Racial and socioeconomic disparities in lung cancer screening in the United States: A systematic review.

Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer deaths. Lung cancer screening (LCS) reduces NSCLC mortality; however, a lack of diversity in LCS studies may limit the generalizability of the results to marginalized groups who face higher risk for and worse outcomes from NSCLC. Identifying sources of inequity in the LCS pipeline is essential to reduce disparities in NSCLC outcomes. The authors searched 3 major databases for studies published from January 1, 2010 to February 27, 2020 that met the following criteria: 1) included screenees between ages 45 and 80 years who were current or former smokers, 2) written in English, 3) conducted in the United States, and 4) discussed socioeconomic and race-based LCS outcomes. Eligible studies were assessed for risk of bias. Of 3721 studies screened, 21 were eligible. Eligible studies were evaluated, and their findings were categorized into 3 themes related to LCS disparities faced by Black and socioeconomically disadvantaged individuals: 1) eligibility; 2) utilization, perception, and utility; and 3) postscreening behavior and care. Disparities in LCS exist along racial and socioeconomic lines. There are several steps along the LCS pipeline in which Black and socioeconomically disadvantaged individuals miss the potential benefits of LCS, resulting in increased mortality. This study identified potential sources of inequity that require further investigation. The authors recommend the implementation of prospective trials that evaluate eligibility criteria for underserved groups and the creation of interventions focused on improving utilization and follow-up care to decrease LCS disparities.

Preparing for the unexpected: Recommendations for returning secondary findings in late-stage cancer care.

PURPOSE: We conducted qualitative interviews with patients with cancer and providers to identify gaps in clinical care and highlight care delivery solutions for the return of secondary germline findings. METHODS: Twelve patients and 19 cancer providers from the United States were interviewed between January 2019 and May 2021. Interviews elicited feedback about patient information needs, emotional responses to secondary findings, and recommendations for improving pre-test education. RESULTS: Patients' responses ranged from gratitude to regret, depending on how much pre-test counseling they received before tumor testing. Providers cited insufficient clinic time as a major barrier to pretest education, favoring online support tools and standardized pre-test education models. Providers had differing perspectives on how pre-test education should be integrated into clinical workflows but agreed that it should include the differences between somatic and germline testing, the likelihood of medically actionable findings, and the possibility of being referred to a genetics provider. CONCLUSION: The spectrum of participants' responses to their secondary findings underscores the importance of adequate pre-test discussions before somatic sequencing. Although educational interventions could address patients' information needs and augment traditional pre-test counseling, health care systems, labs, and genetic providers may be called on to play greater roles in pre-test education.

Giant prolactinomas larger than 60 mm in size: a cohort of massive and aggressive prolactin-secreting pituitary adenomas.

OBJECTIVES: Prolactin (PRL)-secreting macroadenomas usually measure between 10 and 40 mm. Giant (adenoma size ≥40 mm) PRL-tumors are not common, and larger prolactinomas (maximal diameter ≥60 mm) are rare, and their management outcomes have not been well characterized. METHODS: We have identified 18 subjects (16 men, 2 females) with giant PRL-adenomas (size ≥60 mm; PRL > 1000 ng/ml) and summarized their characteristics and response to treatment. RESULTS: Mean age was 36.3 ± 13.5 years (range 12-59 years). Mean adenoma size was 71.8 ± 10.2 mm (60-92 mm). Complaints at presentation included headaches in 11 patients, visual deterioration in 9, sexual dysfunction in 9 males, and behavioral changes in two. Fourteen (78 %) had visual field defects. Mean PRL at presentation was 28,465 ng/ml (range 1300-270,000). All patients were treated with cabergoline (3.9 ± 2.0 mg/week), except for one who received bromocriptine. Treatment achieved PRL normalization in 11/18 patients within a median interval of 20 months. Visual improvement occurred in 12/14 patients with pre-treatment visual abnormalities. Nine patients underwent surgery (transsphenoidal, 7; transcranial, 2). None of the seven patients with elevated PRL before surgery achieved remission post-operatively. After a follow-up of 7.8 ± 5.1 years, 15/18 patients had significant adenoma shrinkage. Eleven patients are normoprolactinemic, 3 are partially controlled (PRL < 3 × ULN), and 4 remain with significantly elevated PRL. Most patients reported disappearance or improvement of their complaints. CONCLUSIONS: These enormous PRL-adenomas are invasive but respond fairly well to medical treatment. Long-term therapy with high dose cabergoline together with a pituitary surgery in some patients was the key for their successful management, achieving biochemical and clinical remission in most patients.

