Diagnostic, therapeutic, and prognostic characteristics of patients with acromegaly according to tumor size at diagnosis.

PURPOSE: To evaluate clinical, laboratory, radiological, therapeutic, and prognostic characteristics of patients with acromegaly according to the size of the growth hormone (GH)-secreting pituitary adenoma at diagnosis. METHODS: Observational, retrospective, single-center study of patients with acromegaly followed at a tertiary center. Data were collected regarding clinical presentation, characteristics of the adenoma in the magnetic resonance imaging, GH and IGF-1 levels, and disease control after surgery or adjuvant treatment (normal IGF-1 levels). Patients were divided according to the adenoma size at diagnosis in: group I < 10 mm; II 10-19 mm; III 20-29 mm; IV 30-39 mm; and V ≥ 40 mm. Comparisons were made between the groups, and correlations of tumor size with disease parameters, ROC curves, and logistic regression analyses were performed to investigate tumor size and confounding factors that could impact the outcomes. RESULTS: 117 patients were studied [59 women, age at diagnosis 43 ± 13 years; group I = 11 patients (9%); group II 54 (46%); group III 34 (29%); group IV 10 (9%); group V 8 (7%)]. Hypopituitarism, cavernous sinus invasion, GH levels, and use of somatostatin receptor ligands had their prevalence increased according to the adenoma size. Age showed a negative correlation with tumor size. A tumor diameter around 20 mm was the best predictor for the presence of hypopituitarism, invasiveness, need of adjuvant therapies, and poorer disease control. CONCLUSION: Adenomas < 20 mm showed lower morbidity and better therapeutic response in acromegaly, while those ≥ 20 mm had similar clinical, therapeutic, and prognostic behavior.

Targeting the PAC1 receptor mitigates degradation of myelin and synaptic markers and diminishes locomotor deficits in the cuprizone demyelination model.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a strong neuroinflammatory component. Current treatments principally target the immune system but fail to preserve long-term myelin health and do not prevent neurological decline. Studies over the past two decades have shown that the structurally related neuropeptides VIP and PACAP (vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide, respectively) exhibit pronounced anti-inflammatory activities and reduce clinical symptoms in MS disease models, largely via actions on their bivalent VIP receptor type 1 and 2. Here, using the cuprizone demyelination model, we demonstrate that PACAP and VIP, and strikingly the PACAP-selective receptor PAC1 agonist maxadilan, prevented locomotor deficits in the horizontal ladder and open field tests. Moreover, only PACAP and maxadilan were able to prevent myelin deterioration, as assessed by a reduction in the expression of the myelin markers proteolipid protein 1, oligodendrocyte transcription factor 2, quaking-7 (APC) and Luxol Fast Blue staining. Furthermore, PACAP and maxadilan (but not VIP), prevented striatal synaptic loss and diminished astrocyte and microglial activation in the corpus callosum of cuprizone-fed mice. In vitro, PACAP or maxadilan prevented lipopolysaccharide (LPS)-induced polarisation of primary astrocytes at 12-24 h, an effect that was not seen with maxadilan in LPS-stimulated microglia. Taken together, our data demonstrates for the first time that PAC1 agonists provide distinctive protective effects against white matter deterioration, neuroinflammation and consequent locomotor dysfunctions in the cuprizone model. The results indicate that targeting the PAC1 receptor may provide a path to treat myelin-related diseases in humans.

Adrenocorticotropic Hormone Producing Pituitary Carcinoma in the Falx Cerebri, Retroclival Region, Ethmoidal Cells, and Other Locations.

