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Evidence-based enhanced recovery after surgery (ERAS) programs aim to improve patient outcomes and shorten hospital stays. The objective of this study is to describe the development, implementation, and evolution of an ERAS protocol to optimize the perioperative management for patients undergoing endoscopic skull base surgery for pituitary tumors. A systematic review of the literature was performed, best practices were discussed with stakeholders, and institutional guidelines were established and implemented. Key performance indicators (KPI) were measured and patient-reported outcome surveys were collected. The ERAS protocol was introduced successfully at our institution. We describe the process of initiation of the program and the perioperative management of our patients. We demonstrated the feasibility of integration of ERAS protocols for pituitary tumors with multidisciplinary engagement, with a particular emphasis on the use of data informatics and metrics to monitor outcomes. We expect that this approach will translate to improved quality of care for these often-complex patients.

Objective The hypothalamic-pituitary-adrenal axis stimulation during pregnancy complicates the investigation of Cushing's syndrome. Our objective is to present a pregnant patient with Cushing syndrome caused by pituitary tumor in which the desmopressin stimulation test helped in the diagnosis and led to appropriate management. Case report A 27-year-old woman with 9-week gestation presented with proximal myopathy for 2 months. She had high blood pressure, wide abdominal purplish striae, and proximal myopathy. Her past medical history revealed hypertension and dysglycemia for 1 year. The 8 AM cortisol was 32.4 μ g/dL (5-18), late-night salivary cortisol at 11 PM was 0.7 μ g/dL ( μ g/day (21.0-143.0). The mean ACTH concentrations at 8 AM were 44.0 pg/mL (0-46.0). Non-gadolinium enhanced pituitary magnetic resonance imaging (MRI) reported no obvious lesion. The desmopressin stimulation test showed a 70% increase in ACTH levels from baseline after desmopressin administration. The pituitary MRI with gadolinium showed an 8x8x7-mm pituitary adenoma. Transsphenoidal surgery with tumor removal was done, which showed ACTH-positive tumor cells. After the surgery, the patient carried on the pregnancy uneventfully. Discussion During pregnancy, the ACTH level may not be an accurate marker to help in the differential diagnosis of Cushing's syndrome. Moreover, non-gadolinium pituitary imaging may not detect small pituitary lesions. Conclusion In the present Case, the desmopressin stimulation test suggested the diagnosis of Cushing's disease, which subsequently led to successful treatment. This suggested that the desmopressin test may serve as a useful test to diagnose Cushing's disease in pregnant individuals.

The central nervous system (CNS) tumors constitute the most common type of solid tumors in the pediatric population. The cerebral and cerebellar parenchyma are the most common site of pediatric CNS neoplasms. Imaging plays an important role in detection, characterization, staging and prognostication of brain tumors. The focus of the current article is pediatric brain tumor imaging with emphasis on pearls and pitfalls of conventional and advanced imaging in various pediatric brain tumor subtypes. The article also elucidates changes in brain tumor terms and entities as applicable to pediatric patients, updated as per World Health Organization (WHO) 2016 classification of primary CNS tumors. This classification introduced the genetic and/or molecular information of primary CNS neoplasms as part of comprehensive tumor pathology report in the routine clinical workflow. The concepts from 2016 classification have been further refined based on current research, by the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) group and published in the form of updates. The updates serve as guidelines in the time interval between WHO updates and expect to be broadly adopted in the subsequent WHO classification. The current review covers most pediatric brain tumors except pituitary tumors, meningeal origin tumors, nerve sheath tumors and CNS lymphoma/leukemia.

BACKGROUND: IL-18 is known as an interferon-inducing factor that belongs to the IL-1 family, and is synthesized as an inactive precursor protein. OBJECTIVE: The present study aims to investigate the expression of IL-18, IL-18R, R and IL-18 binding protein (BP) mRNA in various types of human pituitary tumors, such as adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH)-producing adenomas and non-function adenomas. METHODS: Pituitary adenoma tissues were obtained during the surgery of 41 patients: nine patients had ACTH-producing pituitary adenomas, nine patients had GH-producing pituitary adenomas, five patients had TSH-producing pituitary adenomas, seven patients had PRL-producing pituitary adenomas, and 11 patients had non-functioning adenomas. The mRNA expression levels of IL-18, IL-18BP, IL-18R and IL-18R were quantified using real-time quantitative PCR. RESULTS: The mRNA expression of IL-18 was significantly higher in ACTH-, GH- and PRL-producing adenomas, when compared to non-function tumors. Similarly, a significantly higher mRNA expression of IL-18BP and IL-18R was observed in ACTH-, GH- and PRL-producing adenomas, when compared with non-functional adenomas. In contrast, no upregulation of IL-18R mRNA was observed in any of the pituitary adenomas. CONCLUSIONS: The mRNA levels of IL-18, IL-18BP and IL-18R are significantly elevated in clinical pituitary tumors, such as ACTH-, GH- and PRL-producing adenomas, when compared to non-functional adenomas. These present results suggest the possibility that IL-18 may be involved in the pathogenesis of pituitary adenoma.

Background: Acromegaly is a severe progressive neuroendocrine disease caused by chronic elevated concentrations of growth hormone and insulin-like growth factor 1 in individuals with completed physiological growth and leading to early disability and mortality. The Acromegaly Registry with its regular updates makes it possible to merge and systematize all the available information on the diseases, to assess the efficacy of treatment algorithms and to choose an optimal diagnostic and treatment strategy in a given territory.Aim: To evaluate the efficacy of various treatments for acromegaly based on the analysis of the regional Registry of patients with pituitary tumors in the Republic of Tatarstan.Materials and methods: The study was based on data from 217 patients with somatotropin producing pituitary adenomas entered in the Registry of patients with pituitary tumors in the Republic of Tatarstan as per January 2021. One hundred and eighty one (181 patients) with sufficient data to assess the remission rates and the disease course were included into the analysis.Results: Endonasal endoscopic adenomectomy as a first-line treatment has been performed in 93% (169/181) of the patients, with 34% of the cases (57/169) being in the full postoperative remission. The efficacy of surgical treatment depended on the tumor size, invasion grade and aggressiveness. A 1st generation long-acting somatostatin analog (octreotide) has been prescribed to 50% (91/181) of the patients (11 patients as first-line therapy and 80 patients after adenomectomy), with biochemical remission rate of 56% (51/91). Radiological treatment has been completed in 11,6% (21/181) of the patients. The complete remission rate after all treatment modalities (surgical, medical, and radiation therapy) was 60% (108/181).Conclusion: The effectiveness of treatment for acromegaly in the Republic of Tatarstan is comparable to that in the all-Russian and international registries. Nevertheless, 40% of the patients with acromegaly in the region do not have their disease biochemically controlled indicating the need to optimize drug treatment.

PURPOSE To study for the first time the incidence of adult-onset CNS tumors in Southern Sardinia, Italy. METHODS Clinical records of patients > 18 years old who were diagnosed with primary CNS tumors during 2016-2019 in the study area were reviewed. Meningiomas, cranial/paraspinal nerve tumors, lymphomas, and pituitary tumors were excluded. Cases were classified according to the 2016 WHO classification of CNS tumors and to the morphology codes from the International Classification of Diseases-Oncology, third edition. Age-adjusted incidence rates were calculated by the direct method to the 2011-2020 European standard population. Kulldorff's spatial scan statistic was used to identify geographic clusters of patients who shared increased/decreased tendency to develop CNS tumors. RESULTS CNS tumors were diagnosed in 234 incident patients, but histological diagnosis was available in 222/234 patients (95%) aged 64.3 ± 13.5 years at diagnosis. Crude incidence rate was 7.1 per 100,000 persons-year (95% CI, 6.2-8.1), 6.2 per 100,000 persons-year (95% CI, 5.4-7.0) when age-adjusted. CNS tumors were more frequent in men and after age 40. Glioblastoma accounted for 76% of the total (adjusted rate, 4.7 per 100,000 persons-year; 95% CI, 4.0-5.4). Spatial analysis revealed geographic variations of glioblastoma incidence within the study area. CONCLUSION Although the distribution of tumor diagnoses in Sardinia reflects expected age and gender-related patterns in western populations, our findings would indicate a slightly higher incidence of glial tumors, glioblastoma in particular, in Sardinia than in other European countries. The identification of spatial clusters of high/low risk will serve as a resource for etiological research.

