Stereotactic radiosurgery for nonfunctioning pituitary tumor: A multicenter study of new pituitary hormone deficiency.

BACKGROUND: Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency. METHODS: Patients treated with single-session SRS for a NFPA were included in this retrospective, multicenter study. Tumor control and new pituitary dysfunction were evaluated using Cox analysis and Kaplan-Meier curves. RESULTS: A total of 869 patients (male 476 [54.8%], median age at SRS 52.5 years [Interquartile range (IQR): 18.9]) were treated using a median margin dose of 14Gy (IQR: 4) for a median tumor volume of 3.4 cc (IQR: 4.3). With a median radiological follow-up of 3.7 years (IQR: 4.8), volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression.The probability of tumor control was 95.5% (95% Confidence Interval [CI]: 93.8-97.3) and 88.8% (95%CI: 85.2-92.5) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with tumor control (Hazard Ratio [HR]:0.33, 95% CI: 0.18-0.60, P < 0.001). The probability of new hypopituitarism was 9.9% (95% CI: 7.3-12.5) and 15.3% (95% CI: 11-19.4) at 5 and 10 years, respectively. A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR: 3.47, 95% CI: 1.95-6.19). The cumulative probability of new cortisol, thyroid, gonadotroph, and growth hormone deficiency was 8% (95% CI: 3.9-11.9), 8.3% (95% CI: 3.9-12.5), 3.5% (95% CI: 1.7-5.2), and 4.7% (95% CI: 1.9-7.4), respectively at 10 years. CONCLUSIONS: SRS provides long-term tumor control with a 15.3% risk of hypopituitarism at 10 years.

Radiotherapy and Mortality in Pituitary Adenomas.

BACKGROUND: Pituitary adenomas (PA), comprising 10-20% of intracranial tumors, are classified as functioning and non-functioning and are further divided by size. Non-functioning tumors cause mechanical symptoms while functioning ones result in hormonal hypersecretion syndromes. Initial treatment involves surgery, with medical treatment for prolactinomas. Radiotherapy (RT) is employed as an adjuvant treatment, with various modalities including conventional, stereotactic radiosurgery (SRS), and fractionated stereotactic RT (FSRT). Although effective, RT is associated with complications and toxicities such as hypopituitarism, optic neuritis, secondary CNS tumors, and neurocognitive deficits. AIM: Describe the information on mortality from radiotherapy as treatment of functioning PA. METHODS: A PubMed search spanning 2000-2017 was conducted for articles on pituitary RT. RESULTS: Conventional RT entails high-energy radiation over multiple sessions, while SRS delivers precise high doses in a single session. FSRT offers enhanced precision using a linear accelerator, delivering multiple doses. Optic structure proximity and tumor volume dictate RT modality. Studies have shown SRS and FSRT's efficacy in tumor and endocrine control, with variable risks and complications. Mortality rates in pituitary adenomas treated with RT have been evaluated, revealing complexities. Acromegaly, associated with increased mortality due to cerebrovascular disease, may result from RT. Irradiation of non-functioning pituitary macroadenomas also elevates cerebrovascular risk, while radiotherapy-induced hypopituitarism is associated with increased cardiovascular mortality. RT-induced damage is attributed to microvascular lesions and arteriolar changes. CONCLUSION: Modern techniques mitigate complications, and although safer, long-term studies are needed. Multidisciplinary evaluation guides the treatment decision, optimizing efficacy and minimizing risk, ultimately improving the patient's quality of life.

Metastatic diffuse follicular variant papillary thyroid cancer without cervical lymph node metastasis presenting with symptoms related to hypopituitarism.

