Refractory Pituitary Adenomas Research Articles

The biological behavior and clinical outcome of pituitary adenoma are affected by the microenvironment.

Pituitary adenoma is one of the most common brain tumors. Most pituitary adenomas are benign and can be cured by surgery and/or medication. However, some pituitary adenomas show aggressive growth with a fast growth rate and are resistant to conventional treatments such as surgery, drug therapy, and radiation therapy. These tumors, referred to as refractory pituitary adenomas, often relapse or regrow in the early postoperative period. The tumor microenvironment (TME) has recently been identified as an important factor affecting the biological manifestations of tumors and acts as the main battlefield between the tumor and the host immune system. In this review, we focus on describing TME in pituitary adenomas and refractory pituitary adenomas. Research on the immune microenvironment of pituitary adenomas is currently focused on immune cells such as macrophages and lymphocytes, and extensive research and experimental verifications are still required regarding other components of the TME. In particular, studies are needed to determine the role of the TME in the specific biological behaviors of refractory pituitary adenomas, such as high invasion, fast recurrence rate, and high tolerance to traditional treatments and to identify the mechanisms involved. Overall, we summarize the similarities and differences between the TME of pituitary adenomas and refractory pituitary adenomas as well as the changes in the biological behavior of pituitary adenomas that may be caused by the microenvironment. These changes greatly affect the outcome of patients.

O-01 Case report: Temozolomide treatment of refractory prolactinoma

Abstract Introduction Treatment of refractory prolactinoma is challenging. Temozolomide (TMZ), an oral chemotherapeutic agent, has been recommended as an effective drug for refractory pituitary adenomas or carcinomas. Clinical Case We report a 53-year-old male who presented with diplopia, left eye proptosis, conjunctival congestion, and headache. Magnetic resonance imaging (MRI) showed a macroadenoma 20×17 mm in diameter with compression of the optic chiasm and invasion of both cavernous sinuses. Hormonal evaluation revealed hyperprolactinemia of 2382 ug/L, 120x above the upper limit of normal (ULN), with central hypothyroidism and hypogonadism. Cabergoline was recommended as an initial treatment. Despite the maximum cabergoline dose of 1.5 g daily, tumor volume increased with visual disturbances and headaches. Prolactin (PRL) remained 60x above ULN so the patient underwent transsphenoidal surgery. Tumor histology was consistent with an atypical pituitary adenoma, positively stained for prolactin and sporadically for growth hormone, Ki-67 of 6.4%, no mitosis and negative p53. Postoperatively, the PRL level was still high (25x above ULN) with tumor remnants in both cavernous sinuses. Due to the tumor resistance to dopamine agonist treatment and uncomplete surgical resection, patient underwent stereotactic gamma knife radiosurgery (GK prescription dose 22 Gy, isodose 49%) simultaneously with TMZ treatment. After 2 cycles of TMZ (1. cycle TMZ 300mg/5days, 2. cycle TMZ 400 mg/5days), the PRL level decreased significantly (126 ug/L). The plan is to apply a total of 6 cycles of temozolomide. Conclusion Clinical evidence for the efficacy of TMZ in refractory prolactinoma remains limited, but early use of this agent may be helpful in some cases.

SAT437 Immunotherapy Induced Pituitary Apoplexy

Abstract Disclosure: A. Uddin: None. M.J. Gardner: None. A. Akofu: None. N. Sheung: None. S. Dejhansathit: None. N. Akabogu: None. F. Marium: None. We present a case of a 42 year old male with past history of metastatic melanoma s/p 3 cycles of ipilimumab and nivolumab immunotherapy that originally was referred to endocrinology due to elevated prolactin of 40 and MRI finding of questionable 6 mm pituitary adenoma. There was not a clear other cause of prolactin elevation. Other notable labs in pituitary hormonal evaluation were elevated FSH of 24 and LH 16 with normal testosterone 663. TSH of 4.3 and FT4 of 1.22. After the 4th cycle of ipilimumab and nivolumab he had a severe headache that was unremitting, he called his oncology nurse line which instructed him to hydrate. He presented for admission to the hospital after coming confused, unsteady on his feet and his headache had already improved. Labs demonstrated severe hyponatremia at 111 with serum osm of 238 and urine osmolality of 504 and specific gravity of 1.012. Brain MRI demonstrated a 1.2 cm pituitary lesion compared to less than 1 month prior, consistent with hypophysitis. Repeat pituitary labs showed hypogonadotropic hypogonadism with total testosterone of 39 and inappropriately normal FSH of 7 and LH of 2, central hypothyroidism with TSH 0.232, FT4 0.70, FT3 1.8, secondary adrenal insufficiency with cosyntropin stimulation test up to cortisol of 16 for partial response and ACTH of 17. Hyponatremia was managed inpatient and he was discharged on appropriate hormone replacement. Subsequent brain MRI with normal pituitary finding without enhancing lesions. Repeat hormonal testing showed persistent hormonal deficiencies with undetectable cortisol and ACTH despite holding hydrocortisone therapies. Prolactin was also tested in the 4-10 range on repeat testing. He continued on nivolumab monotherapy with oncology. This case report details a clear case of immunotherapy treatment leading to destruction of prolactinoma and presentation of pituitary apoplexy given the short time line of 1 month and cycle of therapy between radiographic and hormonal assessment. We hope this case helps bring awareness to the evolving list of conditions to survey for with immunotherapy and suggests a role of identifying prolactinomas biochemically and or radiographically to affect management. It may even suggest a role in treatment for medically refractory pituitary adenomas. Presentation: Saturday, June 17, 2023

