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Wait times are associated with mortality on waiting list for transcatheter aortic valve replacement (TAVR). Whether longer wait times are associated with long term mortality after successful TAVR remains unassessed. Consecutive patients successfully treated with elective TAVR in our center between January 2013 and August 2019 were included. The primary end point was one-year all-cause mortality. TAVR wait times were defined as the interval from referral date for valve replacement to the date of TAVR procedure. A total of 383 patients were included with a mean wait time of 144.2 ± 83.87 days. Death occurred in 55 patients (14.4%) at one year. Increased wait times were independently associated with a relative increase of 1-year mortality by 2% per week after referral (Adjusted Hazard Ratio 1.02 [1.002-1.04]; p = 0.02) for TAVR. Chronic kidney disease, left ventricular ejection fraction ≤ 30%, access site and STS score were other independent correlates of 1-year mortality. Our study shows that wait times are relatively long in routine practice and associated with increased 1-year mortality after successful TAVR. Such findings underscore the need of strategies to minimize delays in access to TAVR., (© 2022. The Author(s).)

Background: Many studies link G protein-coupled receptors (GPCRs) to cancer. Some endocrine tumors are unresponsive to standard treatment and/or require long-term and poorly tolerated treatment. This study explored, by bioinformatics analysis, the tumoral profiling of the GPCR transcriptome to identify potential targets in these tumors aiming at drug repurposing., Methods: We explored the GPCR differentially expressed genes (DEGs) from public datasets (Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA)). The GEO datasets were available for two medullary thyroid cancers (MTCs), eighty-seven pheochromocytomas (PHEOs), sixty-one paragangliomas (PGLs), forty-seven pituitary adenomas and one-hundred-fifty adrenocortical cancers (ACCs). The TCGA dataset covered 92 ACCs. We identified GPCRs targeted by approved drugs from pharmacological databases (ChEMBL and DrugBank)., Results: The profiling of dysregulated GPCRs was tumor specific. In MTC, we found 14 GPCR DEGs, including an upregulation of the dopamine receptor ( DRD2 ) and adenosine receptor ( ADORA2B ), which were the target of many drugs. In PGL, seven GPCR genes were downregulated, including vasopressin receptor ( AVPR1A ) and PTH receptor ( PTH1R ), which were targeted by approved drugs. In ACC, PTH1R was also downregulated in both the GEO and TCGA datasets and was the target of osteoporosis drugs., Conclusions: We highlight specific GPCR signatures across the major endocrine tumors. These data could help to identify new opportunities for drug repurposing.

Differentiated thyroid cancers are more frequent in women than in men. These different frequencies may depend on differences in patient's behavior and in thyroid investigations. However, an impact on sexual hormones is likely, although this has been insufficiently elucidated. Estrogens may increase the production of mutagenic molecules in the thyroid cell and favor the proliferation and invasion of tumoral cells by regulating both the thyrocyte enzymatic machinery and the inflammatory process associated with tumor growth. On the other hand, the worse prognosis of thyroid cancer associated with the male gender is poorly explained.

