Nonfunctioning Pituitary Microadenomas: Should Imaging Interval be Extended? A Large Single-center Cohort Study.

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.

Psoas muscle mass, nutritional status, inflammation, and their relationship with prognosis in patients with pancreatic adenocarcinoma / Masa del músculo psoas, estado nutricional, inflamación y su relación con el pronóstico en pacientes con adenocarcinoma de páncreas

Introduction: some factors have been shown to be associated with survival in patients with pancreatic adenocarcinoma. Recently, some studies suggested that malnutrition, muscle mass, and inflammation might have an effect on survival in patients with pancreatic malignancy. Objectives: to investigate the association between psoas muscle mass, inflammation, nutritional status at the time of diagnosis, and survival in patients with pancreatic adenocarcinoma. Methods: this retrospective study included 219 patients diagnosed with pancreatic carcinoma. The nutritional status, inflammation, and psoas muscle mass of the patients at the time of diagnosis were evaluated. Nutritional status was assessed using the Prognostic Nutritional Index (PNI). Leucocyte count and neutrophil/lymphocyte ratio (NLR) were used for inflammation assessment. Psoas muscle mass was calculated by using abdominal computed tomography images of the patients. Results: the mean age of patients (80 female and 139 male) was 66.6 ± 11.7 years. According to the PNI results, 155 patients had a normal nutritional status (70 %), whereas 64 patients were malnourished (30 %). The survival of the patients with normal nutritional status was significantly longer than that of those who were malnourished (p < 0.001). There was no significant relationship between psoas muscle area, leucocyte count, NLR, and survival time. Conclusion: the survival of pancreatic adenocarcinoma patients with malnutrition at the time of diagnosis was significantly shorter than for patients without malnutrition. (AU)

Introducción:se ha demostrado que algunos factores se asocian a la supervivencia en los pacientes con adenocarcinoma de páncreas. Recientemente, algunos estudios sugirieron que la desnutrición, la masa muscular y la inflamación podrían afectar a la supervivencia de los pacientes con neoplasias malignas pancreáticas.Objetivo: investigar la asociación entre masa muscular del psoas, inflamación, estado nutricional en el momento del diagnóstico y supervivencia en pacientes con adenocarcinoma de páncreas. Métodos: este estudio retrospectivo incluyó a 219 pacientes diagnosticados de carcinoma de páncreas. Se evaluaron el estado nutricional, la inflamación y la masa del músculo psoas de los pacientes en el momento del diagnóstico. El estado nutricional de los pacientes se evaluó con el Índice Nutricional Pronóstico (PNI). El recuento de leucocitos y el cociente de neutrófilos/linfocitos (NLR) se emplearon para la evaluación de la inflamación. La masa del músculo psoas se calculó utilizando las imágenes de tomografía computarizada abdominal de los pacientes. Resultados: la edad media de los pacientes (80 mujeres y 139 hombres) fue de 66,6 ± 11,7 años. Según los resultados del PNI, 155 pacientes tenían un estado nutricional normal (70 %) mientras que 64 pacientes estaban desnutridos (30 %). La supervivencia de los pacientes con estado nutricional normal fue significativamente mayor que la de los pacientes desnutridos (p < 0,001). No hubo ninguna relación significativa entre el área del músculo psoas, el recuento de leucocitos, el NLR y el tiempo de supervivencia. Conclusión: la supervivencia de los pacientes con adenocarcinoma de páncreas con desnutrición en el momento del diagnóstico fue significativamente menor que la de los pacientes sin desnutrición. (AU)

Psoas muscle mass, nutritional status, inflammation, and their relationship with prognosis in patients with pancreatic adenocarcinoma.

INTRODUCTION: Introduction: some factors have been shown to be associated with survival in patients with pancreatic adenocarcinoma. Recently, some studies suggested that malnutrition, muscle mass, and inflammation might have an effect on survival in patients with pancreatic malignancy. Objectives: to investigate the association between psoas muscle mass, inflammation, nutritional status at the time of diagnosis, and survival in patients with pancreatic adenocarcinoma. Methods: this retrospective study included 219 patients diagnosed with pancreatic carcinoma. The nutritional status, inflammation, and psoas muscle mass of the patients at the time of diagnosis were evaluated. Nutritional status was assessed using the Prognostic Nutritional Index (PNI). Leucocyte count and neutrophil/lymphocyte ratio (NLR) were used for inflammation assessment. Psoas muscle mass was calculated by using abdominal computed tomography images of the patients. Results: the mean age of patients (80 female and 139 male) was 66.6 ± 11.7 years. According to the PNI results, 155 patients had a normal nutritional status (70 %), whereas 64 patients were malnourished (30 %). The survival of the patients with normal nutritional status was significantly longer than that of those who were malnourished (p < 0.001). There was no significant relationship between psoas muscle area, leucocyte count, NLR, and survival time. Conclusion: the survival of pancreatic adenocarcinoma patients with malnutrition at the time of diagnosis was significantly shorter than for patients without malnutrition.