Octreotide LAR treatment of acromegaly in "real life": long-term outcome at a tertiary care center.

OBJECTIVE: To report our day-to day experience with the long-term use of octreotide LAR in the treatment of acromegaly. PATIENTS AND METHODS: Patients with acromegaly managed between 2003 and 2012 with octreotide LAR for a median of 27 months (interquartile ranges 12-60) and who had not received radiation therapy or concomitant treatment with cabergoline were retrospectively evaluated. Both primarily treated patients (n = 33) and patients who received octreotide after failed pituitary surgery (adjunctive treatment, n = 124) were included. Full biochemical response was defined as the achievement of a GH <2.5 ng/mL and an IGF-1 <1.2 times the upper limit of normal (× ULN); we also evaluated efficacy using a GH cut off of <1 ng/mL. RESULTS: Over 60% of the patients achieved a GH of <2.5 ng/mL. The combined GH (<2.5 ng/mL) and IGF-1 (<1.2 × ULN) target was achieved by 35.5 and 33.6% of the patients treated primarily and adjunctively, respectively; these figures dropped to 22.6 and 23% when using a GH target of <1 ng/mL. All patients reported a significant improvement in acromegalic symptoms. Lower pretreatment GH and IGF-1 levels were both associated with a higher probability of achieving the composite biochemical target. CONCLUSION: Currently recommended GH and IGF-1 targets are reached by <36% of patients treated with octreotide LAR in a day-to day practice context. Nevertheless, in most instances a clinical benefit and an improvement in biochemical markers can be clearly documented.

Neighborhood disadvantage is associated with KRAS-mutated non-small cell lung cancer risk.

PURPOSE: It remains unclear why individuals living in disadvantaged neighborhoods have shorter non-small cell lung cancer (NSCLC) survival. It is possible that living in these deprived areas is linked with increased risk of developing aggressive NSCLC biology. Here, we explored the association of somatic KRAS mutations, which are associated with shorter survival in NSCLC patients, and 11 definitions of neighborhood disadvantage spanning socioeconomic and structural environmental elements. METHODS: We analyzed data from 429 NSCLC patients treated at a Comprehensive Cancer Center from 2015 to 2018. Data were abstracted from medical records and each patient's home address was used to assign publicly available indices of neighborhood disadvantage. Prevalence Ratios (PRs) for the presence of somatic KRAS mutations were estimated using modified Poisson regression models adjusted for age, sex, smoking status, race/ethnicity, educational attainment, cancer stage, and histology. RESULTS: In the NSCLC cohort, 29% had KRAS mutation-positive tumors. We found that five deprivation indices of socioeconomic disadvantage were associated with KRAS mutation. A one decile increase in several of these socioeconomic disadvantage indices was associated with a 1.06 to 1.14 increased risk of KRAS mutation. Measures of built structural environment were not associated with KRAS mutation status. CONCLUSION: Socioeconomic disadvantage at the neighborhood level is associated with higher risk of KRAS mutation while disadvantage related to built environmental structural measures was inversely associated. Our results indicate not only that neighborhood disadvantage may contribute to aggressive NSCLC biology, but the pathways linking biology to disadvantage are likely operating through socioeconomic-related stress.

Health Disparities in Recruitment and Enrollment in Research.

Despite advances in thoracic oncology research, the benefits of new discoveries are not universally experienced. A lack of representation of racial/ethnic minorities and individuals of low socioeconomic status in clinical trials and thoracic research contributes to persistent health care disparities. It is critical that improved racial, ethnic, and socioeconomic diversity is achieved in our trials and research, if we are to attain generalizability of findings and reduction of health care disparities. Culturally tailored and community-based approaches can help improve recruitment and enrollment of marginalized groups in thoracic research, which is an essential step toward achieving health equity and advancing medical science.

A Lung Cancer Screening Education Program Impacts both Referral Rates and Provider and Medical Assistant Knowledge at Two Federally Qualified Health Centers.

