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Introduction Health services generate large amounts of routine health data (eg, administrative databases, disease registries and electronic health records), which have important secondary uses for research. Increases in the availability and the ability to access and analyse large amounts of data represent a major opportunity for conducting studies on the possible relationships between complex diseases. The objective of this study will be to evaluate the design, methods and reporting of studies conducted using observational routinely collected health data for investigating the link between cancer and neurodegenerative diseases. Methods and analysis This is the protocol for a meta-research study. We registered the study protocol within the Open Science Framework: https://ostio/h2qjg. We will evaluate observational studies (eg, cohort and case-control) conducted using routinely collected health data for investigating the associations between cancer and neurodegenerative diseases (such as Alzheimer's disease, amyotrophic lateral sclerosis/motor neuron disease, Huntington's disease, multiple sclerosis and Parkinson's disease). The following electronic databases will be searched (from their inception onwards): MEDLINE, Embase and Web of Science Core Collection. Screening and selection of articles will be conducted by at least two researchers. Potential discrepancies will be resolved via discussion. Design, methods and reporting characteristics in each article will be extracted using a standardised data extraction form. Information on general, methodological and transparency items will be reported. We will summarise our findings with tables and graphs (eg, bar charts, forest plots). Ethics and dissemination Due to the nature of the proposed study, no ethical approval will be required. We plan to publish the full study in an open access peer-reviewed journal and disseminate the findings at scientific conferences and via social media. All data will be deposited in a cross-disciplinary public repository.

Pharmacologic treatment of acromegaly is currently based upon assay-error strategy, the first-generation somatostatin receptor ligands (SRL) being the first-line treatment. However, about 50% of patients do not respond adequately to SRL. Our objective was to evaluate the potential usefulness of different molecular markers as predictors of response to SRL. We used somatotropinoma tissue obtained after surgery from a national cohort of 100 acromegalic patients. Seventy-one patients were treated with SRL during at least 6 months under maximal therapeutic doses according to IGF1 values. We analyzed the expression of SSTR2, SSTR5, AIP, CDH1 (E-cadherin), MKI67 (Ki-67), KLK10, DRD2, ARRB1, GHRL, In1-Ghrelin, PLAGL1 and PEBP1 (RKIP) by RT-qPCR and mutations in GNAS gene by Sanger sequencing. The response to SRL was categorized as complete response (CR), partial (PR) or non-response (NR) if IGF1 was normal, between >23 SDS IGF1 at 6 months of follow-up, respectively. From the 71 patients treated, there were 27 CR (38%), 18 PR (25%) and 26 NR (37%). SSTR2, Ki-67 and E-cadherin were associated with SRL response (P < 0.03, P < 0.01 and P < 0.003, respectively). E-cadherin was the best discriminator for response prediction (AUC = 0.74, P< 0.02, PPV of 83.7%, NPV of 72.6%), which was validated at protein level. SSTR5 expression was higher in patients pre-treated with SRL before surgery. We conclude that somatotropinomas showed heterogeneity in the expression of genes associated with SRL response. E-cadherin was the best molecular predictor of response to SRL. Thus, the inclusion of E-cadherin in subsequent treatment-decision after surgical failure may be useful in acromegaly.

In 2017, the WHO established that pituicytoma, granular cell tumour (GCT) and spindle cell oncocytoma (SCO) are posterior pituitary tumours (PPT). Recent data suggests that these tumours probably arise from the pituicytes and may constitute a spectrum of a unique histopathological entity. Our aim is to report the clinical findings and surgical outcomes of 16 patients with PPT. We also evaluated the tissue specimens available in light of current knowledge.

