Intensity-modulated radiotherapy for cushing's disease: single-center experience in 70 patients.

Context: Intensity-modulated radiotherapy (IMRT) is a modern precision radiotherapy technique for the treatment of the pituitary adenoma. Objective: Aim to investigate the efficacy and toxicity of IMRT in treating Cushing's Disease (CD). Methods: 70 of 115 patients with CD treated with IMRT at our institute from April 2012 to August 2021 were included in the study. The radiation doses were usually 45-50 Gy in 25 fractions. After IMRT, endocrine evaluations were performed every 6 months and magnetic resonance imaging (MRI) annually. Endocrine remission was defined as suppression of 1 mg dexamethasone test (DST) or normal 24-hour urinary free cortisol level (24hUFC). The outcome of endocrine remission, endocrine recurrence, tumor control and complications were retrieved from medical record. Results: At a median follow-up time of 36.8 months, the endocrine remission rate at 1, 2, 3 and 5 years were 28.5%, 50.2%, 62.5% and 74.0%, respectively. The median time to remission was 24 months (95%CI: 14.0-34.0). Endocrine recurrence was found in 5 patients (13.5%) till the last follow-up. The recurrence-free rate at 1, 2, 3 and 5 years after endocrine remission was 98.2%, 93.9%, 88.7% and 88.7%, respectively. The tumor control rate was 98%. The overall incidence of new onset hypopituitarism was 22.9%, with hypothyroidism serving as the most common individual axis deficiency. Univariate analysis indicated that only higher Ki-67 index (P=0.044) was significant favorable factors for endocrine remission. Conclusion: IMRT was a highly effective second-line therapy with low side effect profile for CD patients. Endocrine remission, tumor control and recurrence rates were comparable to previous reports on FRT and SRS.

Effect of pituitary-dependent hypercortisolism on the survival of dogs treated with radiotherapy for pituitary macroadenomas.

BACKGROUND: Radiotherapy (RT) is an effective treatment for dogs presented with neurologic signs caused by pituitary tumors. However, its impact on the outcome of concurrent pituitary-dependent hypercortisolism (PDH) is controversial. OBJECTIVES: Determine whether dogs with PDH have longer survival after pituitary RT compared with dogs with nonhormonally active pituitary masses and to evaluate whether clinical, imaging, and RT variables affect survival. ANIMALS: Ninety-four dogs divided into 2 groups: PDH and non-PDH, based on the presence of hypercortisolism. Forty-seven dogs were allocated to the PDH group and 47 to the non-PDH group. METHODS: Retrospective cohort study in which clinical records of dogs undergoing RT for pituitary macroadenomas between 2008 and 2018 at 5 referral centers were retrospectively evaluated. RESULTS: Survival was not statistically different between PDH and non-PDH groups (median survival time [MST], 590 days; 95% confidence interval [CI], 0-830 days and 738 days; 95% CI, 373-1103 days, respectively; P = .4). A definitive RT protocol was statistically associated with longer survival compared with a palliative protocol (MST 605 vs 262 days, P = .05). The only factor statistically associated with survival from multivariate Cox proportional hazard analysis was total radiation dose (Gy) delivered (P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: No statistical difference in survival was identified between the PDH and non-PDH groups, and longer survival was associated with higher Gy delivered.

Efficacy of whole-sellar gamma knife radiosurgery for magnetic resonance imaging-negative Cushing's disease.