BACKGROUND: Federally Qualified Health Centers (FQHCs) serve minority and low-socioeconomic populations and provide care to high-risk smokers. These centers frequently experience barriers, including low provider and medical assistant (MA) knowledge around lung cancer screening (LCS). Subsequent low LCS referral rates by providers at FQHCs limit utilization of LCS in eligible, high-risk, underserved patients. METHODS: Providers and MAs from two FQHCs participated in a LCS educational session. A pre-educational survey was administered at the start of the session and a post-educational survey at the end. The intervention included a presentation with education around non-small cell lung cancer, LCS, tobacco cessation, and shared-decision making. Both surveys were used to evaluate changes in provider and MA ability to determine eligible patients for LCS. The Pearson's Chi-squared test with Yates' continuity correction was used to measure the impact. RESULTS: A total of 29 providers and 28 MAs enrolled in the study from two FQHCs. There was an improvement, P < .009 and P < .015 respectively, in provider and MA confidence in identifying patients for LCS. Additionally, one year prior to the program, 9 low-dose computed tomography (LDCTs) were ordered at one of the FQHCs and 0 at the other. After the program, over 100 LDCTs were ordered at each FQHC. CONCLUSIONS: A targeted LCS educational program improves provider and MAs' ability to identify eligible LCS patients and is associated with an increase in the number of patients referred to LDCT at FQHCs.

Leveraging an Informatics Approach to Identify an Unmet Clinical Need for BRCA1/2 Testing Among Patients With Ovarian Cancer.

PURPOSE: Although BRCA1/2 testing in ovarian cancer improves outcomes, it is vastly underutilized. Scalable approaches are urgently needed to improve genomically guided care. METHODS: We developed a Natural Language Processing (NLP) pipeline to extract electronic medical record information to identify recipients of BRCA testing. We applied the NLP pipeline to assess testing status in 308 patients with ovarian cancer receiving care at a National Cancer Institute Comprehensive Cancer Center (main campus [MC] and five affiliated clinical network sites [CNS]) from 2017 to 2019. We compared characteristics between (1) patients who had/had not received testing and (2) testing utilization by site. RESULTS: We found high uptake of BRCA testing (approximately 78%) from 2017 to 2019 with no significant differences between the MC and CNS. We observed an increase in testing over time (67%-85%), higher uptake of testing among younger patients (mean age tested = 61 years v untested = 65 years, P = .01), and higher testing among Hispanic (84%) compared with White, Non-Hispanic (78%), and Asian (75%) patients (P = .006). Documentation of referral for an internal genetics consultation for BRCA pathogenic variant carriers was higher at the MC compared with the CNS (94% v 31%). CONCLUSION: We were able to successfully use a novel NLP pipeline to assess use of BRCA testing among patients with ovarian cancer. Despite relatively high levels of BRCA testing at our institution, 22% of patients had no documentation of genetic testing and documentation of referral to genetics among BRCA carriers in the CNS was low. Given success of the NLP pipeline, such an informatics-based approach holds promise as a scalable solution to identify gaps in genetic testing to ensure optimal treatment interventions in a timely manner.

The kinome, cyclins and cyclin-dependent kinases of pituitary adenomas, a look into the gene expression profile among tumors from different lineages.

BACKGROUND: Pituitary adenomas (PA) are the second most common intracranial tumors and are classified according to hormone they produce, and the transcription factors they express. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. METHODS: Here we performed transcriptome and proteome analysis of tumors derived from POU1F1 (GH-, TSH-, and PRL-tumors, N = 16), NR5A1 (gonadotropes and null cells adenomas, n = 17) and TBX19 (ACTH-tumors, n = 6) lineages as well as from silent ACTH-tumors (n = 3) to determine expression of kinases, cyclins, CDKs and CDK inhibitors. RESULTS: The expression profiles of genes encoding kinases were distinctive for each of the three PA lineage: NR5A1-derived tumors showed upregulation of ETNK2 and PIK3C2G and alterations in MAPK, ErbB and RAS signaling, POU1F1-derived adenomas showed upregulation of PIP5K1B and NEK10 and alterations in phosphatidylinositol, insulin and phospholipase D signaling pathways and TBX19-derived adenomas showed upregulation of MERTK and STK17B and alterations in VEGFA-VEGFR, EGF-EGFR and Insulin signaling pathways. In contrast, the expression of the different genes encoding cyclins, CDK and CDK inhibitors among NR5A1-, POU1F1- and TBX19-adenomas showed only subtle differences. CDK9 and CDK18 were upregulated in NR5A1-adenomas, whereas CDK4 and CDK7 were upregulated in POUF1-adenomas. CONCLUSIONS: The kinome of PA clusters these lesions into three distinct groups according to the transcription factor that drives their terminal differentiation. And these complexes could be harnessed as molecular therapy targets.

