OBJECTIVE: To assess the diagnostic features of acromegaly, and analyse its management outcomes over a 15-year period in a tertiary care setting.
METHODS: The descriptive, cohort, retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of adult patients of either gender diagnosed with acromegaly based on biochemical and radiological evidence between January 2005 and December 2019. Data was retrieved from the medical records. Data was analysed using SPSS 19.
RESULTS: Of the 84 subjects, 54(64.3%) were males and 30(35.7%) were female. The overall mean age was 38.69±13.52 years. The patients presented 5.43±4.3 years after the onset of symptoms, with somatic growth features, such as enlarged hands and feet which was the most common complaint 81(96.4%). Of all the patients, 73(86.9%) underwent trans-sphenoidal surgery for the removal of the pituitary adenoma, while 11(13.1%) opted out of the surgical option. Further, 9(12.3%) patients showed biochemical and radiological remission 6 months post-surgery. Out of the remaining 64(87.7%) patients, 38(59.4%) received radiosurgery or radiotherapy, 15(23.4%) underwent repeat trans-sphenoidal surgery, and 11(17.2%) chose medical treatment.
CONCLUSIONS: Majority of patients failed to achieve remission after trans-sphenoidal surgery, which is the first line of treatment. Radiotherapy/repeat surgery was generally the options taken by those with persistent disease.

BACKGROUND: Sellar metastases (SM) are rare manifestations of malignancy. Breast and lung cancer are the most common primary tumors. Most cases are diagnosed in patients with advanced malignant disease; however, symptoms of pituitary involvement can precede the diagnosis of the primary tumor.
METHODS: Retrospective analysis of symptoms at presentation, hormonal, radiological and histological findings, management, and outcome of patients with SM from 2009 to 2020.
RESULTS: Eighteen patients\'cases were included, 11 with histological confirmation. Median (m) age was 53 years (range 35-75), 53% male. Primary malignant tumors: 8 lungs, 6 breast, 1 follicular thyroid carcinoma, 1 Hodgkin lymphoma, and 2 clear cell renal carcinomas. The m time between the diagnosis of the primary neoplasm and the occurrence of the SM was 108 months (range: 11-180). In 8 patients the diagnosis of the primary neoplasm was made after the finding of the symptomatic sellar mass. Insipidus diabetes, adenohypophysis deficit, visual disorders, headache, and cranial nerve deficits were evident in 78, 77, 61, 39 and 39% of the cases, respectively. Fifteen patients harbored supra / parasellar masses, in three a lesion was limited to the pituitary gland, and stalk. Eleven out of 18 (61.1%) of the patients were operated on by the trans-sphenoidal approach, for diagnostic and / or decompressive purposes. Eighteen died, with a median survival time of 6 months (1-36).
CONCLUSIONS: In the presence of a pituitary lesion with diffuse gadolinium uptake, associated with insipidus diabetes and / or visual disorder SM should be suspected even in patients without a history of oncological disease.
Introducción: La región selar es un sitio infrecuente de metástasis, encontrándose en el 1% de las cirugías hipofisarias. Los tumores primarios más habituales son mama y pulmón. En general son diagnosticadas en pacientes con enfermedad avanzada, aunque pueden ser el debut de la enfermedad oncológica. Métodos: Análisis retrospectivo de las características clínicas, bioquímicas, radiológicas de pacientes con metástasis selares o hipofisarias (MS) durante el periodo 2009-2020. Resultados: Se reportaron 18 casos de pacientes, 11 de ellos con confirmación histológica. La mediana de edad fue 53 años (rango: 35-75), 53% hombres. La localización del tumor primario fue: 8 pulmón, 6 mama, 1 carcinoma folicular de tiroides, 1 linfoma Hodgkin y 2 carcinomas renales de células claras. La media de tiempo entre el diagnóstico del tumor primario y la aparición de la MS -en los casos de presentación metacrónica- fue 108 meses (rango: 11-180). En 8 pacientes (44.4%), el diagnóstico de la neoplasia primaria se hizo a partir del hallazgo de la masa selar. Diabetes insípida, hipopituitarismo, trastornos visuales, oftalmoplejía y cefalea se presentaron en el 78, 77, 61, 39 y 39%, respectivamente. Quince pacientes presentaron masas con extensión supra/paraselar; y 3 lesión limitada a la hipófisis y tallo. Fueron operados 11/18 por vía transesfenoidal, para diagnóstico y/o descompresión. Fallecieron 17, con una mediana de sobrevida de 6 meses (1- 36). Discusión: La sospecha de MS debe estar presente ante una masa selar y supraselar con captación difusa del gadolinio, diabetes insípida, hipopituitarismo y/o disfunción visual, aun en pacientes sin antecedentes oncológicos.

Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG+ epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.

OBJECTIVE: An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index.
METHODS: We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55).
RESULTS: IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04).
CONCLUSIONS: Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies.

BACKGROUND: Invasion of the CS is one of the limiting factors for total resection for PitNet tumors with cure rates less than 30%. Extended approaches may be considered in selective and well-studied cases of secreting adenomas.
METHODS: We describe the key steps of the endoscopic transcavernous approach for functional pituitary adenomas with a video illustration. The surgical anatomy is described along with the advantages and limitations of this approach.
CONCLUSIONS: A detailed knowledge of CS anatomy and familiarity with this surgical approach acquired in the laboratory is essential. Proper instrumentation is critical to decrease the risks of vascular injury.

Despite slow growth of most pituitary tumors and high rates of total resection and/or effective therapy, pituitary neoplasms are characterized by aggressive behavior with high growth rate, frequent relapses and resistance to standard treatments in 10% of cases. In modern WHO classifications of tumors of the central nervous system, endocrine and neuroendocrine tumors, the authors propose the definition «pituitary neuroendocrine tumor» instead of previous «pituitary adenoma» and «metastasizing pituitary neuroendocrine tumor» instead of «pituitary carcinoma». Currently, there are no effective prognostic markers of aggressive tumors. This complicates early diagnosis. It is proposed to apply a five-stage prognostic classification based on proliferation rate (including mitotic count, Ki-67 index and p53 immunoexpression) and morphometric markers of invasiveness for all resected pituitary neoplasms. This approach would be valuable for earlier detection of aggressive tumors and pituitary carcinomas. Compression of visual pathways, third ventricle and brain stem due to rapid growth of aggressive tumors usually requires redo surgeries with subsequent radiotherapy. Hormonally active tumors require therapy with somatostatin analogues and dopamine agonists in maximum possible doses. Chemotherapy with temozolomide as first-line option is recommended if standard treatment is ineffective. Alternative treatment includes peptide receptor radionuclide therapy (PRRT), molecular targeted therapy (bevacizumab, tyrosine kinase inhibitors, everolimus and cyclin-dependent kinase inhibitors) and immunotherapy (checkpoint inhibitors). Considering the need for combined treatment, these cases should always be discussed by a multidisciplinary team (neurosurgeon, endocrinologist, radiotherapist, oncologist, pathologist) with necessary qualifications and experience in treating these patients. Treatment of aggressive tumors and pituitary carcinomas is becoming an active and rapidly developing direction in neurosurgery, endocrinology and oncology.
Несмотря на медленный рост большинства опухолей гипофиза, высокие показатели их радикального удаления и/или эффективность медикаментозных методов лечения, в 10% случаев опухоли гипофиза проявляют «агрессивное поведение» с высокой скоростью роста, частыми рецидивами и резистентностью к стандартным методам лечения. В современных классификациях опухолей центральной нервной системы и эндокринных и нейроэндокринных опухолей Всемирной организации здравоохранения вместо ранее применяемого термина «аденома гипофиза» предложено использовать дефиницию «гипофизарная нейроэндокринная опухоль», вместо термина «карцинома гипофиза» — «метастазирующая гипофизарная нейроэндокринная опухоль». В настоящее время отсутствуют надежные прогностические маркеры агрессивного поведения опухолей, вследствие чего их ранняя диагностика затруднена. Предлагается применять пятиступенчатую прогностическую классификацию, основанную на оценке пролиферации (включая количество митозов, индекс мечения Ki-67 и иммуноэкспрессию p53) в сочетании с морфометрическими маркерами инвазивности, всех удаленных новообразований гипофиза для более раннего выявления агрессивных опухолей и карцином гипофиза. Компрессия зрительных путей, III желудочка, ствола мозга вследствие быстрого роста агрессивных опухолей в большинстве случаев требует повторных операций с последующим проведением лучевого лечения, в случае гормонально-активных опухолей — терапии аналогами соматостатина, агонистами дофамина в максимально переносимых дозах. При неэффективности стандартных методов лечения рекомендована химиотерапия, первой линией которой является темозоломид. В качестве альтернативных направлений в лечении применяется пептидная рецепторная радионуклидная терапия, молекулярно-таргетная терапия (бевацизумаб, ингибиторы тирозинкиназы, эверолимус и ингибиторы циклинзависимых киназ), а также иммунотерапия (ингибиторы контрольных точек иммунного ответа). Учитывая необходимость комбинированного лечения, эти случаи всегда должны обсуждаться мультидисциплинарной командой экспертов (нейрохирург, эндокринолог, радиотерапевт, онколог, патоморфолог), обладающих необходимой квалификацией и имеющих опыт лечения больных с этой патологией. Лечение агрессивных опухолей и карцином гипофиза становится активной и быстро развивающейся областью нейрохирургии, эндокринологии и онкологии.