In this article, we present a case of diffuse follicular variant papillary thyroid carcinoma with pituitary metastasis, which is a rare cause of pituitary metastasis. The follicular variant of papillary thyroid carcinoma is an uncommon variant of papillary carcinoma. A 74-year-old male was presented with weakness, fatigue, and a decreased appetite. The patient was diagnosed with secondary adrenal and thyroid insufficiencies. Imaging revealed a pituitary mass with suprasellar extension, right cavernous sinus invasion, and optic chiasm compression. Thyroid ultrasonography revealed a nodule with a maximum size of 7.2cm in the right lobe. Cytological examination via fine-needle aspiration suggested papillary thyroid cancer. Total thyroidectomy with central and right lateral neck dissection confirmed the diagnosis of diffuse follicular variant of papillary thyroid carcinoma. Owing to visual field defects, the patient underwent transsphenoidal surgery. Histological and immunohistochemical evaluations confirmed pituitary metastasis from the papillary thyroid cancer. Radioactive iodine treatment and gamma knife radiotherapy of the pituitary gland were performed. The initiation of sorafenib treatment was deemed appropriate during the follow-up. A significant decrease in the thyroglobulin levels was observed after sorafenib treatment. Pituitary metastasis should be considered in patients diagnosed with hypopituitarism and pituitary lesions at initial evaluation. The presence of visual field defects may be an indication for neurosurgical intervention and guide both diagnosis and treatment. The management of papillary thyroid cancer and the role of treatment modalities in prognosis depend on the biological behavior of the tumor. Early diagnosis and multidisciplinary management are crucial for the treatment of these patients.

Endoscopic endonasal approach for resection of giant nonfunctional pituitary adenoma.

The giant pituitary adenoma (GPA)> 4 cm is considered a surgical challenging pathology and associated with higher surgical complications compared to non-giant pituitary adenoma [1]. These tumors are invasive and had extension to nearby neurovascular structures including cranial nerves and internal carotid artery. Endoscopic endonasal approach (EEA) is increasingly used in the last two decades, however tumors with significant height extension in the supraseller region makes surgeons in favor of transcranial approaches or combined approaches [2]. The accompanied symptoms arise from compression of neighboring structures as well as hypopituitarism [3]. In this video we present 65 year old male with PMH significant for HTN who presented with 2-3 months retro-orbital headaches, confusion, gait instability, urinary/fecal incontinence, found to have 5.1 × 2.1 × 2 cm sellaer-suprasellar mass compressing the floor of the third ventricle, mammillary body, and optic apparatus. The mass was associated with hydrocephalus. The endoscopic endonasal skull base approach (trans-sellar, transtubercular) was performed with significant tumor resection without a need for trans cranial approach. A titanium clips was used to reconstruct the diaphragma sella which was very helpful technique to change high flow CSF leak to low flow. The postoperative course of the patient was smooth with improved gait, memory, and vision. He was kept on a hormonal replacement for hypopituitarism.

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.

Surgery versus conservative care for Rathke's cleft cyst.

BACKGROUND: Rathke's cleft cysts are benign cystic lesions of the sellar region, which may cause headache, pituitary deficiencies and visual disturbances from mass effect. Their management is not standardized yet. This study is about establishing a consensus for medical care of RCC. MATERIAL AND METHODS: We performed a retrospective observational study of all patients that were diagnosed or followed for RCC between 2008 and 2018 (11 years), in the neurosurgical and the adult endocrine departments of our institution. The study's average time length of follow-up is 72.9 months (from 2 to 385 months). RESULTS: The 57 included patients were divided into 2 groups: group A, which included 39 patients that were conservatively managed and group B, which included 18 surgically treated patients. Group A showed either an improvement or a spontaneous resolution of headaches in 56.1% of the cases (P<0.01); a resolution of hyperprolactinemia in 70% of the cases (P=0.21); and of hypogonadism, ACTH deficiency, growth hormone deficiency in 100% of the cases. There was no spontaneous improvement of visual disturbances (P<0.01) or diabetes insipidus (P=0.29) during follow-up. Regarding group B, surgery allowed improvement or complete resolution of headaches in 60% of the cases; visual troubles in 100% of the cases (P<0.01); and hyperprolactinemia in 100% of the cases. Pituitary deficiencies were not improved by surgery. CONCLUSIONS: This study offers guidance in decision-making regarding the management of RCC patients. Surgery is particularly suitable for treating visual disturbances caused by RCC. Regular follow-up is more appropriate than surgery concerning headaches, hyperprolactinemia, endocrine disruptions and diabetes insipidus.