BACKGROUND: Corticotroph adenoma delineation in Cushing's disease (CD) patients with previous surgery can be challenging. This study investigated the outcome of whole-sellar gamma knife radiosurgery (GKRS) in MRI-negative, but hormone-active CD patients with prior failed treatment attempts. METHODS: We retrospectively analyzed data of nine CD cases who underwent whole-sellar GKRS between April 2008 and April 2020 at a single center. Remission was determined as normal morning serum cortisol, normal 24-hour urinary free cortisol (UFC) or extended postoperative requirement for hydrocortisone replacement. RESULTS: Median age was 35.0 years, and most of the cases were female (89%). All subjects had undergone previous surgery. The mean pre-GKRS morning serum cortisol and 24-hour UFC were 27.5 µg/dL and 408.0 µg, respectively. Target volume varied from 0.6 to 1.8 cc, and the median margin dose was 28 Gy. The median duration of endocrine follow-up was 105 months, and initial endocrine remission was achieved in eight subjects (89%) at a median time of 22 months. The actuarial initial remission was 44% at two years, 67% at four years, and 89% at six years. The mean recurrence-free survival was 128 months. Age and pre-GKRS morning serum cortisol was found to be predictors for initial and durable endocrine remissions. New-onset hypopituitarism was observed in two of five patients (40%). None of the patients developed new neurological deficits and had GKRS-related adverse events during the follow-up. CONCLUSIONS: Whole-sellar GKRS is a safe and efficient method to manage MRI-negative CD and provides similar GKRS outcome rates as in MRI-positive CD.

Role of radiosurgery in the treatment of Cushing's disease.

Radiotherapy is a useful adjuvant treatment for patients with Cushing's disease that is not cured by surgery. In particular, Gamma Knife radiosurgery (GKRS) has been increasingly used worldwide as the preferred radiation technique in patients with persistent or recurrent Cushing's disease. The most widely accepted criterion for hormonal remission after GKRS is normalization of urinary free cortisol (UFC) levels. When a clear biological target is not identified, irradiation of the whole pituitary gland can be considered. The 5-year probability of remission is 65%-75%. Normalization of hypercortisolism usually occurs within 3 years from GKRS treatment and control of tumor growth is optimal, approaching more than 90%. No clear predictor of a favorable outcome has emerged up to now, except for the experience of the treating team. In the largest series, development of partial or complete hypopituitarism occurred between 15% and 36%. Severe side effects of GKRS, such as optic neuropathy and oculomotor palsy, are uncommon but have been documented in patients previously exposed to radiation. Recurrence of disease has been reported in as high as 16%-18% of the patients who achieved normalization of UFC levels in the two largest series, whereas smaller series did not describe late failure of GKRS. The reason for this discrepancy is unclear, as is the relationship between hormonal and tumoral recurrence. Another unresolved issue is whether treatment with adrenal blocking drugs can jeopardize the results of GKRS. GKRS is an effective second-line treatment in patients with Cushing's disease not cured by surgery. Hypopituitarism is the most frequent side effect of GKRS, whereas severe neurologic complications are uncommon in radiation-naïve patients.

Role of Radiation in the treatment of Cushing Disease.

In Cushing disease (CD), radiation therapy (RT) is mostly used in the adjuvant setting in patients who have failed transsphenoidal surgery or have recurrent CD. Stereotactic radiotherapy (SRT) is administered as either single or several sessions, and the most commonly used modalities include photon source (Gamma Knife, CyberKnife, and LINAC) or heavy particles (protons). In multicenter studies, Gamma Knife SRT can lead to biochemical control in 80%, with medial time to remission approximately 15 mos, and 70% recurrence free at 10 years. Conventional RT (CRT) consists of administration of small daily fractions over six weeks, with cumulative dose of 45-50 Gy. Biochemical control is achieved in up to 64% of patients with CRT. Choice of radiation modality includes convenience for patients (SRT is more convenient) and proximity to critical structures. Both forms of RT can result in hypopituitarism. RT remains an important modality for the treatment of patients with CD.

Stereotactic radiosurgery for secretory pituitary adenomas: systematic review and International Stereotactic Radiosurgery Society practice recommendations.