INTRODUCCIÓN: Introducción: se ha demostrado que algunos factores se asocian a la supervivencia en los pacientes con adenocarcinoma de páncreas. Recientemente, algunos estudios sugirieron que la desnutrición, la masa muscular y la inflamación podrían afectar a la supervivencia de los pacientes con neoplasias malignas pancreáticas. Objetivo: investigar la asociación entre masa muscular del psoas, inflamación, estado nutricional en el momento del diagnóstico y supervivencia en pacientes con adenocarcinoma de páncreas. Métodos: este estudio retrospectivo incluyó a 219 pacientes diagnosticados de carcinoma de páncreas. Se evaluaron el estado nutricional, la inflamación y la masa del músculo psoas de los pacientes en el momento del diagnóstico. El estado nutricional de los pacientes se evaluó con el Índice Nutricional Pronóstico (PNI). El recuento de leucocitos y el cociente de neutrófilos/linfocitos (NLR) se emplearon para la evaluación de la inflamación. La masa del músculo psoas se calculó utilizando las imágenes de tomografía computarizada abdominal de los pacientes. Resultados: la edad media de los pacientes (80 mujeres y 139 hombres) fue de 66,6 ± 11,7 años. Según los resultados del PNI, 155 pacientes tenían un estado nutricional normal (70 %) mientras que 64 pacientes estaban desnutridos (30 %). La supervivencia de los pacientes con estado nutricional normal fue significativamente mayor que la de los pacientes desnutridos (p < 0,001). No hubo ninguna relación significativa entre el área del músculo psoas, el recuento de leucocitos, el NLR y el tiempo de supervivencia. Conclusión: la supervivencia de los pacientes con adenocarcinoma de páncreas con desnutrición en el momento del diagnóstico fue significativamente menor que la de los pacientes sin desnutrición.

Resting heart rate is associated with colorectal advanced adenoma.

BACKGROUND AND AIMS: Resting heart rate is an independent predictor of colorectal cancer (CRC) development and CRC-related mortality. However, little is known about the relationship between resting heart rate and colorectal adenoma development. We aimed to investigate this association in a population who underwent screening colonoscopy. METHODS: Among 39,021 patients who underwent both electrocardiogram and screening colonoscopy during routine health examinations at the Seoul National University Bundang Hospital, Health Promotion Center, Korea from January 2014 to July 2019, 1,344 patients had advanced adenoma. We performed 1:1 propensity score (PS) matching to establish a control group that mitigated the confounding effects of age and sex. We performed multivariate logistic regression analyses to identify the independent risk factors of advanced adenoma development. RESULTS: Resting heart rate was significantly higher in the advanced adenoma group than in the control group. The prevalence of advanced polyp increased across the quartiles of resting heart rate. Patients with higher resting heart rates were more likely to be older, smokers, and have increased blood pressure and DM and less likely to engage in active exercises than those with lower resting heart rates. Patients with higher resting heart rates had higher serum glucose, triglyceride, hemoglobin A1C, and insulin levels and lower high-density lipoprotein cholesterol levels. Patients with resting heart rate in the highest quartile (≥71 bpm) still showed significantly increased odds ratio (OR) of advanced adenoma development (OR: 1.379, 95% confidence interval: 1.099-1.731, p = 0.006). CONCLUSIONS: High resting heart rate was a meaningful independent risk factor of advanced adenoma development.

ENDOCRINE TUMOURS: Thyrotropin-secreting pituitary adenoma: a structured review of 535 adult cases.