Giant Non-Functioning Pituitary Adenoma: Clinical Characteristics and Therapeutic Outcomes.

BACKGROUND: Giant pituitary adenoma (≥4 cm) is a rare tumor whose clinical features and prognosis are not well known. AIM: To evaluate the clinical characteristics and therapeutic outcomes of giant non-functioning PA (gNFPA). PATIENTS AND METHODS: A retrospective multicenter study of gNFPA patients diagnosed in a 12-year period was performed. In each patient, clinical data and therapeutic outcomes were registered. RESULTS: Forty patients (24 men, age 54.2 ± 16.2 years) were studied. The maximum tumor diameter [median (interquartile range)] was 4.6 cm (4.1-5.1). Women had larger tumors [4.8 cm (4.2-5.4) vs. 4.5 cm (4.0-4.9); p=0.048]. Hypopituitarism [partial (n=22, 55%) or complete (n=9, 22.5%)] at diagnosis was present in 77.5% of the patients. Visual field defects were found in 90.9%. The most used surgical technique was endoscopic endonasal transsphenoidal (EET) surgery (n=31, 77.5%). Radiotherapy was used in 11 (27.5%) patients (median dose 50.4 Gy, range 50-54). Thirty-seven patients were followed for 36 months (10-67 months). Although more than half of these patients showed tumor persistence (n=25, 67.6%), tumor size was significantly reduced [0.8 cm (0-2.5); p<0.001]. At last visit, 12 patients (32.4%) showed absence of tumor on MRI. Hypopituitarism rate was similar (75.0%), although with significant changes (p<0.001) in the distribution of the type of hypopituitarism. The absence of tumor at the last visit was positively associated with positive immunohistochemical staining for FSH (p=0.01) and LH (p=0.006) and negatively with female sex (p=0.011), cavernous sinus invasion (p=0.005) and the presence of Knosp grade 4 (p=0.013). CONCLUSION: gNFPAs are more frequent in men but tumors are larger in women. Surgical treatment is followed by a complete tumor resection rate of approximately 30%. Positive immunostaining for gonadotropins is associated with tumor absence at last revision, while female sex and invasion of the cavernous sinuses with tumor persistence.

Non-communicating hydrocephalus with a primary empty sella presenting with growth hormone deficiency and delayed puberty successfully treated by endoscopic third ventriculocisternostomy.

The authors present the unusual case of a 15-year-old boy with a primary empty sella caused by non-communicating hydrocephalus due to fourth ventricle outflow obstruction whose secondary symptoms of growth hormone deficiency and delayed puberty were successfully treated by endoscopic third ventriculocisternostomy (ETV). Hypopituitarism occurs only rarely in cases of hydrocephalus; rarer still are cases where hypopituitarism is the sole symptom of hydrocephalus. A primary empty sella may indicate elevated intracranial pressure; if the cause is non-communicating hydrocephalus, ETV is indicated as the preferred treatment modality.

A nonsense variant in FGFR1: a rare cause of combined pituitary hormone deficiency.

OBJECTIVES: Variants in fibroblast growth factor receptor-1 (FGFR1) may either cause isolated hypogonadotropic hypogonadism (IHH) or Kallmann syndrome (KS). Although the relationship of genes classically involved in IHH with combined pituitary hormone deficiency (CPHD) is well established, variants in FGFR1 have been presented as a rare cause of this phenotype recently. CASE PRESENTATION: Herein, we report an adopted 16-year-old male presented with delayed puberty and micropenis. He had undergone surgery for bilateral undescended testes in childhood. He was normosmic, and the pituitary imaging was normal. However, hypogonadotropic hypogonadism and growth hormone deficiency were detected, associated with a heterozygous nonsense variant (c.1864 C>T, p.R622X) in FGFR1. CONCLUSIONS: FGFR1 variants are among the causes of IHH and KS, which are inherited in an autosomal dominant manner and can be associated with midline defects. It should also be kept in mind that CPHD may be associated with FGFR1 variants in a subject with normal olfactory function.