Background This report describes the case of a patient whose pituitary microadenoma resolved after he contracted coronavirus disease 2019. To our knowledge, this is one of the first reported cases of pituitary tumor resolution due to viral illness. We present this case to further investigate the relationship between inflammatory response and tumor remission. Case presentation A 32-year-old man in Yemen presented to the hospital with fever, low blood oxygen saturation, and shortness of breath. The patient was diagnosed with coronavirus disease 2019. Past medical history included pituitary microadenoma that was diagnosed using magnetic resonance imaging and secondary adrenal insufficiency, which was treated with steroids. Due to the severity of coronavirus disease 2019, he was treated with steroids and supportive care. Three months after his initial presentation to the hospital, brain magnetic resonance imaging was performed and compared with past scans. Magnetic resonance imaging revealed changes in the microadenoma, including the disappearance of the hypointense lesion and hyperintense enhancement observed on the previous scan. Conclusions Pituitary adenomas rarely undergo spontaneous resolution. Therefore, we hypothesized that tumor resolution was secondary to an immune response to coronavirus disease 2019.

Context Characterization of the clinical features and natural history of nonfunctioning pituitary microadenomas (NFPmAs) is limited by heterogeneous and small-scale studies. Objective To characterize the clinical presentation and natural history of NFPmAs and evaluate if imaging follow-up interval can be extended. Methods Retrospective single-center cohort study (years 2006-2021) of conservatively managed patients with NFPmAs. Initial symptoms, pituitary function, and tumor size were assessed. A change in NFPmA size ≥2 mm, as determined by pituitary or brain magnetic resonance imaging (MRI), was considered significant. Results There were 347 patients in the study cohort. Headache (78.4%) and fatigue (70.0%) were commonly reported despite no evidence of mass effect or significant pituitary hypofunction. Pituitary deficiencies at baseline were rare, with hypogonadism being most common (5.1%). During a median imaging follow-up period of 29 months (range 3-154), 8.1% of NFPmAs grew. Growth incidence was 2.1 per 100 person-years with a mean and median time to growth of 38.1 (SD ± 36.4) and 24.5 (interquartile range 12.0-70.8) months, respectively. Tumor growth was mild and not associated with new pituitary deficiencies or visual deficits. Conclusion These data indicate that the natural history of NFPmAs is overall benign. Consequently, we propose that the initial MRI follow-up timeline for NFPmAs can be extended up to 3 years unless a lesion is close to the optic chiasm, there are worrisome mass effect symptoms, or new pituitary deficiencies.

Non-functioning pituitary adenomas (NFPA) usually present with symptoms of mass effect. Thus, the first-line treatment generally consists of transsphenoidal surgery. Since these tumors are usually large and invasive, post-surgical tumor remnants are common. Active surveillance is the follow-up strategy adopted by most pituitary centers, although the prevalence of residual tumor growth may reach 50% in 5–10 years, often leading to repeat surgery, radiation therapy, or both. NFPA remain the only pituitary tumor type for which no medical therapy has been approved. In this debate, we consider the evidence in favor and against using cabergoline to treat progressing NFPA.

PURPOSE: To examine the contemporary epidemiology of adult pituitary tumors with a particular focus on uncommon tumor types, using the 2017 WHO Classification of pituitary tumors. METHODS: Adult patients presenting with a pituitary or sellar tumor between 2004 and 2017 were identified from the U.S. National Cancer Database, with tumor type categorized according to the 2017 WHO classification. Descriptive epidemiological statistics were evaluated and reported for all pituitary tumor types and subtypes. RESULTS: 113,349 adults with pituitary tumors were identified, 53.0% of whom were female. The majority of pituitary tumors were pituitary adenomas (94.0%), followed by craniopharyngiomas (3.8%). Among pituitary adenomas, whereas 71.6% of microadenomas presented in females, only 46.7% of macroadenomas and 41.3% of giant adenomas did (p < 0.001). For craniopharyngiomas, 71.2% were adamantinomatous and 28.8% were papillary, with adamantinomatous tumors associated with Black non-Hispanic race/ethnicity ( OR(adj) = 2.44 vs. White non-Hispanic, 99.9 %CI = 1.25–4.75, p < 0.001) in multivariable analysis. The remaining 0.7% (n = 676) of pathology-confirmed pituitary tumor types were composed of: 21% tumors of the posterior pituitary, 16% chordomas, 11% pituitary carcinomas (i.e. adenohypophyseal histology with metastasis; herein most frequently to bone), 10% meningiomas, 8% germ cell tumors, 7% hematolymphoid (largely DLBCLs), and 4% neuronal/ paraneuronal (largely gangliogliomas). Pituitary carcinomas and posterior pituitary tumors demonstrated a male predilection (62.2% and 56.0%, respectively), whereas sellar meningiomas predominated in females (84.1%). Age, race/ethnicity, tumor size, and overall survival further varied across uncommon pituitary tumor types. CONCLUSIONS: Our findings provide a detailed contemporary dissection of the epidemiology of common and uncommon adult pituitary tumors in the context of WHO2017.

We present an up-to-date review of all published cases of sellar melanocytoma, a benign melanocytic neoplasm arising from melanocytes present in the leptomeninges surrounding the pituitary. Both the Medline and Embase databases were searched for case reports or case series of patients with a sellar mass consisting of melanocytes. All 14 identified patients developed symptoms due to compression of the surrounding structures. Symptoms included pituitary dysfunction and visual impairment. All patients received a transsphenoidal resection as first-line treatment. The diagnosis is made on pathological examination but deciding whether a sellar melanocytic tumor is best classified as a melanocytoma or a melanoma is not straightforward. Genetic analyses can help differentiate between central nervous system origin and metastasis of a cutaneous melanoma with the presence of a GNAQ and GNA11 mutations or a BRAF mutation, respectively. First choice treatment is complete resection, and in case of incomplete resection or recurrence additional radiotherapy is advised.

This clinical case reflects the variability in the course of chronic adrenal insufficiency after bilateral adrenalectomy for Itsenko — Cushing disease, the development and growth of pituitary adenoma, which can lead to hemorrhagic stroke in the most recurrent pituitary tumor. The objective of pathogenetic treatment is to reduce the secretion of adrenocorticotropic hormone secretion, to restore normal secretion of tropic pituitary hormones, as well as the prevention of further growth of pituitary tumor and adequate compensation of adrenal insufficiency. The case shows labile course of postoperative adrenal insufficiency and, consequently, different approaches to the diagnosis and the need for substitution therapy at different stages of the disease.

The COVID-19 pandemic has had implications in the central nervous system. COVID-19 infection is characterized by coagulation activation and endothelial dysfunction, causing the endocrine system's ischemic and hemorrhagic vascular syndromes. We aimed to provide an overview of the global literature on the impact of COVID-19 on pituitary function and structure. A narrative, nonsystematic review of the literature retrieved from a significant medical online database (PubMed) between February 1, 2020 and June 30, 2021. The relevant literature was narrated in a concise thematic account. Most specific recommendations for managing endocrine disorders during COVID-19 rely on the same principles of epidemiological safety measures, delaying nonemergency admissions and transforming the routine follow-up to telemedicine clinics. Ongoing medications should be continued. Special attention is required to both primary and secondary adrenal disorders. Corticosteroids are a mainstay of treatment in COVID-19 infection. Therefore, it is essential to consider all aspects of high doses, including adverse metabolic reactions, especially in people with diabetes and prediabetes. Surgery is postponed for nonemergency situations, restricting most planned surgeries, and if required in an emergency, plans should include an additional risk. Sick-day rules should be adhered to strictly. Regular contact with endocrinology teams can be maintained through teleconsultations and virtual clinics. In conclusion, special attention is needed to the interaction between COVID-19 infection and pituitary conditions in a bidirectional manner. The direct impact of COVID-19 on pituitary structure and function is possible and should be recognized timely and treated effectively. Furthermore, appropriate organizational adjustments are needed to maintain a coordinated response within the conventional multidisciplinary management to optimize the care of patients with pituitary conditions among the ongoing COVID-19 pandemic.

Purpose Pituitary adenoma (PA) constitutes the third most common intracranial neoplasm. The mostly benign endocrine lesions express no hormone (null cell PA) or the pituitary hormone(s) of the cell lineage of origin. In 0.5–1.5% of surgical specimens and in up to 10% of autopsy cases, two or three seemingly separate PA may coincide. These multiple adenomas may express different hormones, but whether or not expression of lineage-restricted transcription factors and molecular features are distinct within multiple lesions remains unknown. Methods Searching the data bank of the German Pituitary Tumor Registry 12 double pituitary adenomas with diverse lineage were identified among 3654 adenomas and 6 hypophyseal carcinomas diagnosed between 2012 and 2020. The double adenomas were investigated immunohistochemically for expression of hormones and lineage markers. In addition, chromosomal gains and losses as well as global DNA methylation profiles were assessed, whenever sufficient material was available (n = 8 PA). Results In accordance with the literature, combinations of GH/prolactin/TSH–FSH/LH adenoma (4/12), GH/prolactin/TSH–ACTH adenoma (3/12), and ACTH–FSH/LH adenoma (3/12) were observed. Further, two out of 12 cases showed a combination of a GH/prolactin/TSH adenoma with a null-cell adenoma. Different expression pattern of hormones were confirmed by different expression of transcription factors in 11/12 patients. Finally, multiple lesions that were molecularly analysed in 4 patients displayed distinct copy number changes and global methylation pattern. Conclusion Our data confirm and extend the knowledge on multiple PA and suggest that such lesions may origin from distinct cell types.

