| 1. |
- Al-Shamkhi, Nasrin, 1985-, et al.
(författare)
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Pituitary function before and after surgery for nonfunctioning pituitary adenomas-data from the Swedish Pituitary Register.
- 2023
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Ingår i: European journal of endocrinology. - : Bioscientifica. - 1479-683X .- 0804-4643. ; 189:2, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Data on pre- and postoperative pituitary function in nonfunctioning pituitary adenomas (NFPA) are not consistent. We aimed to investigate pituitary function before and up to 5 years after transsphenoidal surgery with emphasis on the hypothalamic-pituitary-adrenal axis (HPA).Data from the Swedish Pituitary Register was used to analyze anterior pituitary function in 838 patients with NFPA diagnosed between 1991 and 2014. Patients who were reoperated or had received radiotherapy were excluded.Preoperative ACTH, TSH, LH/FSH, and GH deficiencies were reported in 31% (236/755), 39% (300/769), 51% (378/742), and 28% (170/604) of the patients, respectively. Preoperative median tumor volume was 5.0 (2.4-9.0) cm3. Among patients with preoperative, 1 year and 5 years postoperative data on the HPA axis (n = 428), 125 (29%) were ACTH-deficient preoperatively. One year postoperatively, 26% (32/125) of them had recovered ACTH function while 23% (70/303) patients had developed new ACTH deficiency. Thus, 1 year postoperatively, 163 (38%) patients were ACTH-deficient (P < .001 vs. preoperatively). No further increase was seen 5 years postoperatively (36%, P = .096). At 1 year postoperatively, recoveries in the TSH and LH/FSH axes were reported in 14% (33/241) and 15% (46/310), respectively, and new deficiencies in 22% (88/403) and 29% (83/288), respectively.Adrenocorticotrophic hormone deficiency increased significantly at 1 year postoperatively. Even though not significant, some patients recovered from or developed new deficiency between 1 and 5 years postoperatively. This pattern was seen in all axes. Our study emphasizes that continuous individual evaluations are needed during longer follow-up of patients operated for NFPA.
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| 2. |
- Backeljauw, Philippe, et al.
(författare)
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Safety and Effectiveness of Recombinant Human Growth Hormone in Children with Turner Syndrome : Data from the PATRO Children Study
- 2021
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 94:3-4, s. 133-143
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: PATRO Children is an international, observational, postmarketing surveillance study for a biosimilar recombinant human growth hormone (rhGH; somatropin, Omnitrope (R); Sandoz), approved by the European Medicines Agency in 2006. We report safety and effectiveness data for patients with Turner syndrome (TS).Methods: The study population included infants, children, and adolescents with TS who received Omnitrope (R) treatment according to standard clinical practice. Adverse events (AEs) were monitored for safety evaluation, and height velocity (HV), height standard deviation score (HSDS), and HVSDS were calculated to evaluate treatment effectiveness.Results: As of August 2019, 348 TS patients were enrolled from 130 centers. At baseline, 314 patients (90.2%) were prepubertal and 284 patients (81.6%) were rhGH treatment naive. The mean ( range) age at baseline was 9.0 (0.7-18.5) years, and mean (SD) treatment duration in the study was 38.5 (26.8) months. Overall, 170 patients (48.9%) reported AEs, which were considered treatment related in 25 patients (7.2%). One treatment-related serious AE was reported (intracranial hypertension). Mean.HSDS after 3 years of therapy was +1.17 in treatment-naive prepubertal patients and +0.1 in pretreated prepubertal patients. In total, 51 patients (31.1%) reached adult height (AH), 35 of whom were rhGH treatment naive; in these patients, mean (SD) HSDS was -2.97 (1.03) at the start of Omnitrope (R) treatment, and they achieved a mean (SD) AHSDS of -2.02 (0.9).Conclusion: These data suggest that biosimilar rhGH is well tolerated and effective in TS patients managed in reallife clinical practice. Optimization of rhGH dose may contribute to a higher AH. (C) 2021 S. Karger AG, Basel
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| 3. |
- Bäcklund, Nils, et al.
(författare)
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Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing’s syndrome
- 2020
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 182:6, s. 569-582
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST).Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves.Results: The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h.Conclusion: Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.