Long-term results of Gamma Knife Radiosurgery for Postsurgical residual or recurrent nonfunctioning Pituitary Adenomas.

Introduction: The aim of this retrospective study was to analyze the long-term outcomes and factors associated with treatment failure of Gamma Knife radiosurgery (GKRS) for postsurgical residual or recurrent nonfunctioning pituitary adenomas (NFPAs). Design and Methods: A total of 148 cases of postsurgical residual or recurrent NFPA patients were enrolled in the study. There were 111 cases with residual tumor and 37 cases with recurrent tumor. The median age was 46.0 years (Range: 10.9-75.8 years). The median tumor volume at GKRS was 3.6 cm3 (Range: 0.3-74.5 cm3), and the median tumor margin dose was 14.0 Gy (Range: 9 - 20 Gy). Results: Tumor shrunk in 111 patients (75%), remained stable in 17 patients (11.5%), and progressed in 20 patients (13.5%) during a median of 64.5 months (Range: 14.5 - 236.0 months) of imaging follow-up. The progression-free survival rates were 99%, 91%, 88% and 74% at 1, 3, 5 and 10 years after GKRS, respectively. In a multivariate analysis, tumor margin dose (<13 Gy) was significantly associated with tumor progression (hazard ratio=3.526, 95% confidence interval=1.400-8.877, p=0.007). New hypopituitarism occurred in 22 out of 80 patients (27.5%), including hypogonadism (n=7), hypothyroidism (n=9), hypocortisolism (n=15) and growth hormone deficiency (n=1). In univariate and multivariate analysis, there were no factors significantly associated with new hypopituitarism. Six patients (4.1%) developed new or worsening visual dysfunction. Four patients (2.7%) developed new cranial neuropathy. Conclusion: In this study, GKRS can offer a high tumor control rate as well as a low rate of complications in postsurgical residual or recurrent NFPA patients.

The implication of giant tumor size on surgical resection, oncological, and functional outcomes in craniopharyngioma.

OBJECTIVE: Implication of the tumor size on oncological and functional outcomes of craniopharyngioma is inconsistently reported. The aim of this study is to assess the postoperative outcome of giant craniopharyngiomas (> 4 cm in diameter) and to elucidate the impact of tumor size on various outcome parameters and survival. MATERIAL AND METHODS: Forty-four patients (children aged ≤ 18 years: 25; adults: 16) with giant craniopharyngioma, operated between January 2001 and December 2015, were included in this study. Various outcomes, progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: Gross total resection (GTR) was achieved in 17 (39%) and subtotal resection (STR) in 27 (61%) patients. Eleven patients (25%) received radiotherapy (RT) after STR. Postoperatively, new cranial nerve and motor deficits were noted in 12 (27%) and 9 (20%) patients, respectively. Tumor recurrence following GTR and STR without adjuvant RT was diagnosed in 3 (17%), and 5 (38%) patients, respectively. Following STR with RT, one (9%) experienced recurrence. PFS at 5-, and 10- year following GTR, STR, and STR + RT was 80.8%, 45.4%, and 90%, respectively. At 5- and 10- year, OS was 86.5%, 77.9% and 100% following GTR, STR, and STR + RT, respectively. The rate of GTR was significantly lower in patients with giant tumors (39% vs. 62%; Chi-square test, p value 0.008). Postoperatively, neurological deficit (20%), hypopituitarism (95%) and hypothalamic dysfunction (26%) were significantly higher for giant craniopharyngiomas. Hazards of recurrence were not significant between giant and non-giant tumors (hazard ratio 1.86; 95% CI 0.94-3.68; p 0.07). There was no significant difference in OS between the patients with giant and non-giant tumors (log-rank test 2.1; p value 0.14). CONCLUSION: Tumor size should be considered as an important predictor of the postoperative functional outcome. Although the rate of GTR is less than that of small tumors, the recurrence rate, progression-free survival, and overall survival of the patients with giant tumor are comparable to non-giant tumors.

