Abstract
Context:
Pheochromocytomas and paragangliomas (PPGLs) in children are often hereditary and may present with different characteristics compared with adults. Hereditary PPGLs can be separated ...into cluster 1 and cluster 2 tumors due to mutations impacting hypoxia and kinase receptor signaling pathways, respectively.
Objective:
To identify differences in presentation of PPGLs between children and adults.
Design:
A retrospective cross-sectional clinical study.
Setting:
Seven tertiary medical centers.
Patients:
The study included 748 patients with PPGLs, including 95 with a first presentation during childhood. Genetic testing was available in 611 patients. Other data included locations of primary tumors, presence of recurrent or metastatic disease, and plasma concentrations of metanephrines and 3-methoxytyramine.
Results:
Children showed higher (P < 0.0001) prevalence than adults of hereditary (80.4% vs 52.6%), extra-adrenal (66.3% vs 35.1%), multifocal (32.6% vs 13.5%), metastatic (49.5% vs 29.1%), and recurrent (29.5% vs 14.2%) PPGLs. Tumors due to cluster 1 mutations were more prevalent among children than adults (76.1% vs 39.3%; P < 0.0001), and this paralleled a higher prevalence of noradrenergic tumors, characterized by relative lack of increased plasma metanephrine, in children than in adults (93.2% vs 57.3%; P < 0.0001).
Conclusions:
The higher prevalence of hereditary, extra-adrenal, multifocal, and metastatic PPGLs in children than adults represents interrelated features that, in part, reflect the lower age of disease presentation of noradrenergic cluster 1 than adrenergic cluster 2 tumors. The differences in disease presentation are important to consider in children at risk for PPGLs due to a known mutation or previous history of tumor.
This study establishes the link between extraadrenal, multifocal, metastatic, reccurent, hereditary PPGLs to a higher prevalence of noradrenergic and cluster 1 tumors in pediatric than adults.
Abstract
Context
Impaired diurnal blood pressure (BP) variability is related to higher cardiovascular risk.
Objective
To assess diurnal variability of BP and its relation to target organ damage (TOD) ...and catecholamine phenotype in a consecutive sample of pheochromocytoma/paraganglioma (PPGL).
Design
We included 179 patients with PPGL All patients underwent 24 hours of ambulatory BP monitoring to determine dipping status. Differences in plasma metanephrine or urine adrenaline were used to distinguish catecholamine biochemical phenotype. To evaluate TOD, renal functions, presence of left ventricle hypertrophy (LVH), and the subgroup (n = 111) carotid-femoral pulse wave velocity (PWV) were assessed. Structural equation modeling was used to find the relationship among nocturnal dipping, catecholamine phenotype, and TOD parameters.
Results
According to the nocturnal dipping, patients were divided into the three groups: dippers (28%), nondippers (40%), and reverse dippers (32%). Reverse dippers were older (P < 0.05), with a higher proportion of noradrenergic (NA) phenotype (P < 0.05), a higher prevalence of diabetes mellitus (P < 0.05), and sustained arterial hypertension (P < 0.01) and its duration (P < 0.05), as opposed to the other groups. All parameters of TOD were more pronounced only in reverse dippers compared with nondippers and dippers. The presence of NA phenotype (=absence of adrenaline production) was associated with reverse dipping and TOD (LVH and PWV).
Conclusions
Patients with reverse dipping had more substantial TOD compared with other groups. The NA phenotype plays an important role, not only in impaired diurnal BP variability but also independently from dipping status in more pronounced TOD of heart and vessels.
Predominantly pure noradrenaline, without concomitant adrenaline overproduction, has a long-term effect on the cardiovascular system in pheochromocytoma/functional paraganglioma.
To describe a patient with a germline succinate dehydrogenase (SDHC) gene mutation presenting with primary hyperparathyroidism and a large catecholamine-producing temporal bone paraganglioma (PGL).
...Evaluation of a SDHC mutation-positive PGL tumor biology using staining for tyrosine hydroxylase (TH), hypoxia-inducible factors 1α (HIF-1α) and 2α (HIF-2α).