OBJECTIVE: A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery (SRS) in the management of secretory pituitary adenomas and develop consensus recommendations. METHODS: The authors performed a systematic review of the English-language literature up until June 2018 using the PRISMA guidelines. The PubMed (Medline), Embase, and Cochrane databases were searched. A total of 45 articles reporting single-institution outcomes of SRS for acromegaly, Cushing's disease, and prolactinomas were selected and included in the analysis. RESULTS: For acromegaly, random effects meta-analysis estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rates were 97.0% (95% CI 96.0%-98.0%), 44.0% (95% CI 35.0%-53.0%), and 17.0% (95% CI 13.0%-23.0%), respectively. For Cushing's disease, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 92.0% (95% CI 87.0%-95.0%), 48.0% (95% CI 35.0%-61.0%), and 21.0% (95% CI 13.0%-31.0%), respectively. For prolactinomas, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 93.0% (95% CI 90.0%-95.0%), 28.0% (95% CI 19.0%-39.0%), and 12.0% (95% CI 6.0%-24.0%), respectively. Meta-regression analysis did not show a statistically significant association between mean margin dose with crude endocrine remission rate or mean margin dose with development of any new hypopituitarism rate for any of the secretory subtypes. CONCLUSIONS: SRS offers effective tumor control of hormone-producing pituitary adenomas in the majority of patients but a lower rate of endocrine improvement or remission.

Updates in the outcomes of radiation therapy for Cushing's disease.

External radiation therapy (RT) directed to the pituitary gland is generally recommended in patients with Cushing's disease (CD) as adjuvant to transsphenoidal surgery, among other second-line therapies offered to patients with residual or recurrent hypercortisolism (i.e., medical treatment, repeat surgery or bilateral adrenalectomy). RT is effective for the control of tumor growth, even in invasive tumors and in Nelson's syndrome. Progress in radiation stereotactic techniques lead to improved tumor targeting and radiation delivery, thus sparing the adjacent brain structures. Stereotactic RT is associated with a 55-65% rate of cortisol normalization after several months to a few years and potentially with a lower risk of long-term complications, compared with conventional RT. Cortisol-lowering medical therapy is recommended while awaiting the radiation effects. Hypopituitarism is the most frequent side-effect, damage to optic or cranial nerves or second brain tumors are rarely reported. This review presents the updates in the efficacy and safety of the stereotactic radiation techniques in CD patients. Practical points which should be considered by the clinician before recommending RT are also presented.

Treatment and outcomes of recurrent/persistent Cushing's disease: a single-center experience.

BACKGROUND: Although transsphenoidal adenomectomy is the first treatment choice for Cushing's disease (CD), tumor recurrence rates are as high as 45%, resulting in a therapeutic challenge for endocrinologists and neurosurgeons. For recurrent/persistent CD (RCD/PCD), Repeat transsphenoidal surgery (RTSS), radiotherapy, gamma knife radiosurgery (GKRS) or bilateral adrenalectomy may be considered. The purpose of the study was to report the treatments and outcomes of RCD/PCD in a single center. METHODS: A retrospective study was performed on 55 RCD/PCD patients from a single center between 2000 and 2012 at Peking Union Medical College Hospital (PUMCH). RESULTS: Among the 55 RCD/PCD patients, 43 achieved remission (78%), and 11 maintained a PCD status (20%). The average times to recurrence after the initial treatment and Repeated treatment were 43.25±10.3 and 5.13±4.7 months, respectively (P=0.006); 17.6% of the patients experienced recurrence within the first year, and 52.9% of the patients experienced recurrence within 1.1-5.0 years. For the Repeated treatments, surgery was more effective for the biochemical remission of serum cortisol and adrenocorticotrophic hormone (ACTH) levels than radiotherapy. Delayed remission occurred in 28.9% (11/38) of the patients after Repeated surgery. Considering the previous biochemical levels after the initial surgery in RCD patients, 19.75% of patients experienced recurrence when serum cortisol levels were less than <3 µg/dL, and 51.4% of patients experienced recurrence under conditions of hypocortisolism and when 24-hour urinary free cortisol (24 UFC) was undetectable. CONCLUSIONS: RTSS remains a recommended treatment option for RCD/PCD patients while radiotherapy is suggested as an adjunctive treatment. Intensive follow-up is recommended, as patients with serum cortisol levels <3 µg/dL or undetectable 24 UFC levels can still experience recurrence after surgical treatment.

Gamma knife radiosurgery in patients with Cushing's disease: Comparison of aggressive pituitary corticotroph tumor versus corticotroph adenoma.