Cystic sellar salivary gland-like lesions.

INTRODUCTION: Cystic sellar salivary gland-like lesions (CSSLs) are exceedingly rare, with fewer than a dozen case reports. They contain amorphous colloid identical to Rathke cleft cyst contents, but the cyst wall additionally shows cohesive aggregates of benign salivary glands. We report three new examples. MATERIALS AND METHODS: Two cases were seen at University of Colorado Denver and one at Memorial Sloan Kettering (MSK). Molecular testing was attempted on two of three. RESULTS: Case 1 is a 20-year-old female who presented with panhypopituitarism and was found to have a suprasellar mass that proved to be a CSSL. She received no postoperative adjuvant therapy, but recurrence of headaches and blurred vision 2 years later prompted return to medical attention. A much smaller local cyst recurrence was now accompanied by a thickened, bulbous infundibular stalk. Second resection yielded a gliotic infundibular stalk and amorphous mucin, but no residual salivary-like glands. She is without further recurrence on 6-year follow-up. Case 2 is a 29-year-old female with headache; while seen initially at a tertiary care center, diagnosis was only made after consultation at MSK. Case 3 is 68-year-old female who had originally presented with apoplexy to an outside hospital 7 years prior to surgery and diagnosis. Molecular testing was uninformative on case 1 and negative for mutations or fusions on case 3. CONCLUSION: Few pathologists or neuropathologists have encountered CSSLs in their practices; case 1 produced recurrence and significant infundibular stalk damage, and case 3 originally manifested apoplexy, features not previously reported.

Non-functioning pituitary macroadenoma: surgical outcomes, tumor regrowth, and alterations in pituitary function-3-year experience from the Iranian Pituitary Tumor Registry.

PURPOSE: The aim of this study was to assess clinical features and therapeutic outcomes in patients with clinically non-functioning pituitary macroadenomas (NFPMAs). METHOD: This is a retrospective cohort study of NFPMA patients treated surgically and followed periodically between 2015 and 2017 in a tertiary care center in Iran. Descriptive analysis was performed applying appropriate tests. Binary logistic regression models were used to determine the predictive factors for subtotal tumor resection (STR) and hormonal recovery. Data were analyzed by Stata software. RESULT: A total of 71 patients with a mean age of 50.6 ± 1.4 years were studied. The mean diameter of the adenoma was 26.8 ± 1.1 mm. The most frequent symptoms were headache (85.75%), visual field defect (VFD) (78.3%), and hypogonadal symptoms (40.3%). Gross total resection (GTR) was achieved in 45.1%. Preoperative hypopituitarism was observed in 50.7% of patients. Recovery of at least one axis occurred in 36.1% of the patients suffering from hypopituitarism preoperatively, while new-onset postoperative hormonal deficiency appeared in 14.3% of patients. Multivariate analyses showing preoperative tumor size (OR = 38.2; P = 0.008) and cavernous sinus extension (OR = 13.4; P = 0.020) were predictors of STR. Moreover, hormonal recovery was observed not to be related to age, gender, tumor size, or the extent of tumor resection. CONCLUSIONS: Tumor size and cavernous sinus extension are the main predictors for STR. Notably, recovery of the gonadal axis in a large proportion of patients supports the surgical resection of NFPAM in patients suffering from gonadal deficiency, even in the absence of VFD.

Non-functioning pituitary adenomas: indications for pituitary surgery and post-surgical management.