Background Resistance to thyroid hormone is a rare autosomal dominant disorder characterized by reduced responsiveness to thyroid hormone and can cause syndrome of inappropriate secretion of thyroid stimulating hormone. Although Graves’ disease is a common autoimmune thyroid disorder, the coexistence of these two diseases is extremely rare and makes the diagnosis and treatment complicated, leading to the delayed diagnosis of resistance to thyroid hormone. We describe the case of a Japanese man with resistance to thyroid hormone coexisting with Graves’ disease, in which the correct diagnosis of resistance to thyroid hormone was delayed by masking of the signs of syndrome of inappropriate secretion of thyroid stimulating hormone, with final diagnosis 30 years after the initial treatment for Graves’ disease. Case presentation A 30-year-old Japanese man presented with diffuse goiter and thyrotoxicosis. Anti-thyroid stimulating hormone receptor antibody was positive. He was diagnosed with Graves’ disease. Anti-thyroid medication was chosen as the initial treatment for Graves’ disease. However, this treatment failed to normalize the free triiodothyronine, free thyroxine, and thyroid stimulating hormone levels. His thyroid hormone levels indicated syndrome of inappropriate secretion of thyroid stimulating hormone. After cessation of methimazole treatment by remission of Graves’ disease, his state of syndrome of inappropriate secretion of thyroid stimulating hormone persisted. Magnetic resonance imaging revealed no pituitary tumor lesions. The results of thyroid stimulating hormone-releasing hormone stimulation test showed a normal response of thyroid stimulating hormone. He was suspected to have resistance to thyroid hormone. Direct sequencing analysis of the thyroid hormone receptor β gene identified a heterozygous missense mutation, R282S. Coexistence of resistance to thyroid hormone with Graves’ disease was confirmed. He has no signs of thyrotoxic symptoms, and is capable in activities of daily living at the present time. Conclusion We described a rare case of resistance to thyroid hormone simultaneously existing with Graves’ disease. This case demonstrated that these diseases can coexist, and indicated some of the difficulties in diagnosis of resistance to thyroid hormone with coexisting Graves’ disease. The diagnosis of resistance to thyroid hormone did not become apparent until after anti-hyperthyroidism treatment. Although rare, careful follow-up after the initial treatment of Graves’ disease is necessary. The coexistence of these two diseases should be considered in patients showing occasional syndrome of inappropriate secretion of thyroid stimulating hormone.

Non-functional pituitary adenomas are a morphologically heterogeneous group and are subdivided into silent adenomas that have immunoreactivity to tropic hormones and are similar in structure to typical adenocytes but do not lead to the development of clinical signs of hormonal hypersecretion (silent gonadal, cortical-, thyroid and mammotropinomas), and tumors that do not have specific markers and are similar to adenohypophyseal cells (zero-cell tumors and oncocytomas). According to the studies conduc­ted, all types of silent adenomas have different biological activity, secretory potential, and postoperative outcomes. Active detection of silent pituitary adenomas during immunohistochemical analysis not only allows identifying patients at high risk of disease recurrence but also developing optimal treatment and follow-up tactics, determining indications and evaluating the feasibility of drug and radiation therapy after a neurosurgical intervention. The review article is devoted to the search for prognostic markers of invasive growth of inactive pituitary adenomas. A high level of Ki-67 can be considered as an independent factor and a marker of poor prognosis in pituitary adenomas. The patients with adenomas with high proliferative activity were more often found to develop invasive growth of the adenoma, as well as its malignant transformation — the development of adenocarcinoma. This marker does not depend on other negative prognostic signs — the age and sex of a patient, the adenoma size. Besides, an increase in the proliferation level is more often observed in somatotropinomas and prolactinomas. In recent years, the concept of the cellular and molecular biology of pituitary tumors has changed significantly. It is known that transcription factors regulate the transformation of progenitor cells into mature secretory cells during embryogenesis. Therefore, the search for prognostic criteria for adenomas continues., Гормонально неактивные аденомы гипофиза представляют собой морфологически гетерогенную группу и подразделяются на «немые» аденомы, которые обладают иммунореактивностью к тропным гормонам и похожи по строению на типичные аденоциты, но не приводят к развитию клинических признаков гормональной гиперсекреции, и опухоли, не имеющие специфических маркеров и сходства с аденогипофизарными клетками (ноль-клеточные опухоли и онкоцитомы). Согласно проводимым исследованиям, все типы «немых» аденом имеют различные биологическую активность, секреторный потенциал и исходы в после­операционном периоде. Активное выявление «немых» аденом гипофиза при проведении иммуногистохимического анализа позволяет не только выявить пациентов из группы высокого риска рецидива заболевания, но и выработать оптимальную тактику лечения и дальнейшего наблюдения, определить показания и оценить целесообразность медикаментозной и лучевой терапии после проведенного нейрохирургического вмешательства. Обзорная статья посвящена вопросам поиска прогностических маркеров инвазивного роста неактивных аденом гипофиза. Высокий уровень Кi-67 может рассматриваться как независимый фактор и маркер неблагоприятного прогноза при аденомах гипофиза. У больных, аденомы которых имеют высокий уровень пролиферативной активности, чаще наблюдается инвазивный рост аденомы, а также ее злокачественное перерождение — развитие аденокарциномы. Этот маркер не зависит от других негативных прогностических признаков — возраста и пола пациента, размера аденомы. Кроме того, повышение уровня пролиферации чаще наблюдается в соматотропиномах и пролактиномах. В последние годы существенно изменилось представление о клеточной и молекулярной биологии опухолей гипофиза. Известно, что транскрипционные факторы регулируют трансформацию клеток-предшественников питуицитов в зрелые секреторные клетки во время эмбриогенеза. Поэтому продолжается поиск прогностических критериев для аденом., Гормонально неактивні аденоми гіпофіза становлять морфологічно гетерогенну групу і поділяються на «німі» аденоми, які мають імунореактивність до тропних гормонів і подібні за будовою до типових аденоцитів, але не призводять до розвитку клінічних ознак гормональної гіперсекреції, і пухлини, що не мають специфічних маркерів і схожості з аденогіпофізарними клітинами (нуль-клітинні пухлини й онкоцитоми). Згідно з проведеними дослідженнями, всі типи «німих» аденом мають різні біологічну активність, секреторний потенціал і результати в післяопераційному періоді. Активне виявлення «німих» аденом гіпофіза при проведенні імуногістохімічного аналізу дозволяє не тільки виявити пацієнтів із групи високого ризику рецидиву захворювання, а й виробити оптимальну тактику лікування і подальшого спостереження, визначити показання та оцінити доцільність медикаментозної і променевої терапії після проведеного нейрохірургічного втручання. Оглядова стаття присвячена питанням пошуку прогностичних маркерів інвазивного росту неактивних аденом гіпофіза. Високий рівень Кі-67 може розглядатися як незалежний фактор і маркер несприятливого прогнозу при аденомах гіпофіза. У хворих, аденоми яких мають високий рівень проліферативної активності, частіше спостерігається інвазивний ріст аденоми, а також її злоякісне переродження — розвиток аденокарциноми. Цей маркер не залежить від інших негативних прогностичних ознак — віку і статі пацієнта, розміру аденоми. Крім того, підвищення рівня проліферації частіше спостерігається в соматотропіномах і пролактиномах. Останнім часом істотно змінилося уявлення про клітинну та молекулярну біологію пухлин гіпофіза. Відомо, що транскрипційні фактори регулюють трансформацію клітин-попередників пітуїцитів у зрілі секреторні клітини під час ембріогенезу. Тому триває пошук прогностичних критеріїв для аденом.

