81 research outputs found
Advances in understanding pituitary tumors.
Pituitary tumors are common in the general population. Since neuroimaging techniques have improved, pituitary tumors are more often diagnosed incidentally. About 16.7% of the general population show changes in the pituitary gland. Predominantly, pituitary tumors are benign pituitary adenomas. Pituitary carcinomas or aggressive pituitary tumors are extremely rare. They might develop from benign adenomas. New genetic and epigenetic abnormalities help us to understand pituitary tumorigenesis and might lead to therapeutical targeting drugs in the future. Macroadenomas (>1 cm) can lead to visual field disturbances, compression of cranial nerves, hypopituitarism, and infiltration of the cavernous sinuses. The functional status of the pituitary tumor is important. About half to one third of all pituitary tumors are non-functioning pituitary adenomas. The other pituitary tumors show a specific pattern of hormone secretion. About 25% to 41% of all pituitary tumors are prolactinomas, acromegaly with production of growth hormone represents 10% to 15% of adenomas, Cushing's disease with production of adrenocorticotropic hormone accounts for 10%, and other hormonal characteristics are less common. Transsphenoidal resection and total adenomectomy are desirable. Radiosurgery has enriched the surgical treatment options. Surgical treatment is the intervention of choice except for prolactinomas, where pharmaceutical treatment is recommended. Pharmaceutical treatment consists of dopamine agonists such as cabergoline and somatostatin analogues that include octreotide and pasireotide; retinoic acid is of theoretical interest while peroxisome proliferator-activated receptor-gamma-ligands are not clinically useful. In acromegaly, pegvisomant is a further treatment option. Temozolomide should be considered in aggressive pituitary tumors. In general, pharmaceutical options developed recently have extended the repertoire of treatment possibilities of pituitary tumors
Three-tiered EGFr domain risk stratification for individualized NOTCH3-small vessel disease prediction
Cysteine-altering missense variants (NOTCH3cys) in one of the 34 epidermal growth-factor-like repeat (EGFr) domains of the NOTCH3 protein are the cause of NOTCH3-associated small vessel disease (NOTCH3-SVD). NOTCH3-SVD is highly variable, ranging from cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) at the severe end of the spectrum to non-penetrance. The strongest known NOTCH3-SVD modifier is NOTCH3cys variant position: NOTCH3cys variants located in EGFr domains 1–6 are associated with a more severe phenotype than NOTCH3cys variants located in EGFr domains 7–34. The objective of this study was to further improve NOTCH3-SVD genotype-based risk prediction by using relative differences in NOTCH3cys variant frequencies between large CADASIL and population cohorts as a starting point.Scientific CADASIL literature, cohorts and population databases were queried for NOTCH3cys variants. For each EGFr domain, the relative difference in NOTCH3cys variant frequency (NVFOR) was calculated using genotypes of 2574 CADASIL patients and 1647 individuals from population databases. Based on NVFOR cut-off values, EGFr domains were classified as either low (LR-EGFr), medium (MR-EGFr) or high risk (HR-EGFr). The clinical relevance of this new three-tiered EGFr risk classification was cross-sectionally validated by comparing SVD imaging markers and clinical outcomes between EGFr risk categories using a genotype-phenotype data set of 434 CADASIL patients and 1003 NOTCH3cys positive community-dwelling individuals.CADASIL patients and community-dwelling individuals harboured 379 unique NOTCH3cys variants. Nine EGFr domains were classified as an HR-EGFr, which included EGFr domains 1–6, but additionally also EGFr domains 8, 11 and 26. Ten EGFr domains were classified as MR-EGFr and 11 as LR-EGFr. In the population genotype–phenotype data set, HR-EGFr individuals had the highest risk of stroke [odds ratio (OR) = 10.81, 95% confidence interval (CI): 5.46–21.37], followed by MR-EGFr individuals (OR = 1.81, 95% CI: 0.84–3.88) and LR-EGFr individuals (OR = 1 [reference]). MR-EGFr individuals had a significantly higher normalized white matter hyperintensity volume (nWMHv; P = 0.005) and peak width of skeletonized mean diffusivity (PSMD; P = 0.035) than LR-EGFr individuals. In the CADASIL genotype–phenotype data set, HR-EGFr domains 8, 11 and 26 patients had a significantly higher risk of stroke (P = 0.002), disability (P = 0.041), nWMHv (P = 1.8 × 10−8), PSMD (P = 2.6 × 10−8) and lacune volume (P = 0.006) than MR-EGFr patients. SVD imaging marker load and clinical outcomes were similar between HR-EGFr 1–6 patients and HR-EGFr 8, 11 and 26 patients. NVFOR was significantly associated with vascular NOTCH3 aggregation load (P = 0.006), but not with NOTCH3 signalling activity (P = 0.88).In conclusion, we identified three clinically distinct NOTCH3-SVD EGFr risk categories based on NFVOR cut-off values, and identified three additional HR-EGFr domains located outside of EGFr domains 1–6. This EGFr risk classification will provide an important key to individualized NOTCH3-SVD disease prediction.Genetics of disease, diagnosis and treatmen
The EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases (TREAT-SVDs) trial: Study protocol for a randomised crossover trial