Objectives: We sought to investigate the safety and potential benefit of administrating glycoprotein IIb-IIIa inhibitors (GPIs) on top of more potent P2Y12 inhibitors., Background: A number of clinical trials, performed at a time when pretreatment and potent platelet inhibition was not part of routine clinical practice, have documented clinical benefits of GPI in ST-segment elevation myocardial infarction (STEMI) patients at the cost of a higher risk of bleeding., Methods: We used the data of a prospective, ongoing registry of patients admitted for STEMI in our center. For the purpose of this study only patients presenting for primary percutaneous coronary intervention and pretreated with new P2Y12 inhibitors (prasugrel or ticagrelor) were included. We compared patients who received GPI with those who did not., Results: Eight hundred twenty-four STEMI patients were included in our registry; GPIs were used in 338 patients (41%). GPI patients presented more often with cardiogenic shock and Thrombolysis in myocardial infarction (TIMI) flow grade <3. GPI use was not associated with an increase in in-hospital or 3-month mortality. Bleeding endpoints were similar in both groups., Conclusions: Our study suggests that GPI may be used safely in combination with recent P2Y12 inhibitors in STEMI patients in association with modern primary percutaneous coronary intervention strategies (radial access and anticoagulation with enoxaparin) with similar bleeding and mortality rates at hospital discharge and 3-month follow-up., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Objective: To explore the programmed death-ligand 1 (PD-L1) expression in varied subtypes of pituitary neuroendocrine tumors with assessment of their clinical behavior at diagnosis and follow-up., Methods: We conducted a retrospective monocentric study, including all patients operated in the Academic Hospital of Angers (France) for a pituitary neuroendocrine tumor between 2012 and 2018. PDL-1 immunostaining was performed using a European Conformity-In Vitro Diagnostic-labeled anti-PDL1 antibody (clone 22C3). PD-L1 immunostaining was evaluated as the percentage of tumor cells showing positive membrane staining, into four grades: grade 0 = < 1%, grade 1 = 1 to 5%, grade 2 = 6 to 49% and grade 3 = ≥ 50%. PD-L1 expression was compared with tumor features (secretion, proliferation, invasion) and outcome., Results: The study included 139 pituitary neuroendocrine tumors, including 84 (60%) nonfunctioning adenomas. Twenty-five pituitary neuroendocrine tumors were PD-L1 positive (18%), including 3 grade 3, 8 grade 2 and 14 grade 1. PD-L1 expression was not different between functioning and nonfunctioning adenomas (p = 0.26). Among 16 tumors with proliferative markers (Ki-67 ≥ 3% and p53 positive), only one was PD-L1 positive., Conclusion: In our series, PD-L1 was expressed in a rather small proportion of PitNET (18%), and this immune marker was not associated with any biological characteristic or behavior of the pituitary tumors. Thus, PD-L1 staining may be necessary before considering PD-L1 blockage in pituitary neuroendocrine tumors, in case of therapeutic impasse.

Resistance to thyroid hormone (RTH) is a syndrome characterized by impaired sensitivity of tissues to thyroid hormone (TH). The alteration of TH-binding proteins, such as in Familial Dysalbuminemic Hyperthyroxinemia (FDH), can mimic the abnormal serum thyroid tests typical of RTH. We aimed to characterize a population referred to our center with suspected RTH and estimate the proportion of patients with FDH. For 303 different families, we collected clinical and hormonal data and sequenced the thyroid hormone receptor β gene ( THRB ) and exon 7 of the albumin gene ( ALB ). We found 56 THRB variants (i.e., 38% of the 303 index cases, called RTHβ group). Among the samples screened for FDH variants, 18% had the variant R218H in ALB (FDH group); in addition, 71% of the cases had neither variant (non-FDH/RTHβ group). Patients with FDH had significantly lower free T3 (fT3) and free T4 (fT4) levels and more often an isolated elevation of fT4 than RTHβ patients. Clinically, patients with FDH had fewer symptoms than patients with RTHβ. Our study suggests that FDH should be systematically considered when examining patients suspected of having RTH. In most cases, they present no clinical symptoms, and their biochemical alterations show an elevation of fT4 levels, while fT3 levels are 1.11 times below the upper limit of the assay.