Pituitary carcinoma is a condition defined by metastasis of a pituitary tumor to a distant location, and it is a very rare type of adenohypophyseal tumor. We present a case of a 29-year-old female who was followed up in our Endocrinology Department. Past medical history included the diagnosis of Cushing disease and transsphenoidal tumor resection at 12 years of age, followed by transcranial resection two years later because of persistently elevated adrenocorticotropic hormone (ACTH). Despite the surgical management, the patient persisted with increased ACTH and hypercortisolism, and, thus, bilateral adrenalectomy was performed a year later. Two years after the procedure, the patient presented with a newly diagnosed pituitary macroadenoma, and the diagnosis of Nelson syndrome was made. Linear accelerator radiotherapy was given, which reduced the size of the tumor. Later, several imaging studies showed multiple lesions on the falx cerebri, posterior clinoid process, retroclival region, cerebellopontine angle, pterygopalatine fossa, infratentorial region, and posterior ethmoidal cells. Biopsy and immunohistochemistry of the falx cerebri lesions described ACTH-producing pituitary adenocarcinoma. Treatment was given with intramuscular octreotide, dabrafenib, and trametinib. Despite persistently elevated ACTH levels, the patient has since remained clinically stable, without new development or worsening of symptoms. There are three unique aspects of our case. First, we reported an unusual presentation of this disease, since the patient in our case was a female with an early age of onset. Second, this is the first reported case demonstrating pituitary carcinoma in the falx cerebri. Third, the prognosis of pituitary carcinoma is usually very poor, and mortality is extremely high; however, the patient in our case has been followed up for seven years since the diagnosis of the metastatic lesions and has remained clinically stable.

Concurrent Papillary Craniopharyngioma and Growth Hormone-Secreting Pituitary Adenoma: A Rare and Aggressive Collision Tumor.

Background/Objective: Collision tumors composed of craniopharyngiomas and pituitary adenomas are extremely rare. We report a collision tumor formed by a papillary craniopharyngioma and a growth hormone-secreting pituitary adenoma, which is the first report of such a tumor, to the best of our knowledge. Case Report: A 49-year-old man presented with 2 months of headaches and blurry vision. An exam demonstrated frontal bossing, enlarged jaw and hands, macroglossia, and bitemporal hemianopsia, and magnetic resonance imaging (MRI) showed a 4.1 cm sellar/suprasellar mass with mass effect on the optic chiasm. The tumor was resected twice via a craniotomy, the second time due to interval growth, with the pathology after both surgeries showing a papillary craniopharyngioma. IGF-1 was 517 ng/mL (68-225) and growth hormone suppression test was positive. Repeat MRI showed residual tumor with ongoing mass effect on the optic chiasm and radiation therapy was initiated. MRI showed interval growth of the mass and IGF-1 rose to 700 ng/mL after which the patient underwent a transsphenoidal resection of the tumor; the pathology showed a residual papillary craniopharyngioma and a PIT1 lineage adenoma with most cells expressing growth hormone. After developing numerous complications, the patient passed away. Discussion: Collision tumors of the sella are often associated with an aggressive clinical course, as they often go undiagnosed preoperatively, thus reducing the likelihood of total resection and leading to higher rates of craniopharyngioma recurrence. Conclusion: A pituitary mass with an aggressive clinical course should prompt a high index of suspicion for a sellar collision tumor, though prognosis remains poor.

The nomogram for predicting nasal bleeding after endoscopic transsphenoidal resection of pituitary adenomas: a retrospective study.

Objective: This study aimed to develop and validate a dynamic nomogram to assess the risk of nasal bleeding after endoscopic transnasal transsphenoidal pituitary tumor resection. Methods: A retrospective analysis was conducted on patients who underwent endoscopic transnasal transsphenoidal pituitary tumor resection from June 2019 to June 2021. Univariate and multivariate logistic regression analyses were used to screen for independent risk factors for nasal bleeding from the training set. A multivariate logistic regression model was established, a nomogram was plotted, and it was validated in an internal validation set. The performance of the nomogram was evaluated based on the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: The nomogram indicators included anticoagulant use, sphenoid sinus artery injury, nasal irrigation, platelet count (PLT), and constipation. The predictive model had an area under the ROC curve of 0.932 (95% CI: 0.873-0.990) and 0.969 (95% CI: 0.940-0.997) for the training and validation sets, respectively, indicating good discrimination. The calibration curve showed good consistency between the actual and predicted incidence of nasal bleeding (p > 0.05). DCA indicated that the nomogram had good clinical net benefit in predicting postoperative nasal bleeding in patients. Conclusion: In summary, this study explored the incidence and influencing factors of nasal bleeding after endoscopic transnasal transsphenoidal pituitary tumor resection and established a predictive model to assist clinical decision-making.

Identifying prognostic predictors for postoperative pituitary neuroendocrine tumour recurrence: an integrated clinical, radiological, and immunohistochemistry assessment.

