Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with potential effects on offspring both genetically and through altered intrauterine environment. Metformin, which ameliorate ...hormonal disturbances in non-pregnant women with PCOS is increasingly used in pregnancy. It passes the placenta, and the evidence on potential consequences for offspring endocrine development is scarce. We explore the potential effects of maternal PCOS status and intrauterine metformin exposure on offspring steroid hormone levels. This is a follow-up study of 5-10 years old children from the PregMet-study-a randomized controlled trial comparing metformin (2000 mg/day) to placebo during PCOS pregnancies. Of the 255 children invited, 117 (46%) were included. There was no intervention in this follow-up study. Outcomes were serum levels of androstenedione, testosterone, SHBG, cortisol, 17-hydroxyprogesterone, 11-deoxycortisol and calculated free testosterone converted to gender-and age adjusted z-scores from a Norwegian reference population. These were compared in i) placebo-exposed children versus children from the reference population (z-score zero) by the deviation in z-score by one-sample t-tests and ii) metformin versus placebo-exposed children by two-sample t-tests. Holm-Bonferroni adjustments were performed to account for multiple endpoints. Girls of mothers with PCOS (n = 30) had higher mean z-scores of androstenedione (0.73 (95% confidence interval (CI) 0.41 to 1.06), p<0.0001), testosterone (0.76 (0.51 to 1.00), p<0.0001), and free testosterone (0.99 (0.67 to 1.32), p<0.0001) than the reference population. Metformin-exposed boys (n = 31) tended to have higher 11-deoxycortisol z-score than placebo-exposed boys (n = 24) (mean difference 0.65 (95% CI 0.14-1.17), p = 0.014). Maternal PCOS status was associated with elevated androgens in 5- to 10-year-old daughters, which might indicate earlier maturation and increased risk of developing PCOS. An impact of metformin in pregnancy on steroidogenesis in children born to mothers with PCOS cannot be excluded. Our findings need confirmation in studies that include participants that have entered puberty.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Context
Testicular growth represents the best clinical variable to evaluate male puberty, but current pediatric hormone references are based on chronological age and subjective assessments ...of discrete puberty development stages. Determination of testicular volume (TV) by ultrasound provides a novel approach to assess puberty progression and stratify hormone reference intervals.
Objective
The objective of this article is to establish references for serum testosterone and key hormones of the male pituitary-gonadal signaling pathway in relation to TV determined by ultrasound.
Design, Setting, and Participants
Blood samples from 414 healthy Norwegian boys between ages 6 and 16 years were included from the cross-sectional “Bergen Growth Study 2.” Participants underwent testicular ultrasound and clinical assessments, and serum samples were analyzed by liquid chromatography tandem–mass spectrometry and immunoassays.
Main Outcome Measures
We present references for circulating levels of total testosterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone–binding globulin in relation to TV, chronological age, and Tanner pubic hair stages.
Results
In pubertal boys, TV accounted for more variance in serum testosterone levels than chronological age (Spearman r = 0.753, P < .001 vs r = 0.692, P < .001, respectively). Continuous centile references demonstrate the association between TV and hormone levels during puberty. Hormone reference intervals were stratified by TV during the pubertal transition.
Conclusions
Objective ultrasound assessments of TV and stratification of hormone references increase the diagnostic value of traditional references based on chronological age or subjective staging of male puberty.
The original HTML version of this Article was updated shortly after publication to add links to the Peer Review file.In addition, affiliations 16 and 17 incorrectly read 'School of Medicine Sydney, ...University of Notre Dame Australia, Sydney, WA, 6160, Australia' and 'St Vincent's Clinical School, University of New South Wales Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.' This has now been corrected in both the PDF and HTML versions of the Article.
Abstract
Background
Diagnosing Cushing syndrome (CS) can be challenging. The 24-hour urine free cortisol (UFC) measurement is considered gold standard. This is a laborious test, dependent on correct ...urine collection. Late-night salivary cortisol is easier and is used as a screening test for CS in adults, but has not been validated for use in children.
Objective
To define liquid chromatography tandem mass spectrometry (LC-MS/MS)-based cutoff values for bedtime and morning salivary cortisol and cortisone in children, and validate the results in children with and without CS.
Methods
Bedtime and morning salivary samples were collected from 320 healthy children aged 4 to 16 years. Fifty-four patients from the children’s outpatient obesity clinic and 3 children with pituitary CS were used for validation. Steroid hormones were assayed by LC-MS/MS. Cutoff levels for bedtime salivary cortisol and cortisone were defined by the 97.5% percentile in healthy subjects.
