RESUMEN
Prader-Willi Syndrome (PWS) is a rare genetic disorder typically characterized by decreased social interaction, hyperphagia, poor behavioral control and temper tantrums, together with a high risk of morbid obesity unless food intake is controlled. The genetic defects that cause PWS include paternal 15q deletion (estimated in 60% of cases), chromosome 15 maternal uniparental disomy (UPD) (estimated in 35% of cases) and imprinting defects and translocations. Several studies indicate an oxytocin deficiency in PWS. Oxytocin is a hypothalamic nonapeptide with receptors located in the brain and in various other tissues in the body. It acts as a neuropeptide in several brain areas of great importance for behavioral and metabolic effects, as well as a neurohypophyseal hormone released into the circulation. Oxytocin in both rats and humans has strong and long-lasting behavioral and metabolic effects. Thus, an oxytocin deficiency might be involved in several of the behavioral and metabolic symptoms characterizing PWS. Treatment with oxytocin has, in some studies, shown improvement in psycho-social behavior and hyperphagia in individuals with PWS. This review focus on the behavioral and metabolic effects of oxytocin, the symptoms of a potential oxytocin deficiency in PWS and the effects of oxytocin treatment.
RESUMEN
OBJECTIVE: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries. METHODS: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale. RESULTS: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. CONCLUSION: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
Asunto(s)
Acromegalia , Técnica Delphi , Somatostatina , Acromegalia/terapia , Humanos , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Países Escandinavos y Nórdicos/epidemiología , Consenso , Hormona de Crecimiento Humana/uso terapéutico , Hormona de Crecimiento Humana/análogos & derivados , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS. METHODS: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves. RESULTS: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs ≥0.96. CONCLUSIONS: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.
Asunto(s)
Cortisona , Síndrome de Cushing , Humanos , Cromatografía Liquida/métodos , Cortisona/análisis , Síndrome de Cushing/diagnóstico , Hidrocortisona , Saliva/química , Espectrometría de Masas en Tándem/métodosRESUMEN
OBJECTIVE: Rathke's cleft cysts are benign, embryological remnants in the pituitary gland. The majority of them are small and asymptomatic but a few may become large, and cause mass effects, pituitary hormone deficiencies and visual impairment. Recommendations for the follow-up of Rathke's cleft cysts vary since data on the natural history are sparse. PATIENTS AND DESIGN: Data at diagnosis and at 1, 5 and 10 years for patients with a Rathke's cleft cyst (434 at diagnosis, 317 females) were retrieved from the Swedish Pituitary Registry. Cysts ≤3 mm in diameter were excluded from the study. MEASUREMENTS: Data included demographics, cyst size, pituitary function, visual defects and surgery. RESULTS: The mean age at diagnosis was 45 years. In patients with cysts <10 mm in diameter (n = 204) 2.9% had pituitary hormone deficiencies and 2% had visual field impairments. Cyst size did not progress during the 5 years. Cysts with a diameter of ≥10 mm that were not operated (n = 174) decreased in size over the years (p < .01). Pituitary hormone deficiencies and visual impairments were more frequent (18% and 5.7%, respectively) but were stable over time. Transphenoidal surgery was performed in 56 patients of whom 51 underwent surgery before the 1-year follow-up. The mean cyst diameter at diagnosis was 18 mm (range: 9â30 mm), 36% had pituitary hormone deficiency, 45% had visual field defects and 20% had impaired visual acuity. One year after surgery 60% had no cyst remnants, 50% had a pituitary deficiency, 26% had visual field defects and 12% had impaired visual acuity. No major changes were observed after 5 years. Twelve of the operated patients had a follow-up at 10 years, in eight the cyst remnants or recurrences increased in size over time (p < .05). CONCLUSIONS: Rathke's cleft cysts with a size less than 10 mm rarely grow and our results indicate that radiological follow-up can be restricted to 5 years. In contrast, progression of postoperative remnants or recurrent cysts is more likely and require long-term follow-up.