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| 4. |
- Fridman-Bengtsson, Ola, et al.
(författare)
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Evaluation of different hydrocortisone treatment strategies in transsphenoidal pituitary surgery
- 2019
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Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 161:8, s. 1715-1721
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHydrocortisone treatment in transsphenoidal pituitary surgery has been debated. Although several publications advocate restrictive treatment, centers around the world administer stress doses of hydrocortisone in patients with presumed intact cortisol production. Our aim with this analysis was to compare postoperative hypocortisolism in patients who received three different protocols of hydrocortisone therapy during and after surgery.MethodThis was a retrospective observational study. Based on perioperative hydrocortisone dose given, patients were divided in three groups: high dose (HD), intermediate dose (ID), and low dose (LD). Postoperative evaluation of the pituitary function was performed using S-cortisol at day 4 and short Synacthen test (SST) at 6–8 weeks. Patients with ACTH-producing adenomas or preoperative hydrocortisone treatment were excluded.ResultThere was no difference between the groups regarding failure rate of SST. The rate of failed SST (all groups) was 51/186 (27%), 24/74 (32%) in the HD group and 26/74 (35%) and 11/38 (29%) in the ID and LD groups respectively. There was no significant difference between the ID and LD groups regarding S-cortisol at postoperative day 4 regarding serum cortisol level below 200 nmol/L. There was a significant but weak correlation, rs 0.330 (P < 0.01) between S-cortisol day 4 and SST at 4–6 weeks.ConclusionsPeri and postoperative hydrocortisone treatment did not affect SST response 6–8 weeks postoperatively, whereas the rate of patients with S-cortisol below 200 nmol/L at postoperative day 4 did. LD hydrocortisone therapy seems to favor a better endogenous production in the early postoperative phase.
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| 5. |
- Himonakos, Christos, et al.
(författare)
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Long-term Follow-up of 84 Patients With Giant Prolactinomas-A Swedish Nationwide Study.
- 2023
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Ingår i: The Journal of clinical endocrinology and metabolism. - : Oxford University Press. - 1945-7197 .- 0021-972X. ; 108:12, s. e1506-e1514
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Tidskriftsartikel (refereegranskat)abstract
- To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas.Register-based study of patients with giant prolactinomas [serum prolactin (PRL) > 1000 µg/L, tumor diameter ≥40 mm] identified in the Swedish Pituitary Register 1991-2018.Eighty-four patients [mean age 47 (SD ±16) years, 89% men] were included in the study. At diagnosis, the median PRL was 6305 µg/L (range 1450-253 000), the median tumor diameter was 47 mm (range 40-85), 84% of the patients had hypogonadotropic hypogonadism, and 71% visual field defects. All patients were treated with a dopamine agonist (DA) at some point. Twenty-three (27%) received 1 or more additional therapies, including surgery (n = 19), radiotherapy (n = 6), other medical treatments (n = 4), and chemotherapy (n = 2). Ki-67 was ≥10% in 4/14 tumors. At the last follow-up [median 9 years (interquartile range (IQR) 4-15)], the median PRL was 12 µg/L (IQR 4-126), and the median tumor diameter was 22 mm (IQR 3-40). Normalized PRL was achieved in 55%, significant tumor reduction in 69%, and combined response (normalized PRL and significant tumor reduction) in 43%. In the primary DA-treated patients (n = 79), the reduction in PRL or tumor size after the first year predicted the combined response at the last follow-up (P < .001 and P = .012, respectively).DAs effectively reduced PRL and tumor size, but approximately 1 patient out of 4 needed multimodal treatment. Our results suggest that the response to DA after 1 year is useful for identifying patients who need more careful monitoring and, in some cases, additional treatment.
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| 6. |
- Hokken-Koelega, Anita, et al.
(författare)
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Bridging the gap: metabolic and endocrine care of patients during transition.
