Christoph Beier

Obesity Among Children and Adolescents With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

OBJECTIVES. Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most common inherited disorder of adrenal steroid biosynthesis. Patients with the classic form of CAH show androgen excess, with or without salt wasting. There are few studies reporting on higher rates of overweight and obesity among children with CAH. In addition to its role in the regulation of energy balance, leptin is involved in various endocrine and metabolic pathways. In this context, elevated serum leptin levels were reported recently for patients with CAH and were thought to be involved in the development of obesity among these patients. Therefore, the aim of this study was to analyze BMI values, compared with population-based references, for children and adolescents with CAH. Possible contributing factors, such as glucocorticoid therapy, skeletal maturation, birth weight and length, and parental BMI, were correlated with current BMI SD scores (SDS). In addition, the implications of serum leptin levels, corrected for BMI, gender, and Tanner stage, were investigated. METHODS. We performed a cross-sectional retrospective study of 89 children and adolescents with cah (48 female and 41 male subjects; age: 0.2-17.9 years) who presented in our outpatient department during 1 year. All individuals had classic cah, confirmed with molecular genetic analyses, and received substitution therapy (glucocorticoids and mineralocorticoids, if necessary). The quality of therapy was monitored in follow-up visits every 3 to 6 months, on the basis of clinical presentation and laboratory measurement findings according to current guidelines. We grouped the patients into salt wasting and simple virilizing groups, as well as according to current metabolic control. Leptin levels were measured with a commercial radioimmunoassay and calculated as sds. For statistical analyses, standard parametric and nonparametric methods were used. RESULTS. The chronologic ages of the children with CAH were between 0.20 and 17.9 years (mean ± SD: 8.9 ± 4.6 years). The BMI SDS of the whole group ranged from −2.7 to 4.3 (mean ± SD: 0.88 ± 1.3) and was significantly elevated above 0. Fifteen subjects (16.8%) had BMI SDS of >2.0, which indicated a significantly greater frequency of obesity among patients with CAH than expected for the normal population (expected: 2.27%). There was no significant difference in age and BMI between genders and clinical forms (salt wasting versus simple virilizing). BMI SDS was correlated positively with chronologic age. The BMI SDS did not differ significantly between children receiving hydrocortisone, prednisone, or dexamethasone. Hydrocortisone dosages (including equivalent dosages of prednisone and dexamethasone) ranged from 6.2 to 30.1 mg/m2 body surface area (mean ± SD: 14.7 ± 4.8 mg/m2 body surface area). Hydrocortisone dosages were correlated positively with BMI SDS. The relative risk of having a BMI SDS of >2.0 was not significantly elevated among children with prednisone/dexamethasone medication, compared with those with hydrocortisone treatment. In contrast to this, fludrocortisone dosage was not correlated with BMI SDS. Bone age delay, as calculated from the difference of bone age and chronologic age, ranged from −2.9 years to 5.6 years (mean ± SD: 1.11 ± 1.8 years) and was significantly elevated; it was correlated positively with BMI SDS. The BMI of parents ranged from 17.8 to 39.0 kg/m2 (median: 24.2 kg/m2). Median BMI values did not differ significantly between fathers and mothers. The relative risk for obesity among our children (BMI SDS of >2.0) was significantly elevated for children with obese parents, compared with those with nonobese parents (relative risk: 4.86). There was no significant correlation of birth length, birth weight, or gestational age with BMI SDS. Serum leptin values ranged from 0.10 to 32 μg/L (median: 4.4 μg/L); they were correlated positively with BMI SDS, chronologic age, and Tanner stage. After transformation into leptin concentration SDS values, the median SDS of 0.42 (range: −5.4 to 3.1) did not differ significantly from 0. CONCLUSIONS. Children and adolescents with CAH have a higher risk of obesity. Glucocorticoid dosage, chronologic age, advanced bone age maturation, and parental obesity contributed to elevated BMI SDS, whereas birth weight and length, serum leptin levels, used glucocorticoid, and fludrocortisone dosage were not associated with obesity. Therefore, children with CAH who become obese should be tightly monitored and should participate concurrently in weight management programs that include obese family members.