Objective: The aim behind this study was to determine the frequency of visual field and visual acuity disturbances before resection and improvement after resection of pituitary tumors in patients. Study Design: Observational study. Setting: Neurosurgery Department of Jinnah Post Graduate Medical Center, Karachi. Period: August 2015 to August 2016. Material & Methods: A total of 30 patients presented with headache and visual deterioration and diagnosed as pituitary adenoma at neurosurgery OPD, ward and ER were included through a consecutive purposive sampling technique. The detailed visual and ocular analysis (visual acuity, visual field, and extra ocular movements) carried out at time of admission and postoperatively. Tumor was removed by consultant neurosurgeon through trans-sphenoidal approach. SPSS version 17.0 was used to analyze the collected data. Results: A total of 30 cases of pituitary adenoma were included. The average age of the patients was 34.5 ± 10.8 years and among them 17 (56.7%) were males and 13 (43.3%) were females. Pre-operative assessment of the mean deviation of visual function was -8.21 ± 6.10 dB which is significantly improved to -4.6 ± 3.9 dB post-operatively (P < 0.0001). While pre-operative Visual Acuity (logMAR) was 0.3 ± 0.26 and post-operative 0.21 ± 0.2 (P

Silent corticotroph adenoma (SCA) is as an aggressive pituitary tumor. A 48 year old man developed hypogonadotrophic hypogonadism. The basal morning adrenocorticotropic hormone (ACTH) was elevated, but the basal morning and peak after ACTH (1–24) stimulation cortisol were normal. A 3.7 cm sellar mass with evidence of internal hemorrhage, encasement of the right internal carotid artery, and invasion of the right cavernous sinus were identified, resected, and stained positive for ACTH. Over the next 5 years, the basal morning ACTH and cortisol were normal, and imaging revealed the presence of a small residual tumor. One year later, the patient became fatigued and nauseated, with elevated ACTH. An overnight metyrapone stimulation test (OMST) revealed glucocorticoid insufficiency, without further increase in ACTH. Symptoms resolved with hydrocortisone treatment. This case study suggests that SCA can secrete an ACTH precursor that is detected by clinical assays but is not active biologically. Postoperative OMST reveals glucocorticoid insufficiency in this context.

Comprehensive investigations on the incidence and prognosis of pituitary tumors are still lacking. The present study aims to summarize the incidence, demographics, and survival outcome of pituitary adenoma on a population-based level. This study includes all pituitary adenomas reported in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 in the United States. Extensive clinical and demographic characteristics were extracted and submitted to group comparisons. The standardized incidence rate was calculated and stratified by year at diagnosis, age/sex and age/treatment groups. The Kaplan–Meier analysis and multivariable regressions were performed to identify the factors associated with overall survival. A total of 47,180 pituitary tumors were identified, including 47,030 typical adenomas, 111 uncertain behavior pituitary adenomas, and 39 pituitary carcinomas. The overall standardized incidence rate was 4.8 cases per 100,000 person-years and the annual incidence rate continually trended upwards, with a peak seen in 2015. We noticed a bimodal age-related distribution in females and a unimodal distribution in males. In the multivariate regression analysis, the factors associated with prolonged survival included typical adenoma, younger age, and smaller tumor size. Whereas, black and male patients had worse overall survival. Our study provides a reliable estimate on the incidence of pituitary adenoma and confirms that the annual standardized incidence rate is increasing. Pituitary adenomas have a satisfactory long-term prognosis and age, tumor size, and tumor subtypes are related to overall survival. Though statistically significant, our inferential findings should be constrained within the limitations of SEER database.

In 2017, WHO published an updated classification of the pituitary adenomas according to the lineages defined by the transcription factors, PIT1, SF1 and TPIT. Nomenclature of the pituitary tumors follows the mature cell types such as somatotroph (GH), lactotroph (LH), thyrotroph, corticotroph, and gonadotroph (FSH, LH). Null cell adenomas are defined by the absence of expression of any hormones and transcription factors. Not infrequently, the pituitary adenomas are invasive to the adjacent structures and are designated as aggressive adenomas. Knosp grading is often used to define the aggressiveness of the tumor. Sparsely granulated somatotroph adenomas and Crooke cell corticotroph adenomas are representative aggressive adenomas. Recently, genomics regarding various adenomas have been clarified, such as GNAS for somatotrophs and USP8 for corticotrophs. Familial pituitary adenomas are another aspect which has been clarified such as MEN1, Carney's complex, familial isolated pituitary adenoma and McCune-Albright syndrome. The pituitary adenomas often produce GH or PRL, hormones of PIT1 transcription factor. It has been agreed that the pituitary adenomas share the characteristics of neuroendocrine neoplasms. The terminology of pituitary neuroendocrine tumor has been discussed. This review article covers various aspects of pituitary adenomas.

Although systemic inflammation has been linked to acromegaly, little is known about the abnormalities in cytokine networks during the disease. The aim of this study was to evaluate the serum concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and activin-A in acromegaly, and to investigate the relationship between TNF-alpha, IL-6, activin-A and comorbidities of acromegaly. A total of 56 subjects were recruited to the study. Serum samples were collected from 31 acromegaly patients and 25 healthy control subjects. Serum activin-A, IL-6 and TNF-alpha were determined using the enzyme-linked immunosorbent assay. Circulating levels of activin-A, TNF-alpha, and IL-6 were higher in patients than in the control group. Receiver operating characteristic analysis for activin-A for the differentiation of acromegaly patients from healthy control subjects showed an area under the curve of 0.90. Higher activin-A levels were determined in patients with residual pituitary tumor. These findings provide evidence for the role of activin-A, TNF-alpha and IL-6 in acromegaly. Serum activin-A levels could be used as a novel biomarker to diagnose acromegaly. These findings confirm previous studies that inflammation might be involved in the pathogenesis of acromegaly. Finally, treatment strategies targeting the regulation of inflammation cannot be sufficient alone in reducing comorbidities.

Pituitary tumors and subsequent treatment with endoscopic transsphenoidal surgery (ETSS) may cause injury to suprasellar structures, causing long-term fatigue and neurocognitive impairment. A method to quantify brain injury after ETSS is not available. In this prospective, exploratory study of patients undergoing ETSS for pituitary tumors, a novel approach to detect possible neuronal damage is presented. Plasma concentrations of brain injury biomarkers (glial fibrillary acidic protein [GFAP], tau, and neurofilament light [NFL]) were measured the day before surgery, immediately after surgery, at day 1 and 5, and at 6 and 12 months after surgery, using enzyme-linked immunosorbent assays. The association between the increase of biomarkers with preoperative tumor extension and postoperative patient-perceived fatigue was evaluated. Suprasellar tumor extension was assessed from MRI scans, and self-perceived fatigue was assessed using the Multidimensional Fatigue Inventory before and 6 months after surgery. Thirty-five patients were included in the analysis. Compared to baseline, GFAP showed a maximal increase at day 1 after surgery (p = 0.0005), tau peaked postoperatively on the day of surgery (p = 0.019), and NFL reached its maximum at day 5 after surgery (p < 0.0001). The increase in GFAP correlated with preoperative chiasmal compression (p = 0.020). The increase in tau was correlated with preoperative chiasmal (p = 0.011) and hypothalamus compression (p = 0.016), and fatigue score 6 months after surgery (p = 0.016). In conclusion, the concentrations of brain injury biomarkers in blood increased after ETSS for pituitary tumors. The results indicate that postoperative plasma GFAP and tau might reflect astroglial and neuronal damage after ETSS.

Functioning gonadotroph adenomas are rare pituitary tumors secreting one or two gonadotropins (follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH)), which are hormonally active. In the majority of cases, gonadotroph tumors are endocrinologically “silent” and make up more than a half of non-functioning pituitary adenomas. In this article we describe a rare clinical case of LH/FSH-secreting pituitary macroadenoma with bitemporal hemianopsia in a 62-year-old man. The patient underwent transnasal transsphenoidal adenomectomy, leading to remission. The distinctive feature of this case is the presence of secondary erythrocytosis due to endogenous hyperandrogenism, which required several blood exfusions to normaliza the level of hematocrit before surgery. It is noteworthy that clinical signs of erythrocytosis were present long before visual impairment. This clinical case demonstrates difficulties in the early diagnosis of functioning gonadotroph adenomas.

We report a case of a 50-year-old male admitted to the Endocrinology Unit because of persistent headaches, nausea, feeling tired, sudden weight loss, cold intolerance, decreased appetite, and lack of sex interest. Diagnostic workup showed a 6-millimeter pituitary tumor without signs of compression, and a condition of progressive panhypopituitarism. After 12 months of hormone replacement therapy, the patient was hospitalized because of sudden weight gain, periorbital-peripheral edema, severe dyslipidemia, hypertension, and proteinuria. Corticosteroid therapy was shifted from oral to continuous intravenous infusion, and once the diagnosis of “immune complex-mediated glomerulonephritis with mesangial deposits suggestive for membranoproliferative glomerulonephritis type IIIIgG4-positive” was made, the immunosuppressant mycophenolate (1500 mg/day) was started. After a 6-month follow-up, the complete resolution of renal symptoms was accompanied by the disappearance of a pituitary lesion and the patient was back to prior hormone replacement therapy. Autoimmune hypophysitis (AH) is a rare autoimmune inflammatory disease of the pituitary gland that can impair hormone secretion and function. IgG4-hypophysitis is rare and is usually associated with other IgG4-related diseases. Herein, we describe a rare case of AH associated with late renal disease, and without any other organ involvement.

