Cushing's disease

2014 ◽  
Author(s):  
Andrea Osswald ◽  
Eva Plomer ◽  
Christina Dimopoulou ◽  
Monika Milian ◽  
Rainer Blaser ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Bilateral Adrenalectomy ◽  
Cushing's Disease ◽  
Term Outcome ◽  
Long Term Outcome

scholarly journals Bilateral adrenalectomy in Cushing's disease: Altered long-term quality of life compared to other treatment options

2019 ◽  
Vol 80 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Pauline Sarkis ◽  
Muriel Rabilloud ◽  
Jean-Christophe Lifante ◽  
Anna Siamand ◽  
Emmanuel Jouanneau ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cushing’S Disease ◽  
Treatment Options ◽  
Bilateral Adrenalectomy ◽  
Cushing's Disease

scholarly journals Cyclic Cushing's disease with misleading inferior petrosal sinus sampling results during a trough phase

2015 ◽  
Vol 38 (2) ◽  
pp. E7 ◽  
Author(s):  
Vivien Bonert ◽  
Namrata Bose ◽  
John D. Carmichael
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Diagnostic Testing ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Inferior Petrosal Sinus ◽  
Inferior Petrosal Sinus Sampling ◽  
Acth Secreting ◽  
Transsphenoidal Resection

Diagnosing Cushing's syndrome is challenging and is further hampered when investigations are performed in a patient with cyclic Cushing's syndrome. A subset of patients with Cushing's syndrome exhibit periods of abnormal cortisol secretion with interspersed normal secretion. Patients can have periods of clinical improvement during these quiescent phases or remain symptomatic. Initial diagnostic testing can be challenging because of the unpredictable durations of the peak and trough phases, and it is especially challenging when the diagnosis of cyclic Cushing's syndrome has not yet been determined. Here, the authors present the case of a patient with Cushing's disease with a pathology-proven adrenocorticotropic hormone (ACTH)–secreting pituitary adenoma and whose initial inferior petrosal sinus sampling (IPSS) results were deemed indeterminate; further studies elucidated the diagnosis of cyclic Cushing's syndrome. Repeat IPSS was diagnostic of a central source for ACTH secretion, and the patient was treated successfully with transsphenoidal resection. Literature concerning the diagnosis and management of cyclic Cushing's syndrome is also reviewed.

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 Significant GH deficiency after long-term cure by surgery in adult patients with Cushing’s disease

2007 ◽  
Vol 156 (2) ◽  
pp. 233-239 ◽  
Author(s):  
Francesca Pecori Giraldi ◽  
Massimiliano Andrioli ◽  
Laura De Marinis ◽  
Antonio Bianchi ◽  
Antonella Giampietro ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Cushing’S Disease ◽  
Gh Deficiency ◽  
Pituitary Surgery ◽  
Male Gender ◽  
Cushing's Disease ◽  
Gh Secretion ◽  
Wide Variability ◽  
Acth Secreting

Objective: Impaired GH secretion usually accompanies Cushing’s syndrome and a variable proportion of patients reportedly fail to recover normal GH secretion after successful treatment. This wide variability is most probably due to differences in the treatment (i.e. surgery and/or radiotherapy), timing of patient re-evaluation after surgery and dynamic tests employed to challenge GH secretion, and hinders a precise assessment of risk of GH deficiency after cure. The aim of the present study is to evaluate GH secretory status after long-term cure of Cushing’s disease achieved by surgery alone. Design and methods: We studied 34 patients (27 females and 7 males, age range 21–68 years) formerly affected by Cushing’s disease. Patients were studied 2–20 years (median 3.3 years) following remission of hypercortisolism; all patients underwent transsphenoidal surgery with the removal of an ACTH-secreting adenoma; repeat pituitary surgery for relapse was performed in two patients while bilateral adrenalectomy was necessary in two patients. In all subjects, the GH response to GHRH+arginine stimulation was evaluated. At the time of testing, 13 patients were still on steroid replacement therapy. Results: In long-term surgical remission, 22 patients (65.0%) presented subnormal GH secretion; partial GH deficiency (GH peak <16.5 μg/l) was found in 11 patients and severe GH deficiency (GH peak <9 μg/l) in another 11. Male gender and length of hypercortisolism were risk factors for postsurgical GH deficiency. Conclusions: This study demonstrates the presence of GH deficiency in a high percentage of patients with Cushing’s disease after long-term remission of hypercortisolism obtained by surgery alone. Male gender and length of hypercortisolism are the most significant predictors of postsurgical GH deficiency. This finding is significant as it highlights that even the most favourable therapeutical course, i.e. remission achieved by surgery alone, is accompanied by impaired GH secretion. Assessment of GH secretion is therefore recommended for all patients cured from Cushing’s disease, even if not submitted to radiotherapy. Studies on the clinical impact of GH deficiency and the use of GH replacement therapy seem warranted in patients cured from Cushing’s disease.