BACKGROUND AND AIMS: Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare entity, occurring in one per million people. We performed a systematic review of 535 adult cases summarizing the clinical, biochemical, hormonal and radiological characteristics of TSHoma. Furthermore, we discussed the current guidelines for diagnosis and treatment. METHODS: A structured research was conducted using Pubmed and Web of Science with the following MeSH terms: 'thyrotropin secreting pituitary adenoma' OR 'TSHoma' OR 'thyrotropinoma.' RESULTS: Our analysis included 535 cases originating from 18 case series, 5 cohort studies and 91 case reports. The mean age at diagnosis was 46 years. At presentation, 75% had symptoms of hyperthyroidism, 55.5% presented with a goitre and 24.9% had visual field defects. The median TSH at diagnosis was 5.16 (3.20-7.43) mU/L with a mean FT4 of 41.5 ± 15.3 pmol/L. The majority (76.9%) of the TSHomas were macroadenoma. Plurihormonality was seen in 37.4% of the adenoma with a higher incidence in macroadenoma. Surgical resection of the adenoma was performed in 87.7% of patients of which 33.5% had residual pituitary adenoma. Post-operative treatment with a somatostatin analogue (SSA) led to a stable disease in 81.3% of the cases with residual tumour. We noticed a significant correlation between the diameter of the adenoma and residual pituitary adenoma (r = 0.490, P < 0.001). However, in patients preoperatively treated with an SSA, this correlation was absent. CONCLUSION: TSHomas are a rare cause of hyperthyroidism and are frequently misdiagnosed. Based on our structured analysis of case series, cohort studies and case reports, we conclude that the majority of TSHomas are macroadenoma being diagnosed in the fifth to sixth decade of life and presenting with symptoms of hyperthyroidism. Plurihormonalitiy is observed in one-third of TSHomas. Treatment consists of neurosurgical resection and SSA in case of surgical failure.

Sporadic foveolar-type gastric adenoma with a raspberry-like appearance in Helicobacter pylori-naïve patients.

Sporadic foveolar-type gastric adenoma (FGA) has been described as an extremely rare polyp that is whitish and flatly elevated. However, we recently found that sporadic FGA with a raspberry-like appearance (FGA-RA) is not rare in Helicobacter pylori (H. pylori)-naïve gastric mucosa. We endoscopically or surgically treated 647 patients with gastric epithelial neoplasms in the last 5 years, with 7.7% (50/647) being H. pylori-naïve. Among these, 43 FGA-RAs were diagnosed based on histologic and endoscopic features in 34 patients, who were all enrolled in this retrospective study. All lesions were observed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). We subsequently analyzed their endoscopic and microscopic features and patient characteristics. The patients were 22 males and 12 females aged 57±23 years (mean±2SD). WLE showed raspberry-like small polyps mimicking gastric hyperplastic polyps in the oxyntic gastric compartment (body/fundus). Multiple growths were confirmed in 20.6% (7/34) of the patients. NBIME revealed irregularly shaped papillary/gyrus-like microstructures with abnormal capillaries. Histologically, all lesions were intraepithelial neoplasms, and most of lesions (62.8%, 27/43) exhibited low-grade dysplasia. Immunohistochemically, neoplastic cells featured strong and diffuse MUC5AC expression, negative or very low MUC6 expression, and negative MUC2/CD10 expression. They also showed Ki-67 hyperexpression with a mean labeling index of 59.4±48.7%. The coexistence of fundic gland polyps in the background mucosa was significantly higher in multiple FGA-RA cases than in solitary cases (100% vs. 55.5%, P< 0.05). FGA-RA is a newly suggested histologic variant of sporadic FGA whose occurrence is not rare in daily endoscopic practice.

The association between treatment and systemic inflammation in acromegaly.

OBJECTIVE: Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function. DESIGN: Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment. RESULTS: Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment. CONCLUSIONS: Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.

Anterior pituitary function in Rathke's cleft cysts versus nonfunctioning pituitary adenomas.

Although Rathke's cleft cysts (RCCs) are common sellar/parasellar lesions, studies examining pituitary function in patients with nonsurgical RCC are limited. This study aimed to clarify the importance of RCCs, including small nonsurgical ones, as a cause of hypopituitarism by determining the prevalence of pituitary hormone secretion impairment and its relationship to cyst/tumor size in patients with RCC and in those with nonfunctioning pituitary adenoma (NFA). We retrospectively investigated the basal levels of each anterior pituitary hormone, its responses in the stimulation test(s), and cyst/tumor size in patients with RCC (n = 67) and NFA (n = 111) who were consecutively admitted to our hospital for endocrinological evaluation. RCCs were much smaller than NFAs (median height, 12 vs. 26 mm). The prevalence of gonadotropin, PRL, and GH secretion impairment in RCC was lower in comparison to NFA (19% vs. 44%, 34% vs. 61%, and 24% vs. 46%, respectively), whereas the prevalence of TSH and ACTH secretion impairment was comparable (21-27% and 17-24%, respectively). A significant positive relationship between cyst/tumor size and number of impaired hormones was observed in both groups, but smaller cysts could cause hormone secretion impairment in RCC. Stimulation tests suggested that most hormone secretion impairment was attributable to the interrupted hypothalamic-pituitary axis in both groups. Therefore, RCC, even small ones, can cause pituitary dysfunction. Different mechanisms may underlie hypothalamic-pituitary interruption in RCC and NFA.