Asunto(s)
Quistes del Sistema Nervioso Central , Neoplasias Hipofisarias , Quistes del Sistema Nervioso Central/cirugía , Femenino , Humanos , Recurrencia Local de Neoplasia , Hipófisis/cirugía , Neoplasias Hipofisarias/cirugía , Sistema de Registros , Suecia , Resultado del TratamientoRESUMEN
PURPOSE: Data on the safety of growth hormone (GH) replacement therapy during pregnancy are limited. We report a combined analysis of data from pregnant women treated with GH while enrolled in two non-interventional, multicenter studies: NordiNet® International Outcome Study (IOS) and the American Norditropin® Studies: Web-Enabled Research (ANSWER) Program. METHODS: Pregnancy data were pooled from NordiNet® IOS and the ANSWER Program. Data were collected during routine clinic visits by participating physicians using a web-based system. Patients exposed to GH replacement therapy during pregnancy were included in the analysis. RESULTS: The study population included 40 female patients with typical causes of adult GH deficiency (GHD). Overall, there were 54 pregnancies. Of these, 47 were exposed to GH between conception and delivery. In 48.9% of pregnancies exposed to GH, the dose was > 0.6 mg/day. GH was continued past conception and then stopped during the first, second, and third trimester, in 27.7%, 17.0%, and 2.1% of pregnancies, respectively. In 29.8%, GH was continued throughout pregnancy, with an unchanged dose in most cases. Of the 47 GH-exposed pregnancies, 37 (78.7%) progressed to normal delivery. There were three adverse events reported in two pregnancies. CONCLUSION: These real-world data suggest that there were no new safety signals related to GH exposure in women with GHD during pregnancy. These results are consistent with findings from previous studies reporting data in pregnancies exposed to GH at conception or throughout pregnancy. This observational study in additional pregnancies provides further evidence that GH exposure does not adversely affect pregnancy outcome. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00960128 (date of registration: August 13, 2009) and NCT01009905 (date of registration: November 5, 2009).
Asunto(s)
Terapia de Reemplazo de Hormonas , Enanismo Hipofisario , Femenino , Hormona del Crecimiento/uso terapéutico , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Factor I del Crecimiento Similar a la Insulina , Evaluación de Resultado en la Atención de Salud , Embarazo , Resultado del Embarazo , Estados UnidosRESUMEN
PURPOSE: To evaluate safety and effectiveness of biosimilar recombinant human growth hormone (rhGH; Omnitrope®) in adults with growth hormone deficiency (GHD), using data from the PATRO Adults study. METHODS: PATRO Adults was a post-marketing surveillance study conducted in hospitals and specialized endocrinology units across Europe. The primary objective was to assess the safety of rhGH in adults treated in routine clinical practice. All adverse events (AEs) were monitored and recorded for the complete duration of Omnitrope® treatment. Effectiveness was evaluated as a secondary objective. RESULTS: As of January 2020, 1447 patients (50.9% male) had been enrolled from 82 centers in 9 European countries. Most patients had adult-onset GHD (n = 1179; 81.5%); 721 (49.8%) were rhGH-naïve at study entry. Overall, 1056 patients (73.0%) reported adverse events (AEs; n = 5397 events); the majority were mild-to-moderate in intensity. Treatment-related AEs were reported in 117 patients (8.1%; n = 189 events); the most commonly reported (MedDRA preferred terms) were arthralgia (n = 19), myalgia (n = 16), headache (n = 14), and edema peripheral (n = 10). In total, 495 patients (34.2%) had serious AEs (SAEs; n = 1131 events); these were considered treatment-related in 28 patients (1.9%; n = 35 events). Mean (standard deviation) IGF-I SDS increased from - 2.34 (1.47) at baseline to - 0.23 (1.65) at 12 months, and remained relatively stable thereafter (up to 3 years). Body mass index remained stable between baseline and 3 years. CONCLUSION: Data from PATRO Adults indicate biosimilar rhGH (Omnitrope®) is not associated with any unexpected safety signals, and is effective in adults with GHD treated in real-world clinical practice.
Asunto(s)
Vigilancia de Productos Comercializados , Biosimilares Farmacéuticos/efectos adversos , Enanismo Hipofisario , Femenino , Trastornos del Crecimiento/tratamiento farmacológico , Hormona del Crecimiento , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Estudios Longitudinales , Masculino , Proteínas RecombinantesRESUMEN
PURPOSE: Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. DATA SOURCES: Systematic literature search in four databases. STUDY SELECTION: Observational studies reporting the prevalence of NS after BA in adult patients with CD. DATA EXTRACTION: Data extraction and risk of bias assessment were performed by three independent investigators. DATA SYNTHESIS: Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. CONCLUSIONS: Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.