Background: Pituitary adenomas (PA) associated with pheochromocytomas/paragangliomas (Pheo/PGL), also known as "the three P association" or "3PAs" could be the results of coincidence, but new evidence supports a common pathogenic mechanism in some patients. Our aim is to report the clinical data, surgical outcome, genetic findings of a large case series and review the current knowledge on this topic. Methods and results: In a retrospective multicentre study, we compiled 10 patients with PAs (6 new unreported cases). Six patients were female with mean age of 51.6 +/- 18.0 years. PA were: 6 acromegaly, 3 prolactinoma and 1 non-functioning PA (NFPA). Among the Pheo/PGL, 7 patients had a single tumour (4 Pheo and 3 PGL) and 3 patients had multiple or bilateral disease (2 PGL and 1 Pheo). Patients with GH-secreting PA and NFPA underwent surgery, while patients with prolactinoma received medical treatment (one patient required surgery). Unilateral adrenalectomy was carried out in all single Pheo and a bilateral procedure was performed in the patient with bilateral tumour. A single tumour was resected in two patients with multiple PGL. We found 3 germline pathogenic mutations: 2 in SDHB (c.166-170delCCTCA and a gross deletion involving exon 1) and 1 SDHD (p.P81L exon 3). Two variants of uncertain significance: 1 in MEN1 (c.1618C > T; p.Pro540Ser) and 1 in RET (c.2556C > G, p.Ile852Met), and finally a RETM918T somatic mutation in a Pheo tissue. Conclusion: We actively suggest considering the possibility of hereditary disease in all cases with 3PA and performing a complete genetic study.

Background Succinate dehydrogenase subunit B (SDHB) immunohistochemistry was considered a valuable tool to identify patients with inherited paraganglioma/pheochromocytoma (PGL/PCC). However, previous studies jointly analyzed 2 related but clinically distinct entities, parasympathetic head and neck paragangliomas (HNPGLs) and sympathetic PCCs/PGLs. Additionally, a role for hypoxia inducible factor-1 alpha (HIF-1 alpha) as a biomarker for succinate dehydrogenase (SDHx)-mutated tumors has not been studied. Here, we evaluated the utility of SDHB/HIF-1 alpha proteins in HNPGLs and PCCs/PGLs as clinically useful biomarkers. Methods The SDHB/succinate dehydrogenase subunit A (SDHA)/HIF-1 alpha immunohistochemistry analysis was performed in 158 genetically defined patients. Results Similarly to PCCs/PGLs, SDHB immune-negativity correlated with SDHx-mutations in HNPGLs (P < .0001). The HIF-1 alpha stabilization was associated with SDHx-mutations in HNPGLs (P = .020), not in PCCs/PGLs (P = .319). However, 25% of SDHx-HNPGLs lacked HIF-1 alpha positive cells. Conclusion As in PCCs/PGLs, SDHB immunohistochemistry in HNPGLs is a valuable method for identification of candidates for SDHx-genetic testing. On the contrary, although SDHx mutations may favor HIF-1 alpha stabilization in HNPGLs, this is not a clinically useful biomarker.

OBJECTIVE To assess the integrity of the hypothalamo–pituitary–adrenal(HPA) axis, many authors have proposed the short synacthen test (ACTH1–24, Tetracosactrin) as a replacement for the insulin tolerance test (ITT). The aim of this study was to compare the plasma cortisol response obtained with both short synacthen tests (high dose (HDT, 250 μg) and low dose (LDT, 1 μg)) with the peak reached during the ITT in healthy volunteers, and to establish the plasma cortisol cut-off level in each test. SUBJECTS AND METHODS Thirty healthy subjects (16 F, 14 M), mean age 34 years, underwent both short synacthen tests. Twenty healthy subjects, 15 of whom (11 F, nine M) belonged to the above group, mean age 30 years, underwent an ITT. Plasma cortisol was measured using a chemiluminiscence immunoassay. RESULTS There were no differences between plasma cortisol 30 minutes after both short synacthen tests (HDT: 684 ± 123, LDT: 669 ± 119 nmol/l) and the peaks reached with the LDT (691 ± 123 nmol/l) and the ITT (673 ± 99 nmol/l).The only difference (P

Since 1997 there is an online National Registry of acromegalic patients in Spain (REA). We aimed to study changes in acromegaly treatment and outcomes over the last four decades in Spain. In REA clinical and biochemical data are collected at diagnosis and updated every one to 2 years. We analyzed the first treatment received and the different treatments administered according to decade of diagnosis of acromegaly: prior to 1980, 1980-1989, 1990-1999 and 2000-2009. Surgical cure rates according to pretreatment with long-acting somatostatin receptor ligands (SRLs) were also analyzed. 1,658 patients were included of which 698 had accurate follow-up data. Treatment of acromegaly changed over time. Surgery was the main treatment option (83.8 %) and medical treatment was widely used (74.7 %) both maintained over decades, while radiation therapy declined (62.8, 61.6, 42.2 and 11.9 % over decades, p