Background: The presence of chemical pollutants in the environment can affect human health. Epidemiological and in vivo experimental studies reveal reprotoxic effects (undescended testis) of phthalates (diethylhexyl phthalate (DEHP), dibutyl phthalate (DBP)) and bisphenol A (BPA), resulting in particular of a decrease in INSL3 (Insulin-Like 3 peptide) production. This hormone is essential for normal testis development and acts on a G protein-coupled receptor: RXFP2., Objectives: The aim of this study was to evaluate the individual and combined impacts of DEHP, DBP, and BPA on human RXFP2 (hRXFP2) activity., Methods: We used HEK293 cells transiently transfected with hRXFP2 and receptor activity was analyzed by measuring intracellular cAMP production. The mixture was established at concentrations reported in human amniotic fluid, for the three compounds., Results: Individually, DEHP, DBP and BPA increased the response to INSL3 by 19.3 to 27.5%. This potentiating effect was specific for RXFP2, because it was absent in the cells which did not express this receptor. On the other hand, and interestingly, the mixture of the three compounds reduced significantly the response to INSL3 by 12%, and the observed effects were opposite to those predicted, suggesting an antagonist effect., Discussion-Conclusion: Taken together, our results demonstrate for the first time that a mixture of phthalates and BPA present in human amniotic fluid disturbs the human RXFP2 function. Moreover, we demonstrate that mixture can produce potential antagonistic effects that are not displayed by the compounds, individually., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Hyperglycaemia impairs tubulo-glomerular feedback. We tested whether variable tubulo-glomerular feedback during hyperglycaemia contributes to renal risk heterogeneity seen in Type 1 diabetes., Methods: During the period 1990-92, we studied the tubulo-glomerular feedback in Type 1 diabetic patients at high or low renal risk [21 of 54 with glomerular hyperfiltration and/or microalbuminuria against 11 of 55 with normal glomerular filtration rate (GFR) and urinary albumin despite uncontrolled diabetes]. The GFR, effective renal plasma flow, mean arterial pressure and fractional reabsorptions of glucose, osmols, sodium and lithium were measured sequentially during normo- and hyperglycaemia. All patients were followed up until 2016 for incident proteinuria, estimated GFR <60 mL/min/1.73 m2, doubling of serum creatinine, end-stage renal disease or all-cause death., Results: Glycaemia increased from 6.1 ± 1.3 to 15.1 ± 1.9 mmol/L in both high-risk and low-risk patients. Glycosuria was lower in the high- versus low-risk patients: 0.34 ± 0.25 versus 0.64 ± 0.44 mmol/min (P = 0.03). Both groups displayed similar kidney function during normoglycaemia. Hyperglycaemia increased more importantly GFR and fractional reabsorptions, and pre-glomerular vasodilatation in the high- than in the low-risk patients (all P < 0.05). Over 21 years, 31.5% high- versus 12.7% low-risk patients developed endpoints (adjusted P = 0.006). In a multi-adjusted survival analysis of patients having undergone renal tests, each 0.10 mmol/min glycosuria during hyperglycaemia reduced the outcome risk by 0.72 (95% confidence interval 0.49-0.97, P = 0.03)., Conclusions: Reduced tubulo-glomerular feedback and glycosuria during hyperglycaemia indicate high renal risk for Type 1 diabetic patients. Inter-individual variability in tubulo-glomerular feedback activity determines renal risk in Type 1 diabetes., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: The combination of vitamin K antagonists (VKA) for atrial fibrillation (AF) and antiplatelet agents following percutaneous coronary intervention (PCI) is associated with an increased bleeding risk., Hypothesis: Direct oral anticoagulants (DOAC) are associated with a greater safety profile but the optimal antithrombotic treatment strategy, especially when considering ischemic events, is unclear., Methods: We performed a meta-analysis of randomized controlled trials comparing outcomes in AF patients following PCI and/or acute coronary syndrome (ACS) when treated with DOAC vs VKA, both in combination with one (dual) or two (triple) antiplatelet regimens. A systematic review was performed by searches of electronic databases MEDLINE (source PubMed) and the Cochrane Controlled Clinical Trials Register Database as well as Cardiology annual meetings. Three studies were finally included., Results: Compared to VKA triple therapy, the use of DOAC was associated with a decreased risk of any bleeding (relative risk [RR] 0.68 [0.62; 0.74]), major bleeding (RR 0.61 [0.51; 0.75]) and intracranial bleeding (RR 0.33 [0.17; 0.66]) and similar rates of the composite efficacy endpoint (RR 1.0 [0.87; 1.14]) and its components. Similar and consistent results were observed with both dual and triple therapy including a DOAC compared to VKA., Conclusion: Our meta-analysis supports the use of dual therapy combining a DOAC and clopidogrel as the default regimen in most AF patients after PCI and/or ACS., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Background: Knowing the genetic status of patients affected by paragangliomas and pheochromocytomas (PPGL) is important for the guidance of their management and their relatives. Our objective was to improve the diagnostic performances of PPGL genetic testing by next-generation sequencing (NGS)., Methods: We developed a custom multigene panel, which includes 17 PPGL genes and is compatible with both germline and tumour DNA screening. The NGS assay was first validated in a retrospective cohort of 201 frozen tumour DNAs and then applied prospectively to 623 DNAs extracted from leucocytes, frozen or paraffin-embedded PPGL tumours., Results: In the retrospective cohort, the sensitivity of the NGS assay was evaluated at 100% for point and indels mutations and 86% for large rearrangements. The mutation rate was re-evaluated from 65% (132/202) to 78% (156/201) after NGS analysis. In the prospective cohort, NGS detected not only germline and somatic mutations but also co-occurring variants and mosaicism. A mutation was identified in 74% of patients for whom both germline and tumour DNA were available., Conclusion: The analysis of 824 DNAs from patients with PPGL demonstrated that NGS assay significantly improves the performances of PPGL genetic testing compared with conventional methods, increasing the rate of identified mutations and identifying rare genetic mechanisms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study was to evaluate the frequency of hypopituitarism following TBI in a cohort of children who had been hospitalized for mild TBI and to identify the predictive factors for this deficiency. Design: A prospective study was conducted on children between 2 and 16 years of age who had been hospitalized for mild TBI according to the Glasgow Coma Scale between September 2009 and June 2013. Clinical parameters, basal pituitary hormone assessment at 0, 6, and 12 months, as well as a dynamic testing (insulin tolerance test) 12 months after TBI were performed. Results: The study included 109 children, the median age was 8.5 years. Patients were examined 6 months ( n = 99) and 12 months ( n = 96) after TBI. Somatotropic deficiency (defined by a GH peak <20 mUI/l in two tests, an IGF-1 <-1SDS and a delta height <0SDS) were confirmed in 2 cases. One case of gonadotrophic deficiency occurred 1 year after TBI among 13 pubertal children. No cases of precocious puberty, 5 cases of low prolactin level, no cases of corticotropic insufficiency (cortisol peak <500 nmol/l) and no cases diabetes insipidus were recorded. Conclusion: Pituitary insufficiency was present 1year after mild TBI in about 7% of children. Based on our results, we suggest testing children after mild TBI in case of clinical abnormalities. i.e., for GH axis, IGF-1, which should be assessed in children with a delta height <0 SDS, 6 to 12 months after TBI, and a dynamic GH testing (preferentially by an ITT) should be performed in case of IGF-1 <-1SDS, with a GH threshold at 20 mUI/L. However, if a systematic pituitary assessment is not required for mild TBI, physicians should monitor children 1 year after mild TBI with particular attention to growth and weight gain.