Asunto(s)
Síndrome de Nelson , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Adrenalectomía , Adulto , Humanos , Síndrome de Nelson/epidemiología , Síndrome de Nelson/cirugía , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/epidemiología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/cirugía , Hipófisis , PrevalenciaRESUMEN
Prader-Labhart-Willi syndrome (PWS) is a rare genetic disorder characterized by intellectual disability, behavioural problems, hypothalamic dysfunction and specific dysmorphisms. Hypothalamic dysfunction causes dysregulation of energy balance and endocrine deficiencies, including hypogonadism. Although hypogonadism is prevalent in males and females with PWS, knowledge about this condition is limited. In this review, we outline the current knowledge on the clinical, biochemical, genetic and histological features of hypogonadism in PWS and its treatment. This was based on current literature and the proceedings and outcomes of the International PWS annual conference held in November 2019. We also present our expert opinion regarding the diagnosis, treatment, care and counselling of children and adults with PWS-associated hypogonadism. Finally, we highlight additional areas of interest related to this topic and make recommendations for future studies.
Asunto(s)
Hipogonadismo , Síndrome de Prader-Willi , Pubertad , Femenino , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/genética , Hipogonadismo/metabolismo , Hipogonadismo/terapia , Masculino , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/metabolismo , Síndrome de Prader-Willi/terapiaRESUMEN
BACKGROUND: In 2007, Omnitrope® was the first biosimilar recombinant human growth hormone (rhGH) to be approved in Sweden for treatment in adults and children. Over 10 years' safety and effectiveness data for biosimilar rhGH can now be presented. METHODS: PATRO Children and PATRO Adults are multicenter, longitudinal, observational, post-marketing surveillance studies. Eligible patients include children 0-18 years and adults receiving biosimilar rhGH treatment. Adverse events (AEs) are monitored for safety evaluation. Growth variables in children and metabolic data in adults are recorded for effectiveness evaluation. RESULTS: As of January 2019, data from 136 children (48% male) were reported from Swedish centers. Mean age in rhGH treatment-naïve patients at study entry (n = 114) was 7.5 years, with mean 3.6 years treatment duration. No severe AEs of diabetes, impaired glucose tolerance, or malignancy were reported. The most frequently reported AE was nasopharyngitis (n = 16 patients). No clinically relevant anti-hGH or neutralizing antibodies were observed. The mean change from baseline in height standard deviation score (SDS) in naïve prepubertal GH deficiency patients was + 0.79 at 1 year, + 1.27 at 2 years, and + 1.55 at 3 years. Data from 293 adults (44% rhGH-naïve, 51% male) were included. Fatigue was the most frequently reported AE (n = 26 patients). The incidence of new neoplasms or existing neoplasm progression was 23.8 patients per 1000 patient-years. Type 2 diabetes mellitus was reported in four patients. At baseline in rhGH-naïve adults, mean (SD) body mass index (BMI) was 29.1 (5.6) kg/m2 and mean (SD) insulin-like growth factor (IGF)-I SDS was - 3.0 (1.4). Mean daily dose increased from 0.1 mg at baseline to 0.3 mg after 4 years. IGF-I SDS normalized during the first year of treatment. Mean BMI and glucose were unchanged over 4 years, while low-/high-density lipoprotein cholesterol ratio decreased. CONCLUSIONS: For the first time, Swedish data from the PATRO Children and Adults studies are presented. The 10-year data suggest that biosimilar rhGH is well tolerated across pediatric and adult indications. Safety and effectiveness were similar to previous reports for other rhGH preparations. These results need to be confirmed in larger cohorts, highlighting the importance of long-term post-marketing studies.