Medical therapy for refractory pituitary adenomas.

Refractory pituitary adenomas are those that have progressed following standard of care treatments. Medical therapy options for these challenging tumors are limited. To review the landscape of tumor directed medical therapies and off-label investigational approaches for refractory pituitary adenomas. Literature on medical therapies for refractory adenomas was reviewed. The established first-line medical therapy for refractory adenomas is temozolomide, which importantly may increase survival, but clinical trial data are still needed to clearly establish its efficacy, identify biomarkers of response, and clarify eligibility and outcome criteria. Other therapies for refractory tumors have only been described in case reports and small case series. There are currently no approved non-endocrine medical therapies for refractory pituitary tumors. There is an urgent need for identifying effective medical therapies and studying them in multi-center clinical trials.

Advances in surgical approaches for refractory pituitary adenomas.

Refractory pituitary adenomas are difficult to control tumors that progress through optimal surgical, medical, and radiation management. Repeat surgery is a valuable tool to reduce tumor volume for more effective radiation and/or medical therapy, and to decompress critical neurovascular structures. Advances in surgical techniques and technologies, including minimally invasive cranial approaches, intraoperative MRI suites, and cranial nerve monitoring, have improved surgical outcomes and expanded indications. Today, repeat transsphenoidal surgery has similar complications rates to upfront surgery in historical cohorts. The decision to operate on refractory adenomas should be made with multidisciplinary teams, balancing the benefit of tumor reduction with the potential for complications, including cranial nerve injury, carotid injury, and cerebrospinal fluid leak.

Inhibition of VEGF receptors induces pituitary apoplexy: An experimental study in mice.

Anti-vascular endothelial growth factor (VEGF) therapy has been developed for the treatment of a variety of cancers. Although this therapy may be a promising alternative treatment for refractory pituitary adenomas and pituitary carcinomas, the effects of anti-VEGF agents on the pituitary gland are not yet well understood. Here, we found that mice administered with OSI-930, an inhibitor of receptor tyrosine kinases including VEGF receptor 1 and 2, frequently exhibited hemorrhage in the pituitary gland. This is the first report that anti-VEGF therapy can cause pituitary apoplexy. C57BL/6 mice were daily injected intraperitoneally with 100 mg/kg body weight of OSI-930 for one to six days. Pituitary glands were immunohistochemically examined. Four of six mice treated for three days and all of five mice treated for six days exhibited hemorrhage in the pituitary gland. In all cases, the hemorrhage occurred just around Rathke's cleft. In OSI-930-administered mice, the vascular coverage and branching were reduced in the anterior lobe, and capillary networks were also decreased in the intermediate lobe in a treatment-day dependent manner. Few blood vessels around Rathke's cleft of the intermediate lobe express VE-cadherin and are covered with platelet-derived growth factor receptor-β (PDGFR-β)-positive cells, which suggests that capillaries around Rathke's cleft of the intermediate lobe were VE-cadherin-negative and not covered with pericytes. The reduction of capillary plexus around Rathke's cleft was observed at the site where hemorrhage occurred, suggesting a causal relationship with the pathogenesis of pituitary hemorrhage. Our study demonstrates that anti-VEGF agents have a risk of pituitary apoplexy. Pituitary apoplexy should be kept in mind as an adverse effect of anti-VEGF therapy.