OBJECTIVE: Pituitary neuroendocrine tumours (PitNETs) are the second most common type of intracranial tumour. Several studies have explored the prognostic factors for PitNETs. However, prognostic factors for postoperative PitNET recurrence remain not fully understood. This study aimed to explore potential prognostic factors for PitNET recurrence, such as surrounding tissue invasion and the extent of surgical resection in patients with postoperative PitNETs. METHODS: We included 106 patients who underwent PitNET surgery between 2013 and 2018, dividing them into two groups: those with recurrence and those without recurrence. Tumours were classified based on demographics, neuroradiological, and immunohistological characteristics. Univariate and multivariate analyses were used to determine factors predicting recurrence. Kaplan-Meier plots and log-rank tests were used to analyse each independent factor based on the cumulative 5-year recurrence rate. RESULTS: During the 5-year follow-up period, 29.2% of the patients (n = 31) had disease recurrence. Univariate analysis showed that predictors of recurrence included cavernous and sphenoid sinus invasions, optic chiasm compression, larger tumour volume, giant adenoma >4 cm, and gross total resection (GTR). Multivariate analysis showed that lactotroph tumour type, sphenoid sinus invasion, and GTR were independent predictors. Kaplan-Meier analysis revealed significant differences in the 5-year recurrence rate among the three independent predictors, with significantly lower recurrence rate in patients with lactotroph tumours and GTR, and a significantly higher recurrence risk in patients with sphenoid sinus invasion. CONCLUSIONS: Lactotroph tumour type, sphenoid sinus invasion, and GTR are independent predictors of postoperative PitNET recurrence. This study provides insights into the factors affecting postoperative PitNET recurrence.

PitNETs are the second most common intracranial tumour typePrognostic factors for postoperative PitNET recurrence remain not fully understoodWe explored potential prognostic factors in patients with postoperative PitNETsProlactin secretion and GTR failure were independent recurrence predictorsProliferative factors did not correlate with recurrence.

Retrospective analysis of the outcomes of endoscopic transsphenoidal surgery for Cushing's disease.

Background: The first-line surgical management of an adrenocorticotropic hormone (ACTH)--secreting pituitary adenoma causing Cushing's disease (CD) is endoscopic transsphenoidal resection of the tumor. This study was performed to assess postoperative (postop) complications and remission in endoscopic surgically resected cases of CD. Methods: Data of patients who underwent endoscopic transsphenoidal surgery (ETSS) for CD were collected from the neurosurgery department at a tertiary care center in a retrospective manner from January 2015 to February 2022 and analyzed. Postoperative remission was categorized as - early morning serum cortisol <138 nmol/L within 7 days of the surgery, as per the Endocrine Society Guidelines, with significant clinical improvement in features of hypercortisolism in the operated patient and strict cutoff rate of <50 nmol/L at postop day 3 was also utilized, to look for the early identification of remission. Results: A total of 41 patients were identified who underwent 44 ETSS during the same timeframe. Preoperative magnetic resonance imaging localized an adenoma in all 41 patients, out of which 32 were microadenoma, and nine were macroadenoma (2 with cavernous sinus invasion). Intrapetrosal sinus sampling was performed in 35 (85%) patients. The rate of remission for the initial surgery was 85.4% using the standard criteria and 68.3% using strict criteria. Three patients underwent early repeat surgery for the persistent disease as the day 3 cortisol was high (306-555 nmol/L). Once the outcome of this surgery was also included, the overall rate of remission was 90.2% (37/41). None of the patients had meningitis, cerebrospinal fluid leakage, visual deterioration, or vascular injury. Permanent and transient diabetes insipidus (DI) occurred in 9.75% and 26.8% following the first ETSS, respectively. We also noted a single case of CD recurrence in 9 months during the total follow-up period of 84 months. Conclusion: ETSS has satisfactory rates of remission for the primary treatment of CD, with rates being higher for microadenomas. A long follow-up period is needed to assess the rates of recurrence. Patients must be counseled regarding the risk of postop DI, whether transient or permanent, as a possible complication.

Pituitary lymphoma appearing 9 years after pituitary adenoma resection.