Asunto(s)
Biosimilares Farmacéuticos/uso terapéutico , Enanismo Hipofisario/tratamiento farmacológico , Trastornos del Crecimiento/tratamiento farmacológico , Hormona del Crecimiento/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Adolescente , Adulto , Anciano , Anticuerpos Neutralizantes , Estatura , Niño , Preescolar , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/epidemiología , Duración de la Terapia , Femenino , Intolerancia a la Glucosa/epidemiología , Terapia de Reemplazo de Hormonas , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Nasofaringitis/inducido químicamente , Neoplasias/epidemiología , Síndrome de Prader-Willi/tratamiento farmacológico , Vigilancia de Productos Comercializados , Proteínas Recombinantes , Suecia , Síndrome de Turner/tratamiento farmacológico , Adulto JovenRESUMEN
BACKGROUND: Prader-Willi syndrome (PWS) is a multisymptomatic, rare, genetic, neurodevelopmental disorder in adults mainly characterized by hyperphagia, cognitive dysfunction, behavioral problems and risk of morbid obesity. Although endocrine insufficiencies are common, hypocortisolism is rare and knowledge on long-term cortisol concentrations is lacking. The aim of this study was to evaluate long-term cortisol levels in PWS by measurements of hair cortisol. METHODS: Twenty-nine adults with PWS, 15 men and 14 women, median age 29 years, median BMI 27 kg/m2, were included. Scalp hair samples were analyzed for cortisol content using liquid-chromatography tandem-mass spectrometry. In addition, a questionnaire on auxology, medication and stress were included. For comparison, 105 age- and sex-matched participants from the population-based Lifelines Cohort study were included as controls. The mean hair cortisol between the groups were compared and associations between BMI and stress were assessed by a generalized linear regression model. RESULTS: In the PWS group large variations in hair cortisol was seen. Mean hair cortisol was 12.8 ± 25.4 pg/mg compared to 3.8 ± 7.3 pg/mg in controls (p = 0.001). The linear regression model similarly showed higher cortisol levels in patients with PWS, which remained consistent after adjusting for BMI and stress (p = 0.023). Furthermore, hair cortisol increased with BMI (p = 0.012) and reported stress (p = 0.014). CONCLUSION: Long-term cortisol concentrations were higher in patients with PWS compared to controls and increased with BMI and stress, suggesting an adequate cortisol response to chronic stress. Hair cortisol demonstrate promising applications in the context of PWS treatment and disease management.
Asunto(s)
Biomarcadores/metabolismo , Cabello/química , Hidrocortisona/metabolismo , Síndrome de Prader-Willi/diagnóstico , Adolescente , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Síndrome de Prader-Willi/metabolismo , Pronóstico , Adulto JovenRESUMEN
BACKGROUND: To evaluate the impact of treatment with recombinant human growth hormone (rhGH; Omnitrope®) on the risk of diabetes mellitus in adults with growth hormone deficiency (GHD), using data from the ongoing PATRO Adults post-marketing surveillance study. METHODS: PATRO Adults is an ongoing post-marketing surveillance study being conducted in hospitals and specialized endocrinology clinics across Europe. All enrolled patients who receive ≥1 dose of Omnitrope® are included in the safety population. Patient profiles, containing all available study database information for each specific patient, were generated for all patients with adverse events (AEs) of diabetes mellitus while participating in the study. Diabetes mellitus was confirmed if fasting plasma glucose was ≥7.0 mmol/L or 2-h plasma glucose ≥11.1 mmol/L during oral glucose tolerance test or glycated hemoglobin ≥6.5%. RESULTS: Up to July 2018, 1293 patients had been enrolled in the study, and 983 (76.0%) remained active. Just under half (n = 687, 49.3%) of the patients were growth hormone (GH) treatment-naïve on entering the study, and most (n = 1128, 87.2%) had multiple pituitary hormone deficiency (MPHD). Diabetes mellitus/inadequate control (worsening) of diabetes mellitus was reported in 21 patients (22 events). The cases were newly diagnosed in 15 patients (age 29-84 years; incidence rate 3.61 per 1000 patient-years) and occurred in 6 patients with pre-existing diabetes mellitus at baseline (age 45-72 years). Most cases of newly diagnosed diabetes mellitus occurred in patients with adult-onset MPHD (n = 13); the remaining cases of new-onset diabetes mellitus occurred in a patient with childhood-onset MPHD who had previously received GH replacement therapy (n = 1), and a patient with adulthood-onset isolated GHD who was naïve to GH replacement therapy (n = 1). All cases of inadequate control/worsening of diabetes mellitus occurred in patients with adult-onset MPHD. CONCLUSIONS: Based on this snapshot of data from PATRO Adults, Omnitrope® treatment is tolerated in adult patients with GHD in a real-life clinical practice setting. No signals of an increased risk for diabetes mellitus have been noted so far, although continued follow-up (both during and after rhGH therapy) is required to confirm this. TRIAL REGISTRATION: Not applicable.