Context Mechanisms underlying pituitary corticotroph adenoma adrenocorticotropin (ACTH) production are poorly understood, yet circulating ACTH levels closely correlate with adenoma phenotype and clinical outcomes. Objective We characterized the 5′ ends of proopiomelanocortin (POMC) gene transcripts, which encode the precursor polypeptide for ACTH, in order to investigate additional regulatory mechanisms of POMC gene transcription and ACTH production. Methods We examined 11 normal human pituitary tissues, 32 ACTH-secreting tumors, as well as 6 silent corticotroph adenomas (SCAs) that immunostain for but do not secrete ACTH. Results We identified a novel regulatory region located near the intron 2/exon 3 junction in the human POMC gene, which functions as a second promoter and an enhancer. In vitro experiments demonstrated that CREB binds the second promoter and regulates its transcriptional activity. The second promoter is highly methylated in SCAs, partially demethylated in normal pituitary tissue, and highly demethylated in pituitary and ectopic ACTH-secreting tumors. In contrast, the first promoter is demethylated in all POMC-expressing cells and is highly demethylated only in pituitary ACTH-secreting tumors harboring the ubiquitin-specific protease 8 (USP8) mutation. Demethylation patterns of the second promoter correlate with clinical phenotypes of Cushing disease. Conclusion We identified a second POMC promoter regulated by methylation status in ACTH-secreting pituitary tumors. Our findings open new avenues for elucidating subcellular regulation of the hypothalamic-pituitary-adrenal axis and suggest the second POMC promoter may be a target for therapeutic intervention to suppress excess ACTH production.

Introduction Endoscopic endonasal surgery (EES) has become the preferred approach for pituitary tumor resection. Nevertheless, research on quality of life related to pituitary adenoma surgery is scarce. Objective The aim of the study is to evaluate short-term quality of life in patients after endoscopic endonasal resection of pituitary tumors and to find predictors for poor quality of life (QOL) outcome. Materials and Methods A prospective cohort study was conducted, including all patients who underwent EES for pituitary tumors in a tertiary medical referral center. Recruited patients completed the Anterior Skull Base Disease-Specific QOL (ASBS-Q) questionnaire and the Sinonasal Outcome Test 22 (SNOT-22) questionnaire before surgery, 2 and 4 to 6 months after surgery. Demographic and clinical data was collected. Results Our study included 49 patients. The overall ASBS-Q scores significantly improved 4 to 6 months after surgery (4.46 vs. 4.2, p Conclusion We found that patients after EES reported improved QOL 4 to 6 months post surgery. Specific improvement was noted in the QOL related to pain and vitality.

The role of transsphenoidal surgery in the recovery of preexisting hormone dysfunction from pituitary tumors remains controversial. This study aimed to investigate the incidence of hormone dysfunction among asymptomatic non-functioning pituitary adenomas and their recovery following endoscopic transsphenoidal surgery. Eligibility criteria included age under 80 years, presence of a non-functioning pituitary adenoma compressing the normal gland resulting in deviation of the stalk, absence of visual symptoms, and availability for regular follow-up using MRI and pre- and post-operative endocrinological assessments. 182 patients with silent non-functioning pituitary adenomas were included in this study between March 2014 and December 2018. All patients underwent endoscopic transsphenoidal surgery and complete hormonal evaluation, with basal hormone assays and a combined pituitary function test before and after surgery until the end of last follow-up. Preoperative assessment of hormonal function revealed that 124 of 182 patients (68.1%) had at least a single hormone dysfunction preoperatively. Among these, 61 of 124 (49.2%) had a dysfunction in a single axis, and 63 (50.8%) had a hormone dysfunction in two or more axes. Overall, the median endocrinological follow-up duration was 15.0 months (6–57 months). At 1 month following surgery, 91 patients (73.4%) with hormone dysfunction experienced improvement in at least a single hormone axis. Prolactin was the most common hormone among those that recovered at the last follow up (92.8% improvement) followed by growth hormone (GH, 50.0%), thyroid stimulating hormone (TSH, 50.0%), gonadotropin (Gn, 46.9%), and adrenocorticotropic hormone (ACTH, 45.0%). Time to recovery varied from 1.1 months (for prolactin) to 2.2 months (for gonadotropin, and ACTH). In patients with preoperative deficiency in GH, and ACTH, postoperative transient diabetes insipidus was associated with poor recovery (GH: HR = 0.50, p = 0.048; ACTH: HR = 0.39, p = 0.023). Non-functioning pituitary adenomas with silent hormone dysfunction are often overlooked by clinicians and patients. We suggest that even silent hormone dysfunction in patients with non-functioning pituitary adenomas can be improved with effective surgical decompression and these tumors may be potential indications of endoscopic transsphenoidal surgery.

We present a rare case of spindle cell oncocytoma (SCO) of the sella turcica with malignant histologic features and rapid progression. A 42-year-old woman experienced bilateral blurred vision and was preoperatively misdiagnosed as having a pituitary macroadenoma on magnetic resonance imaging. After surgery, SCO was diagnosed by the histopathologic features of interlacing fascicles of spindle tumor cells with finely granular, eosinophilic cytoplasm. Focal anaplastic changes and necrosis were present. Immunohistochemically, the tumor cells were positive for vimentin, epithelial membrane antigen, S-100, galectin-3, and thyroid transcription factor 1. Four months later, the tumor had progressed, and second surgery with adjuvant radiotherapy was performed; the patients remains under observation. In this report, we proposed distinctive radiologic features for differential diagnosis between SCO and other pituitary tumors.

Lung neoplasms often co-occur with pituitary adenoma (PA). However, whether co-diagnosis of lung neuroendocrine tumors (LNETs) and PA constitute a unique entity and the impact of such co-diagnosis on patients’ outcome is yet to be defined. The study objective was to compare patients’ clinical characteristics with LNET to patients co-diagnosed with PA. A Retrospective, case-control study based on the Surveillance, Epidemiology, and End Results (SEER) registry database between 2000 and 2016. A total of 2947 patients with LNET, including 2913 with LNET alone (“Sporadic”) and 34 patients with both LNET and PA (“LNET-PA”). PA preceded LNET diagnosis in 85.3% of patients and had higher rates among LNET patients (34/2947) than with any cancer (p

Internal carotid artery (ICA) stenosis rarely occurs in pituitary apoplexy. Little is known of the causes of this condition. The present study investigated the factors related to ICA stenosis associated with pituitary apoplexy.Forty-five patients with pituitary apoplexy were retrospectively examined and divided into the stenotic and normal ICA groups. The baseline characteristics of patient background, tumor properties, clinical findings, and treatment overview were compared between the groups.Eight patients were assigned to the stenotic ICA group and 37 to the normal ICA group. Patient age in the stenotic ICA group was significantly lower than that in the normal ICA group (P = 0.001). Maximum tumor diameter (P = 0.001), tumor volume (P = 0.044), and Knosp grade (P0.001) were significantly greater in the stenotic ICA group than in the normal ICA group. The stenotic ICA group had a significantly greater incidence of sphenoid sinus mucosal thickening than the normal-ICA group (P = 0.039). Multivariate logistic regression analysis demonstrated that age (odds ratio 0.915, 95% confidence interval 0.846-0.991, P = 0.029) was a significant and independent predictor of ICA stenosis associated with pituitary apoplexy. Receiver operating characteristic curve analysis showed that the optimal cut-off point for age was 35.0 years (specificity 0.946, sensitivity 0.750).Our study revealed that age, tumor size, and sphenoid sinus mucosal thickening were strongly related to the occurrence of ICA stenosis in pituitary apoplexy. Among these factors, age had the potential of being an independent predictor of the condition.

Background Patients with growth hormone (GH)-secreting adenoma usually develop glucose intolerance. GH increases metabolic rate and, when secreted aberrantly, may result in metabolic syndrome. Herein, we examine the associations of pituitary tumor-induced secretion of hormone with insulin resistance and metabolic syndrome, and determine the relation of pituitary tumor apoplexy-induced diabetic ketoacidosis (DKA) and acute pancreatitis. Case presentation A 44-year-old male with a history of hypertension presented to the emergency department of our hospital on February 14, 2019 with symptoms of headache, dizziness, and vomiting. Computed tomography of the head revealed pituitary tumor with bleeding. An ultrasound scan of the abdomen revealed fatty liver and acute pancreatitis. Further examination revealed the presence of DKA, hypertriglyceridemia, cortical hypofunction crisis and acute kidney injury. Surgical endoscopic resection of the pituitary tumor resection via the transsphenoidal approach was performed. The patient’s postoperative recovery was remarkable. Conclusions Long-term growth hormone abnormality may trigger insulin resistance, leading to metabolic syndrome and impaired glucose and lipid metabolism. The pituitary adenoma apoplexy may also directly induce DKA, creating a domino effect, which further deteriorate the aberrant metabolism of glucose and lipids.