Background: Pituitary lymphomas (PLs) are very rare, accounting for <0.1% of all intracranial tumors. Of which, PL that is associated with PL is even rarer. Here, we describe a case of PL of a 51-year-old woman that appeared 9 years after pituitary adenoma resection. Case Description: A 51-year-old woman presented with visual disturbance. She had a history of pituitary adenoma resected through endoscopic trans-sphenoidal surgery (eTSS) 9 years before. Although her previous annual follow-up did not show any signs of recurrence, she noticed visual disturbance. One month later, her visual acuity rapidly worsened with headache and fatigue, being referred to our hospital. On examination, she had bilateral quadrantanopia. Her laboratory data showed slightly increased prolactin levels. Magnetic resonance images showed a mass in the sella with suprasellar extension, so she underwent eTSS. The tumor had a fibrous, hard part and a soft gray part, and it was mostly resected. Visual symptoms improved transiently, but ophthalmoplegia appeared 2 weeks after surgery, indicating intrathecal dissemination. Histological analysis confirmed the diagnosis of T-lymphoblastic lymphoma. Positron emission tomography showed tracer accumulation at the pancreas, confirmed as lymphoma through biopsy. However, we could not determine which site of lymphoma was the primary site. She underwent chemotherapy, including cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, and methotrexate. The patient died despite several months of treatment. Conclusion: Recurrence of pituitary adenoma cannot be carelessly assumed from a pituitary growing mass after pituitary adenoma resection. PLs have poor prognosis due to their aggressive character. Immediate biopsy and confirmation of the diagnosis are necessary for the treatment of pituitary masses with aggressive features.

Loss of ATRX Protein Expression in an Aggressive Null Cell Pituitary Tumor.

Somatic alpha thalassemia/mental retardation syndrome X-linked (ATRX) pathogenic variants have been shown to predict a malignant phenotype in neuroendocrine tumors. They were recently identified in aggressive pituitary tumors and carcinomas, mainly of corticotrophic origin. To our knowledge, these tumors are rare in a general cohort of pituitary tumors, with no cases described in null cell tumors. These variants can lead to loss of protein expression as revealed by immunohistochemistry. We describe a case of an aggressive null cell pituitary tumor with loss of ATRX expression. The patient underwent two transsphenoidal surgeries and radiotherapy and exhibited tumor growth despite conventional therapy. Analysis of the tumor samples revealed loss of ATRX expression in both surgical specimens, suggesting that ATRX may be a useful biomarker for the early identification of aggressive pituitary tumors.

Integration analysis of pituitary proteome and transcriptome reveals fertility-related biomarkers in FecB mutant Small Tail Han sheep.

The Booroola fecundity mutation (FecB) in Small Tail Han sheep has been shown to enhance ovulation rates and litter sizes by affecting the hypothalamic-pituitary-gonadal (HPG) axis. Despite the pituitary's role in reproductive regulation, its involvement in FecB-induced ovulation remains understudied. Our study aimed to fill this gap by analyzing pituitary tissues from FecB homozygous (BB) and wild-type (WW) ewes during luteal and follicular phases using tandem mass tag-based protein quantification and the DIABLO framework for proteomic and transcriptomic data integration. Significant differences in 277 proteins were observed across estrus periods, with network analysis highlighting the voltage-dependent calcium channel L-type alpha-1C as a key convergence point in oxytocin signaling and GnRH secretion pathways. The DIABLO method revealed a strong correlation (0.98) between proteomic and transcriptomic datasets, indicating a coordinated response in FecB ewes. Notably, higher expression levels of Follicle Stimulating Hormone Subunit Beta (FSHB) and Luteinizing Hormone Subunit Beta (LHB) were found in BB ewes during the follicular phase, potentially due to elevated E2 concentrations. Furthermore, our analysis identified genes related to the Gamma-aminobutyric acid type A receptor family (GABRA2, GABRG1, GABRB1) in the pituitary, with GABRB1 showing higher expression in BB ewes. This suggests a role for GABA in modulating GnRH and gonadotropin feedback loops, potentially contributing to the FecB mutation's effect on ovulation. This study provides novel insights into the pituitary's role in fertility among FecB sheep, identifying GABA as a potential regulatory factor within the HPG axis. The findings also open avenues for discovering new biomarkers in pituitary endocrinology for sheep breeding purposes.

Increase in Testosterone Levels and Improvement of Clinical Symptoms in Eugonadic men With a Prolactin-secreting Adenoma.

