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- Kvernebo-Sunnergren, Kjersti, 1974, et al.
(författare)
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Adrenal and Gonadal Activity, Androgen Concentrations, and Adult Height Outcomes in Boys With Silver-Russell Syndrome
- 2019
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously shown that adult height (AH) in males with Silver-Russell syndrome (SRS) correlated negatively with prepubertal estradiol concentrations. We aimed to identify the source of estradiol by analyzing androgen secretion profiles and measuring anti-Mullerian hormone (AMH) and inhibin B concentrations during childhood and puberty in this group of patients. Methods: In a retrospective longitudinal single-center study, 13 males with SRS were classified as non-responders (NRs = 8) or responders (Rs = 5), depending on the AH outcome. From 6 years of age, androgens were determined by mass spectrometry, and AMH, inhibin B and sex hormone-binding globulin concentrations were analyzed by immunoassays. Results: AH outcome correlated negatively with dehydroepiandrosterone-sulfate (DHEAS) at 8 (r = -0.72), 10 (r = -0.79), and 12 years (r = -0.72); testosterone at 10 (r = -0.94), 12 (r = -0.70) and 14 years (r = -0.64); dihydrotestosterone (DHT) at 10 (r = -0.62) and 12 years; (r = -0.57) and AMH at 12 years (r = 0.62) of age. Compared with Rs, NRs had higher median concentrations of DHEAS (mu mol/L) at 10 years (2.9 vs. 1.0); androstenedione (nmol/L) at 10 (1.1 vs. 0.6) and 12 years (1.7 vs. 0.8); testosterone (nmol/L) at 10 (0.3 vs. 0.1), 12 (7.8 vs. 0.2) and 14 years (15.6 vs. 10.4); and DHT (pmol/L) at 10 (122 vs. 28) and 12 years (652 vs. 59) of age. AMH (ng/mL) was lower in NRs than in Rs at 12 years of age (11 vs. 50). No significant differences were observed in the inhibin B concentrations at any age. Conclusions: The elevated androgen concentrations before and during puberty, originated from both adrenal and gonadal secretion and correlated negatively with AH outcomes in males with SRS.
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2. |
- Kvernebo-Sunnergren, Kjersti, 1974, et al.
(författare)
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Adrenal androgen trajectories are established during childhood in preterm boys
- 2021
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 110:11, s. 3116-3123
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Tidskriftsartikel (refereegranskat)abstract
- Aim We investigated longitudinal adrenal androgen concentrations and any relationship between gestational age, birth size, anthropometric parameters and adrenal androgen concentrations during childhood in boys born moderate to late preterm. Methods This longitudinal, prospective study included 58 boys born at 32+0 to 36+6 weeks of gestation. Dehydroepiandrosterone sulphate and androstenedione were analysed by liquid chromatography-tandem mass spectrometry, and anthropometric data were recorded from 5 to 10 years of age. Results Dehydroepiandrosterone sulphate concentrations correlated with weight standard deviations scores (SDS) from 7 to 10 years of age and waist-to-height ratios at seven and 10 years of age. Androstenedione correlated with weight SDS from 7 to 10 years of age and waist-to-height ratios at 10 years of age. Longitudinal analysis showed a relationship between weight SDS and waist-to-height SDS and dehydroepiandrosterone sulphate (p p < 0.001, respectively) and androstenedione (p = 0.002 and p = 0.003, respectively), independently of age. Conclusion The trajectories of anthropometric parameters and adrenal androgen secretion were consistent from 5 to 10 years of age in this cohort. The body composition reflected by current weight and the waist-to-height ratio, rather than gestational age and birth size, was associated with adrenal androgen secretion.
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3. |
- Kvernebo-Sunnergren, Kjersti, 1974, et al.