Clinical and biochemical characteristics of acromegalic patients with different abnormalities in glucose metabolism.

To determine the prevalence of diabetes, glucose intolerance and impaired fasting glucose in Mexican patients with acromegaly and establish associations with clinical, anthropometric and biochemical variables. 257 patients with acromegaly were evaluated by a 75 g-oral glucose tolerance test with measurements of both GH and glucose (0, 30, 60, 90 120 min) as well as baseline IGF-1. Normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes (DM) were defined based on the 2003 ADA criteria. NGT, IFG, IGT and DM were found in 27.6, 8.9, 31.6 and 31.9% of the subjects, respectively; 42 of the DM patients were unaware of the diagnosis. Patients with diabetes were older than subjects in the other 3 categories (P = 0.001), and the proportion of women was significantly higher in the DM (74%) and IGT (68%) groups than in the NGT group (52%) (P = 0.004). Odds ratio for the development of DM was 3.29 (95% CI 3.28-3.3). GH and IGF-1 levels were comparable among the different groups. In a multivariable analysis DM was significantly associated with age, presence of a macroadenoma, disease duration and a basal GH > 30 µg/dl. DM and probably IGT are more prevalent in acromegaly than in the general Mexican population. DM was more frequent in females of all ages, in subjects with severely elevated GH concentrations, in patients with macroadenomas, and long-standing disease duration. The odds ratio for DM in our subjects with acromegaly is more than 3 times higher than in the general population.

The impact of income and education on lung cancer screening utilization, eligibility, and outcomes: a narrative review of socioeconomic disparities in lung cancer screening.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths in the US and worldwide. In particular, vulnerable populations such as those of low socioeconomic status (SES) are at the highest risk for and suffer the highest mortality from NSCLC. Although lung cancer screening (LCS) has been demonstrated to be a powerful tool to lower NSCLC mortality, it is underutilized by eligible smokers, and disparities in screening are likely to contribute to inequities in NSCLC outcomes. It is imperative that we collect and analyze LCS data focused on individuals of low socioeconomic position to identify and address barriers to LCS utilization and help close the gaps in NSCLC mortality along socioeconomic lines. Toward this end, this review aims to examine published studies that have evaluated the impact of income and education on LCS utilization, eligibility, and outcomes. We searched the PubMed, Ovid MEDLINE, and CINAHL Plus databases for all studies published from January 1, 2010, to October 21, 2020, that discussed socioeconomic-based LCS outcomes. The review reveals that income and education have impact on LCS utilization, eligibility, false positive rates and smoking cessation attempts; however, there is a lack of studies evaluating the impact of SES on LCS follow-up, stage at diagnosis, and treatment. We recommend the intentional inclusion of lower SES participants in LCS studies in order to clarify appropriate eligibility criteria, risk-based metrics and outcomes in this high-risk group. We also anticipate that low SES smokers and their providers will require increased support and education regarding smoking cessation and shared decision-making efforts.

Personalized Cancer Medicine in the Media: Sensationalism or Realistic Reporting?

BACKGROUND: Given that media coverage can shape healthcare expectations, it is essential that we understand how the media frames "personalized medicine" (PM) in oncology, and whether information about unproven technologies is widely disseminated. METHODS: We conducted a content analysis of 396 news reports related to cancer and PM published between 1 January 1998 and 31 December 2011. Two coders independently coded all the reports using a pre-defined framework. Determination of coverage of "standard" and "non-standard" therapies and tests was made by comparing the media print/broadcast date to the date of Federal Drug Administration approval or incorporation into clinical guidelines. RESULTS: Although the term "personalized medicine" appeared in all reports, it was clearly defined only 27% of the time. Stories more frequently reported PM benefits than challenges (96% vs. 48%, p < 0.001). Commonly reported benefits included improved treatment (89%), prediction of side effects (30%), disease risk prediction (33%), and lower cost (19%). Commonly reported challenges included high cost (28%), potential for discrimination (29%), and concerns over privacy and regulation (21%). Coverage of inherited DNA testing was more common than coverage of tumor testing (79% vs. 25%, p < 0.001). Media reports of standard tests and treatments were common; however, 8% included information about non-standard technologies, such as experimental medications and gene therapy. CONCLUSION: Confusion about personalized cancer medicine may be exacerbated by media reports that fail to clearly define the term. While most media stories reported on standard tests and treatments, an emphasis on the benefits of PM may lead to unrealistic expectations for cancer genomic care.