Objective: Testosterone concentrations, albeit rarely, may be in the normal range (>3.0 ng/mL) in men with a prolactin-secreting pituitary adenoma (PSPA-nt). The evolution of total, bioavailable testosterone, gonadotropin levels, and that of graded symptoms of testosterone deficiency (TD) are uncertain in these patients. Design: Retrospective case-control longitudinal study at a tertiary referral center. Methods: From 287 men, we selected 25 PSPA-nt men undergoing prolactin normalization (<20.0 ng/mL) during the follow-up. Graded symptoms of TD were investigated by structured interviews. Biochemical changes and TD symptoms were compared to those of a matched cohort of 61 men with pituitary neoplasms and normal testosterone levels (PA-nt). Results: Baseline testosterone levels were similar between PSPA-nt and PA-nt subjects. The prevalence of specific and suggestive symptoms of TD was higher in PSPA-nt (20% and 68%) than in PAnt (3.3 and 29.5%; P = .02 and P = .0015, respectively). At the follow-up, total and bioavailable testosterone levels increased in PSPA-nt but not in PA-nt patients (Δ change: 1.28 ± 2.1 vs0.03 ± 1.5 ng/mL, + 0.33 ± 0.55 vs-0.26 ± 0.60 ng/mL; P = .0028 and P = .0088, respectively). LH and FSH levels also increased in PSPA-nt men (P < .05). Specific and suggestive, but not nonspecific symptoms of TD, improved only in PSPA-nt men (P < .05 for both). Baseline testosterone and LH were the strongest predictors of testosterone improvement in PSPA-nt patients. Conclusion: Despite having normal testosterone levels at baseline, patients with PSPA-nt experience a relief of TD symptoms and an improvement of their pituitary-gonadal axis function following prolactin normalization, especially when baseline TT and LH levels are in the low-normal range.

A rare case of pituitary stalk interruption syndrome (PSIS) presenting as short stature in an 8-year-old female.

Pituitary stalk interruption syndrome is a rare, congenital abnormality. Early identification and treatment can improve patient prognosis and quality of life and prevent adverse effect on growth and development. The patient described is an 8-year-old child with a history of short stature.

Hypopituitarism after gamma knife radiosurgery for pituitary adenomas: long-term results from a single-center experience.

OBJECTIVE: The aim of this study was to investigate the incidence and risk factors of new-onset hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenomas in a single center. METHODS: In this retrospective study, 241 pituitary adenoma patients who underwent GKRS from 1993 to 2016 were enrolled. These patients had complete endocrine, imaging, and clinical data before and after GKRS. The median follow-up time was 56.0 (range, 12.7-297.6) months. RESULTS: Fifty patients (20.7%) developed new-onset hypopituitarism after GKRS, including hypogonadism (n = 22), hypothyroidism (n = 29), hypocortisolism (n = 20), and growth hormone deficiency (n = 4). The median time to new-onset hypopituitarism was 44.1 (range, 13.5-141.4) months. The rates of new-onset hypopituitarism were 7%, 16%, 20%, 39%, and 45% at 1, 3, 5, 10, and 15 years, respectively. For those patients treated with a single GKRS, sex (p = 0.012), suprasellar extension (p = 0.048), tumor volume (≥ 5 cm3) (p < 0.001), tumor progression (p = 0.001), pre-existing hypopituitarism (p = 0.011), and previous surgery (p = 0.009) were significantly associated with new-onset hypopituitarism in univariate analysis. In the multivariate analysis, tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism (hazard ratio [HR] = 3.401, 95% confidence interval [CI] = 1.708-6.773, p < 0.001 and HR = 3.594, 95% CI = 1.032-12.516, p = 0.045, respectively). For patients who received 2 or more times GKRS, no risk factors associated with new-onset hypopituitarism were found. CONCLUSION: New-onset hypopituitarism was not uncommon after GKRS for pituitary adenomas. In this study, large tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism after a single GKRS.

scRNA sequencing technology for PitNET studies.

Pituitary neuroendocrine tumors (PitNETs) are common, most likely benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNET types are classified according to their expression of specific transcriptional factors (TFs) and hormone secretion levels. Some types show aggressive, invasive, and reoccurrence behavior. Current research is being conducted to understand the molecular mechanisms regulating these high-heterogeneous neoplasms originating from adenohypophysis, and single-cell RNA sequencing (scRNA-seq) technology is now playing an essential role in these studies due to its remarkable resolution at the single-cell level. This review describes recent studies on human PitNETs performed with scRNA-seq technology, highlighting the potential of this approach in revealing these tumor pathologies, behavior, and regulatory mechanisms.