(författare)
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Hyperestrogenism Affects Adult Height Outcome in Growth Hormone Treated Boys With Silver-Russell Syndrome
- 2018
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intrauterine growth retardation and short stature are common features in Silver-Russell syndrome (SRS). Despite recombinant growth hormone (rGH) treatment, poor pubertal height gain, affecting adult height (AH), is common. This study investigated whether growth patterns and estrogen concentrations are associated with AH outcome in rGH treated SRS males. Methods: In this retrospective longitudinal single-center study, 11 males with SRS were classified as non-responders (NR = 6) or responders (R = 5), depending on AH adjusted for midparental height. Epigenetic analysis and longitudinal growth measures, including bone age, rGH related parameters, pubertal development, gonadotropins and estrogen concentrations, were analyzed until AH. Results: Pubarche before 9 years was only observed in one NR. At 10 years of age, there was no difference in gonadotropins between NR and R. However, estradiol (E2) concentrations at 10 years of age showed a strong association to AH adjusted for MPH (r = -0.78, p < 0.001). Serum E2 (pmol/L) was significantly higher in NR at ages 10 years [median (range) 2 (<2-5) vs. <2 (<2)], 12 years [23 (10-57) vs. 2 (<2-2)] and 14 years [77 (54-87) vs. 24 (<2-38)] but not at 16 years. Birth weight standard deviation score (SDS) was lower in NR [-4.1 (-4.7 to -2.1) vs. -2.7 (-3.3 to -1.7)]. Weight gain (SDS) until pubertal onset was greater in NR [2.4 (1.4-3.5) vs. 0.8 (-0.4 to 1.7)] and pubertal height gain (SDS) was lower in NR [-1.0 (-2.7-0.4) vs. 0.1 (-0.1 to 1.1)]. At AH, a number of NR and R had high E2 concentrations and small testes. Conclusion: Increased E2 concentrations at age 10, 12, and 14 years were associated to less pubertal height gain, thus affecting AH. Due to the small number of patients, the results need to be confirmed in larger cohorts. The finding of impaired testicular development stresses the need of hormonal evaluation as a complement to clinical and radiological assessment when predicting AH in males with SRS.
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4. |
- Kvernebo-Sunnergren, Kjersti, 1974, et al.
(författare)
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Mini review shows that a testicular volume of 3 mL was the most reliable clinical sign of pubertal onset in males
- 2023
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Ingår i: Acta Paediatrica. - 0803-5253. ; 112:11, s. 2300-06
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Forskningsöversikt (refereegranskat)abstract
- AimWe aimed to evaluate aspects of pubertal development to identify the most reliable clinical sign of pubertal onset in males. MethodsWe performed a mini review of the literature. ResultsIn 1951 Reynolds and Wines categorised pubic hair growth and genital development in five stages by visual inspection. Today the Tanner scale is used to assess the five stages of pubertal development, The second genital stage, characterised by enlargement of the scrotum defines pubertal onset in males. Testicular volume may be evaluated by using a calliper or by ultrasound scan. The Prader orchidometer, described in 1966, offers a method for evaluating testicular growth by palpation. Pubertal onset is commonly defined as testicular volume >3 or & GE;4 mL. The development of sensitive laboratory methods has enabled studies analysing hormonal activity in the hypothalamus-pituitary-gonadal axis. We review the relationships between physical and hormonal signs of puberty. We also discuss the results of studies assessing different aspects of pubertal development with a focus on identifying the most reliable clinical sign of pubertal onset in males. ConclusionA substantial amount of evidence supports testicular volume of 3 mL as the most reliable clinical sign of male pubertal onset.
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5. |
- Kvernebo-Sunnergren, Kjersti, 1974, et al.
(författare)
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Pre- and peripubertal sex steroids are inversely associated with birth weight in preterm boys
- 2022
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265.
