| 1. |
- Agnarsson, Hjalmar Ragnar, et al.
(författare)
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The impact of glucocorticoid replacement on bone mineral density in patients with hypopituitarism before and after 2 years of growth hormone replacement therapy.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:4, s. 1479-1485
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Tidskriftsartikel (refereegranskat)abstract
- Context: Patients with hypopituitarism have reduced bone mineral density (BMD) and increased fracture risk. Objective: The aim of this study was to analyze the effects of glucocorticoid (GC) replacement on BMD before and after two years of growth hormone (GH) therapy in hypopituitary patients. The main hypothesis was that patients on GC replacement demonstrate greater improvement in BMD when treated with GH. Design: This was a post hoc analysis of data from a prospective single centre study. Patients: Data on 175 adult patients with hypopituitarism and verified GH deficiency due to non-functioning pituitary adenoma were analyzed. Ninety-eight (56%) were GC insufficient, receiving a mean±SD hydrocortisone equivalent dose of 20.9±5.0 mg/day. Main outcome measure: BMD before and after two years of GH replacement therapy, measured by using dual-energy X-ray absorptiometry. Results: BMD at baseline did not differ between GC sufficient and insufficient patients, neither at lumbar spine nor femur neck. After two years on GH replacement BMD increased in both groups. After adjustment for weight, age, gender, free T4 concentrations, change in IGF-I levels and sex hormone treatment, GC sufficiency was associated with greater increase in BMD at femur neck (ΔT-score in GC insufficient patients 0.09±0.46, in GC sufficient patients 0.19±0.43; P<0.05) but not at lumbar spine. Conclusions: GH replacement therapy for 2 years increased BMD in hypopituitary patients. In contrast to our hypothesis, GC insufficient patients receiving near physiological doses of hydrocortisone do not show a greater therapeutic response to GH therapy than their GC sufficient counterparts.
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| 2. |
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| 3. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:11, s. 4342-4350
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH).OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls.DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden.INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated.SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population.MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS.RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations.CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.
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| 4. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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Mortality is not increased in rhGH-treated patients when adjusting for birth characteristics.
- 2016
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 101:5, s. 2149-2159
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment. Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA). Participants:The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982). Main Outcome Measures: Death. Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P < .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P < .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P < .001). Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.
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| 5. |
- Allvin, Kerstin, 1970, et al.
(författare)
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Elevated serum levels of estradiol, dihydrotestosterone, and inhibin B in adult males born small for gestational age
- 2008
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:4, s. 1464-9
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Prenatal growth restriction may affect future fertility in both females and males. Studies have shown that growth-retarded male rats have different sexual behavior and disturbed steroidogenesis. OBJECTIVE: We hypothesized that adult human males born small for gestational age (SGA) have an altered sex hormone profile. DESIGN, SETTING, AND PATIENTS: Twenty-five adult males born SGA with median birth weight -2.2 sd scores (SDS) and birth length -2.4 SDS were studied. Median age was 23.1 yr and final height -0.5 SDS. They were compared with 44 male controls with median age 20.5 yr and final height 0.4 SDS. MAIN OUTCOME MEASURE: The primary outcome before the study started was 17beta-estradiol (E(2)) levels in SGA males. RESULTS: The SGA group showed significantly higher median levels of E(2), 17.9 pg/ml (P < 0.001), and dihydrotestosterone (DHT), 0.543 ng/ml (P < 0.05), compared with controls, 12.6 pg/ml and 0.423 ng/ml, respectively. Testosterone (T) levels did not differ between groups. E(2) to T ratio correlated negatively to birth weight (r = -0.40, P < 0.01) and birth length (r = -0.44, P < 0.001). DHT to T ratio correlated negatively to birth weight (r = -0.51, P < 0.001) and birth length (r = -0.38, P < 0.01). Males born SGA also had significantly higher median levels of inhibin B, 164 pg/ml (P < 0.05), compared with controls, 137 pg/ml. Inhibin B correlated negatively to birth length (r = -0.34, P < 0.01). CONCLUSION: SGA males of normal stature have higher levels of E(2), DHT, and inhibin B than controls, indicating a disturbed steroid synthesis or metabolism. Aromatase activity, calculated as E(2) to T ratio, and 5alpha-reductase activity, calculated as DHT to T ratio, is negatively correlated to size at birth.
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| 6. |
- Allvin, Kerstin, 1970, et al.
(författare)
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Longitudinal Sex Steroid Data in Relation to Birth Weight in Preterm Boys
- 2022
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:10
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Tidskriftsartikel (refereegranskat)abstract
- Context There is a lack of knowledge on longitudinal sex steroid patterns during infancy, especially for boys born preterm or with low birth weight (LBW). Objective To find out whether LBW boys have a disturbed sex steroid profile during infancy. Design and setting Population-based longitudinal study performed at Sahlgrenska University Hospital, Gothenburg, Sweden. Participants Ninety-eight singleton boys (47 LBW) born at gestational age 32.0 to 36.9 weeks were included. Because of dropout, 83 of the boys were still in the study at 10 months' corrected age. Main outcome measures Serum androgen and estrogen concentrations were analyzed by gas chromatography-tandem mass spectrometry and IGF-I was determined with radioimmunoassay in umbilical cord and at 0, 2, 5, and 10 months' corrected age. Results Serum levels of androstenedione, estrone, and estradiol declined gradually from birth to 10 months corrected age. In both LBW boys and their counterparts, a surge was seen at 2 months' corrected age (3 months' chronological age) for testosterone, median (range) 6.5 (2.0-18.9) nmol/L, and in dihydrotestosterone 1.2 (0.4-4.3) nmol/L. At birth, LBW boys had higher median testosterone (0.7 vs 0.4 nmol/L, P = 0.019), and at 0 months' corrected age, both had higher testosterone (5.7 vs 3.5 nmol/L, P = 0.003) and dihydrotestosterone (1.2 vs 0.9 nmol/L, P = 0.006) than their counterparts. At 10 months' corrected age, catch-up in weight SD score from birth correlated with testosterone (rho = 0.27, P = 0.044) and androstenedione (rho = 0.29, P = 0.027). Conclusions Moderately to late preterm LBW boys showed a disturbed sex hormone profile, with elevated concentrations of androgens in early infancy.