Asunto(s)
Trastornos del Metabolismo de la Glucosa/epidemiología , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Biosimilares Farmacéuticos , Diabetes Mellitus/epidemiología , Diabetes Mellitus/terapia , Europa (Continente)/epidemiología , Glucosa/metabolismo , Hemoglobina Glucada/análisis , Terapia de Reemplazo de Hormonas , Hormona de Crecimiento Humana/efectos adversos , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Hormonas Hipofisarias/deficiencia , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Factores de RiesgoRESUMEN
BACKGROUND: Studies on the incidence of Cushing's disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden. METHODS: Patients registered with a diagnostic code for Cushing's syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data. RESULTS: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4-1.8) cases per million. 1987-1995, 1996-2004, and 2005-2013, the mean annual incidence was 1.5 (1.1-1.8), 1.4 (1.0-1.7) and 2.0 (1.7-2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05). CONCLUSION: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987-2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.
Asunto(s)
Síndrome de Cushing/epidemiología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/epidemiología , Hormona Adrenocorticotrópica/sangre , Estudios de Cohortes , Síndrome de Cushing/sangre , Humanos , Hidrocortisona/sangre , Incidencia , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/sangre , Suecia/epidemiologíaRESUMEN
BACKGROUND: Hydrocortisone 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. METHOD: This 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. RESULT: There 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. CONCLUSIONS: Peri 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.
Asunto(s)
Hidrocortisona/efectos adversos , Procedimientos Neuroquirúrgicos/efectos adversos , Hipófisis/cirugía , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Femenino , Humanos , Hidrocortisona/administración & dosificación , Hidrocortisona/uso terapéutico , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodosRESUMEN
OBJECTIVES: To compare the effect of time on cognitive impairments after Subarachnoid Haemorrhage and Traumatic Brain Injury and explore associations with baseline variables and global function. METHODS: Patients with a Glasgow Coma Scale score of 3-13, were assessed at 3, 6 and 12 months post injury by use of BNIS for cognitive impairment, RLAS-R to categorise cognitive and behavioural function, Barthel Index to assess performance of daily living, HADS to screen for depression and anxiety, and EuroQoL-5D, LiSat-11 and Glasgow Outcome Scale Extended to assess global function. RESULTS: BNIS T-scores did not differ significantly between groups and the proportion of patients with cognitive impairments was not significantly different at any time point. Cognition improved significantly between all time points in both groups except from 6 to 12 months after TBI. Generalised estimating equation showed non-significant signs of slower recovery of BNIS T-scores over time after SAH. Acute GCS scores were associated with BNIS T-scores after TBI but not after SAH. At 12 months, similar proportions of patients with SAH and TBI had good outcome. CONCLUSIONS: Cognitive improvements after SAH and TBI exhibit similarities and correlate with global function. GCS scores are associated with outcome after TBI but not after SAH.