Oncocytic adrenocortical tumors are a rare subtype of adrenal tumors with challenging diagnosis and histoprognostic assessment. It is usually believed that oncocytic adrenocortical tumors have a more indolent clinical behavior than conventional adrenocortical tumors. As the Weiss score overestimates the malignancy of oncocytic adrenocortical tumors owing to intrinsic parameters, alternative scores have been proposed. The Lin-Weiss-Bisceglia score is currently recommended. We performed a large nationwide multicenter retrospective clinicopathologic study of oncocytic adrenocortical tumors. Among the 43 patients in our cohort, 40 patients were alive without disease, 2 patients died of their disease and 1 patient was alive with relapse after a median follow-up of 38 months (20-59). Our data revealed that over 50% of the oncocytic adrenocortical tumor cases were diagnosed as carcinoma whatever the classification systems used, including the Lin-Weiss-Bisceglia score. The exception is the Helsinki score, which incorporates the Ki-67 proliferation index and was the most specific prognostic score for oncocytic adrenocortical tumor malignancy without showing a loss in sensitivity. A comparison of malignant oncocytic adrenocortical tumors with conventional adrenocortical carcinomas matched for age, sex, ENS@T stage and surgical resection status showed significant better overall survival of malignant oncocytic adrenocortical tumors.

A partial response (PR) has been proposed as a surrogate for overall survival in advanced adrenocortical carcinoma (ACC). The primary endpoint of the study was to characterize the time until a PR in patients with metastatic ACC treated with a standard therapy is achieved. Long-term survivors were selected to allow evaluation of delayed tumor response to mitotane. Records from patients with metastatic ACC that survived for > 24 months were retrieved. Tumor response was analyzed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Time until a tumor response, after treatment initiation or therapeutic plasma mitotane level, was analyzed. Sixty-eight patients were analyzed. The first-line systemic therapy was mitotane as a monotherapy (M) (n = 57) or cytotoxic polychemotherapy plus/minus mitotane (PC ± M) (n = 11). The second-line therapy was M (n = 2) or PC ± M (n = 41). Thirty-two PRs occurred in 30/68 patients (44.1%): this was obtained for 13 (40.6%) during M and during PC ± M for 19/32 responders (59.4%). PRs were observed within 6 months of starting M or PC ± M in 76.9 and 94.7% of responses, respectively, within 6 months of therapeutic plasma mitotane being first observed in 88.9% of responses with M and in 53.3% of responses with PC ± M. All PRs (but one) occurred within 1 year after initiating treatment. To conclude, Most patients with metastatic ACC and long survival times had PRs within the first 6 months of standard systemic therapy, and almost all within the first year. The absence of response after that period could be considered as a treatment failure. Maintenance of mitotane therapy in non-responders after 1 year should be questioned in future randomized trials.