Contemporary radiotherapy and radiosurgery techniques for refractory pituitary adenomas.

The pituitary gland is a potential site for a range of pathologies, for which treatment can involve resection and/or ionizing radiation. Modern stereotactic radiosurgery (SRS) involves highly conformal radiation, allowing for the delivery of high doses to the tumor while simultaneously sparing nearby healthy structures. SRS has become a standard treatment option for residual or recurrent pituitary adenomas. It has been used for both functioning and nonfunctioning pituitary adenomas, with reported local tumor control over 90% and moderate rates of endocrine remission in functioning adenomas. We aim to briefly review the existing indictions and supporting literature for the use of SRS for refractory adenomas.

Contribution of PROP1 in the pathogenesis of Cushing’s disease: A preliminary study

Prophet of Pit1 (PROP1) is the pituitary specific transcription factor which was cloned as an upstream regulator of PIT1. Cushing’s disease is caused by corticotroph adenomas which does not belong to the PIT1 lineage. The aim of this study was to elucidate the involvement of PROP1 in the pathogenesis of Cushing’s disease. Since it is difficult to accurately evaluate PROP1 expression in pituitary adenomas by RT-PCR analysis due to the inevitable contamination of surgical tissue specimens with normal pituitary cells, we examined six corticotroph adenomas by immunohistochemistry. Adenomas were classified into 2 subtypes based on their staining patterns of CAM5.2: diffuse and non-diffuse types. It is likely that diffuse-type adenomas are composed of more differentiated tumor cells. PROP1 was positive in all three cases of non-diffuse-type adenomas, but negative in all three cases of diffuse-type adenomas, suggesting that PROP1 was prominently expressed in less differentiated non-PIT1 lineage corticotroph adenomas. This study is the first report to analyze PROP1 expression in pituitary adenomas by immunohistochemistry. PROP1 may have a role in tumorigenesis of pituitary adenomas in Cushing’s disease, and is expected to be a new therapeutic target for refractory pituitary adenomas.

The Clinical and Pathological Characteristics of Refractory Pituitary Adenomas: A Single Center Experience.

BackgroundMost of pituitary adenomas (PAs) are slow-growing benign tumors which can be cured or controlled by conventional therapies, including surgery, medical treatment or radiotherapy. A small set of PAs, usually known as aggressive PAs or refractory PAs, present with more aggressive behavior and lead to poorer prognosis than classical PAs.MethodsWe retrospectively analyzed the clinical and pathological characteristics of 44 patients who were diagnosed with refractory PAs by a multidisciplinary team (MDT). All the patients’ demographic characteristics, radiological findings, Knosp grade, treatment details and clinical outcomes were abstracted from the medical records. Additionally, 44 patients with nonrefractory PAs (NRPAs) matched for age and gender were selected to serve as the control group.ResultsDespite using all combined treatments including surgery, radiotherapy and conventional medical treatments, all the refractory PAs showed tumor progression or hormone hypersecretion which caused increased morbidity and mortality and remained challenging to management. Compared with those of the non-refractory PAs, the tumor size, invasive rate and tumor growth rate (TGR) were significantly higher in the refractory PAs. TGR >2.2% per month may be considered as a preoperative indicator of refractoriness. The Ki-67 index in the refractory PAs were all ≥3%. EGFR, but not MMP2 or MMP9, was significantly overexpressed in refractory PAs compared with the corresponding levels in nonrefractory PAs.ConclusionRefractory PAs are unresponsive to surgery, radiotherapy and conventional medical treatments with a poor prognosis. Moreover, a TGR ≥2.2% per month, Ki-67 index ≥3% and EGFR overexpression may be independent predictors of clinical refractoriness.

Anti-VEGF Therapy in Refractory Pituitary Adenomas and Pituitary Carcinomas: A Review.