An overview of thyroid function tests in subjects with resistance to thyroid hormone and related disorders.

Confirmation of sustained syndrome of inappropriate secretion of thyrotropin (SITSH) is a milestone in diagnosis of ß type of resistance to thyroid hormone (RTHß). The differential diagnoses of RTHß include TSH-producing pituitary adenoma (TSHoma) and familial dysalbuminemic hyperthyroxinemia (FDH), which also present SITSH. Recently, patients with RTHα caused by a mutation in thyroid hormone receptor α were reported and they did not present SITSH but a decline in the serum T4/T3 ratio. This review was aimed to overview thyroid function tests in RTH and related disorders. First, the characteristics of the thyroid function in RTHß, TSHoma, and FDH obtained from a Japanese database are summarized. Second, the degrees of SITSH in patients with truncations and frameshifts were compared with those in patients with single amino acid deletions and single amino acid substitutions obtained from the literature. Third, the degrees of SITSH in homozygous patients were compared with those in heterozygous patients with cognate mutations. Finally, the FT3/FT4 ratios in RTHα are summarized. In principle, the TSH values in FDH were within the normal range and apparent FT4 values in FDH were much higher than in RTHß and TSHoma. The FT3/FT4 values in RTHß were significantly lower than in TSHoma. The degrees of SITSH in patients with truncations and frameshifts were more severe than those in patients with single amino acid deletions and single amino acid substitutions, and those in homozygous patients were more severe than those in heterozygous patients with cognate mutations. The FT3/FT4 ratios in RTHα were higher than 1.0.

The "Double-Peak" Pattern of Pituitary Adenoma Intrasellar Pressure and Its Effects on the Microvascular Structure.

OBJECTIVE: The purpose of the present study was to investigate the relationship between the intrasellar pressure (ISP) and the microvascular structure of pituitary adenomas. METHODS: We retrospectively analyzed the ISP in 66 patients with pituitary adenomas. The corresponding microvascular structure was obtained using immunohistochemistry and analyzed for its correlation with the ISP. RESULTS: The average ISP was 25.89 ± 8.27 mm Hg, and the ISP was not related to the size of the adenoma (Pearson correlation coefficient, 0.103; P = 0.415). The ISPs of adenomas with different Knosp grades were significantly different (P < 0.05). From grade 0 to grade 4, at first, the ISP increased with the Knosp grade and reached the first peak at grade 2. It then decreased at grade 3 and increased again at grade 4, showing a "double-peak" pattern. The minimal diameter and perimeter of the microvessels and the vessel-covered area percentage were positively related to the ISP. When these parameters were compared among the adenomas of different Knosp grades, they also exhibited a "double-peak" pattern. CONCLUSIONS: In the present study, we found that with the increase in pituitary adenoma size and invasion of the surrounding tissues, the ISP of pituitary adenomas showed a "double-peak" pattern. The ISP and certain parameters of the microvascular structure are related, because the microvasculature adaptively changes its structure in response to the changing ISP to ensure a sufficient blood supply to the adenoma. The specific mechanism of this phenomenon requires further study.

Lactate-induced M2 polarization of tumor-associated macrophages promotes the invasion of pituitary adenoma by secreting CCL17.

Background: Lactate greatly contributes to the regulation of intracellular communication within the tumor microenvironment (TME). However, the role of lactate in pituitary adenoma (PA) invasion is unclear. In this study, we aimed to clarify the effects of lactate on the TME and the effects of TME on PA invasion. Methods: To explore the correlation between TME acidosis and tumor invasion, LDHA and LAMP2 expression levels were quantified in invasive (n = 32) and noninvasive (n = 32) PA samples. The correlation between immune cell infiltration and tumor invasion was evaluated in 64 PAs. Critical chemokine and key signaling pathway components were detected by qPCR, Western blotting, siRNA knockdown, and specific inhibitors. The functional consequences of CCR4 signaling inhibition were evaluated in vitro and in vivo. Results: Lactate was positively associated with PA invasion. Of the 64 PA tissues, invasive PAs were related to high infiltration of M2-like tumor-associated macrophages (TAMs) (P < 0.05). Moreover, lactate secreted from PA cells facilitated M2 polarization via the mTORC2 and ERK signaling pathways, while activated TAMs secreted CCL17 to promote PA invasion via the CCL17/CCR4/mTORC1 axis. According to univariate analysis of clinical data, high CCL17 expression was associated with larger tumor size (P = 0.0438), greater invasion (P = 0.0334), and higher susceptibility to postoperative recurrence (P = 0.0195) in human PAs. Conclusion: This study illustrates the dynamics between PA cells and immune TME in promoting PA invasion via M2 polarization. CCL17 levels in the TME are related to the PA invasiveness and clinical prognosis, and the CCL17/CCR4/mTOCR1 axis may serve as potential therapeutic targets for Pas.