Structure and Function of Somatostatin and its Receptors in Endocrinology.

Somatostatin analogs, such as octreotide (OCT), lanreotide, and pasireotide, which function as somatostatin receptor ligands (SRLs), are the main drugs used for the treatment of acromegaly. These ligands are also used as important molecules for radiation therapy and imaging of neuroendocrine tumors (NETs). Somatostatin receptors (SSTRs) are canonical G protein-coupled proteins (GPCRs) that play a role in metabolism, growth, and pathological conditions such as hormone disorders, neurological diseases, and cancers. Cryogenic electron microscopy (cryo-EM) combined with the protein structure prediction platform AlphaFold has been used to determine the three-dimensional structures of many proteins. Recently, several groups published a series of papers illustrating the three-dimensional structure of SSTR2, including that of the inactive/activated SSTR2-G protein complex bound to different ligands. The results revealed the residues that contribute to the ligand binding pocket and demonstrated that Trp8-Lys9 (the W-K motif) in somatostatin analogs is the key motif in stabilizing the bottom part of the binding pocket. In this review, we discuss the recent findings related to the structural analysis of SSTRs and SRLs, the relationships between the structural data and clinical findings, and the future development of novel structure-based therapies.

Medical treatment of acromegaly - When the tumor size matters: A narrative review.

Medical treatment of acromegaly is generally positioned as a second line of treatment after pituitary adenoma surgery. With the rising availability and variety of medications for acromegaly increases our understanding of their effectiveness and safety. Volume of the published data on the impact of medical therapy on biochemical control of acromegaly, contrasts a relative lack of publications which comprehensively address pituitary tumor alterations under different drug modalities. Assessment of changes in GH-secreting adenoma volume is often overshadowed by clinicians' focus on GH and IGF-I levels during acromegaly treatment. Close analysis of studies published in the last two decades, reveals that both an increase and decrease in somatotropinoma volume are possible during treatment with any of available drugs for acromegaly. Changes in pituitary tumor size may arise from the biological nature of adenoma itself, independently of the administered medications. Therefore, an individual approach is necessary in the treatment of patients with acromegaly, based on repeated insight to their clinical, biochemical, pathological and imaging characteristics. In this review, we summarize and comment how pituitary tumor size is affected by the treatment with all currently available drugs in acromegaly: long-acting somatostatin receptor ligands of the first generation (octreotide LAR and lanreotide autogel) and the second generation (pasireotide-LAR), as well as pegvisomant (PEG) and cabergoline (CAB).

The Relationship Between Race, Social Vulnerability Index, and Clinical Follow-up After Surgical Resection of Pituitary Tumors.

INTRODUCTION: Socioeconomic status and race have been found to influence patient outcomes for various cancer subtypes. In particular, minority and economically vulnerable patients present with more advanced disease and experience decreased survival compared to others. The aim of this study was to analyze the association between demographic or socioeconomic variables and rates of post-surgical follow-up after pituitary neuroendocrine tumor (PitNET) resection. METHODS: A retrospective review was completed for patients with PitNETs who underwent surgery between 2018-2021. Patient demographics and information related to post-operative appointments and MRIs were obtained. Social vulnerability index (SVI) scores were recorded from the Centers for Disease Control based on nationwide census tracts. RESULTS: One-hundred and sixteen patients were included in the analysis (57 males). In this cohort, 50% were Black, 34% Hispanic, 9% White, and 1% Asian. Mean overall SVI score was 0.81±0.23. The mean number of cancelled appointments was significantly higher in the moderate-high/high SVI group (p=0.034). Additionally, 30% of patients with moderate-high/high SVI had ≥2 cancelled follow-up visits compared to 0% among patients with low/low-moderate SVI (p=0.035). On average, White patients were less likely than non-White patients to have at least one cancelled follow-up appointment (p=0.048). CONCLUSION: Black patients and those with high social vulnerability have decreased rates of follow-up after PitNET resection. Follow-up delays can lead to failed identification of tumor recurrence, potentially resulting in more advanced disease by the time medical care is re-initiated and increasing rates of patient morbidity and mortality. As a result, further work is needed to address and bridge these care gaps.