Aggressive pituitary corticotroph tumors causing Cushing's disease are rare, and there is limited data about their clinical management. Here, we aimed to report our long-term experience with gamma knife radiosurgery (GKRS) as adjuvant treatment in patients with residual or recurrent pituitary corticotroph tumors. This retrospective study included 45 adult patients (M/F, 7/38; mean age, 40.2 ±â€¯13.1 years) with residual tumor or recurrence after initially successful surgical resection. Single-session GKRS was performed in all patients. Tumors with a Ki-67 value higher than 3 % and radiologic invasion to surrounding tissues were classified as aggressive tumor group. Clinical, hormonal and radiological findings were compared between the aggressive (n = 10) and non-aggressive adenoma (n = 35) groups. Following GKRS, tumor volumes were significantly reduced in both groups. The mean time to hormonal remission in the non-aggressive group was significantly shorter than in the aggressive group (23.5 ±â€¯6.3 vs 33.0 ±â€¯5.0 month, respectively, p < 0.05). New-onset hypopituitarism was identified in only seven patients (15 %) after GKRS in the whole cohort. The present study introduces several essential findings about aggressive corticotroph tumors. First, aggressive behavior tends to occur more frequently in male subjects. Second, time to GKRS was significantly shorter in the aggressive group. Moreover, a tumor volume ≥2 cm3 may be associated with clinical aggressiveness in corticotroph tumors. In conclusion, we suggest that early adjuvant GKRS is an effective treatment option in aggressive pituitary corticotroph tumors.

Modern Methods of Stereotactic Radiosurgery and Radiotherapy for the Treatment of Cushing Disease.

Cushing's disease is caused by a pituitary tumor causing increased production of adrenocorticotropic hormone, which leads to chronic hypersecretion of cortisol through adrenal cortices. Endoscopic trans-sphenoidal adenomectomy is the first choice of treatment with greatest efficiency for the treatment of the disease. However, in the absence of remission or recurrence of hypercortisolism after neurosurgical resection (adenomectomy), as well as in cases when surgical intervention cannot be carried due to medical contraindications to surgical intervention, radiation treatment is used as an alternative or adjoining therapy. In this literature review the efficiency of different radiation techniques (the conventional and the modern techniques), as well as possible complications of modern methods of radiosurgery and radiotherapy have been looked for.

Cabergoline may act as a radioprotective agent in Cushing's disease.

CONTEXT: Conventional fractionated radiotherapy (CRT) achieves control of pathological hypercortisolism in 75%-80% of patients with persistent or recurrent Cushing's disease (CD), over a mean period of 18-24 months. Medical therapy is recommended as bridge therapy while awaiting RT effect. OBJECTIVE: To determine long-term outcome of CRT and its predictors in CD patients. DESIGN, SETTING AND PATIENTS: This is a retrospective case record analysis of 42 patients with CD who received CRT as a treatment modality and had at least 12 months post-RT follow-up. The dose delivered was 45 Gy in 25 fractions over 5 weeks. Demographic details, hormonal evaluation and radiological data were extracted from case records. Dexamethasone suppressed cortisol at cut-off of 1.8 µg/dL was used to define remission or recurrence. Possible predictors for remission and recurrence were analysed. RESULTS: The mean age at the time of CRT administration was 23.7 ± 10.7 (range: 12-48) years. A total of 29 (69%) patients achieved remission 26.5 ± 28.5 (median: 18, range: 3-120) months after RT, while 13 (31%) patients had persistent disease at last follow-up. There were no significant predictors of disease remission after CRT. Six (20.7%) patients had recurrence after a documented initial remission. Recurrence occurred 66.6 ± 25.9 (median: 74; range: 18 to 90) months after documented remission. Recurrence of the disease was exclusively seen in patients who received peri-RT cabergoline. Peri-CRT use of cabergoline was significantly associated with increased recurrence rates (P = .016). CONCLUSION: Use of cabergoline in the peri-CRT period did not affect initial remission after CRT but was associated with increased recurrence after initial remission in CD.

Surgical Outcomes and Comorbidities in Cushing Disease: 30 Years of Experience in a Referral Center.