Gonadotroph Pituitary Adenoma Causing Treatable Infertility and Ovarian Hyperstimulation Syndrome in Female Patients: Neurosurgical, Endocrinologic, Gynecologic, and Reproductive Outcomes.

BACKGROUND: Gonadotroph pituitary adenoma (Gn-PA) may rarely cause ovarian hyperstimulation syndrome, leading to infertility in women, although this remains poorly described. METHODS: We present a quantitative systematic review including 2 patients from our institutional and 48 from the literature with Gn-PA causing ovarian hyperstimulation syndrome to thoroughly describe the clinical features and therapeutic outcomes from multidisciplinary aspects. RESULTS: The patients had a mean age of 31.5 years and a mean follicle-stimulating hormone level of 14.4 IU/L. Estradiol level was high in 82% of patients, at >350 pg/mL. The mean maximal adenoma diameter was 22 mm, with a Knosp grade ≥3 in 10 patients. Abdominal surgery preceded adenoma resection in 24 patients (48%). Among 25 patients for whom extent of resection was recorded, total adenoma resection was achieved in 12. Through a mean follow-up of 25 months, adenoma recurrence was observed in 5 patients, who were treated with re-resection (n = 2), radiation (n = 2), and medical therapy followed by bilateral oophorectomy (n = 1). Medical therapies were partially effective or ineffective, and adenoma shrinkage did not follow; gonadotropin-releasing hormone agonists/antagonists were partially effective in 20% of patients (2/10), dopamine agonists in 44% (8/18), and somatostatin analogues in 50% (1/2). Four experienced swelling of tumor/ovaries after gonadotropin-releasing hormone agonists/antagonists administration. Overall, chemical remission was obtained in 26 of 28 patients, normalization of ovaries in 25 of 27, and successful pregnancy in 12 of 14. CONCLUSIONS: Adenoma resection is the main treatment, leading to reduction in ovarian size and biochemical remission, with a high likelihood of subsequent spontaneous pregnancy. Increased awareness of this rare condition may help avoid unnecessary abdominal procedures.

Early Experience of Endoscopic Endonasal Transphenoidal Surgery for Pituitary Adenoma: Preliminary Report of 56 Cases Operated in a West African Institution.

BACKGROUND: Although endoscopic endonasal approach (EEA) has been popularized worldwide for pituitary adenoma surgery, in sub-Saharan Africa, neurosurgeons are still only starting their experience with it. This study was designed to assess the early results of EEA for pituitary adenoma from an under-equipped environment, namely, the Department of Neurosurgery of the Teaching Hospital of Yopougon Abidjan and Bouaké in Ivory Coast. METHODS: The data of 56 cases of EEA for pituitary adenoma surgery performed between 2016 and March 2019 at the Teaching Hospital of Yopougon-Abidjan and Bouaké were retrospectively assessed. Pre- and postoperative neuro-ophthalmologic and hormonal status were analyzed. Moreover, the quality of tumor removal, and pre- and postoperative complications were also evaluated. RESULTS: In this study, there were nonfunctional adenomas (20), prolactinoma (18), Cushing disease (9), and acromegaly (3). A reduced visual acuity and/or visual field defect was observed in 49 cases. The mean operation time was 225 ± 94.7 minutes. The tumor removals were complete in 57.14%, subtotal in 35.71%, and partial in 7.14%. These led to a visual improvement in 69.64%. Postoperative complications were cerebrospinal fluid leaks (19.64%), diabetes insipidus (12.50%), visual worsening (7.14%), meningitis (3.57%), and carotid injury (3.57%) that led to death. CONCLUSIONS: This study represents the early surgical experience using EEA for treating pituitary adenoma in an under-equipped environment. Although the postoperative complication rate was relatively high, refinements of local surgeons' technique would lead to a better patient outcome.

Endoscopic Endonasal Approach to Giant Pituitary Adenomas: Surgical Outcomes and Review of the Literature.