The Association between Polluted Neighborhoods and TP53-Mutated Non-Small Cell Lung Cancer.

BACKGROUND: Poor patients often reside in neighborhoods of lower socioeconomic status (SES) with high levels of airborne pollutants. They also have higher mortality from non-small cell lung cancer (NSCLC) than those living in wealthier communities. We investigated whether living in polluted neighborhoods is associated with somatic mutations linked with lower survival rates, i.e., TP53 mutations. METHODS: In a retrospective cohort of 478 patients with NSCLC treated at a comprehensive cancer center between 2015 and 2018, we used logistic regression to assess associations between individual demographic and clinical characteristics, including somatic TP53 mutation status and environmental risk factors of annual average particulate matter (PM2.5) levels, and neighborhood SES. RESULTS: 277 patients (58%) had somatic TP53 mutations. Of those, 45% lived in neighborhoods with "moderate" Environmental Protection Agency-defined PM2.5 exposure, compared with 39% of patients without TP53 mutations. We found significant associations between living in neighborhoods with "moderate" versus "good" PM2.5 concentrations and minority population percentage [OR, 1.06; 95% confidence interval (CI), 1.04-1.08]. There was a significant association between presence of TP53 mutations and PM2.5 exposure (moderate versus good: OR, 1.66; 95% CI, 1.02-2.72) after adjusting for patient characteristics, other environmental factors, and neighborhood-level SES. CONCLUSIONS: When controlling for individual- and neighborhood-level confounders, we find that the odds of having a TP53-mutated NSCLC are increased in areas with higher PM2.5 exposure. IMPACT: The link between pollution and aggressive biology may contribute to the increased burden of adverse NSCLC outcomes in individuals living in lower SES neighborhoods.

Transcriptome and methylome analysis reveals three cellular origins of pituitary tumors.

Pituitary adenomas (PA) are the second most common intracranial tumors. These neoplasms are classified according to the hormone they produce. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. The present transcriptomic and methylomic analysis of PA revealed that they segregate into three molecular clusters according to the transcription factor driving their terminal differentiation. First cluster, driven by NR5A1, consists of clinically non-functioning PA (CNFPA), comprising gonadotrophinomas and null cell; the second cluster consists of clinically evident ACTH adenomas and silent corticotroph adenomas, driven by TBX19; and the third, POU1F1-driven TSH-, PRL- and GH-adenomas, segregated together. Genes such as CACNA2D4, EPHA4 and SLIT1, were upregulated in each of these three clusters, respectively. Pathway enrichment analysis revealed specific alterations of these clusters: calcium signaling pathway in CNFPA; renin-angiotensin system for ACTH-adenomas and fatty acid metabolism for the TSH-, PRL-, GH-cluster. Non-tumoral pituitary scRNAseq data confirmed that this clustering also occurs in normal cytodifferentiation. Deconvolution analysis identify potential mononuclear cell infiltrate in PA consists of dendritic, NK and mast cells. Our results are consistent with a divergent origin of PA, which segregate into three clusters that depend on the specific transcription factors driving late pituitary cytodifferentiation.

Molecular alterations in non-functioning pituitary adenomas.

BACKGROUND: Clinically non-functioning Pituitary Adenomas (NFPA) are among the most common neoplasms of the sellar region. They usually present with compressive symptoms such as headache and visual field defects and not infrequently, are found incidentally. NFPA are classified as gonadotropinomas, null cell adenomas, according to their immunohistochemical phenotype. The molecular alterations responsible for the development of these lesions are incompletely understood, and there is scarce information regarding the molecular alterations and markers. OBJECTIVE: We carried out an in-silico analysis aimed at identifying the molecular alterations in NFPA and to discover new molecular markers. METHODS: Twenty-three microarray libraries were analyzed. Fourteen correspond to NFPA and 9 to control tissue gland. They were analyzed using Partek Genomic Suite to identify differentially expressed genes and WebGestalt and Metascape to understand the meaning behind the gene lists. RESULTS: Pituitary adenomas showed a markedly different transcriptome compared to the non-tumoral gland, regardless of their putative immunophenotype. Genes related to calcium metabolism such as CACNA2D4, immune-related CXCR4, and stem cell-related KLF8 and PITX2 were altered. CONCLUSIONS: Differentially expressed calcium metabolism and immune-related genes in NFPA represent attractive molecular markers and potential therapeutic targets.