- 2016
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Ingår i: Endocrine connections. - 2049-3614. ; 5:6, s. R44-R54
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Tidskriftsartikel (refereegranskat)abstract
- Seamless transition of endocrine patients from the paediatric to adult setting is still suboptimal, especially in patients with complex disorders, i.e., small for gestational age, Turner or Prader-Willi syndromes; Childhood Cancer Survivors, and those with childhood-onset growth hormone deficiency.An expert panel meeting comprised of European paediatric and adult endocrinologists was convened to explore the current gaps in managing the healthcare of patients with endocrine diseases during transition from paediatric to adult care settings.While a consensus was reached that a team approach is best, discussions revealed that a 'one size fits all' model for transition is largely unsuccessful in these patients. They need more tailored care during adolescence to prevent complications like failure to achieve target adult height, reduced bone mineral density, morbid obesity, metabolic perturbations (obesity and body composition), inappropriate/inadequate puberty, compromised fertility, diminished quality of life and failure to adapt to the demands of adult life. Sometimes it is difficult for young people to detach emotionally from their paediatric endocrinologist and/or the abrupt change from an environment of parental responsibility to one of autonomy. Discussions about impending transition and healthcare autonomy should begin in early adolescence and continue throughout young adulthood to ensure seamless continuum of care and optimal treatment outcomes.Even amongst a group of healthcare professionals with a great interest in improving transition services for patients with endocrine diseases, there is still much work to be done to improve the quality of healthcare for transition patients.
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| 7. |
- Holmer, Helene, et al.
(författare)
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Fracture incidence in GH-deficient patients on complete hormone replacement including GH
- 2007
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 22:12, s. 1842-1850
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Tidskriftsartikel (refereegranskat)abstract
- Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. Introduction: The objective of this study was to evaluate fracture incidence in patients wilh confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. Results: A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR. 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI 0.34-0.86) was recorded in AO GHD men. Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.
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| 8. |
- Höybye, Charlotte, et al.
(författare)
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Change in baseline characteristics over 20 years of adults with growth hormone (GH) deficiency on GH replacement therapy
- 2019
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 181:6, s. 629-638
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Clinical observations over time of adults with growth hormone (GH) deficiency (GHD) have indicated a shift in patient characteristics at diagnosis. The objective of this study was to compare baseline characteristics of patients diagnosed with adult-onset GHD naive to GH replacement during t hree study periods (1994-1999 (P1), 2000-2004 (P2), and 2005-2012 (P3)) using the KIMS (Pfizer's International Metab olic) database. Methods: Data were retrieved for a total of 6069 patients with adult-on set GHD from six countries (Belgium, Germany, Netherlands, Spain, Sweden, and UK): P1 (n = 1705), P2 (n = 2397), and P3 (n = 1967). Results: The proportions of patients with pituitary/hypothalamic tumors and patients with multiple pituitary hormone deficiencies decreased per entry year period, while the proporti ons with hypertension and diabetes increased. The lag time from diagnosis of pituitary disease to start of GH treatme nt decreased by 2.9 years over the entry year periods. IGF-1 increased by 0.1 standard deviation score per entry year period. Maximum GH following various stimulation tests, BMI, and waist circumference increased. The use of radio therapy, glucocorticoid replacement doses, and the proportion of women >50 years on estrogen replacement therapy decreased. The effects of 1 year of GH replacement were similar over the entry year periods despite changes in the patients' baseline characteristics. An expected increase in fasting blood glucose was seen after 1 year of GH treatment. Conclusions: The degree of confirmed GHD became less pronounced and more pat ients with co-morbidities and diabetes were considered for GH replacement therapy, possibly r eflecting increased knowledge and confidence in GH therapy gained with time.
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| 9. |
- Höybye, Charlotte, et al.
(författare)
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Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease.