PURPOSE: Non-functioning pituitary adenomas (NFPAs) are associated with impaired well-being, increased comorbidities, and reduced long-term survival. Data on optimal management of NFPAs around surgical treatment are scarce, and postoperative treatment and follow-up strategies have not been evaluated in prospective trials. Here, we review the preoperative, perioperative, and early postoperative management of patients with NFPAs. METHODS: We searched Medline and the Cochrane Library for articles published in English with the following items "Pituitary neoplasms AND Surgery" and "Surgery AND Hypopituitarism". Studies containing detailed analyses of the management of NFPAs in adult patients, including pituitary surgery, endocrine care, imaging, ophthalmologic assessment and long-term outcome were reviewed. RESULTS: Treatment options for NFPAs include active surveillance, surgical resection, and radiotherapy. Pituitary surgery is currently recommended as first-line treatment in patients with visual impairment due to adenomas compressing the optic nerves or chiasma. Radiotherapy is reserved for large tumor remnants or tumor recurrence following one or more surgical attempts. There is no consensus of optimal pre-, peri-, and postoperative management such as timing, frequency, and duration of endocrine, radiologic, and ophthalmologic assessments as well as management of smaller tumor remnants or tumor recurrence. CONCLUSIONS: In clinical practice, there is a great variation in the treatment and follow-up of patients with NFPAs. We have, based on available data, suggested an optimal management strategy for patients with NFPAs in relation to pituitary surgery. Prospective trials oriented at drawing up strategies for the management of NFPAs are needed.

Entirely Suprasellar Rathke Cleft Cysts: Clinical Features and Surgical Efficacy of Endoscopic Endonasal Transtuberculum Sellae Approach.

BACKGROUND: Rathke cleft cysts (RCCs) arise from the remnant of Rathke pouch and are usually found in the intermediate lobe. In most cases, RCCs remain intrasellar and extend into the suprasellar region. Rarely, they emerge entirely into the suprasellar cistern-entirely suprasellar Rathke cleft cyst (ESSRCC). METHODS: We retrospectively reviewed medical records of 7 patients (5.5%) with ESSRCC among 128 patients with a diagnosis of RCC from January 1994 to September 2018. Of RCC cases, 70 were treated surgically. Patient age and sex, symptoms, magnetic resonance imaging findings, cyst diameter, presence of preoperative or postoperative hypopituitarism, operative procedures and complications, and functional outcomes at the final follow-up were investigated. RESULTS: All patients with ESSRCC were women with mean age 45.7 years (range, 29-69 years) at diagnosis. All patients experienced headache, mainly in the retro-orbital region. Mean ESSRCC diameter was 9.9 mm (range, 6-14 mm). Most cases exhibited hyperintensity on both T1-weighted and T2-weighted imaging. The endoscopic endonasal transtuberculum sellae approach relieved headache effectively and safely in 5 patients. Postoperative endocrinologic functions were almost entirely preserved. No patient experienced recurrence during the follow-up period. CONCLUSIONS: RCCs should be considered in the differential diagnosis of suprasellar cysts. The endoscopic endonasal transtuberculum sellae approach has an advantage in visualizing these lesions owing to the direction of light from the endoscope. Headache could be treated effectively with the endoscopic endonasal transtuberculum sellae approach without recurrence of cysts or pituitary dysfunction.

A neurosurgical approach to traumatic brain injury and post-traumatic hypopituitarism.

PURPOSE: Traumatic brain injury (TBI) is a common cause of mortality and major disability worldwide. The initial management often depends on the severity of the injury. Pituitary dysfunction can develop as a sequela of TBI, and can have long-term, debilitating impact on the patients. Early identification and prompt intervention of post-traumatic hypopituitarism (PTHP) is essential to prevent or minimize the adverse consequences of this condition. We hereby provide an overview of the current management of TBI from a neurosurgical standpoint. We then review the pathophysiology and risk factors of developing PTHP, as well as our recommendations for its management. METHODS: A review of current literature on TBI and PTHP, including primary research articles, reviews and clinical guidelines. RESULTS: The current neurosurgical approach to the management of TBI is presented, followed by the pathophysiology and risk factors of PTHP, as well as our recommendations for its management. CONCLUSIONS: Post-traumatic hypopitutiarism is a serious and potentially debilitating condition that is likely under-recognised and under-diagnosed. From a neurosurgical perspective, we advocate a pragmatic approach, i.e. screening those considered at high risk of developing PTHP based on clinical features and biochemical/endocrinological testings; and referring them to a specialist endocrinologist for further management as indicated.