Most pituitary tumors are considered benign adenomas, and only 0.1%–0.2% of them present metastasis and are defined as pituitary carcinomas (PCs). Refractory pituitary adenomas (PAs) lie between benign adenomas and true malignant PCs and are defined as aggressive-invasive PAs, characterized by a high Ki-67 index, rapid growth, frequent recurrence, and resistance to conventional treatments. Refractory PAs and PCs are notoriously difficult to manage because of limited therapeutic options. Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis not only during development but also during pathological processes in pituitary tumors. Recently, increasing numbers of preclinical studies and clinical research have demonstrated that anti-VEGF therapy plays an important role in pituitary tumors. The purpose of this review is to report the role of VEGF in the development and pathology of pituitary tumors and the progress of anti-VEGF therapy in pituitary tumors, including refractory PAs and PCs. Previous preclinical studies indicated that cyclin-dependent kinase 5 (CDK5)-mediated VEGF expression might play a crucial role in the development of PAs. Vascular endothelial growth inhibitors have been reported as independent predictors of invasion in human PAs and have been indicated as markers for poor outcome. Furthermore, several studies have reported that angiogenesis decreases tumor sizes in experimental animal models of pituitary tumors. The expression of VEGF is relatively high in PAs; therefore, anti-VEGF therapy has been used in some refractory PAs and PCs. To date, anti-VEGF has been reported as monotherapy, in combination with temozolomide (TMZ), TMZ and radiotherapy, and with pasireotide, which might be a promising alternative therapy for refractory PAs and PCs resistant to conventional treatments. However, the role of anti-VEGF therapy in pituitary tumors is still controversial due to a lack of large-scale clinical trials. In summary, the results from preclinical studies and clinical trials indicated that anti-VEGF therapy monotherapy or in combination with other treatments may be a promising alternative therapy for refractory PAs and PCs resistant to conventional treatments. More preclinical studies and clinical trials are needed to further evaluate the exact efficacy of anti-VEGF in refractory PAs and PCs.

Diagnosis and treatment of refractory pituitary adenomas: a narrative review.

Although aggressive pituitary adenomas (PAs) have been proposed and widely discussed for more than a decade, there is no general agreement regarding their definition, diagnosis or management. As one of the largest pituitary centers in China, we have diagnosed and treated more than fifty cases of aggressive PA and 3 pituitary carcinomas in the past 5 years and proposed a new term, i.e., refractory PAs, to define these adenomas. The definitions of aggressive and refractory PAs overlap with each other, though there are some differences between them. We interpret the definition for refractory PA in this review, emphasizing that more attention and early identification of these adenomas are needed. Although temozolomide (TMZ) has been used to treat pituitary carcinomas and refractory PA since 2006, which has significantly improved the prognosis of these patients, treatment of refractory PA is a tremendous challenge for endocrinologists and neurosurgeons. Overall, refractory PA is defined as PA with a Ki-67 labeling index ≥3%, a faster growth rate than that of normal PA, infiltration of surrounding tissues, recurrence or regrowth in the early postoperative period, and continued growth and/or secretion of excessive hormones despite attempts to control it. These criteria for refractory PA are stricter than for aggressive PA. The diagnosis and treatment of refractory PA requires the collaboration of a multidisciplinary team to achieve the best results.

The Progress of Immunotherapy in Refractory Pituitary Adenomas and Pituitary Carcinomas