Asunto(s)
Lesiones Traumáticas del Encéfalo/fisiopatología , Lesiones Traumáticas del Encéfalo/psicología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/psicología , Hemorragia Subaracnoidea/fisiopatología , Hemorragia Subaracnoidea/psicología , Sobrevivientes , Actividades Cotidianas , Adulto , Anciano , Ansiedad , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/rehabilitación , Disfunción Cognitiva/etiología , Disfunción Cognitiva/rehabilitación , Depresión , Progresión de la Enfermedad , Femenino , Escala de Coma de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/rehabilitación , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: To evaluate gender differences in GH dosing, IGF-I and cardiovascular risk markers in adults with GH deficiency (GHD). DESIGN: NordiNet® International Outcome Study (NCT00960128), a noninterventional, multicentre study, evaluates the long-term effectiveness and safety of Norditropin® (Novo Nordisk A/S) in the real-life clinical setting. PATIENTS: Nondiabetic patients (n = 252; 41·7% female) with adult-onset GHD (age ≥20 years at GH start), ≥4 years' GH therapy and glycosylated haemoglobin (HbA1c ) data at baseline and 4 years. MEASUREMENTS: Effects of gender (adjusted for baseline age and body mass index [BMI], average GH dose, treatment duration and concomitant medication) on change from baseline to 4 years (∆) in HbA1c , fasting plasma glucose (FPG), IGF-I, lipids and waist circumference were evaluated. RESULTS: GH dose (mean [SE]; mg/day) was similar between females (0·22 [0·02]) and males (0·21 [0·01]) at baseline, but higher in females from year 1 (year 4, females, 0·45 [0·03]; males, 0·32 [0·02]). Mean IGF-I standard deviation score [SDS] was lower in females vs males at each treatment year; more than one-third of females still had an IGF-I SDS below 0 at year 4, compared with only 21·8% of men. An adverse lipid profile at baseline remained poor in more females than males at 4 years. Improvement in total cholesterol was significantly associated with gender (P < 0·0001), improving less in females than in males. CONCLUSIONS: These data highlight that, even after 4 years, GH dose is suboptimal in many female patients, which may impact clinical outcomes; therefore, GH titration for women requires further improvement.
Asunto(s)
Hormona de Crecimiento Humana/administración & dosificación , Hormona de Crecimiento Humana/deficiencia , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Hemoglobina Glucada/análisis , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Evaluación de Resultado en la Atención de Salud , Adulto JovenRESUMEN
OBJECTIVE: To assess the effect of 4 years' growth hormone (GH) replacement on glucose homeostasis and evaluate factors affecting glycosylated haemoglobin (HbA1c ) in adults with growth hormone deficiency (GHD). DESIGN: NordiNet® International Outcome Study, a noninterventional study, monitors long-term effectiveness and safety of GH replacement [Norditropin® (somatropin), Novo Nordisk A/S] in real-life clinical practice. PATIENTS: Nondiabetic patients (n = 245) with adult-onset GHD (age ≥20 years at GH start), ≥4 years' GH replacement and HbA1c values at baseline and 4 years were included in the analysis. MEASUREMENTS: Changes from baseline (∆) to 4 years in HbA1c , fasting plasma glucose (FPG), IGF-I, lipids (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides), waist circumference, glycaemic (HbA1c <5·7%; HbA1c , 5·7-6·5%; HbA1c , ≥6·5%) and metabolic health status were evaluated. Effects of baseline HbA1c , gender, baseline age, average GH dose and baseline body mass index (BMI) on ΔHbA1c were investigated. The models were adjusted for concomitant medication use. RESULTS: Mean (standard deviation) baseline HbA1c was 5·13 (0·65)% and remained at the same level at 4 years. Age at treatment start (P = 0·0094) and BMI (P = 0·0008) had a significant impact on ∆HbA1c . At 4 years, 85% of patients with HbA1c <5·7% (normal levels) at baseline and 55% of patients with HbA1c 5·7-6·5% (impaired glucose tolerance) at baseline remained in the same glycaemic health category. Nineteen patients improved from impaired glucose tolerance to normal HbA1c . Seven patients developed diabetes. CONCLUSIONS: These data demonstrate that 4 years' GH replacement therapy did not adversely affect glucose homeostasis in the majority of adults with GHD.