Long-Term Efficacy and Tolerability of Gamma Knife Radiosurgery for Growth Hormone-Secreting Adenoma: A Retrospective Multicenter Study (MERGE-001).

OBJECTIVE: Little is known about the long-term efficacy, prognostic factors, and tolerability of gamma knife radiosurgery (GKS) for acromegaly. The aim of this study was to investigate long-term hormonal effects, prognostic factors, and tolerability of GKS in patients with growth hormone-secreting adenoma. METHODS: A retrospective multicenter study over 25 years with a median follow-up of 85.2 months was performed. A total of 138 patients from 3 tertiary referral centers in South Korea were included in this study between 1991 and 2017. Main outcome measures were endocrine remission, endocrine control under somatostatin analogues, and hypopituitarism. RESULTS: With a mean follow-up period of 85.2 months (range, 12-304 months), overall median time to the endocrine remission and control under long-acting somatostatin analogues was 138 months and 96 months, respectively. Female sex, normal age-adjusted insulin growth factor-1 (IGF-1) ≤ 2, and GKS as an adjuvant treatment were significantly favorable factors for remission (P = 0.004, P = 0.001, P = 0.010, respectively). The early response group had a significantly lower proportion of normal age-adjusted IGF-1 levels >2 than did the late response group (22.2% vs. 51.7%, P = 0.035); also, the early response group had lower radiation dose than the late response group (24.3 Gy vs. 27.0 Gy, P = 0.003). The incidence of GKS-induced hypopituitarism (1 or more) was 12 of 138 patients (8.6%) at the last follow-up. CONCLUSIONS: In acromegalic patients, women with normal age-adjusted IGF-1 ≤ 2 and GKS as an adjuvant treatment have a better response to GKS. We should take into account the variability of radiosensitivity of the tumor according to the gender and IGF-1 level.

Single fraction and multisession Gamma Knife radiosurgery for craniopharyngioma.

PURPOSE: The optimal management of residual or recurring craniopharyngioma is still a matter of debate even though adjuvant radiation therapy plays a crucial role. Aim of our study is to report the results of single fraction or multisession Gamma Knife radiosurgery (GKRS) in patients with craniopharyngioma. METHODS: We included 50 consecutive patients treated from 1994 to 2016. All patients had at least one post GKRS magnetic resonance imaging reviewed at our center. Vital status of all patients was assessed at the end of 2016. RESULTS: There were 29 males (58.0%) and 21 females (42.0%). Mean age was 41.5 ± 2.8 year. Single session GKRS was delivered in 29 patients (58.0%). The mean tumor volume was 2.15 ± 0.3 cm3 and the mean prescription dose to the tumor margin was 14.3 ± 0.3 Gy. During a mean follow-up of 74.6 ± 8.4 months, seven patients (14.0%) had recurrence of disease. The 5- and 10-year recurrence-free survivals were 90.3% (95% CI, 81.0-99.6%) and 78.4% (95% CI, 59.9-96.9%), respectively. Multisession GKRS was not less effective than single fraction GKRS. Eighteen of the 28 patients (64.3%) had a tumor volume decrease of at least 10%. No serious side effects occurred after GKRS treatment, except for one case of mild visual worsening. CONCLUSIONS: GKRS was effective for controlling the growth of residual or recurrent craniopharyngioma. Serious side effects were uncommon. Multisession GKRS seems a very promising tool to allow performing GKRS even in patients with large residual or recurrent craniopharyngioma.

Clinical Parameters to Distinguish Silent Corticotroph Adenomas from Other Nonfunctioning Pituitary Adenomas.

