Successful treatment of medically and surgically refractory lymphocytic hypophysitis with fractionated stereotactic radiotherapy: a single-center experience and systematic literature review.

PURPOSE: To explore the potential role of focused radiotherapy in managing the lymphocytic hypophysitis (LH) refractory to medical therapy and surgery. METHOD: A systematic literature review was conducted following PRISMA guidelines to identify the studies on radiation treatment for hypophysitis, along with the experience in our institution. RESULTS: The study included eight patients, three from our institution and five from existing literature. The age at presentation ranged from 37 to 75 years old, with a median age of 58. The presenting symptoms involved headache in seven patients and diplopia in two patients. Pre-radiation visual field defects were noticed in four patients. All patients exhibited variable degrees of hypopituitarism before radiation, with oral corticosteroids being the initial medical treatment. Immunosuppressive therapy was attempted in two patients prior to radiation. Seven patients had a history of transsphenoidal surgery with a histologically confirmed LH. Three patients underwent stereotactic radiosurgery (SRS), while the remaining received FSRT, with a mean irradiation volume of 2.2 cm3. A single-session total dose of 12 -15 Gy was administered in the SRS group. In the FSRT group, doses ranged from 24 to 30 Gy with a median dose of 25 Gy, delivered in 2 Gy fractions. Four patients achieved a resolution of visual field defects, while another two patients demonstrated improvement in their associated focal neurologic deficits. No change in pre-existing endocrine status was shown after radiation, except in one patient. Clinical response was achieved in seven patients after a single course of radiation, while one patient required the second course. Six patients remained stable on low-dose glucocorticoid during at least a 12-month follow-up period, and one discontinued it entirely without experiencing relapse. Three patients demonstrated a complete radiologic response, while the remaining showed a partial radiologic response. CONCLUSIONS: Focused radiation, including FSRT, can play a role in symptomatic relief, effective mass shrinkage, and minimizing radiation exposure to critical surrounding structures in patients with refractory LH. However, further research efforts are necessary to better clarify its effects and optimal dose planning.

RANK-L inhibitor as a promising agent for refractory extensive craniofacial fibrous dysplasia: A case report.

BACKGROUND: McCune-Albright syndrome is a rare disorder characterized by polyostotic fibrous dysplasia (FD), café-au-lait skin pigmentation, and endocrine dysfunction. Extensive FD in the craniofacial region can present significant challenges in terms of disease control and carries a high risk of permanent visual impairment. METHODS: We present a case of medically and surgically resistant FD that required nine optic nerve decompressions. RESULTS: The condition was ultimately controlled with the use of the denosumab agent. CONCLUSION: The case highlights the importance and potential efficacy of denosumab in resistant FD management, particularly in cases involving sensitive organs.

Surveillance Imaging Strategies for Pituitary Adenomas: When, How Frequent, and When to Stop.

OBJECTIVE: To describe a practical approach of when and how often to perform imaging, and when to stop imaging pituitary adenomas (PAs). METHODS: A literature review was carried out and recommendations provided are derived largely from personal experience. RESULTS: Magnetic resonance imaging is the mainstay imaging modality of choice in the assessment, treatment planning, and follow-up of PAs. These adenomas are discovered incidentally during imaging for a variety of unrelated conditions, because of clinical symptoms related to mass effects on the adjacent structures, or during workup for functional alterations of the adenoma. Imaging is also used in the preoperative and postoperative phases of assessment of PAs, for surgical and radiotherapy planning, for postoperative surveillance to assess for adenoma stability and detection of adenoma recurrence, and for surveillance to monitor for adenoma growth in unoperated PAs. Currently, because there are no evidence-based consensus recommendations, the optimal strategy for surveillance imaging of PAs is not clearly established. Younger age, initial adenoma size, extrasellar extension, mass effect, cavernous sinus invasion, functional status, histopathologic characteristics, cost considerations, imaging accessibility, patient preference, and patient contraindications (eg, implanted metallic devices and patient claustrophobia) are all important factors that influence the strategy for surveillance imaging. CONCLUSIONS: This review provides a practical approach of performing surveillance imaging strategies for PAs that should be individualized based on clinical presentation, history, adenoma morphology on imaging, and histopathologic characteristics.

Efficacy and Safety of Endoscopic Transsphenoidal Resection for Prolactinoma: A Retrospective Multicenter Case-series.