Asunto(s)
Glucemia/análisis , Hormona del Crecimiento/deficiencia , Homeostasis/efectos de los fármacos , Terapia de Reemplazo de Hormonas/métodos , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/efectos de los fármacos , Diabetes Mellitus , Femenino , Hemoglobina Glucada/análisis , Hormona del Crecimiento/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Maternal S-cortisol levels increase throughout pregnancy and peak in the third trimester. Even higher levels are seen during the physical stress of delivery. Since analgesia for women in labor has improved, it is possible that maternal stress during labor is reduced. The aim of this study was to compare maternal S-cortisol during vaginal delivery and elective cesarean section. MATERIALS AND METHODS: Twenty healthy women with spontaneous vaginal delivery and healthy women (n = 20) undergoing elective cesarean section were included in the study. S-cortisol was measured during three stages of spontaneous vaginal delivery (tvd1, tvd2 and tvd3), as well as before and after elective cesarean section (tcs1 and tcs2). RESULTS: In the vaginal delivery group, mean S-cortisol at tvd1 was 1325 ± 521 nmol/L, at tvd2 1559 ± 591 nmol/L and at tvd3 1368 ± 479 nmol/L. In the cesarean section group, mean S-cortisol at tcs1 was 906 ± 243 nmol/L and at tcs2 831 ± 257 nmol/L. S-cortisol was higher in the vaginal delivery group at the onset of labor as compared to the cesarean section preoperative group (p = 0.006). There were also significant differences between S-cortisol levels postpartum as compared to postoperatively (p < 0.001). CONCLUSIONS: Maternal S-cortisol was higher during vaginal delivery compared to elective cesarean section, indicating higher stress levels. A reduction in the hydrocortisone dose at childbirth in women with adrenal insufficiency should be considered, particularly in women undergoing an elective cesarean section.
Asunto(s)
Cesárea , Parto Obstétrico , Hidrocortisona/metabolismo , Adulto , Femenino , Humanos , Trabajo de Parto , Parto , Embarazo , Adulto JovenRESUMEN
AIM: Growth hormone (GH) treatment is a relatively new concept in adults, and the knowledge of its long-term effects is limited. We studied ten men with Prader-Willi Syndrome (PWS) after more than 5 years of GH treatment. METHODS: Study participants underwent a detailed physical examination, including blood tests. Five had received GH as childhood and five had started GH as adults. RESULTS: The total duration of GH treatment was 16 ± 4 years in the childhood PWS group and 15 ± 1 years in the adulthood PWS group. Their respective mean ages were 27 ± 4 years and 44 ± 4 years, mean heights were 178 ± 11 cm and 156 ± 5 cm, and mean body mass indexes were 32.4 ± 10.3 kg/m(2) and 28.9 ± 4.6 kg/m(2) . There were no differences in body composition between the groups and all lipids and insulin-like growth factor 1 were normal or close to normal. Four had well-controlled type 2 diabetes. The GH doses in the childhood and adulthood groups were 0.4 mg and 0.3 mg, respectively. CONCLUSION: Men with PWS who received GH treatment displayed positive effects on body composition independent of when the GH treatment had started. Only patients who gained weight developed diabetes. The duration of GH treatment should balance the benefits and observed side effects.
Asunto(s)
Composición Corporal/efectos de los fármacos , Hormona de Crecimiento Humana/farmacología , Hormona de Crecimiento Humana/uso terapéutico , Adulto , Estudios Transversales , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Prader-Willi/tratamiento farmacológico , Factores de Tiempo , Adulto JovenAsunto(s)
Hormona de Crecimiento Humana , Síndrome de Prader-Willi , Humanos , Obesidad , Prevalencia , Adulto JovenRESUMEN
Prader-Willi syndrome (PWS) is a rare genetic disorder typically characterized by body composition abnormalities, hyperphagia, behavioral challenges, cognitive dysfunction, and hormone deficiencies. Hypogonadism is common but knowledge on potential side effects of testosterone replacement is limited, in particular, the long-term effects on behavior and PSA. PATIENTS AND METHODS: Retrospective case studies of seven men, median age 46 years, with genetically verified PWS, testosterone treated hypogonadism and available PSA values were included. Long-term follow-up of PSA was accessible in four patients. Medical records were reviewed for adverse effects. RESULTS: Five men were treated with intramuscular testosterone undecanoate, two had no hypogonadism. Median PSA was 0.68 µg/L (0.23-1.3), median testosterone 15 nmol/L. After a median time of 17 years of testosterone replacement median PSA was 0.75 µg/L (range 0.46-1.4). Testosterone replacement was well tolerated, and no major behavioral changes were reported. Five were treated with growth hormone for >20 years. CONCLUSION: Levels of PSA were low. Long-term treatment with testosterone was working well and did not result in any clinically meaningful increase in PSA. Our results indicate that testosterone replacement is neither associated with serious adverse events regarding changes in behavior or effect on PSA. However, larger studies are needed to confirm our results.