OBJECTIVE: To present the outcomes of endoscopic endonasal surgery for giant pituitary adenomas and discuss the extent of resection to minimize morbidity and mortality. METHODS: We retrospectively reviewed medical records of 44 patients with giant pituitary adenomas who underwent endoscopic endonasal surgery. Clinical presentation, laboratory results, imaging studies, clinical outcomes, extent of resection, and complications were collected and analyzed. Factors affecting long-term outcome according to surgical technique were identified and analyzed. RESULTS: Radical resection (RR) was defined as either gross total resection or near-total resection (90%-100% of the tumor). There were 28 patients (63.6%) who underwent RR, 10 patients (22.7%) who underwent subtotal resection, and 6 patients (13.6%) who underwent partial resection. Visual improvement was achieved in 27 patients (81.8%). Thirteen patients (72.2%) with pituitary dysfunction had improvement in at least 1 preoperative endocrinological dysfunction. RR rates for dumbbell and multilobular tumors were 44.4% and 28.6%, respectively. Surgical complications were observed in 14 (31.8%) patients. Major vascular injury occurred in 3 patients (6.8%). Mean follow-up period was 38.5 months (range, 1-70 months). No patients with RR had recurrence or residual tumor progression. Ten patients (22.7%) received adjuvant radiation therapy after resection. Two patients were reoperated on for tumor regrowth, and 3 patients (including the 2 patients with tumor regrowth) were lost to follow-up. CONCLUSIONS: Long-term follow-up results and low recurrence rate of tumors indicate that RR is effective to decrease morbidity and mortality.

Body Habitus Across the Lifespan and Risk of Pituitary Adenoma.

CONTEXT: No studies have examined the association between body habitus and incidence of pituitary adenoma. OBJECTIVE: To determine if body mass index (BMI), waist circumference, body somatotype, or height are associated with risk of pituitary adenoma. DESIGN: Pooled analysis of 3 prospective cohort studies. SETTING: Population-based study. PARTICIPANTS: Participants of the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), and the Health Professionals Follow-Up Study (HPFS), totaling 284 946 American health professionals. EXPOSURES: BMI, waist circumference, body somatotype, and height. OUTCOME MEASURES: Self-reported incident pituitary adenoma. Multivariable (MV)-adjusted hazard ratios (HRs) of pituitary adenoma were estimated using Cox proportional hazards models. RESULTS: During 7 350 156 person-years of follow-up, 387 incident pituitary adenomas were reported. Comparing BMI of ≥30 to <25 kg/m2, higher adult BMI was associated with higher risk of pituitary adenoma (MV HR = 1.74; 95% CI, 1.33-2.28), as was higher maximum adult BMI (MV HR = 1.76; 95% CI, 1.34-2.30), higher waist circumference (MV HR = 1.06; 95% CI, 1.04-1.09 per inch), and higher BMI during early adulthood (at age 18 to 21, MV HR = 2.65; 95% CI, 1.56-4.49). Taller adult height was associated with pituitary adenoma (MV HR = 1.05; 95% CI, 1.01-1.09 per inch). Overall findings were similar in women and men, although power was limited in men (n = 62 cases). Sensitivity analyses demonstrated that the association between adult BMI and pituitary adenoma extended to at least 14 years prior to diagnosis and that the results were not affected when analyses were restricted to participants with similar healthcare utilization. CONCLUSION: Higher BMI and waist circumference, from early adulthood to the time of diagnosis, were associated with higher risk of pituitary adenoma.

Is there any gender difference in epidemiology, clinical presentation and co-morbidities of non-functioning pituitary adenomas? A prospective survey of a National Referral Center and review of the literature.

PURPOSE: Gender differences in patients diagnosed with non-functioning Pituitary Adenomas (NFPA) in a National Referral Center for Pituitary Tumors at the Federico II University of Naples, Italy. METHODS: Patients newly diagnosed with non-functioning sellar masses found on pituitary Magnetic Resonance Imaging from January 1st 2016 to December 31th 2018 underwent anthropometric measurements, basal evaluation of pituitary function, and metabolic assessment. Fatty live index (FLI) and visceral adiposity index (VAI) were calculated. RESULTS: Seventy-three patients (35 males, 51.1 ± 17.0 years; 38 females, 41.8 ± 18.1 years) presented with NFPA. Lesions > 1 cm (85.7% vs. 47.3%; χ2 = 10.26, p = 0.001) and hypopituitarism (77.1% vs. 7.9%; χ2 = 33.29, p = 0.001) were more frequent in males than females. The highest sizes of pituitary adenomas were significantly associated with male gender (OR = 1.05, p = 0.049; R2 = 0.060; IC 1.00-1.10). Headache (62.8% vs. 31.6%; χ2 = 5.96, p = 0.015) and visual field deficits (57.1% vs. 26.3%; χ2 = 5.93, p = 0.015) were significantly more frequent in males than in females. There was no sex difference in obesity prevalence, but the metabolic syndrome was more common among males than females (60.6% vs. 26.3%; χ2 = 7.14, p = 0.001). FLI was also higher in males (69.6 ± 27.3 vs. 49.2 ± 31.3; p < 0.001), while there were no differences in VAI. CONCLUSIONS: Apart from the possible delay in the diagnosis induced by the gender differences in symptom presentation, the higher prevalence of macroadenomas amongst NFPA in males compared with females let to hypothesize a key role of the sex hormone profile as predictive factors of their biological behavior and metabolic profile. Further studies are, however, mandatory to better support the influence of gender differences on onset, progression, and metabolic consequences of NFPA.