OBJECTIVE: Cushing disease (CD) is a rare, poorly understood entity. Our aim was to add our clinical experience of >30 years in a multidisciplinary specialized unit to the global knowledge of CD. METHODS: This descriptive retrospective study included all patients admitted to the Endocrinology and Nutrition Department of the Virgen del Rocío University Hospital, Seville, Spain, from January 1980 to May 2016. All patients had a definitive diagnosis of CD. RESULTS: Total sample included 119 patients; 100 (84%) were female. Median age at diagnosis was 37.97 years (interquartile range [IQR]: 25.89-45.07 years). Median follow-up was 88 months (IQR: 45.50-157.00 months). Most tumors were microadenomas (62/95) (5.1 mm [IQR: 4.0-7.0 mm]) without sinus invasion. Surgical procedures were conventional transsphenoidal surgery (CTSS) (101/108; cured 70 after first attempt) and expanded endoscopic transsphenoidal surgery (EETSS) (7/108; cured 5 after first attempt); 11 patients did not receive surgical treatment. Fourteen patients received radiotherapy after a first surgery and 5 patients after a second surgical removal attempt. In 13 patients (12.04%), CD relapse was demonstrated after initial CTSS (median disease-free period 65 months [IQR: 45-120 months]). Ten patients developed panhypopituitarism owing to the surgical procedure (CTSS); 8 patients developed panhypopituitarism after adjuvant radiotherapy. CONCLUSIONS: We observed slightly inferior cure rate after first surgery compared with moderately better relapse rates and time to relapse. Radiotherapy after surgery failure seemed to be more effective than CTSS; however, EETSS may be a valid alternative. Postoperative panhypopituitarism rate after first surgery was lower than expected; after radiotherapy, our results were comparable to other series.

Radiotherapy as a tool for the treatment of Cushing's disease.

Treatment of Cushing's disease (CD) is one of the most challenging tasks in endocrinology. The first-line treatment, transsphenoidal pituitary surgery, is associated with a high failure rate and a high prevalence of recurrence. Re-operation is associated with an even higher rate of a failure and recurrence. There are three main second-line treatments for CD - pituitary radiation therapy (RT), bilateral adrenalectomy and chronic cortisol-lowering medical treatment. All these treatments have their limitations. While bilateral adrenalectomy provides permanent cure of the hypercortisolism in all patients, the unavoidable chronic adrenal insufficiency and the risk of development of Nelson syndrome are of concern. Chronic cortisol-lowering medical treatment is not efficient in all patients and side effects are often a limiting factor. RT is efficient for approximately two-thirds of all patients with CD. However, the high prevalence of pituitary insufficiency is of concern as well as potential optic nerve damage, development of cerebrovascular disease and secondary brain tumours. Thus, when it comes to decide appropriate treatment for patients with CD, who have either failed to achieve remission with pituitary surgery, or patients with recurrence, the pros and cons of all second-line treatment options must be considered.

Outcomes After Gamma Knife Stereotactic Radiosurgery in Pediatric Patients with Cushing Disease or Acromegaly: A Multi-Institutional Study.

OBJECTIVE: Pituitary adenomas comprise about 3% of all intracranial tumors in pediatric patients. This study examines the role of stereotactic radiosurgery in the management of pediatric acromegaly or patients with Cushing disease (CD). METHODS: From an international consortium, we retrospectively collected treatment and outcome data on pediatric adrenocorticotrophic hormone and growth hormone-secreting pituitary adenomas treated with Gamma Knife radiosurgery (GKRS). There were a total of 36 patients including 24 with CD and 12 with acromegaly. The data were analyzed to assess outcomes including tumor control, endocrine remission, and adverse effects. Statistical analysis was performed to determine correlation between clinical/treatment parameters and outcomes. RESULTS: At the last follow-up after GKRS, endocrine remission rates for CD and acromegaly were 80% and 42%, respectively. Tumor control was achieved in 87.5% of patients with CD and in 42% of patients with acromegaly. New pituitary hormone deficiency occurred in 7 of the 36 patients at a median time of 18 months after GKRS (range, 12-81 months). The predictive factors for endocrine remission were age <15 years (P = 0.015) and margin dose (P = 0.042). The median endocrine follow-up was 63.7 months (range, 7-246 months). CONCLUSIONS: GKRS affords reasonable rates of endocrine remission and tumor control in most pediatric patients with functioning adenomas. The most common post-GKRS complication was hypopituitarism, although this occurred in only a few patients. Given the larger at-risk period for pediatric patients, further study is required to evaluate for delayed recurrences and hypopituitarism.