Magma genesis by rifting of oceanic lithosphere above anomalous mantle: Terceira Rift, Azores

[1] The Terceira Rift formed relatively recently (∼1 Ma ago) by rifting of the old oceanic lithosphere of the Azores Plateau and is currently spreading at a rate of 2–4mm/a. Together with the Mid-Atlantic Ridge, the Terceira Rift forms a triple junction that separates the Eurasian, African, and American Plates. Four volcanic systems (Sao Miguel, Joao de Castro, Terceira, Graciosa), three of which are islands, are distinguished along the axis and are separated by deep avolcanic basins similar to other ultraslow spreading centers. The major element, trace element and Sr-Nd-Pb isotope geochemistry of submarine and subaerial lavas display large along-axis variations. Major and trace element modeling suggests melting in the garnet stability field at smaller degrees of partial melting at the easternmost volcanic system (Sao Miguel) compared to the central and western volcanoes, which appear to be characterized by slightly higher melting degrees in the spinel/garnet transition zone. The degrees of partial melting at the Terceira Rift are slightly lower than at other ultraslow mid-ocean ridge spreading axes (Southwest Indian Ridge, Gakkel Ridge) and occur at greater depths as a result of the melting anomaly beneath the Azores. The combined interaction of a high obliquity, very slow spreading rates, and a thick preexisting lithosphere along the axis probably prevents the formation and eruption of larger amounts of melt along the Terceira Rift. However, the presence of ocean islands requires a relatively stable melting anomaly over relatively long periods of time. The trace element and Sr-Nd-Pb isotopes display individual binary mixing arrays for each volcanic system and thus provide additional evidence for focused magmatism with no (or very limited) melt or source interaction between the volcanic systems. The westernmost mantle sources beneath Graciosa and the most radiogenic lavas from the neighboring Mid-Atlantic Ridge suggest a mantle flow from Graciosa toward the Mid-Atlantic Ridge and hence a flux of mantle material from one spreading axis into the other. The Terceira Rift represents a unique oceanic rift system situated within the thickened, relatively old oceanic lithosphere and thus exhibits both oceanic and continental features.

Lava penetrating water: Submarine lava flows around the coasts of Pico Island, Azores

Bathymetry data collected with a multibeam echo sounder around Pico Island, Azores (Portugal), reveal a remarkable series of lava flows on the islands shelf with a variety of pristine structures that suggest how lava behaves on entering water. Many flows are dendritic in plan view, some with channels and tumuli. Dendritic geometries are interpreted to arise from flow fronts repeatedly arrested by enhanced cooling and magma pressure subsequently causing new breakouts. Cascades of elongated flow fingers also occur, with individual fingers of comparable diameters to the largest known megapillows. Some flows have wide transverse clefts, in cases separating flows into segments, which are interpreted as caused by their upper surfaces having solidified, while their still-fluid cores allowed the surfaces to extend. A number of flows moved onto the shelf as large bodies, stopped, and then sourced smaller lobes forming the dendritic patterns. This two-stage evolution and the tumuli (which lie on a low gradient immediately below a steep nearshore gradient) suggest that, after initial emplacement and development of a crust by cooling, some flows pressurized. Once movements ceased and viscous stresses dissipated, magma static pressure developed from the weight of flow interiors passing over cliffs and nearshore gradients. One group of flows traverses the islands submarine slope, so direct supply of lava to the slopes is possible, although volumetrically how important it is to the islands internal composition is difficult to tell from these data. On the basis of observed strong surf erosion of historical flows, these delicate structures probably could not have survived passage through a moving sea level unmodified by erosion so they are unlikely to be pre-Holocene subaerial flows. They are interpreted to have formed in the Holocene from flows penetrating sea level or possibly some from nearshore tube openings or vents. Such flows and abundant clastic deposits are ephemeral features that become remobilized by surf during times of lower sea level. The shelves of active volcanic islands are therefore active geologically and are far from being simple products of erosional truncation as was once envisaged.