Pituitary adenomas in older adults (≥ 65 years): 90-day outcomes and readmissions: a 10-year endoscopic endonasal surgical experience.

INTRODUCTION: Longer lifespan and newer imaging protocols have led to more older adults being diagnosed with pituitary adenomas. Herein, we describe outcomes of patients ≥ 65 years undergoing endoscopic adenoma removal. To address selection criteria, we also assess a conservatively managed cohort. METHODS: A retrospective analysis of 90-day outcomes of patients undergoing endoscopic pituitary adenomectomy from 2010 to 2019 by a neurosurgical/ENT team was performed. Tumor subtype, cavernous sinus invasion, extent of resection/early remission, endocrinology outcomes, complications, re-operations and readmissions were analyzed. A comparator cohort ≥ 65 years undergoing clinical surveillance without surgery was also analyzed. RESULTS: Of 468 patients operated on for pituitary adenoma, 123 (26%) were ≥ 65 years (range 65-93 years); 106 (86.2%) had endocrine-inactive adenomas; 18 (14.6%) had prior surgery. Of 106 patients with endocrine-inactive adenomas, GTR was achieved in 70/106 (66%). Of 17 patients with endocrine-active adenomas, early biochemical remission was: Cushing's 6/8; acromegaly 1/4; prolactinomas 1/5. Gland function recovery occurred in 28/58 (48.3%) patients with various degrees of preoperative hypopituitarism. New anterior hypopituitarism occurred in 3/110 (2.4%) patients; permanent DI in none. Major complications in 123 patients were: CSF leak 2 (1.6%), meningitis 1 (0.8%), vision decline 1 (0.8%). There were no vascular injuries, operative hematomas, anosmia, deaths, MIs, or thromboembolic events. Median length of stay was 2 days. Readmissions occurred in 14/123 (11.3%) patients, 57% for delayed hyponatremia. Intra-cohort analysis by age (65-69, 70-74, 75-79, ≥ 80 years) revealed no outcome differences. Cavernous sinus invasion (OR 7.7, CI 1.37-44.8; p = 0.02) and redo-surgery (OR 8.5, CI 1.7-42.8; p = 0.009) were negative predictors for GTR/NTR. Of 105 patients evaluated for presumed pituitary adenoma beginning in 2015, 72 (69%) underwent surgery, 8 (7%) had prolactinomas treated with cabergoline and 25 (24%) continue clinical surveillance without surgery, including two on new hormone replacement. CONCLUSION: This study suggests that elderly patients carefully selected for endoscopic adenoma removal can have excellent short-term outcomes including high resection rates, low complication rates and short length of stay. Our experience supports a multidisciplinary approach and the concept of pituitary centers of excellence. Based on our observations, approximately 25% of elderly patients with pituitary adenomas referred for possible surgery can be monitored closely without surgery.

Vessel morphology depicted by three-dimensional power Doppler ultrasound as second-stage test in adnexal tumors that are difficult to classify: prospective diagnostic accuracy study.