Objective To determine salivary and serum T levels by an RIA method after a single injection of 250mg IM of commercially available T enanthate. Design Research study. Setting Patients attended in a hospital environment. Patients Sixteen men with secondary hypogonadism. Interventions Testosterone enanthate was administered, and salivary samples were taken before the injection. Thereafter, these samples were obtained daily until day 7 and then on alternate days until day 28 after injection. Blood samples were taken previously and after the injection (5 samples during the month). Main Outcome Measure Salivary and serum T. Results Salivary T levels rose from 3.46±3.16 to 13.82±7.78ng/100mL (0.12±0.11 to 0.48±0.27nmol/L) within 24hours and remained in that range until day 7. From day 9, 7.20±2.88ng/100mL (0.25±0.10nmol/L), a progressive decrease of these values was observed until day 14: 5.18±2.88ng/100mL (0.18±0.10nmol/L). From day 16 until day 28, salivary concentrations returned to hypogonadal levels. Conclusion We conclude that T salivary concentrations may be applied to assess the effectiveness of T substitutive therapy in hypogonadal men and could replace serum in the monitoring of this type of therapy.

Objective No consensus exists until now about the suitable dose of tetracosactin in the ACTH stimulation test for detecting adrenal insufficiency. Our aim was to characterize both the ACTH(1–24) and the cortisol profiles after standard high-dose test (250 µg) (HDT) and low-dose test (1 µg) (LDT) in healthy subjects in order to provide a deeper knowledge about the relationship between stimulus and response. Design and patients ACTH tests were performed in 10 healthy volunteers (five men, five women) with at least 1 week of difference. Measurements Plasma ACTH(1–24) and ACTH(1–39) and serum cortisol were measured before tetracosactin i.v. injection and at 5, 15, 30, 45, 60, 75 and 90 min after stimulus. Area under the curve (AUC) of ACTH(1–24) and cortisol, as well as mean residence time (MRT) for ACTH(1–24) were calculated in both tests. Results Elimination of ACTH(1–24) was faster in HDT than in LDT (MRTs of 0·14 vs 0·37, respectively, P = 0·008), but plasma concentrations were higher up to 60 min cortisol production in HDT reaching a higher maximum concentration (Cmax: 1144 vs 960 nmol/l) but delayed in time (75 vs 52·5 min). No significant relationship was observed between AUC or Cmax of ACTH(1–24) and AUC, Cmax and increment of cortisol in any of the tests. However, a negative correlation of basal cortisol values was observed with relative cortisol increment (HDT: r = 0·77 P = 0·009; LDT: r = 0·94 P

Well-differentiated (WD) pancreatic neuroendocrine tumors (pNET) are uncommon neoplasms and one of the challenges lies in predicting tumor behavior and managing these patients. The aim of this study is to evaluate patient outcomes associated with the surgical management of WD pNET and to assess the prognostic and biological behavior differences between the two grades of WD …

Pituitary apoplexy into nonadenomatous tissue is extremely rare. The authors describe a 20-year-old woman with symptomatic pituitary hemorrhage into an apparently intra-sellar malignant teratoma, which caused headache, visual impairment, involvement of III, IV, VI, and 1st division of the V cranial nerves, and hypopituitarism. Diabetes insipidus had developed previously. Magnetic resonance scans had a high-intensity signal in the pituitary on T1-and T2-weighted images, and lack of the signal of the posterior pituitary. Transsphenoidal approach, radiotherapy, and chemotherapy management did not preclude a fatal outcome.

A 52-year-old woman was admitted to our hospital presenting with subarachnoid hemorrhage, left ophthalmoplegia, and right hemiparesis. Previous symptoms and signs suggested the presence of panhypopituitarism. A giant intracranial aneurysm of the internal carotid artery, diagnosed by magnetic resonance imaging, showed the characteristic flow void phenomenon with black appearance. Analysis of endocrine function disclosed panhypopituitarism and hyperprolactinemia. After proximal balloon occlusion of the aneurysm, diabetes insipidus developed. Pituitary function reassessed 6 months after initial admission confirmed anterior and posterior hypopituitarism and hyperprolactinemia. Possible mechanisms are discussed. A review of the literature on pituitary dysfunction caused by carotid artery aneurysms discloses that the pituitary-gonadal axis is the most frequently involved (67.5% of cases), followed by the pituitary-adrenal axis (48.6%) and the pituitary-thyroid axis (40.5%). These frequencies are very similar to those described in other types of hypopituitarism.