BACKGROUND: Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up to 90%), low recurrence (5-20%) rates highlighted that surgery might be first-line treatment. AIMS: To report on outcomes of ETSS in a cohort of prolactinomas. METHODS: Multicenter retrospective cohort of 137 prolactinoma patients (age 38.2 ± 13.7 years; 61.3% female, median follow-up 28.0 [15.0-55.5] months) operated between 2010-2019 with histopathological confirmation. RESULTS: Median preoperative prolactin levels were 166 (98-837 µg/L; males 996 [159-2145 µg/L] vs. females 129 [84-223 µg/L], p <0.001). 56 (40.9%) microprolactinomas, 69 (50.4%) macroprolactinomas, and 7 (5.1%) giant prolactinomas were included, whereas no adenoma was detected in 5 (3.6%) patients. Males had larger tumors (macroprolactinomas: 38, 71.7%) vs. 31 (36.9%), p <0.001; giant prolactinomas: 7 (13.2%) vs. 0 (0.0%), (p <0.001). Prolactinomas were graded as KNOSP-3 in 15 (11.5%), and KNOSP-4 in 20 (15.3%) patients. Primary indication was DA intolerance (59, 43.1%); males 14 (26.4%) vs. females 45 (53.6%), p = 0.006. Long-term remission (i.e., DA-free prolactin level <1xULN) was achieved in 87 (63.5%) patients, being higher in intended complete resection (69/92 [75.0%]), and lower in males (25 [47.2%] vs. 62 females [73.8%], p = 0.002). Transient DI (n = 29, 21.2%) was the most frequent complication. CONCLUSIONS: Despite high proportions of macroprolactinoma and KNOSP 3-4, long-term remission rates were 63.5% overall, and 83.3% in microprolactinoma patients. Males had less favorable remission rate compared to females. These findings highlight that ETSS may be a safe and efficacious treatment to manage prolactinoma.

A silent corticotroph adenoma: making the case for a pars intermedia origin. Illustrative case.

BACKGROUND: Silent corticotroph adenomas (SCAs) are the only pituitary adenomas thought to originate from the pars intermedia. This case report presents the rare finding of a multimicrocystic corticotroph macroadenoma displacing the anterior and posterior lobes of the pituitary gland on magnetic resonance imaging (MRI). This finding supports the hypothesis that silent corticotroph adenomas may originate from the pars intermedia and should be considered in the differential for tumors arising from this location. OBSERVATIONS: A 55-year-old man presented with an episode of confusion and blurred vision. MRI demonstrated separation of the anterior and posterior glands by a solid-cystic lesion located within the pars intermedia that superiorly displaced the optic chiasm. Endocrinologic evaluation was unremarkable. The differential diagnosis included pituitary adenoma, Rathke cleft cyst, and craniopharyngioma. The tumor was confirmed to be an SCA on pathology and was completely removed through the endoscopic endonasal transsphenoidal approach. LESSONS: The case highlights the importance of preoperative screening for subclinical hypercortisolism for tumors arising from this location. Knowledge of a patient's preoperative functional status is critical and dictates their postoperative biochemical assessment to determine remission. The case also illustrates surgical strategies for resecting pars intermedia lesions without injuring the gland.

Intraoperative Predictor of Remission in Cushing Disease.

BACKGROUND: Cushing disease represents a challenge for neurosurgeons, with high recurrence rates reported. Characteristics associated with remission are incompletely understood; thus, an intraoperative predictor for outcome would be valuable for assessing resection of adrenocorticotropic hormone (ACTH) secreting tissue. OBJECTIVE: To evaluate whether intraoperative ACTH measurement could predict outcome after surgery for Cushing disease. METHODS: Retrospective cohort study of 55 consecutive encounters with Cushing disease who had peripheral plasma ACTH levels measured intraoperatively before, during, and after tumor resection. The primary outcome measure was remission, defined by either 2 negative 24-hour urine free cortisol or 2 negative midnight salivary cortisol measurements. A logistic regression machine learning model was generated using recursive feature elimination. RESULTS: Fifty-five operative encounters, comprising 49 unique patients, had a mean follow-up of 2.73 years (±2.11 years) and a median follow-up of 2.07 years. Remission was achieved in 69.1% (n = 38) of all operations and in 78.0% (n = 32) of those without cavernous sinus invasion. The final ACTH level measured intraoperatively correctly predicted outcome (area under the curve = 0.766; P value = .002). The odds ratio of remission in patients with the lowest quartile vs highest quartile final intraoperative ACTH was 23.4 ( P value = .002). Logistic regression machine learning model resulted in incorporating postoperative day 1 morning cortisol, final intraoperative ACTH that predicted outcome with an average area under the curve of 0.80 ( P = .0027). CONCLUSION: Intraoperative ACTH may predict outcome after surgery in Cushing disease; furthermore, investigation is warranted.

Pituitary Stalk Stretch Predicts Postoperative Diabetes Insipidus After Pituitary Macroadenoma Transsphenoidal Resection.