The widespread use of diagnostic imaging has led to an increase in the incidence of pituitary tumors. The majority of incidentalomas are hormone-inactive (HI) pituitary microadenomas. The most common clinically relevant pituitary adenomas are prolactin-secreting, followed by HI, and far less common are growth hormone (GH)-, adrenocorticotropic hormone (ACTH)- and thyroid-stimulating hormone (TSH)-secreting adenomas. Pituitary adenomas are usually benign, although aggressive growth and invasion occurs in individual cases. Very rarely, they give rise to metastases and are then termed pituitary carcinomas. All pituitary tumors require endocrine testing for pituitary hormone excess. In addition to the medical history and clinical examination, laboratory diagnostics are very important. Symptoms such as irregular menstruation, loss of libido or galactorrhea often lead to the timely diagnosis of prolactinomas, and hyperprolactinemia can easily confirm the diagnosis (considering the differential diagnoses). Diagnosis is more difficult for all other hormone-secreting pituitary adenomas (acromegaly, Cushing\'s disease, TSHoma), as the symptoms are often non-specific (i.e., headaches, weight gain, fatigue, joint pain). Furthermore, comorbidities such as hypertension, diabetes, and depression are such widespread diseases that pituitary adenomas are rarely considered as the underlying cause. Timely diagnosis and appropriate treatment have a significant impact on morbidity, mortality, and quality of life. Therefore, the role of primary care physicians is very important for achieving an early diagnosis. In addition, patients with pituitary adenomas should always be referred to endocrinologists to ensure optimal diagnosis as well as treatment.
UNASSIGNED: Durch die Zunahme der bildgebenden Untersuchungen nimmt auch die Diagnosehäufigkeit hypophysärer Raumforderungen (Hypophyseninzidentalome) zu. Ein Großteil der Inzidentalome sind hormoninaktive Hypophysenmikroadenome, gefolgt von zystischen Raumforderungen und prolaktinsezernierenden Adenomen. Weitaus seltener sind Adenome, die Wachstumshormon (GH) oder adrenokortikotropes Hormon (ACTH) sezernieren, und TSHome, das heißt Adenome, die thyreoideastimulierendes Hormon (TSH) produzieren. Hypophysenadenome sind in der Regel gutartige Tumoren, wobei in einzelnen Fällen ein aggressives Wachstum auftreten kann. Treten Metastasen auf, spricht man von Hypophysenkarzinomen. Bei jedem Hypophysentumor ist es unerlässlich, eine Hormonaktivität auszuschließen. Neben Anamnese und klinischer Untersuchung steht hier die Labordiagnostik im Vordergrund. Bei Prolaktinomen führen Symptome wie Zyklusstörungen, Libidoverlust oder Galaktorrhö in der Regel schnell zur Diagnosestellung, und eine Hyperprolaktinämie bestätigt die Diagnose (unter Beachtung der Differenzialdiagnosen). Bei den übrigen hormonaktiven Hypophysenadenomen (Akromegalie, Morbus Cushing, TSHom) kann sich die Diagnosestellung verzögern, da die Symptome zum Teil unspezifisch sind (beispielsweise Kopfschmerzen, Gewichtszunahme, Abgeschlagenheit, Gelenkschmerz), obwohl die klinischen Stigmata eindrücklich sein können. Des Weiteren stellen die Komorbiditäten, etwa Hypertonie, Diabetes oder Depression, Volkskrankheiten dar, sodass primär nicht an eine dieser seltenen Hypophysenentitäten gedacht wird. Frühzeitige Diagnosestellung und Therapieeinleitung haben einen maßgeblichen Einfluss auf Morbidität, Mortalität und Lebensqualität. Daher ist die Rolle der betreuenden Internistinnen und Internisten, die früh an eine entsprechende Diagnose denken sollten, von großer Bedeutung. Um eine optimale Diagnostik und Therapie zu gewährleisten, sollten Patientinnen und Patienten mit Hypophysenadenomen immer durch Endokrinologinnen und Endokrinologen (mit-)betreut werden.

BACKGROUND: Adenoma hemorrágico que imita a un aneurisma de la arteria comunicante anterior.