Die WHO-Klassifikation der Hypophysentumoren aus dem Jahr 2017 basiert bez. der Adenome weiterhin auf Strukturanalysen und der immunhistologischen Expressionen hypophysarer Hormone, aber als erster entscheidender Neuerung auch auf der Expression der 3 hypophysaren Transkriptionsfaktoren Pit‑1, T‑Pit und SF‑1. Die 2. Neuerung ist der Ersatz des Begriffs „atypisches Adenom“ durch „aggressives Adenom“. Die 3. Neuerung betrifft die 3 neurohypophysaren Tumoren Pituizytome, Spindelzellonkozytome und Granularzelltumoren, die durch ihre gemeinsame TTF-1-Expression definiert sind. Die Kraniopharyngeome lassen sich als adamantinomatoser Subtyp durch ihren fokalen nuklearen β‑Catenin-Nachweis und als papillarer Subtyp durch den BRAF(V600E)-Mutationsnachweis identifizieren. Weitere primar hypophysare Tumoren sind extrem selten. Sie sind ebenso wie die Tumoren der Sellaregion nahezu immer im Zweifelsfall mit immunhistologischen Methoden von Hypophysentumoren sicher unterscheidbar.

We report a case of sudden death in a 31-year-old male diagnosed at autopsy with clinical undiagnosed acromegaly. The purpose of this report is to underline the importance of health professionals reacting to phenotypic acromegaly, such as acral enlargement and/or unexplained hypertension, including a range of severe comorbidities, to avoid a fatal outcome. Recent studies have shown that the increased mortality seen in acromegaly patients can be reversed with modern treatment aimed at normalizing GH and IGF-I levels. One year before death, the presented case was diagnosed with hypertension, but was otherwise described as healthy. The forensic autopsy, including post-mortem CT, showed phenotypic facial and body characteristics for acromegaly, general visceromegaly, and a pituitary tumor. The cause of death was heart failure due to end-stage acromegalic cardiopathy. Because the disease is slowly progressive, the individual himself, and the people close to him, might not have considered the acromegaly-related facial changes as abnormal.

To examine the clinical presentation and longitudinal outcome of Pituitary Apoplexy (PA) after gonadotropin-releasing hormone agonist (GnRHa) in a series of patients and compare to prior reports. A retrospective chart review was performed on seven patients receiving GnRHa who developed PA. Prior reported cases were analyzed. Six men (median age 72 years) with prostate cancer and one woman (aged 22 years) undergoing oocyte donation presented with PA between 1990 and 2020. Most presented with within 24 h of the first dose, but two developed PA 1 to 5 months after GnRHa initiation. The main clinical manifestations were headache (100%), nausea and vomiting (86%). While no patients had a previously known pituitary tumor, all had imaging demonstrating sellar mass and/or hemorrhage at presentation. Among those surgically treated (5/7), 80% (4/5) of patients had pathologic specimens that stained positive for gonadotropins; the remaining patient’s pathologic specimen was necrotic. At the time of PA, the most common pituitary dysfunction was hypocortisolism. Central adrenal insufficiency and central hypothyroidism were reversible in a subset. Pituitary imaging remained stable. This is the first report of a case series with PA after GnRHa administration with longitudinal follow-up. Although infrequent, PA can be life-threatening and should be suspected among patients receiving GnRHa, with or without a known pituitary adenoma, who develop acute headache, nausea and/or vomiting. Since hypopituitarism was reversible in a subset, ongoing pituitary function testing may be indicated.

Superb knowledge of surgical anatomy and nuances to remove the natural barriers preventing full access to the paramedian skull base determines the ease of using the expanded sellar/parasellar approaches as the main gateway for all the parasagittal modules during endoscopic endonasal access (EEA) to pituitary tumors with cavernous sinus (CS) invasion. Throughout stepwise-cadaveric dissections and pertinent intraoperative analysis, we describe surgical pearls and pitfalls of the parasellar-EEA with special references to the utility of various lines/classifications on neuroimaging correlated with strategies to enhance surgical safety and tumor resection. EEA to invasive parasellar pathologies needs to address strict bleeding control and displacement of neurovascular structures inside the CS, posing a chance for neurologic morbidities/ICA injury. Meticulous utilization of operative landmarks and strategies can help avoid and mitigate surgical complications.

Background: Pituitary adenomas are benign neoplasms representing 10 to 15% of intracranial lesions. Giant pituitary adenomas describe tumors more than 4 cm in maximum diameter and represent 6-10% of pituitary tumors. The introduction oftruly ‘extended endonasal’ approaches has enabled thepituitary surgeon to achieve a more radical resection safely. The aim of the work: Evaluation of efficacy of the endoscopic endonasal approach in managing giant pituitary adenoma. Patients and methods: Fifteenpatients with giant pituitary adenomas were enrolled. They were submitted to full clinical examination, radiological, visual, and hormonal assessment in the pre and postoperative period. A purely endoscopic endonasal approach was used as the primary surgical management for all the patients. The collected data included preoperative data, tumor characteristics, resection rate, clinical outcome, recurrence rate, and need for adjuvant radiotherapy Results: The mean age was 40.7 [range 16-57] years, with a male predominance [60%]. Visual affection was reported in [86.6%] with pituitary hormonal hypersecretion in 53.3%. There was an improvement in 80% of patients with visual field defects and 83.3% of patients with diminished visual acuity. Prolactin hormone levels normalized in 40%, while growth hormone normalized in 33.3%. Follow-up MRI revealed gross total resection [GTR] in 41.6% of patients with suprasellar extension, subtotal removal [about 80% of the tumor] in 50% of patients, partial tumor resection in one patient [8.4%]. In para-sellar extension, subtotal resection achieved [in 66.6%], and partial resection in 33.3%. Postoperative CSF leak occurred in 13.3% due to uncomplete reconstruction of the sella. They were reoperated for sella repair and augmentation. Three patients [20%] had transient [for 3 weeks] postoperative diabetes insipidus [DI] in the early postoperative period. Conclusion: Endoscopic endonasal approach is an effective and safe approach for managing giant pituitary adenomas.

Significant restoration of visual function can occur following pituitary tumor resection, although the time course of visual recovery remains poorly understood. This single-centre, two-year, prospective cohort study investigated the temporal patterns of visual recovery in consecutive patients undergoing pituitary tumor resection, between 2009 and 2018. Eyes were stratified based on pre-operative optical coherence tomography (OCT) retinal nerve fibre layer (RNFL) thickness measurements, with thin RNFL being defined as those within the fifth-percentile of age-matched normative values, and normal RNFL as those above the fifth-percentile. Visual function and OCT parameters were assessed pre-operatively, and at 6 weeks, 6 months, and 2 years post-operatively. 456 eyes of 228 patients (mean ± SD age, 53 ± 15 years) were included, of which 114 (25%) eyes had thin RNFL pre-operatively. Visual field recovery was observed in both groups during the first 6 weeks post-operatively (all Q ≤ 0.02), although improvements in visual field parameters between 6 weeks to 6 months were limited to eyes with thin RNFL (both Q 0.05). No further improvements in visual function were detected beyond 6 months in both groups (both Q 0.50). Similar trends were observed in linear regression analysis according to baseline visual function in both groups. In summary, eyes with normal RNFL thickness at baseline experienced most of their recovery within the first six weeks following surgery, while eyes with thin RNFL exhibited gradual improvements during the first six months. These findings have important implications when providing patient counselling and prognostication in the pre-operative setting.

Dopamine receptor agonists are typically used to treat Parkinson’s disease and certain pituitary tumors, such as prolactinoma or a growth hormone‐producing tumor. A 53‐year‐old woman with a history of prolactinoma was referred to Kumamoto University Hospital (Kumamoto, Japan) with poorly controlled type 2 diabetes. Her glycated hemoglobin and serum prolactin levels were increased (8.8% and 160.3 ng/mL, respectively). Bromocriptine, a dopamine D2 receptor agonist, was administered to reduce her serum prolactin level. Because bromocriptine‐QR (quick release) has been approved for the treatment of type 2 diabetes mellitus in the USA, a continuous glucose monitoring system, FreeStyle Libre Pro, was utilized to examine the effect of bromocriptine on glycemic control. After the initial administration of bromocriptine, glucose levels were rapidly and dramatically ameliorated, and the time in range (70–180 mg/dL) improved from 90% between 1 week before and after the initial administration of bromocriptine., The areas of time above range (>180 mg/dL, shown in yellow) almost disappeared immediately after bromocriptine administration.