Type 2 acrodysostosis (ACRDYS2), a rare developmental skeletal dysplasia characterized by short stature, severe brachydactyly and facial dysostosis, is caused by mutations in the phosphodiesterase (PDE) 4D (PDE4D) gene. Several arguments suggest that the mutations should result in inappropriately increased PDE4D activity, however, no direct evidence supporting this hypothesis has been presented, and the functional consequences of the mutations remain unclear. We evaluated the impact of four different PDE4D mutations causing ACRDYS2 located in different functional domains on the activity of PDE4D3 expressed in Chinese hamster ovary cells. Three independent approaches were used: the direct measurement of PDE activity in cell lysates, the evaluation of intracellular cAMP levels using an EPAC-based (exchange factor directly activated by cAMP) bioluminescence resonance energy transfer sensor , and the assessment of PDE4D3 activation based on electrophoretic mobility. Our findings indicate that PDE4D3s carrying the ACRDYS2 mutations are more easily activated by protein kinase A-induced phosphorylation than WT PDE4D3. This occurs over a wide range of intracellular cAMP concentrations, including basal conditions, and result in increased hydrolytic activity. Our results provide new information concerning the mechanism whereby the mutations identified in the ACRDYS2 dysregulate PDE4D activity, and give insights into rare diseases involving the cAMP signaling pathway. These findings may offer new perspectives into the selection of specific PDE inhibitors and possible therapeutic intervention for these patients., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Two types of immune checkpoint inhibitors, both antibodies that target cytotoxic T-lymphocyte antigen-4 and those that target programmed cell death-protein 1, have been approved for use in melanoma, non-small-cell lung cancer, and renal cell carcinoma as first-line or second-line therapy. Their adverse events are primarily regarded as immune-related adverse events. We felt it was important to pinpoint and discuss certain preconceptions or misconceptions regarding thyroid dysfunction, hypophysitis, and diabetes induced by immune checkpoint inhibitors. We have identified areas of uncertainty and unmet requirements, including essential interaction between endocrinologists and oncologists. Five issues have been identified for discussion: (1) diagnosis of endocrine toxicity, (2) assessment of toxicity severity, (3) treatment of toxicity, (4) withdrawal or continuation of immunotherapy, (5) preventive action., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Abrogation of ICOS/ICOS ligand (ICOSL) costimulation prevents the onset of diabetes in the non-obese diabetic (NOD) mouse but, remarkably, yields to the development of a spontaneous autoimmune neuromyopathy. At the pathological level, ICOSL -/- NOD mice show stronger protection from insulitis than their ICOS -/- counterparts. Also, the ICOSL -/- NOD model carries a limited C57BL/6 region containing the Icosl nul mutation, but, in contrast to ICOS -/- NOD mice, no gene variant previously reported as associated to NOD diabetes. Therefore, we aimed at providing a detailed characterization of the ICOSL -/- NOD model. The phenotype observed in ICOSL -/- NOD mice is globally similar to that observed in ICOS -/- and ICOS -/- ICOSL -/- double-knockout NOD mice, manifested by a progressive locomotor disability first affecting the front paws as observed by catwalk analysis and a decrease in grip test performance. The pathology remains limited to peripheral nerve and striated muscle. The muscle disease is characterized by myofiber necrosis/regeneration and an inflammatory infiltrate composed of CD4 + T-cells, CD8 + T-cells, and myeloid cells, resembling human myositis. Autoimmune neuromyopathy can be transferred to NOD. scid recipients by CD4 + but not by CD8 + T-cells isolated from 40-week-old female ICOSL -/- NOD mice. The predominant role of CD4 + T-cells is further demonstrated by the observation that neuromyopathy does not develop in CIITA -/- ICOSL -/- NOD in contrast to β2microglobulin -/- ICOSL -/- NOD mice. Also, the cytokine profile of CD4 + T-cells infiltrating muscle and nerve of ICOSL -/- NOD mice is biased toward a Th1 pattern. Finally, adoptive transfer experiments show that diabetes development requires expression of ICOSL, in contrast to neuromyopathy. Altogether, the deviation of autoimmunity from the pancreas to skeletal muscles in the absence of ICOS/ICOSL signaling in NOD mice is strictly dependent on CD4 + T-cells, leads to myofiber necrosis and regeneration. It provides the first mouse model of spontaneous autoimmune myopathy akin to human myositis.