Results of Gamma Knife surgery for Cushing's disease

2013 ◽  
Vol 119 (6) ◽  
pp. 1486-1492 ◽  
Author(s):  
Jason P. Sheehan ◽  
Zhiyuan Xu ◽  
David J. Salvetti ◽  
Paul J. Schmitt ◽  
Mary Lee Vance
Keyword(s):  
Median Time ◽  
Gamma Knife ◽  
Cushing’S Disease ◽  
Cranial Nerves ◽  
Gamma Knife Surgery ◽  
High Rate ◽  
Cushing's Disease ◽  
Tumor Control

Object Cushing's disease is a challenging neuroendocrine disorder. Although resection remains the primary treatment option for most patients, the disease persists if there is residual or recurrent tumor. Stereotactic radiosurgery has been used to treat patients with persistent Cushing's disease after a prior resection. The authors report on the long-term risks and benefits of radiosurgery for Cushing's disease. Methods A retrospective review of a prospectively collected database of radiosurgery patients was undertaken at the University of Virginia. All patients with Cushing's disease treated with Gamma Knife surgery (GKS) were identified. Those without at least 12 months of clinical and radiological follow-up were excluded from this analysis. Rates of endocrine remission, tumor control, and adverse events were assessed. Statistical methods were used to identify favorable and unfavorable prognostic factors. Results Ninety-six patients with the required follow-up data were identified. The mean tumor margin dose was 22 Gy. The median follow-up was 48 months (range 12–209.8 months). At the last follow-up, remission of Cushing's disease occurred in 70% of patients. The median time to remission among all patients was 16.6 months (range 1–165.7 months). The median time to remission in those who had temporarily stopped taking ketoconazole at the time of GKS was 12.6 months, whereas it was 21.8 months in those who continued to receive ketoconazole (p < 0.012). Tumor control was achieved in 98% of patients. New loss of pituitary function occurred in 36% of patients. New or worsening cranial neuropathies developed in 5 patients after GKS, with the most common involving cranial nerves II and III. Conclusions Gamma Knife surgery offers a high rate of tumor control and a reasonable rate of endocrine remission in patients with Cushing's disease. The cessation of cortisol-lowering medications around the time of GKS appears to result in a more rapid rate of remission. Delayed hypopituitarism and endocrine recurrence develop in a minority of patients and underscore the need for long-term multidisciplinary follow-up.

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

2003 ◽  
pp. 195-200 ◽  
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.

scholarly journals Successful long-term control of Cushing’s disease after partial resection of gigantic ACTH-secreting pituitary adenoma

2016 ◽  
Vol 2 (1) ◽  
pp. 88-93
Author(s):  
Vatroslav Čerina ◽  
◽  
Luigi Cavallo ◽  
Ivan Kruljac ◽  
Jelena Marinković Radošević ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Partial Resection ◽  
Cushing's Disease ◽  
Acth Secreting

scholarly journals Does pituitary compression/empty sella syndrome contribute to MRI-negative Cushing’s disease? A single-institution experience

2020 ◽  
Vol 48 (6) ◽  
pp. E3
Author(s):  
Benjamin T. Himes ◽  
Adip G. Bhargav ◽  
Desmond A. Brown ◽  
Timothy J. Kaufmann ◽  
Irina Bancos ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Empty Sella ◽  
Cushing's Disease ◽  
Relative Reduction ◽  
Single Institution ◽  
Empty Sella Syndrome ◽  
Tissue Diagnosis ◽  
Acth Secreting

OBJECTIVECushing’s disease arises from functioning adrenocorticotropic hormone (ACTH)–secreting pituitary adenomas. These tumors can be very small and evade detection by MRI. Empty sella syndrome is a phenomenon by which an arachnoid outpouching of CSF into the sella leads to compression of the pituitary, likely due to intracranial hypertension (a common issue in Cushing’s disease), further leading to difficulty in visualizing the pituitary gland that may contribute to difficulty in finding a tumor on MRI, so-called MRI-negative Cushing’s disease. The authors sought to examine the association between empty sella syndrome and MRI-negative Cushing’s disease.METHODSA single-institution database of Cushing’s disease cases from 2000 to 2017 was reviewed, and 197 cases were included in the analysis. One hundred eighty patients had a tissue diagnosis of Cushing’s disease and 17 had remission with surgery, but no definitive tissue diagnosis was obtained. Macroadenomas (tumors > 1 cm) were excluded. The degree of empty sella syndrome was graded on the degree of CSF visualized in the sella on midline sagittal T1-weighted MRI.RESULTSOf the 197 cases identified, 40 (20%) presented with MRI-negative disease, and empty sella syndrome was present in 49 cases (25%). MRI-negative disease was found in 18 (37%) of 49 empty sella cases versus 22 (15%) of 148 cases without empty sella syndrome present. Empty sella syndrome was significantly associated with MRI-negative disease (OR 3.32, 95% CI 1.61–6.74, p = 0.0018). Decreased thickness of the pituitary gland was also associated with MRI-negative disease (mean thickness 5.6 vs 6.8 mm, p = 0.0002).CONCLUSIONSEmpty sella syndrome is associated with an increased rate of MRI-negative Cushing’s disease. Pituitary compression causing a relative reduction in the volume of the pituitary for imaging is a plausible cause for not detecting the tumor mass with MRI.

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.

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