A 66-year-old man was noted to have a lytic skull base mass during work-up for his primary hyperparathyroidism. Biochemical evaluation with 24-hour urine catecholamines and metanephrines revealed marked elevation of norepinephrine and normetanephrine. Genetic testing revealed a germline SDHC mutation. A partial excision of skull base tumor was performed, which upon further examination revealed PGL. Immunohistochemistry of skull base PGL demonstrated heavy expression of TH and HIF-2α but reduced expression of HIF-1α. The remaining skull base PGL was treated with adjuvant radiation therapy. The patient's normetanephrine levels significantly decreased after surgery and radiation.
Here, we report an unusual case of a patient presenting with a germline SDHC mutation-related functional PGL along with concomitant primary hyperparathyroidism. The present case illustrates that overexpression of HIF-2α but not of HIF-1α is linked to the pathogenesis of SDHC mutation-related PGL, and it may be responsible for the aggressive clinical behavior of a usually indolent course of SDHC-related PGLs.
Práce je zaměřena na kreativní účetnictví, jehož aplikování znehodnocuje hlavní funkci finančního účetnictví. Vysvětluje samotný pojem a klasifikuje praktiky kreativního účetnictví jako proces ...manipulace s účetními údaji a jako proces využívající ekonomických transakcí. Zabývá se specifickou oblastí earnings managementu a v jeho rámci praktikami income smoothing a big bath. Dále vyjmenovává motivy, upozorňuje na možnou prevenci, kterou lze uplatnit, a hodnotí následky, které s využíváním kreativního účetnictví souvisí.
•We studied fraternal pairs as simplest social units in two mouse subspecies.•The two taxa differ in developmental trajectories of their behaviour.•The process of establishing social hierarchy is ...extended in eastern M. m. musculus.•Prolonged stress coerces subordinate musculus males to leave the territory.
In social species such as house mouse, being dominant is vital. Determination of dominance may start early in life and vary during ontogeny. We asked whether pre-pubertal and adolescent behaviour predicts the rank a male mouse finally obtains. Moreover, we asked how dominant vs. subordinate adults differ in exploration and propensity to emigrate. We studied fraternal pairs as the simple social units, from weaning to full-grown adulthood. By utilizing two mouse subspecies known to differ in many behavioural traits, we take into account any potential subspecific idiosyncrasies.
We did not find any significant effect of future social status on any behavioural type displayed before adulthood, but the subspecies themselves differ in behaviours prevailing in particular ontogeny phases. While musculus males start as more pro-social, they later became significantly more passive. Conversely, domesticus are slightly less passive at the beginning but significantly more proactive close to adulthood and rapidly establishing hierarchy through overt conflicts. We found no difference in exploration between ranks, however, domesticus males were significantly more active in an unknown area than musculus. Most importantly, while dominant domesticus males seem to be more prone to emigration, in musculus it was the subordinate males who left base significantly more often. This is consistent with extended contests of musculus males over dominance found in this study as well as with differences in endocrinological changes we have reported previously.
Chemical communication is important for many social mammals. Scent-related gene clusters have undergone extraordinary expansion in some species, such as the house mouse (Mus musculus). One such ...family encodes major urinary proteins (MUPs). MUPs can provide recipients with complex information about the signaller and potentially serve as honest signals of social rank. In this study, we examined the development of overall MUP production in two mouse subspecies in the context of establishing their social hierarchy during the critical period between weaning and 100 days of age. We used fraternal pairs as simple social units, where dominant/subordinate ranks were naturally established between two brothers raised together, to test the hypothesis that dominant males of both taxa excrete higher amounts of MUPs in their urine than subordinates. The results were compared to data on ontogeny of steroid hormone levels gathered in the same individuals during an earlier experiment. Higher MUP levels in dominant males were only corroborated in one subspecies (domesticus), whereas musculus males revealed similar MUP quantities irrespective of rank. These results are consistent with the notion that these closely related taxa adopted different strategies for establishing social hierarchy.
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