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Tidskriftsartikel (refereegranskat)abstract
- Objective The relationship between sex hormone concentrations during childhood and birth weight (BW) is poorly understood. We aimed to investigate this relationship and the associations with anthropometric data at 5, 6, 7, 8, and 10 years of age in preterm boys. Design A prospective longitudinal single-centre study, including 58 boys with a BW of 1325-3320 g and gestational age (GA) of 32 + 2 to 36 + 6 weeks. Patients and Measurements Data on GA, BW and anthropometric data between 5 and 10 years of age were recorded. Testicular development was assessed at 8 and 10 years of age. Serum concentrations of sex steroids were analysed with gas chromatography-tandem mass spectrometry at 5-10 years and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) with immunoassays at 10 years of age. Results At 8 years of age, testosterone and estrone correlated negatively with BW, (rho = -0.35, p = .021) and (rho = -0.34, p = .024), respectively. At 10 years of age, testosterone, dihydrotestosterone, estrone and estradiol correlated negatively with BW (rho = -0.39, p = .010), (rho = -0.38, p = .013), (rho = -0.44, p = .003) and (rho = -0.36, p = .019), respectively. Weight gain from birth correlated with testosterone at 5 years (rho = 0.40, p = .002), 7 years (rho = 0.30, p = .040), 8 years (rho = 0.44, p = .003) and 10 years (rho = 0.40, p = .008) of age. At 10 years of age, testosterone correlated with LH (rho = 0.42, p = .006) and FSH (rho = 0.33, p = .033) but not with testicular volume. Conclusions Lower BW was associated with increased sex steroid concentrations from 8 years of age, independently of clinical signs of puberty.
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6. |
- Kvernebo-Sunnergren, Kjersti, 1974
(författare)
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Sex steroid secretion during childhood in males - with focus on prematurity, birth size, and growth patterns
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: The overall aim of the thesis was to evaluate sex steroid secretion patterns during childhood in boys and to study how sex steroid concentrations relate to gestational age, birth weight, growth patterns, and adult height outcome. Patients and Methods: In paper I, 11 growth hormone-treated boys with Silver–Russell syndrome (SRS) who had reached adult height were included. In paper II, two further patients were added. Data on birth characteristics and growth at 6, 8, 10, 12, 14, and 16 years of age were collected retrospectively. Blood samples taken at the same ages, were analyzed for sex steroid concentrations. Two groups were defined and compared, those who reached an unexpected short adult height (non-responders) and those with an expected adult height (responders). Correlations between sex steroid concentrations and adult height were assessed. In papers III and IV, 58 boys born at gestational age 32+0 to 36+6 were followed prospectively. Growth data and sex steroid concentrations were analyzed at 5, 6, 7, 8, and 10 years of age, and correlations between sex steroid concentrations and both birth characteristics and growth patterns were assessed. Mass-spectrometry-based methods were used for sex steroid analysis in all four papers. Results: Paper I showed that non-responders had higher estradiol (E2) at 10–14 years of age and less pubertal height gain compared to responders. E2 at 10 years of age correlated strongly and negatively with adult height. In paper II, non-responders had higher adrenal androgens from 10–12 years and higher gonadal androgens from 10–14 years of age, compared to responders. There were strong negative correlations between dehydroepiandrosterone-sulfate (DHEAS) (8–12 years), testosterone (10–14 years), and dihydrotestosterone (DHT) (10 and 12 years of age), and adult height. In paper III, DHEAS and androstenedione (A4), correlated with weight at 7–10 years and DHEAS with waist-to-height ratio (WHtR) at 7 and 10 years of age; longitudinal analysis also showed significant associations between weight and WHtR and DHEAS and A4. The trajectories of adrenal androgens were established at 5 years of age. Paper IV showed negative correlations between both testosterone at 8 and 10 years and E2 at 10 years of age and birth weight, both in grams and standard deviation score. Conclusions: Birth weight was inversely associated with concentrations of testosterone from 8 to 10 years and E2 at 10 years of age in preterm boys. Childhood adrenal androgen concentrations were associated with body weight and WhtR but not with birth weight and adrenal androgen trajectories were established at 5 years of age. In boys with SRS, non-responders had higher concentrations of sex steroids from 10 to 14 years of age. Prepubertal and pubertal sex steroid concentrations correlated inversely with adult height and higher levels of adrenal androgens and earlier increase in gonadal androgens and E2 were associated with shorter adult height. The results of this thesis suggest that there is a relationship between birth weight, childhood sex steroid secretion patters and growth patterns both in boys with SRS and in preterm boys without SRS.
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