Association between Temperament and Stress-related Gene Expression in Day-old Chickens.

Stress in day-old chickens from commercial hatcheries is associated with problematic behavior in adult animals. Recently, we developed a new behavioral handling test for day-old chickens and demonstrated that it assessed temperament differences between seven breeds of native Japanese and Western chickens. In this study, we used 2-day-old male chicks from five of the above breeds to investigate the relationship between temperament and mRNA levels of three stress-related genes (nuclear receptor subfamily 3 group C member 1 (NR3C1), cytochrome P450 family 11 subfamily A member 1, and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) involved in the hypothalamic-pituitary-adrenal axis. Principal component analysis of 10 behavioral traits for the handling test revealed that the Fayoumi breed and Hiroshima line of the Chabo breed, both of which exhibited boisterous temperament, clustered separately from the other breeds. Only NR3C1 expression showed a significant positive correlation with two behavioral traits (general vocalization and approaching the wall), and a negative correlation with movement. These results suggest that the complex temperament of day-old chickens is regulated, in part, by stress-related genes along the hypothalamic-pituitary-adrenal axis.

Spontaneous Cushing's Disease Remission Induced by Pituitary Apoplexy.

Spontaneous remission of Cushing's disease (CD) is uncommon and often attributed to pituitary tumor apoplexy. We present a case involving a 14-year-old female who exhibited clinical features of Cushing's syndrome. Initial diagnostic tests indicated CD: elevated 24h urinary cortisol (235 µg/24h, n < 90 µg/24h), abnormal 1 mg dexamethasone overnight test (cortisol after 1 mg dex 3.4 µg/dL, n < 1.8 µg/dL), and elevated adrenocorticotropic hormone concentrations (83.5 pg/mL, n 10-60 pg/mL). A pituitary adenoma was suspected, so a nuclear MRI was performed, with findings suggestive of a pituitary microadenoma. The patient was referred for a transsphenoidal resection of the microadenoma. While waiting for surgery, the patient presented to the emergency department with a headache and clinical signs of meningism. A computed axial tomography of the central nervous system was performed, and no structural alterations were found. The symptoms subsided with analgesia. One month later, she presented again to the emergency department with clinical findings of acute adrenal insufficiency (cortisol level of 4.06 µg/dL), and she was noted to have spontaneous biochemical remission associated with the resolution of her symptoms of hypercortisolism. For that reason, spontaneous CD remission induced by pituitary apoplexy (PA) was diagnosed. The patient has been managed conservatively since the diagnosis and remains in clinical and biochemical remission until the present time, after 10 months of follow-up. There are three unique aspects of our case: the early age of onset of symptoms, the spontaneous remission of CD due to PA, which has been rarely reported in the medical literature, and the fact that the patient presented a microadenoma because there are fewer than 10 clinical case reports of PA associated with microadenoma.

Research progress on nonsteroidal anti-inflammatory drugs in the treatment of pituitary neuroendocrine tumors.

Pituitary neuroendocrine tumor is the third most common primary intracranial tumor. Its main clinical manifestations include abnormal hormone secretion symptoms, symptoms caused by tumor compression of the surrounding pituitary tissue, pituitary stroke, and other anterior pituitary dysfunction. Its pathogenesis is yet to be fully understood. Surgical treatment is still the main treatment. Despite complete resection, 10%-20% of tumors may recur. While dopamine agonists are effective in over 90% of prolactinomas, prolonged use and individual variations can lead to increased drug resistance and a gradual decline in efficacy, which ultimately requires surgical intervention. Nonsteroidal anti-inflammatory drugs reduce the production of inflammatory mediator prostaglandins by inhibiting the activity of cyclooxygenase and exert antipyretic, analgesic, antiplatelet, and anti-inflammatory effects. In recent years, many in-depth studies have confirmed the potential of nonsteroidal anti-inflammatory drugs as a preventive and antitumor agent. It has been extensively utilized in the prevention and treatment of various types of cancer. However, their specific mechanisms of action still need to be fully elucidated. This article summarizes recent research progress on the expression of cyclooxygenase in pituitary neuroendocrine tumors and the treatment of nonsteroidal anti-inflammatory drugs. It provides a feasible theoretical basis for further research on pituitary neuroendocrine tumors and explores potential therapeutic targets.