Background Adjuvant endocrine therapy is recommended for the treatment of hormone-receptor-positive breast cancer. Aromatase inhibitors are associated with significant musculoskeletal adverse effects, likely through growth hormone/insulin-like growth factor 1 modulation, while tamoxifen reduces insulin-like growth factor 1 production. We describe the case of a patient who was treated successfully with tamoxifen for her hormone-receptor-positive breast cancer and acromegaly. Case presentation A 57-year old White female with hormone-receptor-positive breast cancer was diagnosed with acromegaly. She received adjuvant endocrine therapy with anastrozole but could not tolerate this medication because of severe arthralgia, so she was switched to tamoxifen. Shortly after starting tamoxifen, the patient’s musculoskeletal symptoms resolved and her insulin-like growth factor 1 levels normalized. She has remained in remission of her acromegaly and breast cancer since initiating tamoxifen. Conclusion This case highlights the dual benefit of tamoxifen therapy in the treatment of hormone-receptor-positive breast cancer and acromegaly. Unlike anastrozole, tamoxifen has the benefit of lowering insulin-like growth factor 1 levels, which underscores its advantage in reducing adverse musculoskeletal symptoms during the treatment of hormone-receptor-positive breast cancer. We offer the first reported use of tamoxifen monotherapy for the successful treatment of acromegaly and hormone-receptor-positive breast cancer. While tamoxifen may offer an additional, oral option for acromegaly patients who do not respond to or tolerate conventional growth-hormone-lowering therapy, additional studies are necessary.

Introduction. Recurrent vomiting is a commonly overlooked debilitating symptom which causes significant impact on the quality of life. There are several causes for vomiting, ranging from commonly known causes to rare causes. Nonfunctioning pituitary macroadenomas generally present with visual disturbances, headache, and symptoms due to anterior pituitary hormone deficiencies. This case report is about an atypical presentation of a nonfunctioning pituitary macroadenoma in which the patient presented with cyclical vomiting with severe hyponatremia. Case Report. A 23-year-old girl presented with four to five episodes of vomiting per day for two days duration. She had a history of similar episodes of vomiting since 2016, with each episode generally lasting for 4-5 days and occurring in every four to six months. All episodes exhibited similar symptomatology and she was free of symptoms in-between. Generalized body weakness, postural dizziness, reduced appetite, and secondary amenorrhea were other symptoms she has had since 2016. Examination findings showed a low body mass index (BMI) (16 kg/m2) with normal system examination. Investigations showed severe hyponatremia (110 mmol/L) with hypokalemia (3.2 mmol/L) and hypochloremia (74 mmol/L). Her urinary excretion of potassium, sodium, and serum osmolality was low. Urine osmolality was mildly elevated compared to serum osmolality. Blood urea was normal. Severe hyponatremia with minimal hyponatremic symptoms was suggestive of chronic hyponatremia, which was accentuated by ongoing vomiting and possible reduced intake of salt. Further investigations showed evidence of secondary hypoadrenalism, central hypothyroidism, hypogonadotropic hypogonadism, and mild hyperprolactinemia. Magnetic resonance imaging (MRI) revealed a pituitary macroadenoma with mass effect on the optic chiasma. Hydrocortisone and levothyroxine were started, and she underwent transsphenoidal resection of the pituitary tumor. She recovered from cyclical vomiting. Conclusion. There can be multiple overlapping aetiologies for every observed symptom, sign, and abnormal investigation finding. Therefore, aetiological diagnosis is challenging, especially in the presence of an atypical clinical presentation. Cyclical vomiting and severe hyponatremia are atypical presentations of nonfunctioning pituitary macroadenomas.

Objective We report a case of pituitary apoplexy (PA) with negative radiographic findings for PA and cerebrospinal fluid (CSF) analysis consistent with neutrophilic meningitis. PA is a rare endocrinopathy requiring prompt diagnosis and treatment. Presentation with acute neutrophilic meningitis is uncommon. Methods The diagnostic modalities included pituitary function tests (adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, prolactin), brain computed tomography and magnetic resonance imaging (MRI), and CSF analysis. Results A 67-year-old man presented with worsening headache, nausea, and retching. He was somnolent with an overall normal neurologic examination other than a peripheral vision defect in the left eye. MRI showed a pituitary mass bulging into the suprasellar cistern with optic chiasm elevation, consistent with pituitary macroadenoma. Laboratory evaluation revealed decreased levels of adrenocorticotropic hormone, random cortisol, thyroid-stimulating hormone, thyroxine, luteinizing hormone, and testosterone. He had worsening encephalopathy with left eye ptosis and decreased vision, prompting a repeat computed tomography and MRI, showing no interval change in the pituitary adenoma or evidence of bleeding. CSF analysis revealed a leukocyte count of 1106/mm3 (89% neutrophils), a total protein level of 138 mg/dL, red blood cell count of 2040/mm3 without xanthochromia, and glucose level of 130 mg/dL. The CSF culture result was negative. Transsphenoidal resection revealed a necrotic pituitary adenoma with apoplexy. Conclusions Including PA in the differential diagnosis of acute headache is important, particularly in patients with visual disturbances. PA can present with sterile meningitis, mimicking acute bacterial meningitis. While neuroimaging can help detect PA, the diagnosis of PA remains largely clinical.

Although non-functioning pituitary tumors are frequent, diagnostic and therapeutic concepts are not well standardized. We here present the first German multidisciplinary guideline on this topic. The single most important message is to manage the patients by a multidisciplinary team (consisting at least of an endocrinologist, a neurosurgeon, and a (neuro-) radiologist). The initial diagnostic work-up comprises a detailed characterization of both biochemical (focusing on hormonal excess or deficiency states) and morphological aspects (with magnetic resonance imaging of the sellar region). An ophthalmological examination is only needed in presence of symptoms or large tumors affecting the visual system. Asymptomatic, hormonally inactive tumors allow for a 'wait and scan' strategy. In contrast, surgical treatment by an experienced pituitary surgeon is standard of care in case of (impending) visual impairment. Therapeutic options for incompletely resected or recurrent tumors include re-operation, radiotherapy, and observation; the individual treatment plan should be developed multidisciplinary. Irrespective of the therapeutic approach applied, patients require long-term follow-up. Patient with larger pituitary tumors or former surgery/radiotherapy should be regularly counseled regarding potential symptoms of hormonal deficiency states.

Objective: Our objective is to present a case of Cushing’s disease (CD) with 2 adrenocorticotropic hormone (ACTH)-secreting pituitary tumors. Multiple monohormonal pituitary tumors are rare. This case supports a consideration of repeat transsphenoidal surgery (TSS) in patients with initial surgical failure. Methods: Salivary, 24-h urine, serum cortisol testing, and magnetic resonance imaging (MRI) were used to diagnose CD. Treatment included TSS and postoperative hydrocortisone. Results: A 36-year-old woman followed for hypothyroidism presented with a new left supraclavicular fossa swelling and underwent Cushing’s syndrome screening. The levels of late-night salivary cortisol were 0.636 and 0.316 μg/dL, 24-h urine cortisol was 162 μg/24 h, cortisol after 1-mg dexamethasone suppression was 14.0 μg/dL, and serum morning cortisol was 26.4 μg/dL with ACTH of 66.7 pg/mL. A 7-mm hypoenhancing anterior pituitary lesion was noted on pituitary MRI. The cortisol level was 2.7 μg/dL after an 8-mg dexamethasone suppression. She underwent TSS, and her histopathology read as pituitary adenoma staining positive for ACTH. No residual tumor was seen intraoperatively. Postoperative morning serum cortisol was 17.9 μg/dL, and ACTH level was 79 pg/mL. Repeat TSS revealed a second adenoma previously unseen on MRI, which also stained positive for ACTH. Postoperative morning cortisol was 0.7 μg/dL, and ACTH was

Background: Acromegaly is an uncommon clinical disorder driven by high serum levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Over 99% of patients with acromegaly harbor a GH emitting pituitary adenoma. Pituitary tumors represent about 15% of essential intracranial neoplasms. Case presentation: A 38 years old woman, was referred to the H. Adam Malik central public hospital on December 15th, 2020, with chief complaints of enlarged fingers and toes. The patient complained that the patient's fingers and toes were getting bigger in the past 2 years. The brain MRI was performed showed intrasella spherical intensity lesions measuring ± 2.3x1.5x2 cm with the impression of macroadenoma. The patient later diagnosed with acromegaly due to pituitary macroadenoma. Therefore the patient was treated with administration of sandostatin injection, novorapid 6-6-6 IU SC, then 0-0-12 IU SC, 3x1 salt capsules. The patient is also consulted to the neurosurgery department for surgical management plans and a consulted to the Ophthalmology Department. Conclusion: We report an instance of acromegaly suspected because of pituitary macroadenoma in a patient with unmistakable clinical highlights, with comprehensive management.

