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- 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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- Albertsson-Wikland, Kerstin, et al.
(författare)
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Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics
- 2016
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 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 amp;lt; .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 amp;lt; .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P amp;lt; .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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- Almby, Kristina E., et al.
(författare)
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Time course of metabolic, neuroendocrine, and adipose effects during 2 years of follow-up after gastric bypass in patients with type 2 diabetes
- 2021
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 106:10, s. E4049-E4061
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Tidskriftsartikel (refereegranskat)abstract
- Context: Roux-en-Y gastric bypass surgery (RYGB) markedly improves glycemia in patients with type 2 diabetes (T2D), but underlying mechanisms and changes over time are incompletely understood.Objective: Integrated assessment of neuroendocrine and metabolic changes over time inT2D patients undergoing RYGB.Design and Setting: Follow-up of single-center randomized study.Patients: Thirteen patients with obesity andT2D compared to 22 healthy subjects.Interventions: Blood chemistry, adipose biopsies, and heart rate variability were obtained before and 4, 24, and 104 weeks post-RYGB.Results: After RYGB, glucose-lowering drugs were discontinued and hemoglobin A1c fell from mean 55 to 41 mmol/mol by 104 weeks (P < 0.001). At 4 weeks, morning cortisol (P < 0.05) and adrenocorticotropin (P = 0.09) were reduced by 20%. Parasympathetic nerve activity (heart rate variability derived) increased at 4 weeks (P < 0.05) and peaked at 24 weeks (P < 0.01). C-reactive protein (CRP) and white blood cells were rapidly reduced (P < 0.01). At 104 weeks, basal and insulin-stimulated adipocyte glucose uptake increased by 3-fold vs baseline and expression of genes involved in glucose transport, fatty acid oxidation, and adipogenesis was upregulated (P < 0.01). Adipocyte volume was reduced by 4 weeks and more markedly at 104 weeks, by about 40% vs baseline (P < 0.01).Conclusions: We propose this order of events: (1) rapid glucose lowering (days); (2) attenuated cortisol axis activity and inflammation and increased parasympathetic tone (weeks); and (3) body fat and weight loss, increased adipose glucose uptake, and whole-body insulin sensitivity (months-years; similar to healthy controls).Thus, neuroendocrine pathways can partly mediate early glycemic improvement after RYGB, and adipose factors may promote long-term insulin sensitivity and normoglycemia.
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- Bengtsson, Daniel, 1975-, et al.
(författare)
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Corticotroph Pituitary Carcinoma in a Patient With Lynch Syndrome (LS) and Pituitary Tumors in a Nationwide LS Cohort
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : OXFORD UNIV PRESS INC. - 0021-972X .- 1945-7197. ; 102:11, s. 3928-3932
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Tidskriftsartikel (refereegranskat)abstract
- Context: Lynch syndrome (LS) is a cancer-predisposing syndrome caused by germline mutations in genes involved in DNA mismatch repair (MMR). Patients are at high risk for several types of cancer, but pituitary tumors have not previously been reported. Case: A 51-year-old man with LS (MSH2 mutation) and a history of colon carcinoma presented with severe Cushing disease and a locally aggressive pituitary tumor. The tumor harbored a mutation consistent with the patients germline mutation and displayed defect MMR function. Sixteen months later, the tumor had developed into a carcinoma with widespread liver metastases. The patient prompted us to perform a nationwide study in LS. Nationwide Study: A diagnosis consistent with a pituitary tumor was sought for in the Swedish National Patient Registry. In 910 patients with LS, representing all known cases in Sweden, another two clinically relevant pituitary tumors were found: an invasive nonsecreting macroadenoma and a microprolactinoma (i.e., in total three tumors vs. one expected). Conclusion: Germline mutations in MMR genes may contribute to the development and/or the clinical course of pituitary tumors. Because tumors with MMR mutations are susceptible to treatment with immune checkpoint inhibitors, we suggest to actively ask for a family history of LS in the workup of patients with aggressive pituitary tumors.
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| 7. |
- Bengtsson, Daniel, et al.
(författare)
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Psychotropic Drugs in Patients with Cushing's Disease Before Diagnosis and at Long-Term Follow-Up: A Nationwide Study
- 2021
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:6, s. 1750-1760
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Tidskriftsartikel (refereegranskat)abstract
- Context: Psychiatric symptoms are common in Cushing's disease (CD) and seem only partly reversible following treatment. Objective: To investigate drug dispenses associated to psychiatric morbidity in CD patients before treatment and during long-term follow-up. Design: Nationwide longitudinal register-based study. Setting: University Hospitals in Sweden. Subjects: CD patients diagnosed between 1990 and 2018 (N = 372) were identified in the Swedish Pituitary Register. Longitudinal data was collected from 5 years before, at diagnosis, and during follow-up. Four matched controls per patient were included. Cross-sectional subgroup analysis of 76 patients in sustained remission was also performed. Main outcome measures: Data from the Swedish Prescribed Drug Register and the Patient Register. Results: In the 5-year period before and at diagnosis, use of antidepressants (odds ratio [OR] 2.2 [95% confidence interval (CI) 1.3-3.7]) and 2.3 [1.6-3.5]), anxiolytics [2.9 (1.6-5.3) and 3.9 (2.3-6.6)], and sleeping pills [2.1 (1.2-3.7) and 3.8 (2.4-5.9)] was more common in CD than controls. ORs remained elevated at 5-year follow-up for antidepressants [2.4 (1.53.9)] and sleeping pills [3.1 (1.9-5.3)]. Proportions of CD patients using antidepressants (26%) and sleeping pills (22%) were unchanged at diagnosis and 5-year follow-up, whereas drugs for hypertension and diabetes decreased. Patients in sustained remission for median 9.3 years (interquartile range 8.1-10.4) had higher use of antidepressants [OR 2.0 (1.1-3.8)] and sleeping pills [2.4 (1.3-4.7)], but not of drugs for hypertension. Conclusions: Increased use of psychotropic drugs in CD was observed before diagnosis and remained elevated regardless of remission status, suggesting persisting negative effects on mental health. The study highlights the importance of early diagnosis of CD, and the need for long-term monitoring of mental health.