- 2010
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 162:4, s. 677-84
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients in remission from Cushing's disease (CD) have many clinical features that are difficult to distinguish from those of concomitant GH deficiency (GHD). In this study, we evaluated the features of GHD in a large cohort of controlled CD patients, and assessed the effect of GH treatment. DESIGN AND METHODS: Data were obtained from KIMS, the Pfizer International Metabolic Database. A retrospective cross-sectional comparison of background characteristics in unmatched cohorts of patients with CD (n=684, 74% women) and nonfunctioning pituitary adenoma (NFPA; n=2990, 39% women) was conducted. In addition, a longitudinal evaluation of 3 years of GH replacement in a subset of patients with controlled CD (n=322) and NFPA (n=748) matched for age and gender was performed. RESULTS: The cross-sectional study showed a significant delay in GHD diagnosis in the CD group, who had a higher prevalence of hypertension, fractures, and diabetes mellitus. In the longitudinal, matched study, the CD group had a better metabolic profile but a poorer quality of life (QoL) at baseline, which was assessed with the disease-specific questionnaire QoL-assessment of GHD in adults. After 3 years of GH treatment (mean dose at 3 years 0.39 mg/day in CD and 0.37 mg/day in NFPA), total and low-density lipoprotein cholesterol decreased, while glucose and HbAlc increased. Improvement in QoL was observed, which was greater in the CD group (-6 CD group versus -5 NFPA group, P<0.01). CONCLUSION: In untreated GHD, co-morbidities, including impairment of QoL, were more prevalent in controlled CD. Overall, both the groups responded similarly to GH replacement, suggesting that patients with GHD due to CD benefit from GH to the same extent as those with GHD due to NFPA.
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| 10. |
- Höybye, Charlotte
(författare)
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Endocrine and metabolic aspects of adult Prader Willi syndrome with special emphasis on the effect of growth hormone treatment
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prader Willi Syndrome (PWS) is a complex genetic disorder characterized by muscular hypotonia, hyperphagia, obesity and behavioural problems. Partial growth hormone (GH) deficiency and hypogonadism are common. Results of several GH treatment studies in children with PWS have shown improvements not only in growth, but also in body composition, physical strength and agility. The partial GH deficiency seen in PWS might render these patients at risk of metabolic diseases in adult life and of reduced life span. The non-growth effects of GH treatment in PWS children have directed the interest towards the PWS adults in preventing the long-term consequences of GH deficiency. Until recently, neither the endocrine and metabolic consequences of the syndrome in adult patients, nor the potential effects of GH treatment have been known in detail. Aims: To study endocrine, metabolic and psycho-social functions, in adult PWS patients and the impact of GH treatment on these parameters. Patients and methods: We examined a cohort of 19 adult patients with clinical PWS (13 with PWS genotype) of which 17 (9 men and 8 women) with a mean age of 25 years and a mean BMI of 35 k g/M 2, subsequently completed a 12 months GH treatment trial. Results and discussion: At baseline all but three patients were obese despite a strict diet. Waist/hip ratio was increased in all women, and the mean percentage body fat was high in both genders. The activity of the GH-insulin-like-growth-factor-I (IGF-I) system was impaired with low GH values, low total IGF-I and in relation to the obesity low levels of free IGF-I and non-suppressed IGF-binding- protein-1 (IGFBP-1). Approximately two thirds were biochemically hypogonadal. Bone mineral density (BMD) was low. Four patients had impaired glucose tolerance and 9 patients high homeostasis model assessment (HOMA) index, indicating insulin resistance. A moderate dyslipidemia was seen in seven patients. The 13 patients with genetically confirmed diagnosis were shorter and had significantly lower IGF-I. GH treatment showed beneficial effects on body composition with reduction in body fat and increase in lean body mass following 6 and 12 months of therapy with doses, that normalized total IGF-I levels. The effects were more pronounced in the patients with the PWS genotype. Carbohydrate and lipid metabolism was not significantly affected by GH treatment. The aetiology of hyperphagia in PWS is not known. Examination of peptides involved in appetite regulation, showed that leptin levels were high reflecting obesity, and as a consequence NPY levels were low. In view of the adiposity of the patients circulating oxytocin levels were abnormally low and circulating ghrelin levels abnormally high. Therefore oxytocin as well as ghrelin might be involved in the hyperphagia. The peptides involved in appetite regulation did not change during GH treatment. Psychological evaluation revealed positive effects on intellectual speed and flexibility, reaction time and motor speed. When GH was discontinued significant impairments in physical and social function as well as in the over-all functioning were seen, as judged from questionnaires to relatives and caretakers. Conclusion: GH treatment might offer an opportunity to reduce some of the adverse consequences of the PWS syndrome. It should be remembered, however, that dysfunction of the GH-IGF-I axis and the potential effects hereof are only minor parts of the clinical syndrome. Larger and longer term studies on the effect of GH replacement in adult PWS patients should be carried out.
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