Introduction Pituitary carcinomas are challenging tumors to diagnose and treat due to their rarity and limited data surrounding their etiology. Traditionally, these patients have exhibited poor survival. Over the last several decades, our understanding of pituitary carcinomas has dramatically increased, and there have been recent initiatives to improve patient access to health care, including the Affordable Care Act (ACA). This study investigates whether there were any changes in incidence and treatment outcomes of pituitary carcinoma that correlated with these advances. Methods A retrospective case review was conducted utilizing the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. Those with primary site pituitary tumors with noncontiguous metastases were identified from 1975 to 2016. Demographic data, overall, and cause-specific outcomes were obtained. The data were analyzed using SPSS to generate 5-year Kaplan–Meier curves. Results The incidence of pituitary carcinoma pre- and post-ACA was 0.31 and 2.14 diagnoses/year, respectively. This represents a significant increase (Chi-square, p Conclusion The survival for pituitary carcinoma has improved significantly which signals a change in how practitioners should counsel their patients. There is a significant surge in the number of cases in the post-ACA timeline, which suggests that improving patient access has played a part in wider recognition and treatment initiation for this disease.

Purpose To evaluate whether presurgical treatment using long-acting somatostatin receptor ligands (SRL) may change pituitary tumor consistency and improve surgical outcome in GH-secreting pituitary macroadenomas. Methods Retrospective study of 40 patients with GH-secreting pituitary macroadenomas operated for the first time by endoscopic transsphenoidal approach. Tumor consistency was evaluated intraoperatively and then correlated with histopathological fibrosis parameters and surgical outcomes. Surgical remission was reported based on the 2010 criteria. Results The mean tumor size of GH-secreting macroadenomas was of 16.9 ± 8.2 mm and 25 were invasive pituitary adenomas (PAs). Presurgical treatment with long-acting SRL was performed in 17 patients (11 lanreotide, 6 octreotide). The cure rate was higher in those patients pre-treated with monthly doses ≥30 mg of octreotide or ≥90 mg of lanreotide than in those treated with lower doses or untreated (8/11 (72.7%) vs 11/29 (37.9%), P = 0.049). However, although the proportion of soft tumors increased as higher doses of SRL were considered in the pre-treated group, no statistical significance was reached, even when the highest approved monthly doses were used (6/6 (100%) vs 23/34 (67.7%), P = 0.102). Moreover, we found that the remission rate was similar between fibrous and soft tumors (P = 0.873) and also of surgical complications (P = 0.859), despite of the higher prevalence of Knosp >2 (P = 0.035) and very large PA (P = 0.025) in fibrous tumors than in soft tumors. Conclusions Although presurgical treatment with high doses of SRL was associated with a 2.2-fold greater chance of surgical remission, this benefit was not related with changes in tumor consistency induced by the presurgical treatment.

Acromegaly is a rare disease associated with comorbidities that are common in the general population. Most patients undergo screening for classic phenotypical (CP) or mass effect manifestations. By retrospective review of pituitary tumor surgeries performed between 1994 and 2016 (1836), we identified patients with acromegaly (112). Main presentations were: CP (43%), mass effect (26%), incidentally detected (ID) tumors (17%), and other (14%). We compared the ID and CP groups regarding prevalence, clinical, biochemical, radiological and histopathological characteristics, and postoperative outcomes. The prevalence of ID among all surgeries increased after 2011 from 0.6% to 1.9% (p=0.01), while prevalence of CP remained stable (2.8% and 2.33%, p=0.65). Almost half of ID (47.4%) presented with otolaryngological manifestations. The ID and CP groups were similar regarding age, gender, comorbidities (hypertension, diabetes, hypopituitarism), tumor diameter and cavernous sinus invasion. Median insulin-like growth factor (IGF-1) and growth hormone (GH) levels were lower in the ID than CP (p

Resection of pituitary adenomas presents a number of unique challenges in neuro-oncology. The proximity of these lesions to key vascular and endocrine structures as well as the need to interpret neuronavigation in the context of shifting tumor position increases the complexity of the operation. More recently, substantial advances in fluorescence-guided surgery have been demonstrated to facilitate the identification of numerous tumor types and result in increased rates of complete resection and overall survival. A review of the literature was performed, and data regarding the mechanism of the fluorescence agents, their administration, and intraoperative tumor visualization were extracted. Both in vitro and in vivo studies were assessed. The application of these agents to pituitary tumors, their advantages and limitations, as well as future directions are presented here. Numerous laboratory and clinical studies have described the use of 5-ALA, fluorescein, indocyanine green, and OTL38 in pituitary lesions. All of these drugs have been demonstrated to accumulate in tumor cells. Several studies have reported the successful use of the majority of the agents in inducing intraoperative tumor fluorescence. However, their sensitivity and specificity varies across the literature and between functioning and non-functioning adenomas. At present, numerous studies have shown the feasibility and safety of these agents for pituitary adenomas. However, further research is needed to assess the applicability of fluorescence-guided surgery across different tumor subtypes as well as explore the relationship between their use and postoperative clinical outcomes.

Introduction: Cabergoline is the treatment of choice for prolactinomas. However, 10–20% of prolactinomas are resistant to cabergoline. Metformin, a biguanide widely used in the treatment of diabetes mellitus, has been shown to reduce prolactin secretion in various pituitary tumor-cell lineages both in vitro and in vivo and in human pituitary adenomas in vitro. The aim of this study is to test the effects of metformin addition to cabergoline treatment on prolactin levels in patients with resistant prolactinomas. Subjects and Methods: This is a prospective study performed in an outpatient clinic in a reference center. Ten adult patients (26–61 years) with prolactinomas (7 M), persistent hyperprolactinemia (38–386 ng/mL) under cabergoline treatment (2–7 mg/week) for at least 6 months (6–108 months), features of metabolic syndrome, and not taking metformin were included. Metformin (1.0–2.5 g v.o./day) was given according to patients’ tolerance. Cabergoline doses were kept unchanged. Serum prolactin levels were measured before and after short- (30–60 days) and long-term (120–180 days) metformin treatment. Results: Mean prolactin levels did not show any significant changes (148 ± 39 vs. 138 ± 42 vs. 133 ± 39 ng/mL, before, at 30–60 days, and at 120–180 days, respectively, p = 0.196) after metformin (mean dose: 1.25 g/day; range: 1.0–2.0 g/day). No patient reached a normal prolactin level during metformin treatment. Two patients were considered partial responders for exhibiting prolactin decreases ≥50% at a single time point during metformin. Conclusion: Metformin addition to ongoing high-dose cabergoline treatment in patients with cabergoline-resistant prolactinomas failed to show a consistent inhibitory effect in serum prolactin levels.

Background Pituitary apoplexy (PA) is a rare complication of pituitary tumors that can present with a myriad of symptoms, including sudden onset cranial nerve deficits. After patient stabilization and hormone replacement, surgical decompression is often recommended. The timing of surgical decompression remains controversial. In this case series, we describe our institutional experience pertaining to the cranial nerve recovery in patients who underwent endoscopic endonasal transsphenoidal (EETS) surgery for PA while evaluating outcome based on tumor stage using the suprasellar infrasellar parasellar anterior posterior (SIPAP) classification. Design Present study is a single-institution retrospective cohort. Methods A retrospective review of all EETS cases for pituitary tumor resection between November 2009 and August 2018. Queries of the hospital database were completed by trained personnel to identify cases of PA treated using the EETS approach. Baseline characteristics, tumor type, endocrine data, and SIPAP classification based on preoperative magnetic resonance imaging (MRI) and operation characteristics were extracted from medical records. Postoperative results were extracted for the duration of the follow-up period available for each patient. Results Fifteen cases of PA were identified. Patient follow-up period was a mean of 30 months. The cranial nerve deficits present at admission were visual deficit (33%); unilateral third nerve palsy (47%) and unilateral sixth nerve palsy (27%). No fourth nerve palsies were observed. Following EETS, 60% of patients with preoperative visual deficit had normal visual fields. For those with third and sixth nerve palsies preoperatively, 43 and 75%, respectively, had return to normal function postoperatively. SIPAP tumor characteristics were not related to postoperative cranial nerve recovery. Conclusion In this series of surgically treated patients with pituitary apoplexy, all cranial nerve deficits normalized or improved following surgery. The tumor SIPAP classification was not associated with patient outcome. Though in a small series, the presented results suggest surgical treatment is beneficial for these patients.