OBJECTIVES: To assess whether vessel morphology depicted by three-dimensional (3D) power Doppler ultrasound improves discrimination between benignity and malignancy if used as a second-stage test in adnexal masses that are difficult to classify. METHODS: This was a prospective observational international multicenter diagnostic accuracy study. Consecutive patients with an adnexal mass underwent standardized transvaginal two-dimensional (2D) grayscale and color or power Doppler and 3D power Doppler ultrasound examination by an experienced examiner, and those with a 'difficult' tumor were included in the current analysis. A difficult tumor was defined as one in which the International Ovarian Tumor Analysis (IOTA) logistic regression model-1 (LR-1) yielded an ambiguous result (risk of malignancy, 8.3% to 25.5%), or as one in which the ultrasound examiner was uncertain regarding classification as benign or malignant when using subjective assessment. Even when the ultrasound examiner was uncertain, he/she was obliged to classify the tumor as most probably benign or most probably malignant. For each difficult tumor, one researcher created a 360° rotating 3D power Doppler image of the vessel tree in the whole tumor and another of the vessel tree in a 5-cm3 spherical volume selected from the most vascularized part of the tumor. Two other researchers, blinded to the patient's history, 2D ultrasound findings and histological diagnosis, independently described the vessel tree using predetermined vessel features. Their agreed classification was used. The reference standard was the histological diagnosis of the mass. The sensitivity of each test for discriminating between benign and malignant difficult tumors was plotted against 1 - specificity on a receiver-operating-characteristics diagram, and the test with the point furthest from the reference line was considered to have the best diagnostic ability. RESULTS: Of 2403 women with an adnexal mass, 376 (16%) had a difficult mass. Ultrasound volumes were available for 138 of these cases. In 79/138 masses, the ultrasound examiner was uncertain about the diagnosis based on subjective assessment, in 87/138, IOTA LR-1 yielded an ambiguous result and, in 28/138, both methods gave an uncertain result. Of the masses, 38/138 (28%) were malignant. Among tumors that were difficult to classify as benign or malignant by subjective assessment, the vessel feature 'densely packed vessels' had the best discriminative ability (sensitivity 67% (18/27), specificity 83% (43/52)) and was slightly superior to subjective assessment (sensitivity 74% (20/27), specificity 60% (31/52)). In tumors in which IOTA LR-1 yielded an ambiguous result, subjective assessment (sensitivity 82% (14/17), specificity 79% (55/70)) was superior to the best vascular feature, i.e. changes in the diameter of vessels in the whole tumor volume (sensitivity 71% (12/17), specificity 69% (48/70)). CONCLUSION: Vessel morphology depicted by 3D power Doppler ultrasound may slightly improve discrimination between benign and malignant adnexal tumors that are difficult to classify by subjective ultrasound assessment. For tumors in which the IOTA LR-1 model yields an ambiguous result, subjective assessment is superior to vessel morphology as a second-stage test. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Rapid progression of scoliosis curve in a mature patient with undiagnosed pituitary macroadenoma: A rare case report.

Growth hormone secreting pituitary tumor or gigantism has not been previously reported to be associated with rapid progression of scoliosis in the literature. However, there are some reports indicating scoliosis can be worsened by growth hormone therapy in children and adolescents. A 19-year-old boy was referred to our institution for the treatment of a right thoracolumbar scoliosis. The Cobb angle had worsened from 29° to 83° over two years' duration. He attained puberty at the age of 13. He had a previous history of slipped upper femoral epiphysis (SUFE), which was operated in 2015, with no clinical features of gigantism. Preoperative assessment was performed. He was diagnosed with growth hormone secreting pituitary macroadenoma by magnetic resonance imaging with a high serum level of insulin-like growth factor-I (IGF-I). Computed tomography (CT) of the pancreas showed a pancreatic endocrine tumor. The patient was later diagnosed with multiple endocrine neoplasia type 1 (MEN 1). He underwent endoscopic endonasal excision of the pituitary mass and distal pancreatectomy. This case indicates that growth hormone secreting pituitary macroadenoma could result in rapid progression of scoliosis.

A single-center observational study assessing the predictive factors associated with the prognosis of acromegaly.

AIM: The aim of this study was to clarify the prognostic values of various preoperative factors, including the surgeon's ability as well as the patient's age, gender, tumor size, cavernous sinus invasion, compression of the optic chiasm, hypopituitarism, immunohistochemical (IHC) staining pattern of the adenoma, and insulin-like growth factor-1 (IGF-1) level, in acromegalic patients who had undergone pituitary surgery. STUDY DESIGN: This single-center, retrospective study assessed the medical records of 108 patients who had undergone pituitary surgery with the same neurosurgical team. RESULTS: The mean total follow-up period after surgery was 44.8 (min: 24, max: 59) months. Remission was reported in 67 (62.0%) patients, and 57 (52.8%) patients did not experience recurrence. Initial tumor volume, IGF-1 level, and optic chiasm compression, but not patients' age, gender, cavernous sinus invasion, and IHC staining patterns of the adenoma, were prognostic of either remission or recurrence. An IGF-1 level of 860 ng/mLwas found to be a convenient cut-off point for determining remission. CONCLUSIONS: The experience of the surgical team suggests that the initial tumor volume, IGF-1 level, and optic chiasm compression have high prognostic values in relation to pituitary surgery for patients with acromegaly.