U‐Th‐Ra disequilibria and the extent of off‐axis volcanism across the East Pacific Rise at 9°30′N, 10°30′N, and 11°20′N

There is widespread interest in the distance that mid-ocean ridge magmatism extends beyond the neovolcanic zone. Off-axis magmas also provide a means to map out variations across the melting zone. We present 238U-230Th-226Ra data for 35 well-characterized samples that extend up to 50 km away from the ridge axis across the East Pacific Rise at 9°30′N, 10°30′N, and 11°20′N. The (230Th/238U) ratios range from 1.00 to 1.19, and the (226Ra/230Th) ratios range from 1 to 2.78. The samples have a bimodal (230Th/238U) distribution with approximately half overlying published axial data on the U-Th diagram and the remainder lying close to the equiline. The U series disequilibria in the majority of the samples can be explained by aging subsequent to eruption in a zone ∼8 km wide about the neovolcanic zone, consistent with visual evidence for sample age. Nevertheless, seven of the samples lie above calculated (230Th/238U) axial decay curves and/or have 226Ra excesses implying eruption tens of kilometers off axis. These are consistent with evidence from seamounts and seismic interpretations that magmatism can extend up to 20 km off axis. The implication is that magma is not as efficiently focused beneath the ridge axis as has generally been believed. There is a decrease in initial (230Th/238U) in both these and published samples inferred to have formed off axis, but there is no compelling evidence that this reflects source heterogeneity. Simple modeling suggests that this could be explained by a decrease in fertility and melt column length as the overlying lithosphere thickens with age and the solidus shallows.

Lithospheric control on geochemical composition along the Louisville Seamount Chain

Major and trace element and Sr, Nd, and Pb isotope data for lavas from 12 seamounts along the western (older) 1500 km section of the Louisville Seamount Chain in the southwest Pacific show remarkably uniform compositions over a similar to 30-40 Myr period of volcanism. All 56 samples analyzed are alkalic to transitional in composition. Unlike Hawaiian volcanoes, Louisville volcanoes appear not to pass through a sequence of evolutionary stages characterized by older tholeiitic basalts overlain by incompatible element enriched alkalic and silica-undersaturated lavas. The youngest lavas from a given Louisville seamount tend to have the least enriched incompatible element compositions. This unusual chemical evolution may be the result of re-melting of heterogeneous hot spot mantle that was partially depleted during the earlier, age progressive stages. The oldest Louisville seamounts were constructed close to the extinct Osbourn Trough spreading center, located north of the chain, but age-progressive lavas from these older seamounts are not significantly different to lavas from younger seamounts. This may indicate that spreading at this fossil ridge ceased several tens of millions of years before the oldest Louisville seamounts were constructed. Large fracture zones apparently had no significant effects on the composition of Louisville magmatism. However, lavas from the central part of the Louisville Seamount Chain, where volcanoes are smaller and more widely spaced, tend to have more variable and more enriched compositions. We suggest this may reflect smaller degrees of melting resulting from greater lithosphere thickness, and hence a shorter melting column for this section of the Louisville Seamounts.

Influence of subducted components on back-arc melting dynamics in the Manus Basin

Lavas erupted in back-arc basins afford the opportunity to explore the extent to which decompression and subduction-related components influence partial melting in this setting. We present U-Th-Ra disequilibria data from 24 well-characterized lavas from the Manus Basin behind the New Britain volcanic arc, supplemented by some additional trace element and Sr-Nd-Pb isotope data. The lavas range in composition from 49.6 to 57.7 wt % SiO2 and can be subdivided into those that are broadly like mid-ocean ridge basalts (MORB) with Ba/Nb 16. Rifts closest to the arc are dominated by BABB, whereas both lavas types erupt further away at the Manus Spreading Center. The MORB have small 230Th excesses (up to 5%) and are displaced below the global correlation of (230Th/238U) with ridge depth. In most respects the BABB closely resemble lavas erupted along the New Britain arc front, including 238U excesses that reach 26%. The Pb isotope data can be explained by mixing of a subduction component into an Indian MORB mantle source. The Pb in the subduction component is derived from both the subducted sediment (5%) and fluids from the subducting altered Solomon Sea oceanic crust (95%), and these were mixed prior to addition to the mantle wedge. U/Th ratios, Fe3+/ΣFe, and H2O contents all increase with increasing 206Pb/204Pb. A model in which addition of the subduction component to the mantle wedge is followed by 230Th in-growth during decompression and dynamic melting all less than 140 kyr prior to eruption can simulate the data. However, our preferred model is one of dynamic decompression melting in which subduction-modified, more oxidized mantle had DU ≪ DTh leading to 238U excesses in contrast to unmodified mantle that yields 230Th excess. Large 226Ra excesses in some southern rift samples require addition of a fluid <8 kyr ago but elsewhere reflect melting under low-porosity conditions.

Tectonic control of ocean island basalt sources on Sao Miguel, Azores?