Background: Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs. Aims: To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and whether losartan has a beneficial effect when compared to atenolol in patients with symptomatic SVDs. Design: TREAT-SVDs is an investigator-led, prospective, open-label, randomised crossover trial with blinded endpoint assessment (PROBE design) conducted at five study sites across Europe. Patients aged 18 years or older with symptomatic SVD who have an indication for antihypertensive treatment and are suffering from either sporadic SVD and a history of lacunar stroke or vascular cognitive impairment (group A) or CADASIL (group B) are randomly allocated 1:1:1 to one of three sequences of antihypertensive treatment. Patients stop their regular antihypertensive medication for a 2-week run-in period followed by 4-week periods of monotherapy with amlodipine, losartan and atenolol in random order as open-label medication in standard dose. Outcomes: The primary outcome measure is cerebrovascular reactivity (CVR) as determined by blood oxygen level dependent brain MRI signal response to hypercapnic challenge with change in CVR in normal appearing white matter as primary endpoint. Secondary outcome measures are mean systolic blood pressure (BP) and BP variability (BPv). Discussion: TREAT-SVDs will provide insights into the effects of different antihypertensive drugs on CVR, BP, and BPv in patients with symptomatic sporadic and hereditary SVDs. Funding: European Union's Horizon 2020 programme
Oxytocin release deficit and social cognition in craniopharyngioma patients
Oxytocin is a neuropeptide known to affect social behaviour and cognition. Craniopharyngioma patients are considered to have an oxytocin-release-deficit caused by a rare tumour affecting the pituitary and/or the hypothalamus relevant for oxytocin production and release. To assess social behaviour and socio-cognitive abilities in this patient group, we tested 13 patients and 23 healthy controls on self-report questionnaires and an eye-tracking paradigm including fast facial emotion recognition. Additionally, saliva oxytocin levels acquired before and after a physical stress induction were available from a previous study, representing the reactivity of the oxytocin system. The data revealed three major results. First, patients with an oxytocin-release-deficit scored higher on self-reported autistic traits and reduced levels of hedonia for social encounters, although they showed no impairments in attributing mental states. Second, patients showed more difficulties in the fast emotion recognition task. Third, although automatic gaze behaviour during emotion recognition did not differ between groups, gaze behaviour was related to the reactivity of the oxytocin system across all participants. Taken together, these findings demonstrate the importance of investigating the reactivity of the oxytocin system and its relationship with social cognition. Our findings suggest that reduced emotional processing abilities may represent a pathological feature in a group of craniopharyngioma patients, indicating that this patient group might benefit from specific treatments within the social domain
Primary Empty Sella Syndrome and the Prevalence of Hormonal Dysregulation : A Systematic Review
Background: Empty sella is the neuroradiological or pathological finding of an apparently empty sella turcica containing no pituitary tissue. The prevalence of primary empty sella, i.e., empty sella without any discernible cause, is not precisely known; estimates range from 2% to 20%. Technical advances in neuroradiology have made empty sella an increasingly common incidental finding. It remains unclear whether, and to what extent, asymptomatic adult patients with an incidentally discovered empty sella should undergo diagnostic testing for hormonal disturbances. Methods: To answer this question, the authors carried out a systematic search in the PubMed and Web of Science databases for publications that appeared in the period 1995-2016 and that contained the search term "empty sella" (registration: PROS-dPERO 2015: CRD42015024550). Results: The search yielded 1282 hits. After the exclusion of duplicates, pediatric reports, case reports, and veterinary studies, 120 publications on primary empty sella syndrome (PES) were identified. 4 of these dealt with the prevalence of pituitary insufficiency in patients with PES as an incidental finding. Among patients with PES, the relative frequency of pituitary insufficiency in the pooled analysis was 52% (95% confidence interval [38; 65]). Conclusion: The data on PES as an incidental finding are too sparse to enable any evidence-based recommendation on the potential indications for hormone testing or its nature and extent. We advise basic neuroendocrinological testing (fasting cortisol, free thyroxine [fT4], estradiol or testosterone, insulin-like growth factor 1 [IGF-1], and prolactin). There is an unexplained discrepancy between the reported high prevalence of pituitary insufficiency among persons with PES and its low prevalence in epidemiologic studies. We suspect that the former may be high because of selection bias in the publications that we reviewed, or else the latter may be erroneously low
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