Proteomic and Transcriptomic Analysis Identify Spliceosome as a Significant Component of the Molecular Machinery in the Pituitary Tumors Derived from POU1F1- and NR5A1-Cell Lineages.

BACKGROUND: Pituitary adenomas (PA) are the second most common tumor in the central nervous system and have low counts of mutated genes. Splicing occurs in 95% of the coding RNA. There is scarce information about the spliceosome and mRNA-isoforms in PA, and therefore we carried out proteomic and transcriptomic analysis to identify spliceosome components and mRNA isoforms in PA. METHODS: Proteomic profile analysis was carried out by nano-HPLC and mass spectrometry with a quadrupole time-of-flight mass spectrometer. The mRNA isoforms and transcriptomic profiles were carried out by microarray technology. With proteins and mRNA information we carried out Gene Ontology and exon level analysis to identify splicing-related events. RESULTS: Approximately 2000 proteins were identified in pituitary tumors. Spliceosome proteins such as SRSF1, U2AF1 and RBM42 among others were found in PA. These results were validated at mRNA level, which showed up-regulation of spliceosome genes in PA. Spliceosome-related genes segregate and categorize PA tumor subtypes. The PA showed alterations in CDK18 and THY1 mRNA isoforms which could be tumor specific. CONCLUSIONS: Spliceosome components are significant constituents of the PA molecular machinery and could be used as molecular markers and therapeutic targets. Splicing-related genes and mRNA-isoforms profiles characterize tumor subtypes.

Clinical and biochemical impact of the d3 growth hormone receptor genotype in acromegaly.

CONTEXT: Lack of exon 3 of the GH receptor (d3-GHR) has been associated with increased responsiveness to GH therapy. By analogy, we hypothesized that patients with acromegaly bearing the d3-GHR genotype may have a more morbid clinical and biochemical picture. OBJECTIVE: Our objective was to determine whether the GHR genotype, by modifying tissue sensitivity to GH, influences the clinical/biochemical expression of acromegaly and its outcome after treatment. SETTING: The study was conducted at a specialized clinic at a tertiary care hospital. DESIGN, PATIENTS, AND METHODS: We conducted a prospective genotype investigation and retrospective analysis and correlation with clinical, biochemical, and outcome data from a group of 148 patients. Samples from 175 healthy blood donors were used as controls. GHR genotyping was performed by real-time PCR. MAIN OUTCOME MEASURES: We assessed prevalence of the three GHR genotypes (fl/fl, d3/d3, and d3/fl), associations between the genotypes, and baseline as well as post-therapeutic characteristics. RESULTS: Prevalence of the fl/fl, d3/d3, and d3/fl genotypes was 45, 22, and 32%, respectively, similar to what was found in the controls. Baseline characteristics were similar in carriers of the three genotypes. A positive correlation between IGF-I and log GH concentrations was significant only in homo- or heterozygous d3 carriers. Among d3-GHR carriers, diabetes, but no other comorbidities, was more prevalent (odds ratio = 2.02; 95% confidence interval = 0.96-4.2). d3-GHR carriers had significantly higher IGF-I concentrations after treatment. Multiple regression analysis revealed that the homo- or heterozygous lack of exon 3 was the strongest predictor of persistent biochemical activity (odds ratio = 1.29; 95% confidence interval = 0.65-2.58). CONCLUSIONS: The absence of exon 3 of the GHR may be associated with a more morbid acromegalic clinical and biochemical picture and a lower chance of achieving IGF-I normalization after therapy.

[Treatment of acromegaly with octreotide LAR]. / Tratamiento de la acromegalia con octreotida LAR.