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| 7. |
- Amundson, Emily, et al.
(författare)
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Impact of growth hormone therapy on quality of life in adults with turner syndrome.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95:3, s. 1355-9
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Tidskriftsartikel (refereegranskat)abstract
- Context: GH and/or oxandrolone are used to promote growth in Turner syndrome (TS). Objective: The aim of this study was to compare quality of life (QoL) in TS women with controls and determine the impact of growth promoting therapy on QoL in TS women. Design: This was a cross-sectional, case-control study. Setting: The study was conducted at an outpatient clinic at Sahlgrenska University Hospital, Göteborg, Sweden. Patients: Patients included 111 TS women (age range 18-59 yr) and 111 randomly selected, age-matched women (25-54 yr) from the World Health Organization Monitoring Trends and Determinants for Cardiovascular Disease project (Göteborg, Sweden) served as controls. Main Outcome Measures: QoL was estimated by the Psychological General Well-Being scale (anxiety, depressed mood, positive well-being, self-control, general health and vitality) and the Nottingham Health Profile (physical mobility, pain, sleep, energy, social isolation, and emotional reactions). Results: TS women reported more social isolation than controls (P < 0.001). After age adjustment, significantly less pain (<0.05) was reported attributable to GH treatment within TS. No significant difference in any other subscales used could be shown. In TS, QoL was negatively affected by higher current age and age at diagnosis and positively affected by better body balance, fine motor function, and higher bone mineral density. Conclusions: Social isolation was more commonly reported in the whole TS cohort than in the population. Except for less pain, no significant impact on QoL attributable to GH treatment could be found, despite the mean +5.1 cm final height.
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| 8. |
- Andersson, Björn, et al.
(författare)
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Raloxifene does not affect insulin sensitivity or glycemic control in postmenopausal women with type 2 diabetes mellitus: a randomized clinical trial.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 87:1, s. 122-8
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the metabolic or cardiovascular effects of selective ER modulators (SERMs), such as raloxifene hydrochloride (RLX), in postmenopausal women with type 2 diabetes mellitus (DM). Therefore, the effect of RLX vs. placebo (PL) on glycemic control, insulin sensitivity, as well as effects on a number of hormone, lipid, coagulation, and safety factors were determined in 30 postmenopausal women with type 2 DM in a randomized, double blind, cross-over trial. All participants had a SHBG serum concentration below 60 nmol/liter at baseline and had stable diabetes controlled by either oral hypoglycemic agents or diet for 1 month. In the first treatment period, participants received 12 wk of either PL or RLX, followed by an 8-wk washout before the second treatment period. In the second treatment period, participants were crossed over to the other treatment. Compared with PL, RLX did not significantly affect fasting blood glucose, hemoglobin A(1c), lipids, fasting insulin, or insulin sensitivity (as measured by the euglycemic clamp technique). Compared with PL, RLX reduced fibrinogen levels by 0.77 g/liter (P < 0.001), IGF-I by 2.4 nmol/liter (P < 0.001), and free T by 0.73 pmol/liter (P = 0.038) and increased SHBG by 5.5 nmol/liter (P = 0.001) and IGF-binding protein-3 by 0.57 ng/ml (P = 0.007). Our results demonstrate that RLX does not significantly affect glycemic control and has favorable or neutral effects on selected surrogate markers of cardiovascular risk in postmenopausal women with type 2 diabetes mellitus while decreasing hyperandrogenicity in these patients.
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| 9. |
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| 10. |
- Ankarberg-Lindgren, Carina, 1963, et al.
(författare)
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Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls.
- 2001
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X .- 1945-7197. ; 86:7, s. 3039-44
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Tidskriftsartikel (refereegranskat)abstract
- The objective of pubertal induction in children with hypogonadism is to mimic spontaneous puberty in terms of physical and psychological development. In a clinical observation study, we induced puberty in 15 girls with hyper- or hypogonadotropic hypogonadism using low doses of transdermal estradiol patches attached only during the night and compared the estradiol concentrations obtained with those in healthy girls. Pubertal induction was started between the ages of 12.3 and 18.1 yr. A transdermal matrix patch of 17beta-estradiol (25 microg/24 h; Evorel, Janssen Pharmaceuticals-Cilag) was cut into pieces corresponding to 3.1, 4.2, or 6.2 microg/24 h initially and attached to the buttock. After 4-14 months, the dose was increased gradually. Serum 17beta-estradiol concentrations were measured every 2 h by RIA (detection limit, 6.0 pmol/L; 1.6 pg/mL). The results show that it is possible to mimic the spontaneous levels as well as the diurnal pattern of serum 17beta-estradiol in early puberty, by cutting a transdermal 17beta-estradiol matrix patch and attaching a part of it, corresponding to 0.08-0.12 microg estradiol/kg BW, to the buttock nocturnally. In most of the girls, breast development occurred within 3-6 months of the start of treatment.
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