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| 8. |
- Bergman, Jonathan, et al.
(författare)
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Alendronate use and the risk of nonvertebral fracture during glucocorticoid therapy : a retrospective cohort study
- 2018
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Cary : Oxford University Press. - 0021-972X .- 1945-7197. ; 103:1, s. 306-313
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Tidskriftsartikel (refereegranskat)abstract
- Context: Glucocorticoids increase the risk of nonvertebral fracture, but no clinical trial has shown that nonvertebral fractures can be prevented by co-administration of an anti-osteoporotic drug.Objective: To estimate the effect of alendronate on the risk of nonvertebral fracture in older adults taking oral glucocorticoids.Design: Retrospective cohort study using national Swedish registers.Setting: Hospitalized care and ambulatory specialist care.Patients: Among adults aged 50 years or older (N=3,347,959), we identified those who initiated oral glucocorticoid therapy from 2006 through 2011 (≥2.5 mg/day of prednisone or equivalent for ≥91 days). The final analysis included 16,890 alendronate users and 16,890 nonusers, who were matched using time-dependent propensity scores.Main Outcome Measure: Nonvertebral fracture. This was not pre-specified.Results: Over a median follow-up of 14.5 months, the incidence rate of nonvertebral fracture was 2.0 cases per 100 person-years in alendronate users and 2.4 cases in nonusers. This difference corresponded to a 16% lower rate in users (hazard ratio 0.84, 95% confidence interval 0.75 to 0.94). For hip fractures specifically, the rate was 34% lower in alendronate users relative to nonusers (hazard ratio 0.66, 95% confidence interval 0.55 to 0.78). The association of alendronate use with a lower risk of nonvertebral fracture was strongest in patients who received high doses of glucocorticoid.Conclusion: Alendronate use was associated with a lower risk of nonvertebral fracture, including hip fracture. Similar, but not statistically significant, associations have been reported in meta-analyses of clinical trials.
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| 9. |
- Bjarnason, Ragnar, 1959, et al.
(författare)
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Cartilage oligomeric matrix protein increases in serum after the start of growth hormone treatment in prepubertal children
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:10, s. 5156-60
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Tidskriftsartikel (refereegranskat)abstract
- Both GH and IGF-I stimulate bone growth, but the molecular mechanisms mediating their effects on the growth plate are not fully understood. We measured gene expression by microarray analysis in primary cultured human chondrocytes treated with either GH or IGF-I. One of the genes found to be up-regulated by both GH and IGF-I was that encoding cartilage oligomeric matrix protein (COMP). This protein is predominantly found in the extracellular matrix of cartilage. Mutations in the COMP gene have been associated with syndromes of short stature. To verify that COMP is regulated by GH in vivo, we measured COMP levels in serum in short children treated with GH. The study included 113 short prepubertal children (14 girls and 99 boys) with a mean (+/- sd) age of 8.84 +/- 2.76 yr, height sd score of -2.74 +/- 0.67, and IGF-I sd score of -1.21 +/- 1.07 at the start of GH administration. Serum levels of COMP were 1.58 +/- 0.28, 1.83 +/- 0.28 (P < 0.0001), 1.91 +/- 0.28 (P < 0.0001), 1.78 +/- 0.28 (P < 0.001), and 1.70 +/- 0.24 (P < 0.05) microg/ml at baseline and after 1 wk and 1, 3, and 12 months, respectively.In conclusion, we have demonstrated that COMP expression is up-regulated by both GH and IGF-I in primary cultured human chondrocytes. Furthermore, serum levels of COMP increase after the start of GH treatment in short children.
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| 10. |
- Björn, Inger, 1953-, et al.
(författare)
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Increase of estrogen dose deteriorates mood during progestin phase in sequential hormonal therapy
- 2003
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 88:5, s. 2026-2030
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have indicated that the addition of progestinsduring sequential hormonal replacement therapy (HRT)causes negative mood and physical symptoms. History of premenstrualsyndrome, type of progestin, and dose of progestinhave thus far been shown to influence the progestin-inducedadverse mood symptoms during HRT.The aim of this study was to compare adverse mood effectsof two different doses of estradiol, in combination with a progestin,during postmenopausal HRT. Twenty-eight perimenopausalwomen were included in this randomized, doubleblind,crossover study comparing 2- or 3-mg continuousestradiol, with an addition of 10 mg medroxyprogesteroneacetate on d 17–28 during each treatment cycle. The mainoutcome measures were mood and physical symptoms kept ona daily rating scale. Together with the progestin, the higherdose of estrogen caused significantly more negative moodsymptoms than the lower dose. Tension, irritability, and depressedmood were all significantly augmented during theprogestin phase of cycles with 3mg estradiol (P<0.001). Physicalsymptoms also increased during the progestin phase of3-mg estradiol cycles (P<0.001), whereas positive mood symptomswere less affected. The only positive mood that changedwith estrogen dose was friendliness, which decreased duringthe progestin phase of high estradiol cycles compared withcycles with lower estradiol (P < 0.05).Our conclusion is that an increase of the estrogen doseaccentuates negativemoodand physical symptoms during theprogestin phase of sequential hormonal therapy.
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