The role of Crooke's changes in recurrence and remission after gamma knife radiosurgery.

PURPOSE: The objective of this study is to evaluate the role of Crooke's changes (CC) in normal the peri-tumoral anterior pituitary gland, in patients with Cushing's disease (CD) with a histopathological confirmed corticotroph adenoma, and determine if there is any difference in the recurrence and remission rates in CD patients after treatment with Gamma Knife Radiosurgery (GKRS). METHODS: All patients treated with GKRS for CD from 2005 to 2016 at our institution were identified. Patients had a confirmed adrenocorticotropic (ACTH)-secreting adenoma, i.e. corticotroph adenoma, and normal pituitary gland included in the surgical specimen, and specimens were stained with hematoxylin and eosin and also immunostaining for cytokeratin and ACTH. Statistical analyses were performed in a total of 61 patients who met the inclusion criteria. Additionally, we analyzed 20 patients in each group, with and without CC, after they were matched in a propensity score fashion. RESULTS: Endocrine remission defined as, a normal 24 h urine free cortisol while off suppressive medication, occurred in 48 patients (78.7%), with 76.9% in those with CC and 81.8% in those without CC. There was no statistical significant difference between the two groups in regarding remission (p = 0.312) or recurrence (p = 0.659) in either the unmatched or matched cohorts. CONCLUSION: The presence or absence of CC in normal pituitary gland does not appear to confer a lower rate of remission or a higher rate of recurrence after GKRS. Patients with pituitary corticotroph adenomas that present with CC features may be well served by Stereotactic radiosurgery (SRS).

Outcomes of Pituitary Radiation for Cushing's Disease.

Achievement of biochemical remission with preservation of normal pituitary function is the goal of treatment for Cushing's disease. For patients with persistent or recurrent Cushing's disease after transsphenoidal resection, radiation therapy may be a safe and effective treatment. Stereotactic radiosurgery is favored over conventional fractionated external beam radiation. Hormonal recurrence rates range from 0% to 36% at 8 years after treatment. Tumor control rates are high. New pituitary hormone deficiency is the most common adverse effect after stereotactic radiosurgery and external beam radiation. The effects of radiation planning optimization and use of adjuvant medication on endocrine remission rates warrant investigation.

Repeat stereotactic radiosurgery for Cushing's disease: outcomes of an international, multicenter study.

Stereotactic radiosurgery (SRS) is frequently used for Cushing's disease (CD) after failed pituitary surgery. Management of patients with persistent CD after failed SRS is complex, as the alternative therapeutic options harbor significant risks. The outcomes of repeat pituitary radiosurgery, however, have not been described. We sought to determine the outcomes of repeat SRS in patients with CD. We pooled data from five institutions participating in the International Gamma Knife Research Foundation for patients with recurrent or persistent CD ≥ 12 months after initial SRS. Patients were included in the study if they had ≥ 6 months endocrine follow-up after repeat SRS. Twenty patients were included in the study. Repeat single-session SRS was performed 1.3-9.7 years after initial SRS. Median endocrine follow-up was 6.6 years (1.4-19.1 years). Median margin dose was 20 Gy (range 10.8-35 Gy). Endocrine remission after second SRS was noted in 12 patients (60%), with a median time to remission of 6 months (range 2-64 months). Biochemical recurrence occurred in two patients (17%) after initial remission. Overall, the cumulative rates of durable endocrine remission at 5 and 10 years were 47 and 53%, respectively. Two patients (10%) experienced adverse radiation effects, including transient visual loss and permanent diplopia. Repeat SRS achieves lasting biochemical remission in approximately half of patients with CD refractory to both prior microsurgery and SRS. Because of the morbidity of refractory or recurrent CD, repeat SRS should be considered for carefully selected patients with hypercortisolism confirmed one or more years after initial SRS.