BACKGROUND: It is difficult to distinguish silent corticotroph adenomas (SCAs) from other nonfunctioning pituitary adenomas (NFPAs) preoperatively. This study aimed to determine the preoperative clinical parameters associated with SCAs. METHODS: This was a retrospective single-center study of patients who underwent surgery for NFPAs during 2011-2016 in our tertiary hospital and who had preoperative combined pituitary function test (CPFT) and immunohistochemical staining results available. After we excluded patients with increased 24-hour urinary free cortisol to preclude overt Cushing's disease, 341 patients were finally enrolled. The medical records, including the CPFT and immunohistochemistry results, of the patients were reviewed. RESULTS: The age and tumor size were similar between patients with SCAs and other NFPAs. The SCA group had a greater proportion of women (89.2% vs. 57.6%, P < 0.001), cavernous sinus invasion (35.1% vs. 20.7%, P = 0.047), and intratumoral hemorrhage on preoperative sella magnetic resonance imaging (32.4% vs. 9.2%, P < 0.001) compared with the NFPA group. In the preoperative CPFT, the cortisol response was not significantly different between groups. However, the peak adrenocorticotropic hormone (ACTH) (67.80 ± 49.83 vs. 85.67 ± 78.97 pg/mL, P = 0.061) tended to be lower, and the ΔACTH (53.71 ± 50.14 vs. 72.67 ± 75.82 pg/mL, P = 0.046) was significantly lower in SCAs. After we excluded patients with preoperative hypopituitarism caused by mass effects, the peak ACTH (69.39 ± 39.45 vs. 119.75 ± 89.84 pg/mL, P = 0.001) and ΔACTH (58.58 ± 36.51 vs. 107.66 ± 86.05 pg/mL, P = 0.001) were significantly lower in SCAs than in other NFPAs. CONCLUSIONS: Female sex, cavernous sinus invasion, intratumoral hemorrhage on sella magnetic resonance imaging, and decreased ACTH response in the CPFT are independent indicators of SCAs.

Outcome of diabetes insipidus in patients with Rathke's cleft cysts.

OBJECTIVES: It is well-known that Rathke's cleft cysts (RCCs) infrequently cause headache, endocrinological dysfunction, and visual disturbance, and in rare cases, cause diabetes insipidus (DI). Although surgical evacuation of the cyst content can result in high rates of symptomatic improvement, not only the treatment efficacy but also the pathophysiology of DI with RCC are undetermined. The aim of this study is to elucidate the underlying mechanisms and outcomes of DI associated with RCCs. PATIENTS AND METHODS: We retrospectively studied 109 patients with RCCs treated at Kanazawa University Hospital between 2000 and 2016. Their age, sex, symptoms, endocrinological status, DI, visual disturbance, neuroradiological findings, pathological appearances, and pre-/post-operative hormone levels and status of anti-diuretic hormone replacements were assessed. RESULTS: Among 109 cases of RCCs, five cases (4.6%, 2 males and 3 females) manifested with DI as initial presentation were included. These five cases could be divided into two types: the acute type and the chronic type, based on the onset and duration of symptoms. Three acute onset cases presented with not only strong thirst but also sudden headaches without pituitary dysfunction, whereas the two chronic onset cases presented with chronic headaches and hypopituitarism. Pathological examination in the acute type revealed inflammatory cell infiltration into only the posterior lobe of the pituitary and disruption of the cyst wall adjacent to the posterior lobe, which might suggest RCC rupture. In contrast, the chronic type showed inflammatory cell infiltration into both the anterior and posterior lobes of the pituitary and thickened fibrosis beneath the cyst wall. Postoperatively, two cases of the acute type could be controlled with a smaller amount of 1-deamino-8-D-arginine vasopressin (DDAVP) than that required preoperatively, whereas no change was observed in the cases of the chronic type. CONCLUSION: The cases of DI onset caused by RCCs could be divided into the acute type and the chronic type. In the chronic type, surgical treatment could not affect the status of DI. However, in acute type, urgent surgical intervention partially relieved DI.