BACKGROUND: Manipulation of the pituitary stalk, posterior pituitary gland, and hypothalamus during transsphenoidal pituitary adenoma resection can cause disruption of water electrolyte regulation leading to diabetes insipidus (DI). OBJECTIVE: To determine whether pituitary stalk stretch is an independent risk factor for postoperative DI after pituitary adenoma resection. METHODS: A retrospective review was performed of patients undergoing endoscopic endonasal resection of pituitary macroadenoma between July 2010 and December 2016 by a single neurosurgeon. We analyzed preoperative and postoperative imaging metrics to assess predictors for postoperative DI. RESULTS: Of the 234 patients undergoing resection, 41 (17.5%) developed postoperative DI. DI was permanent in 10 (4.3%) and transient in 31 (13.2%). The pituitary stalk stretch, measured as the change in stalk length from preoperative to postoperative imaging, was greater in the DI compared with the non-DI group (10.1 mm vs 5.9 mm, P < .0001). The pituitary stalk stretch was associated with DI with significant difference in mean pituitary stalk stretch between non-DI group vs DI group (5.9 mm vs 10.1 mm, P < .0001). Multivariate analysis revealed that pituitary stalk stretch >10 mm was a significant independent predictor of postoperative DI [odds ratios = 2.56 (1.10-5.96), P = .029]. When stratified into transient and permanent DI, multivariable analysis showed that pituitary stalk stretch >10 mm was a significant independent predictor of transient DI [odds ratios = 2.71 (1.0-7.1), P = .046] but not permanent DI. CONCLUSION: Postoperative pituitary stalk stretch after transsphenoidal pituitary adenoma surgery is an important factor for postoperative DI. We propose a reconstruction strategy to mitigate stalk stretch.

Intraoperative Prediction of Long-Term Remission in Acromegaly.

BACKGROUND: The features of long-term remission in acromegaly adenomectomy are incompletely understood. An intraoperative predictor for long-term outcome would be valuable for assessing resection of growth hormone (GH)-secreting tumors in real-time. OBJECTIVE: To evaluate whether intraoperative GH measurement could predict long-term outcomes for acromegaly. METHODS: In 47 patients, peripheral blood GH levels were measured thrice intraoperatively: once before tumor dissection, once during tumor dissection, and once after tumor dissection. Long-term remission was defined by age-appropriate, normalized insulin-like growth factor-1 at most recent follow-up and a random GH less than 1.0 ng/mL. Patients were only considered to be in long-term remission without the use of postoperative medical therapy for acromegaly or radiation therapy. RESULTS: The median length of follow-up was 4.51 (range: 0.78-9.80) years. Long-term remission was achieved in 61.7% (29/47) of operations. Like previous studies, cavernous sinus invasion (odds ratio [OR]: 0.060; 95% CI: 0.014-0.260; P value < .01), suprasellar extension (OR: 0.191; 95% CI: 0.053-0.681; P value<.01), and tumor size greater than 1 cm (OR: 0.177; 95% CI: 0.003-0.917; P value = .03) were associated with not being in long-term remission. The minimum GH measured intraoperatively predicted long-term outcome (area under the curve: 0.7107; 95% CI: 0.537-0.884; P value < .01). The odds ratio of remission in patients with the lowest quartile minimum intraoperative GH compared with patients with the highest quartile minimum intraoperative GH was 27.0 (95% CI: 2.343-311.171; P value < .01). CONCLUSION: Minimum intraoperative GH may predict long-term outcome for acromegaly, which in principle could provide the pituitary neurosurgeon with real-time feedback and inform intraoperative decision making.

Sellar Cholesterol Granuloma Mimicking Cystic Sellar Lesions: A Report of Three Cases and Literature Review.

BACKGROUND: Cystic lesions in the sellar region include a variety of entities, such as craniopharyngioma, Rathke cleft cyst (RCC), intrasellar arachnoid cyst, cystic pituitary adenomas, cholesterol granulomas (CGs), and xanthogranulomas (XGs). The distinction among them remains a preoperative challenge due to similarities in their clinical and radiologic findings. CASE DESCRIPTION: We describe 3 cases with cystic sellar lesions. The first patient is a woman who presented with headache and hormonal disturbances, including high levels of prolactin, with a sellar and suprasellar cystic lesion discovered on magnetic resonance imaging. She was initially treated with dopamine agonists with normalization of prolactin levels but no changes on the size of the lesion. She underwent an endoscopic endonasal resection and the histology resulted in a CG/XG. The second patient is a woman who consulted for an incidentally discovered sellar cyst. During the follow-up, the lesion demonstrated enlargement with compression of the optic chiasm. With a preoperative diagnosis of RCC, the lesion was removed through an endoscopic endonasal transsellar approach. Final pathologic diagnosis was consistent with CG/XG. The third case was that of a man who presented with refractory headaches and vision loss, with a sellar/suprasellar cystic lesion on magnetic resonance imaging. He underwent endoscopic endonasal transsellar surgery for resection of what preoperatively was thought to be a giant RCC; final pathology again was consistent with CG/XG. CONCLUSIONS: CG/XG is an uncommon pathology with unspecific clinical and radiologic features. However, this pathology should be considered in the differential diagnosis of mixed cystic/solid lesions in the sellar region.