Pituitary size alteration and adverse effects of radiation therapy performed in 9 dogs with pituitary-dependent hypercortisolism.

The purpose of this study was to determine the therapeutic and/or adverse effects of radiation therapy (RT) against pituitary tumors in dogs with pituitary-dependent hypercortisolism, as monitored by frequent post-RT detailed MRI examinations, clinical signs, and changes in hormone concentrations. Nine dogs with an adrenocorticotropic hormone (ACTH)-secreting pituitary mass diagnosed by magnetic resonance imaging (MRI) underwent RT for 4weeks (total of 48Gy in 4-Gy fractions). Pituitary height/brain area (P/B) value, clinical signs, basal plasma ACTH concentrations, serum cortisol concentrations (pre- and post-ACTH stimulation test) and adverse effects of RT were evaluated before and post-RT. The P/B value was significantly lower in all nine dogs post-RT. One dog lacking any neurological signs demonstrated no change in clinical signs pre and post-RT. Out of 8 dogs which exhibited neurological signs pre-RT, half of them demonstrated complete resolution of their signs, whereas the other half showed transient resolution. In all animals with recurrence of neurological signs, pituitary tumor regrowth was not observed; however, MRI revealed moderate to severe pituitary hemorrhage. Late adverse effect (bilateral otitis media) was observed in three of nine dogs post-RT. RT did not induce any significant changes in the dogs' basal plasma ACTH concentration and pre- and post-ACTH serum cortisol concentrations. In conclusion, RT is effective to reduce pituitary size and the mass effect, but does not appear to affect blood hormone concentrations, necessitating additional medical treatment against hypercortisolism. Periodic MRI imaging post-RT enables early detection of adverse effects of RT.

CyberKnife Radiosurgery in the Multimodal Management of Patients with Cushing Disease.

BACKGROUND: Surgery is the primary treatment for Cushing disease. When surgery is unsuccessful in normalizing hypercortisolism, adjuvant radiation, such as stereotactic radiosurgery, may be useful to improve biochemical control. METHODS: This retrospective study included a cohort of consecutive patients treated with CyberKnife (CK) radiosurgery for active Cushing disease at Stanford Hospital and Clinics. RESULTS: As first-line treatment, all patients underwent transsphenoidal surgery with histologic demonstration of an adrenocorticotropic hormone-producing pituitary adenoma. CK was performed as adjuvant therapy for persistent or recurrent disease. The median time between surgery and CK was 14 ± 34 months. Before CK, median maximal diameter of tumors was 9 mm (range, 7-32 mm), with cavernous sinus invasion in all patients (100%) and abutment of the optic chiasm in 1 patient (14.2%). With an average follow-up of 55.4 months, normalization of hypercortisolism was achieved in 4 patients (57.1%): 2 patients (28.5%) achieved normalization of the hypothalamic-pituitary-adrenal axis without glucocorticoid replacement, and 2 patients developed hypoadrenalism (28.5%). The median time to biochemical remission was 12.5 months. Hypopituitarism occurred in only 1 patient (14.2%), and no patients had visual complications. Time between surgery and radiotherapy of <14 months was associated with a significantly improved biochemical remission rate (P = 0.02). CONCLUSIONS: In a cohort of patients with Cushing disease, we demonstrate that CK is an effective treatment with rare complications.

Cavernous carotid stenosis following stereotactic radiosurgery for Cushing's disease: A rare complication and review of the literature.

Intracranial carotid stenosis or occlusion after SRS is an extraordinarily rare event. Because of the rarity of this event, increased awareness within the neurosurgical community is required. For those with post-radiosurgical carotid stenosis who are asymptomatic, longitudinal follow up is recommended. Management depends on whether the patient is symptomatic or asymptomatic. Those who are symptomatic may require balloon angioplasty, stenting, or bypass surgery.