Most pituitary adenomas (PAs) are considered benign tumors, but approximately 0.2% can present metastasis and are classified as pituitary carcinomas (PCs). Refractory PAs lie between benign adenomas and true malignant PC and are defined as aggressive-invasive PAs characterized by a high Ki-67 index, rapid growth, frequent recurrence, and resistance to conventional treatments, including temozolomide. It is notoriously difficult to manage refractory PAs and PC because of the limited therapeutic options. As a promising therapeutic approach, cancer immunotherapy has been experimentally used for the treatment of many tumors, including pituitary tumors. The purpose of this review is to report the progress of immunotherapy in pituitary tumors, including refractory PAs and PCs. The tumor immune microenvironment has been recognized as a key contributor to tumorigenesis, progression, and prognosis. One study indicated that the number of CD68+ macrophages was positively correlated with tumor size and Knosp classification grade for tumor invasiveness. The infiltration of CD4+ and CD8+ T cells was relatively scant in these adenomas, but pituitary growth hormone (GH) adenomas exhibited significantly more CD4+ and CD8+ T cells than non-GH adenomas. These results suggest an association of CD68+ macrophage infiltration with an increase in pituitary tumor size and invasiveness. Another study suggested that a lower number of CD8+ lymphocytes is associated with cavernous sinus invasion and resistance to treatment with first-generation somatostatin analogs in acromegaly patients, highlighting a potential role of the tumor immune microenvironment in determining the prognosis of somatotroph pituitary tumors. Preclinical studies have indicated that widely varying degrees of programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) are found among different subtypes. Functional PAs and aggressive PAs express significantly higher levels of PD-L1 and TILs than other subtypes, indicating that PD-1 blockade might be a promising alternative therapy for patients with aggressive PAs. PD-L1 transcript and protein levels were found to be significantly increased in functioning (GH and prolactin-expressing) pituitary tumors compared to nonfunctioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary tumors harbored higher levels of PD-L1 mRNA than recurrent tumors. These findings suggest the possibility of considering checkpoint blockade immunotherapy for functioning pituitary tumors refractory to conventional management. Animal models of Cushing’s disease also demonstrated PD-L1 and TIL expression in cultured tumors and murine models, as well as the effectiveness of checkpoint blockade therapy in reducing the tumor mass, decreasing hormone secretion, and increasing the survival rate. Clinical studies show that immunotherapy may be an effective treatment in patients with pituitary tumors. One corticotroph carcinoma patient showed a significant reduction in hormone levels and shrinkage of the tumor size of primary and metastatic lesions immediately after investigational treatment with ipilimumab and nivolumab. However, another patient with corticotroph adenoma progressed rapidly after four cycles of anti-PD-1 (pembrolizumab) treatment. To date, there are two registered clinical trials of immunotherapy for pituitary tumors. One of them is the phase II clinical trial of nivolumab combined with ipilimumab for patients with aggressive pituitary tumors (NCT04042753). The other one is also a phase II clinical trial of the combination of nivolumab and ipilimumab for rare tumors, including pituitary tumors (NCT02834013). Both clinical trials are in the stage of recruiting patients and have not been completed. In summary, the results from preclinical research and clinical studies indicated that immunotherapy might be a promising alternative therapy for PCs and refractory PAs resistant to conventional treatments. The combination of immunotherapy and radiotherapy or temozolomide may have synergistic effects compared to a single treatment. More preclinical and clinical studies are needed to further indicate the exact efficacy of immunotherapy in pituitary tumors.

Recent Progress in Stem Cell Research of the Pituitary Gland and Pituitary Adenoma

Regenerative medicine and anti-tumoral therapy have been developed through understanding tissue stem cells and cancer stem cells (CSCs). The concept of tissue stem cells has been applied to the pituitary gland (PG). Recently, PG stem cells (PGSCs) were successfully differentiated from human embryonic stem cells and induced pluripotent stem cells, showing an in vivo therapeutic effect in a hypopituitary model. Pituitary adenomas (PAs) are common intracranial neoplasms that are generally benign, but treatment resistance remains a major concern. The concept of CSCs applies to PA stem cells (PASCs). Genetic alterations in human PGSCs result in PASC development, leading to treatment-resistant PAs. To determine an efficient treatment against refractory PAs, it is of paramount importance to understand the relationship between PGSCs, PASCs and PAs. The goal of this review is to discuss several new findings about PGSCs and the roles of PASCs in PA tumorigenesis.

Long-term outcomes of hypofractionated stereotactic radiotherapy for refractory functional pituitary adenoma

Refractory functional pituitary adenomas are often treated with single-session stereotactic radiosurgery (SRS) or conventionally fractionated intensity-modulated radiotherapy (IMRT). While single-fraction SRS offers convenience and short time to biochemical remission, large tumors with cranial nerve or chiasmatic involvement often preclude single-fraction SRS, and toxicity may be worse following single-fraction SRS compared with IMRT. The purpose of our study was to explore the long-term outcomes of a unique hypofractionated stereotactic radiotherapy (HSRT) regimen delivered in 2–5 fractions. After approval, we studied 16 consecutive patients treated with HSRT for refractory functional pituitary adenoma. Study endpoints included local control, biochemical control, and toxicity. Descriptive statistics summarized endpoints and clinicopathologic factors. Sixteen patients with adrenocorticotropic hormone secretion (n = 9, 56%), growth hormone secretion (n = 4, 25%), and prolactin secretion (n = 3, 19%) were studied with a median follow-up time after HSRT of 10 years (IQR 2–14 years). Patients were treated with two (n = 8), three (n = 1), or five (n = 7) fractions to median dose of 20.5 Gy (range 16–32 Gy). HSRT was well-tolerated with no acute side effects greater than CTCAE grade 1. Local control was 100%, and biochemical control at last follow-up was 58%. Over 142 years patient-years, no instances of optic neuropathy, secondary malignancy, malignant transformation, radionecrosis, cavernous sinus cranial neuropathy, or cerebrovascular complications were noted. HSRT for refractory pituitary adenoma is well-tolerated with long-term local and biochemical control comparable with single-fraction SRS or IMRT. Prospective studies should evaluate whether HSRT provides non-inferior biochemical control and improved toxicity compared with single-fraction SRS.