UNASSIGNED: Postoperative nonfunctioning pituitary tumor (NFPT) regrowth is a significant concern, but its predictive factors are not well established. This study aimed to elucidate the pathological characteristics of NFPTs indicated for reoperation for tumor regrowth.
UNASSIGNED: Pathological, radiological, and clinical data were collected from patients who underwent repeat operation for NFPT at Moriyama Memorial Hospital (MMH) between April 2018 and September 2023. For comparison, we also gathered data from patients who underwent initial surgery for NFPT during the same period at MMH.
UNASSIGNED: Overall, 61 and 244 NFPT patients who respectively underwent reoperation and initial operation were evaluated. The mean period between the previous operation and reoperation was 113 months. Immunonegativity for any adenohypophyseal hormone was significantly more frequent in the reoperation group than in the initial operation group. In addition, the rate of hormone-negative but transcription factor-positive (H-/TF+) tumors among silent gonadotroph tumors was significantly higher in the reoperation group than in the initial operation group. Furthermore, seven silent corticotroph tumors (SCTs) in the reoperation group were ACTH-negative but TPIT-positive. Because most of the previous surgeries were performed in other hospitals a long time ago, we could procure the previous pathological results with immunohistochemistry (IHC) only from 21 patients. IHC for TF had not been performed in all the previous specimens. IHC for adenohypophyseal hormone was almost the same as the current results, and many H-/TF+ tumors were previously diagnosed as NCT. In addition, the reoperated patients were classified into 3 groups on the basis of the condition of the previous operation: gross total resection (GTR), 12 patients; subtotal resection (STR), 17 patients; and partial resection (PR), 32 patients. The mean Ki-67 LI in the GTR, STR, and PR subgroups were 1.82, 1.37, and 0.84, respectively, with the value being significantly higher in the GTR subgroup than in the PR subgroup (P < 0.05).
UNASSIGNED: The ratio of H-/TF+ tumors is significantly higher in symptomatically regrown tumors than in the initial cases, which used to be diagnosed as NCT. PR cases tend to grow symptomatically in a shorter period, even with lower Ki-67 LI than GTR cases.

OBJECTIVE: This study aimed to investigate the limitations, barriers, and complications in the early transition from the microscopic transsphenoidal approach (MTA) to the endonasal endoscopic approach (EEA) to the skull base in our institution.
METHODS: Technical challenges, as well as clinical features and complications, were compared between MTA, EEA, and mixed cases during the early surgical curve.
RESULTS: The period from the early learning curve was 1 year until the EEA protocol was used routinely. A total of 34 patients registered a resection using a transsphenoidal approach. Eighteen patients underwent EEA, 11 underwent MTA, and five underwent a mixed endonasal and microscopic approach. Non-significant differences were found in endocrine outcomes between the three groups. Patients with unchanged or improved visual function were higher in the EEA group (p = 0.147). Non-significant differences were found in terms of the extent of resection (EOR) between groups (p = 0.369). Only 1 (2.9%) patient in the whole series developed a post-operative CSF leaking that resolved with medical management, belonging to the EEA group (5.5%).
CONCLUSIONS: The early phase of the learning curve did not affect our series significantly in terms of the EOR, endocrine status, and visual outcomes.
OBJECTIVE: Investigar las limitaciones, las barreras y las complicaciones en la transición del abordaje transesfenoidal microscópico (ATM) al abordaje endonasal endoscópico (AEE) para la base del cráneo en nuestra institución.
UNASSIGNED: Se compararon las características clínicas y las complicaciones entre ATM, AEE y casos mixtos durante la curva quirúrgica temprana.
RESULTS: El periodo desde la curva de aprendizaje inicial fue de 1 año hasta que se utilizó el protocolo AEE de forma sistemática. Un total de 34 pacientes tuvieron una resección por vía transesfenoidal. A 18 pacientes se les realizó AEE, a 11 ATM y a 5 abordaje mixto endonasal y microscópico. Se encontraron diferencias no significativas en los resultados endocrinos entre los tres grupos. Los pacientes con función visual sin cambios o mejorada fueron más en el grupo AEE (p = 0.147). No se encontraron diferencias significativas respecto a la extensión de la resección (p = 0.369). Solo 1 (2.9%) paciente desarrolló una fístula de líquido cefalorraquídeo que se resolvió con manejo médico, perteneciente al grupo AEE (5.5%).
CONCLUSIONS: La fase inicial de la curva de aprendizaje no afectó significativamente a nuestra serie en términos de extensión de la resección, estado endocrino y resultados visuales.