Results
Bedtime cutoff levels for cortisol and cortisone were 2.4 and 12.0 nmol/L, respectively. Applying these cutoff levels on the verification cohort, 1 child from the obesity clinic had bedtime salivary cortisol exceeding the defined cutoff level, but normal salivary cortisone. All 3 children with pituitary CS had salivary cortisol and cortisone far above the defined bedtime cutoff levels. Healthy subjects showed a significant decrease in salivary cortisol from early morning to bedtime.
Conclusions
We propose that bedtime salivary cortisol measured by LC-MS/MS with a diagnostic threshold above 2.4 nmol/L can be applied as a screening test for CS in children. Age- and gender-specific cutoff levels are not needed.
Field scale reactive transport models of CO \(_2\) and H \(_2\) S mineral sequestration in basalts were developed with a focus on Reykjavik Energy's ongoing CarbFix and SulFix sour gas re-injection ...tests at Hellisheidi geothermal power plant, SW-Iceland. Field data, such as drill cuttings and a calcite cap-rock overlying the high-temperature geothermal reservoir, suggest that mineral CO \(_2\) and H \(_2\) S sequestration already plays an important role within Hellisheidi geothermal system. The data indicate CO \(_2\) sequestration to be most intensive from 550-800-m depth below surface, while H \(_2\) S sequestration is most intensive below 800-m depth. Injecting and precipitating CO \(_2\) and H \(_2\) S into nearby formations with the objective of imitating and accelerating natural sequestration processes should therefore be considered as an environmentally benign process. Reactive transport simulations predict rapid and efficient mineralization of both CO \(_2\) and H \(_2\) S into thermodynamically stable minerals, with calcite, magnesite, and pyrrhotite being the favored carbonate and sulfide minerals to form. At intermediate depths and low temperatures (25-90 \( logical or circ \) C), calcite is the main CO \(_2\) sequestering carbonate predicted to form, while magnesite is the only carbonate predicted to form at high temperatures ( \(>\) 250 \( logical or circ \) C). Despite only being indicative, it is concluded from this study that the capture and sequestration of CO \(_2\) and H \(_2\) S from geothermal power plants are a viable option for reducing their gas emissions and that basalts may comprise ideal geological CO \(_2\) and H \(_2\) S storage formations.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A 4-generation family with multiple synostoses syndrome type 4 (SYNS4) is reported, the third family identified so far. The phenotype segregated with a previously undescribed Asn399Lys (c.1197C>A) ...substitution in GDF6. N399 is part of a hydrophobic pocket critical for binding the BMP/GDF antagonist noggin. The N399K substitution renders GDF6 more similar to noggin-resistant members of the BMP family, namely GDF2 and BMP10, both of which contain lysine in the corresponding position. To further define the SYNS4 phenotype, we examined 6 of 9 affected family members. The phenotype was carpal and tarsal synostoses with painful feet after walking, but the condition could also be asymptomatic. Interestingly, unlike the previous SYNS4 families, the family presented here has no history of hearing loss, and a 73-year-old mutation carrier had normal audiometry for his age. Based on structure modelling, BMPR2 binding should not be affected by the GDF6-N399K substitution, unlike the S429R and Y444N mutations found in the 2 other families. Hypothetically, this difference may be related to lack of hearing loss.
Field scale reactive transport models of CO
2
and H
2
S mineral sequestration in basalts were developed with a focus on Reykjavík Energy’s ongoing CarbFix and SulFix sour gas re-injection tests at ...Hellisheidi geothermal power plant, SW-Iceland. Field data, such as drill cuttings and a calcite cap-rock overlying the high-temperature geothermal reservoir, suggest that mineral CO
2
and H
2
S sequestration already plays an important role within Hellisheidi geothermal system. The data indicate CO
2
sequestration to be most intensive from 550–800-m depth below surface, while H
2
S sequestration is most intensive below 800-m depth. Injecting and precipitating CO
2
and H
2
S into nearby formations with the objective of imitating and accelerating natural sequestration processes should therefore be considered as an environmentally benign process. Reactive transport simulations predict rapid and efficient mineralization of both CO
2
and H
2
S into thermodynamically stable minerals, with calcite, magnesite, and pyrrhotite being the favored carbonate and sulfide minerals to form. At intermediate depths and low temperatures (25–90
∘
C), calcite is the main CO
2
sequestering carbonate predicted to form, while magnesite is the only carbonate predicted to form at high temperatures (
>
250
∘
C). Despite only being indicative, it is concluded from this study that the capture and sequestration of CO
2
and H
2
S from geothermal power plants are a viable option for reducing their gas emissions and that basalts may comprise ideal geological CO
2
and H
2
S storage formations.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
378.
Special outpatient clinic for skeletal dysplasias Rosendahl, Karen; Houge, Gunnar; Gradek, Gyri Aasland ...
Tidsskrift for den Norske Lægeforening,
2015-Mar-10, 20150310, Volume:
135, Issue:
5
Journal Article
PDF