Pituitary carcinomas: review of the current literature and report of atypical case.

Introduction: Pituitary carcinomas are poorly understood, rare entities. They are distinguished from adenomas not by histopathological features but rather by the presence of metastases.Objective: We discuss the diagnosis, mechanism of dissemination and pathogenesis based on a review of the literature and illustrated by a singular case.Case Report: A 59-year-old male presented with a dural-based posterior fossa lesion. He had been diagnosed with a pituitary chromophobe adenoma 43 years earlier that was treated at the time with surgery and radiation therapy. A presumptive diagnosis of a radiation-induced meningioma was made and surgery was recommended. At surgery the tumour resembled a pituitary adenoma. Histopathology, laboratory findings, and the patient's medical history confirmed the final diagnosis of a prolactin-secreting pituitary carcinoma. To our knowledge, this is the longest reported interval between the pituitary adenoma and metastatic lesion diagnosis (43 years).Conclusion: Management should be tailored to individual patient and may include a combination of treatments (surgery, radiation therapy, chemotherapy, and hormone-targeted therapy). Functionally active tumours may be monitored with hormone levels as tumour markers.

Physicians' awareness of gadolinium retention and MRI timing practices in the longitudinal management of pituitary tumors: a "Pituitary Society" survey.

PURPOSE: In view of mounting attention related to possible brain retention of gadolinium-based contrast agents (GBCAs) in patients with normal renal function, our purpose was to detail results from a survey of pituitary experts to assess: 1) the timing interval and frequency of pituitary magnetic resonance imaging (MRI) following surgical and/or medical and/or radiation therapy of pituitary tumors, 2) awareness of the types of GBCAs used and their possible safety issues. METHODS: The Pituitary Society Education Committee composed a survey with 12 multiple choice questions, 8 of which specifically addressed the time interval and frequency of MRI in the longitudinal management of pituitary tumors. The survey was distributed at two meetings; the International Pituitary Neurosurgeons Society conference in San Diego, CA, on February 18th, 2018, and the Pituitary Society Membership and Career Development Forum, Chicago, IL on March 18th, 2018. RESULTS: There is consensus among pituitary endocrinologists and neurosurgeons that long-term repeated imaging is recommended in most pituitary tumors, although the precise strategy of timing varied depending on the specialist group and the specific clinical context of the adenoma. The data also suggest that International Pituitary Neurosurgeons Society neurosurgeons, as well as Pituitary Society neuroendocrinologists, are sometimes unaware of which contrast agents are used by their institution, and many are also unaware that evidence of long-term brain retention has been reported with the use of GBCAs in patients with normal function. CONCLUSIONS: International pituitary endocrinologists and pituitary neurosurgeons experts suggest ongoing MRIs for the management of pituitary tumors; strategies vary based on clinical context, but also on individual experience and practice.

Predictors of Postoperative Diabetes Insipidus Following Endoscopic Resection of Pituitary Adenomas.

CONTEXT: The development of diabetes insipidus (DI) following transsphenoidal resection of pituitary adenomas has been associated with higher postsurgical morbidity and longer hospitalizations. Identifying these patients promptly and efficiently can lead to improved health care outcomes. OBJECTIVE: We evaluated our institution's incidence of DI following pituitary adenoma resection and assessed for preoperative risk factors that were associated with postoperative DI. DESIGN: A retrospective review of 271 patients who underwent endoscopic endonasal resection of a pituitary adenoma between July 2010 and December 2016 by a single neurosurgical provider was completed. SETTING: All cases were from a single-center, academic institution. PATIENTS: Patients with a pituitary adenoma diagnosis confirmed on histology were included in the study. Those with previous surgery by a different provider were excluded. RESULTS: The incidence of DI at our institution was 16.6% (45 of 271 patients), with only 4% (11 patients) having permanent DI. The presence of visual abnormalities (CI 1.29 to 4.75), suprasellar extension (CI 1.36 to 6.88), and maximal tumor diameter (1.02 to 1.08) was significantly associated with an increased incidence of postoperative DI (P < 0.05). Hyperprolactinemia, tumor functionality, and cerebrospinal fluid exposure were not associated with higher rates of postoperative DI (P > 0.05). CONCLUSION: Pituitary adenoma patients presenting with visual abnormalities, suprasellar extension, or large tumors are at higher risk of developing DI postoperatively. These patients warrant closer postoperative monitoring as well as adequate preoperative counseling to decrease their postsurgical morbidity.