[1] The calderas of the two isotopically distinct volcanoes Sete Cidades and Agua de Pau on Sao Miguel are only 30 km apart. Sete Cidades lavas generally have Sr-87/Sr-86 0.7040. Two overlapping rift zones exist between the two volcanoes and the lava compositions show that each rift zone is connected to the neighbouring volcano. Limited mixing between the volcanic systems implies separate ascent paths and magma sources with diameters of similar to 20 km. The two volcanic systems follow contrasting directions; the Sete Cidades volcanic rift strikes NW parallel to the extensional Terceira Rift, while the Agua de Pau volcanic rift zone strikes E-W. The covariation of magma sources and lithospheric tectonics may suggest that the tectonic structure of the lithosphere controls the mantle upwelling beneath Sao Miguel.

Oxygen isotopes in the Azores islands: Crustal assimilation recorded in olivine

Oxygen isotope ratios of olivine have become a widely used tool for the study of magmatic systems, especially in the interpretation of source heterogeneities in mantle plume–derived ocean island basalts. The underlying assumption is that fresh minerals provide a better guide to magma δ 18 O than bulk rock analyses and that olivine is also likely to be a major phenocryst phase in primitive magmas. However, distinctions between source compositions and the effects of subsequent magma evolution have not always been thoroughly scrutinized. For the Azores samples investigated here, we can demonstrate that the δ 18 O variation (+4.84‰ to +5.25‰ Vienna standard mean ocean water) observed in the olivine phenocryst population is closely linked to evolution in the host magmas during ascent to the surface. We observe a linear, positive correlation between forsterite (Fo) content and δ 18 O in all of the individual island lava suites. This forces us to conclude that the low oxygen isotope ratios result from combined assimilation and fractional crystallization processes, the assimilant being hydrothermally (temperature > 250 °C) altered, lower oceanic crust. Linear regression of the measured δ 18 O olivine values to Fo 89 suggests a homogeneous mantle source with δ 18 O =

Louisville Seamount Chain: Petrogenetic processes and geochemical evolution of the mantle source

The Louisville Seamount Chain is a ∼4300 km long chain of submarine volcanoes in the southwestern Pacific that spans an age range comparable to that of the Hawaiian-Emperor chain and is commonly thought to represent a hot spot track. Dredging in 2006 recovered igneous rocks from 33 stations on 22 seamounts covering some 49 Myr of the chains history. All samples are alkalic, similar to previous dredge and drill samples, providing no evidence for a Hawaiian-type tholeiitic shield-volcano stage. Major and trace element variations appear to be predominantly controlled by small but variable extents of fractional crystallization and by partial melting. Isotopic values define only a narrow range, in agreement with a surprising long-term source homogeneity—relative to the length scale of melting—and overlap with proposed fields for the “C” and “FOZO” mantle end-members. Trace element and isotope geochemistry is uncorrelated with either seamount age or lithospheric thickness at the time of volcanism, except for a small number of lavas from the westernmost Louisville Seamounts built on young (<20 Ma old) oceanic crust. The Louisville hot spot has been postulated to be the source of the ∼120 Ma Ontong Java Plateau, but the Louisville isotopic signature cannot have evolved from a source with isotopic ratios like those measured for Ontong Java Plateau basalts. On the other hand, this signature can be correlated with that of samples dredged from the Danger Islands Troughs of the Manihiki Plateau, which has been interpreted as a rifted fragment of the “Greater” Ontong Java Plateau.

Cone morphologies associated with shallow marine eruptions: east Pico Island, Azores

Eruptions in shallow water typically produce cones of volcaniclastic material. In order to identify any systematic effects of water depth and other environmental parameters on cone morphology, we have measured the heights and widths of cones in multibeam echo-sounder data from a submarine ridge extending southeast from Pico Island, Azores. XRF analyses of dredged samples show that lavas here vary compositionally from alkali basalt to trachybasalt and trachyandesite. Cones in deeper water are generally steep-sided with upper flanks close to 30°, the dip of talus at the angle of repose. However, height/width ratios of cones vary more in shallow water (200–400-m summit depth) with extreme values below 0.1; while some shallow-water cones are steep-sided as in deep water, others are much flatter. Three such cones lie on a bench at 300-m depth immediately east of Pico Island and have flank slopes of only 10–20°. We speculate that exceptionally shallow cone slopes here were produced by forced spreading of the erupting columns on reaching the water–air density barrier.