Temozolomide Treatment in Patients with Refractory Pituitary Adenomas; A Case Series (4543)

Temozolomide Treatment in Patients with Refractory Pituitary Adenomas; A Case Series (4543)

The Effect of Chemoradiotherapy in Patients With Refractory Pituitary Adenomas

The Effect of Chemoradiotherapy in Patients With Refractory Pituitary Adenomas

The Treatment of Refractory Pituitary Adenomas.

Refractory pituitary adenomas (PAs) are defined as aggressive-invasive PAs characterized by a high Ki-67 index, rapid growth, frequent recurrence, and resistance to conventional treatments. It is notoriously difficult to manage refractory PAs because the efficacy of current therapeutic options is limited. The purpose of this review is to address currently employed and promising therapeutic strategies for the treatment of refractory PAs. Except for prolactinomas, neurosurgery is the first-line option, but most refractory PAs often recur or re-grow after initial surgery and require further treatments. Medical therapy, radiotherapy and re-operation are explored when surgery has failed to completely resect tumors; however, refractory PAs are usually resistant to these treatments. As a salvage treatment, temozolomide (TMZ) has shown promising results and is currently used for all types of refractory PAs. However, not all refractory PAs are responsive to TMZ treatment, and some of these PAs are resistant to TMZ. Although targeted therapies such as vascular endothelial growth factor, epidermal growth factor and mTOR inhibitors have also been used to treat refractory PAs, the effectiveness of these targeted therapies is still not known due to a lack of data from randomized prospective trials. As a novel therapeutic method, cancer immunotherapy is a promising strategy for the treatment of refractory PAs, but further preclinical research and clinical trials are needed to assess the efficacy of this new approach. In summary, early identification and a multidisciplinary approach are required to treat refractory PAs.

Using multidisciplinary cooperation in the diagnosis and treatment of refractory pituitary adenomas

基于难治性垂体腺瘤临床表现的多样性、诊断的复杂性以及治疗方法的多选择性，本文提出难治性垂体腺瘤患者应该到设有神经外科医生、内分泌科医生、放射科医生、放疗科医生、麻醉科医生以及专科护士组成的垂体腺瘤卓越中心就医，以保证其得到准确的诊断和最恰当的治疗。.

Growth hormone-secreting pituitary macroadenoma presenting concurrently with non-Hodgkin’s lymphoma and responding to doxorubicin treatment: case report and review of the literature

We present a case report of a patient who presented with nausea and vomiting, as well as acromegalic features. Following testing, a pituitary adenoma and mediastinal non-Hodgkin's lymphoma were diagnosed. Following two cycles of R-CHOP chemotherapy, imaging showed significant decrease in size of the sellar tumor. Following resection of tumor, both frozen and permanent section revealed only necrotic material. Further research into the potential utility of doxorubicin for the treatment of recurrent or refractory pituitary adenomas may be warranted.

Comprehensive review of stereotactic radiosurgery for medically and surgically refractory pituitary adenomas

Despite advances in surgical techniques and medical therapies, a significant proportion of pituitary adenomas remain endocrinologically active, demonstrate persistent radiographic disease, or recur when followed for long periods of time. While surgical intervention remains the first-line therapy, stereotactic radiosurgery is increasingly recognized as a viable treatment option for these often challenging tumors. In this review, we comprehensively review the literature to evaluate both endocrinologic and radiographic outcomes of radiosurgical management of pituitary adenomas. The literature clearly supports the use of radiosurgery, with endocrinologic remission rates and time to remission varying by tumor type [prolactinoma: 20–30%, growth hormone secreting adenomas: ~50%, adrenocorticotrophic hormone (ACTH)-secreting adenomas: 40–65%] and radiographic control rates almost universally greater than 90% with long-term follow-up. We stratify the outcomes by tumor type, review the importance of prognostic factors (particularly, pre-treatment endocrinologic function and tumor size), and discuss the complications of treatment (with special attention to endocrinopathy and visual complications). We conclude that the literature supports the use of radiosurgery for treatment-refractory pituitary adenomas, providing the patient with a minimally invasive, safe, and effective treatment option for an otherwise resistant tumor. As such, we provide literature-based treatment considerations, including radiosurgical dose, endocrinologic, radiographic, and medical considerations for each adenoma type.