BACKGROUND: Treatment of acromegaly with somastostatin analogues, albeit highly effective, is not curative and its elevated cost represents a major disadvantage. Hereby we describe our Center's experience using a fixed, 20 mg q.4 weeks- dose of octreotide LAR. METHODS: 97 patients, 69 females, 71 with macroadenomas, treated with 20-mg im injections of octreotide LAR every 4 weeks, in 23 as primary therapy. No dose escalation was allowed. Patients were evaluated with GH and IGF-1 levels at 4 weeks after the third injection; thereafter, assessments occurred at 3 to 6 months intervals. In 27 unselected patients, evaluations were also performed 6 weeks after the SA injection. RESULTS: A GH concentration < 2.5 ng/mL was reached by 71%, 75% and 83% of patients at the 3rd , 6th and 12th months of follow up respectively, whereas over 30% achieved an IGF-1 index < or = 1.0 at each of these time points, and both biochemical goals were achieved by 30%, 33% and 32% of patients at the same time points. Biochemical success was the same for those patients treated primarily and those treated secondarily and prior radiation made no difference. A baseline GH level > 10 ng/mL was associated with a poor response. CONCLUSIONS: A biochemical control rate comparable with other published series it is feasible to reach with the treatment with a fixed dose of 20 mg.

Ectopic ACTH-secreting syndrome: a single center experience report with a high prevalence of occult tumor.

BACKGROUND: Differentiation between the two forms of ACTH-dependent Cushing's syndrome is a challenging task. Although the majority of these cases will be diagnosed as Cushing's disease secondary to an ACTH-secreting pituitary adenoma, 10-15% result from the ectopic ACTH secretion syndrome (EAS), which is usually due to neuroendocrine tumors. In the present study we report our experience with EAS in eight patients evaluated and treated during the past 10 years. METHODS: Our experience in the evaluation and management of EAS was retrospectively reviewed. The latter included a standard biochemical assessment (urinary free cortisol, low- and high-dose dexamethasone suppression tests), petrosal sinus sampling when indicated and imaging techniques such as pituitary MRI, total body CT and somatostatin receptor scintigraphy. RESULTS: The ectopic nature of the ACTH hypersecretion was confirmed with inferior petrosal sinus samplings in all cases. CT scanning localized a putative tumor in 6/8 patients, whereas octreotide scintigraphy was positive in only five. In all cases, the source was traced to the lungs. However, upon performing thoracotomy, a documented ACTH-secreting bronchial carcinoid tumor was found in only four patients. Thus, 4/8 patients with EAS remained "occult." All of these patients underwent adrenalectomy for hypercortisolism control. CONCLUSIONS: EAS is a rare cause of ACTH-dependent Cushing's syndrome. Truly "occult" tumors were frequent and these patients need to be under close surveillance for the detection of neuroendocrine tumors.

Giant prolactinomas: are they really different from ordinary macroprolactinomas?

Giant prolactinomas (gPRLomas) are rare tumors of the lactotroph defined by an unusually large size (>4 cm) and serum PRL levels >1000 ng/mL. The purpose of this study is to characterize the clinical spectrum of gPRLomas comparing them with non-giant prolactinomas. This is a retrospective study at a large referral center. Data from patients harboring gPRLomas and macroprolactinomas were retrieved from medical records of the Prolactinoma Clinic. Analysis was focused on clinical, biochemical, and tumor volume characteristics, as well as on the response to treatment with dopamine agonists. Among 292 patients with prolactinomas followed between 2008 and 2015, 47 (16 %) met the diagnostic criteria for gPRLomas (42 males). The most common complaint was a visual field defect; headache was reported by 79 % and sexual dysfunction was present in over half of the patients. Median basal PRL level and tumor volume were 6667 ng/mL (3750-10,000) and 32 cm(3) (20-50), respectively; hypogonadotropic hypogonadism was documented in 87 %. Cabergoline treatment resulted in the normalization of PRL levels in 68 % and in the reduction of >50 % in tumor volume in 87 % of the gPRLoma patients. The composite goal of PRL normalization and >50 % tumor reduction was achieved by 55 % (n = 26) of patients with gPRL and by 66 % (n = 100) of patients with no giant macroprolactinomas (p = 0.19). Recovery of hypogonadism and improvement of visual fields defects occurred in 32 % and 68 % of the patients, respectively. Cabergoline treatment was equally effective in patients with gPRLoma and those with macroprolactinomas in regard of achieving treatment goals, although the median CBG dose was slightly higher in the gPRLoma group (2 vs. 1.5 mg/w). Six patients required surgery. Beyond their impressive dimensions and the huge amount of PRL they secrete, the clinical behavior of gPRLoma is not different from macroprolactinomas. These tumors are highly responsive to cabergoline treatment, and pituitary surgery is seldom required.