In humans, activating mutations in the PRKAR1A gene cause acrodysostosis 1 (ACRDYS1). These mutations result in a reduction in PKA activation caused by an impaired ability of cAMP to dissociate mutant PRKAR1A from catalytic PKA subunits. Two striking features of this rare developmental disease are renal resistance to PTH and chondrodysplasia resulting from the constitutive inhibition of PTHR1/Gsa/AC/cAMP/PKA signaling. We developed a knock-in of the recurrent ACRDYS1 R368X PRKAR1A mutation in the mouse. No litters were obtained from [R368X]/[+] females (thus no homozygous [R368X]/[R368X] mice). In [R368X]/[+] mice, Western blot analysis confirmed mutant allele heterozygous expression. Growth retardation, peripheral acrodysostosis (including brachydactyly affecting all digits), and facial dysostosis were shown in [R368X]/[+] mice by weight curves and skeletal measurements (μCT scan) as a function of time. [R368X]/[+] male and female mice were similarly affected. Unexpected, however, whole-mount skeletal preparations revealed a striking delay in mineralization in newborn mutant mice, accompanied by a decrease in the height of terminal hypertrophic chondrocyte layer, an increase in the height of columnar proliferative prehypertrophic chondrocyte layer, and changes in the number and spatial arrangement of proliferating cell nuclear antigen (PCNA)-positive chondrocytes. Plasma PTH and basal urinary cAMP were significantly higher in [R368X]/[+] compared to WT mice. PTH injection increased urinary cAMP similarly in [R368X]/[+] and WT mice. PRKACA expression was regulated in a tissue (kidney not bone and liver) manner. This model, the first describing the germline expression of a PRKAR1A mutation causing dominant repression of cAMP-dependent PKA, reproduced the main features of ACRDYS1 in humans. It should help decipher the specificity of the cAMP/PKA signaling pathway, crucial for numerous stimuli. In addition, our results indicate that PRKAR1A, by tempering intracellular cAMP levels, is a molecular switch at the crossroads of signaling pathways regulating chondrocyte proliferation and differentiation. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

GH-secreting pituitary adenomas can be hypo-, iso- or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 3 months were included in the study. Hormonal, clinical and general MRI assessments were performed and assessed centrally. We included 120 patients with acromegaly. At diagnosis, 84, 17 and 19 tumors were T2-hypo-, iso- and hyper-intense, respectively. SSA treatment duration, cumulative and mean monthly doses were similar in the three groups. Patients with T2-hypo-intense adenomas had median SSA-induced decreases in GH and IGF-1 of 88% and 59% respectively, which were significantly greater than the decreases observed in the T2-iso- and hyper-intense groups (P < 0.001). Tumor shrinkage on SSA was also significantly greater in the T2-hypo-intense group (38%) compared with the T2-iso- and hyper-intense groups (8% and 3%, respectively; P < 0.0001). The response to SSA correlated with the calculated T2 intensity: the lower the T2-weighted intensity, the greater the decrease in random GH (P < 0.0001, r = 0.22), IGF-1 (P < 0.0001, r = 0.14) and adenoma volume (P < 0.0001, r = 0.33). The T2-weighted signal intensity of GH-secreting adenomas at diagnosis correlates with hormone reduction and tumor shrinkage in response to primary SSA treatment in acromegaly. This study supports its use as a generally available predictive tool at diagnosis that could help to guide subsequent treatment choices in acromegaly., (© 2016 Society for Endocrinology.)

Pituitary apoplexy, a rare clinical syndrome secondary to abrupt hemorrhage or infarction, complicates 2%-12% of pituitary adenomas, especially nonfunctioning tumors. Headache of sudden and severe onset is the main symptom, sometimes associated with visual disturbances or ocular palsy. Signs of meningeal irritation or altered consciousness may complicate the diagnosis. Precipitating factors (increase in intracranial pressure, arterial hypertension, major surgery, anticoagulant therapy or dynamic testing, etc) may be identified. Corticotropic deficiency with adrenal insufficiency may be life threatening if left untreated. Computed tomography or magnetic resonance imaging confirms the diagnosis by revealing a pituitary tumor with hemorrhagic and/or necrotic components. Formerly considered a neurosurgical emergency, pituitary apoplexy always used to be treated surgically. Nowadays, conservative management is increasingly used in selected patients (those without important visual acuity or field defects and with normal consciousness), because successive publications give converging evidence that a wait-and-see approach may also provide excellent outcomes in terms of oculomotor palsy, pituitary function and subsequent tumor growth. However, it must be kept in mind that studies comparing surgical approach and conservative management were retrospective and not controlled.