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Patients with hypopituitarism of various etiologies have excess mortality. The mortality in patients with nonfunctioning pituitary adenoma (NFPA), regardless of pituitary function, is less well studied.Our aim was to investigate mortality in patients with NFPA and to examine whether age at diagnosis, gender, tumor treatments, or hormonal deficiencies influence the outcome.NFPA patients were identified and followed up in nationwide health registries in Sweden, 1987-2011. The criteria for identification were tested and validated in a subpopulation of the patients.This was a nationwide, population-based study.A total of 2795 unique patients with NFPA (1502 men, 1293 women) were identified and included in the study. Mean age at diagnosis was 58 years (men, 60 y; women, 56 y) and mean follow-up time was 7 years (range 0-25 y).There were no interventions.Standardized mortality ratios (SMRs) and annual incidence rates were calculated using the Swedish population as reference and presented with 95% confidence intervals.Annual incidence of NFPA was 20.3 (18.8-21.9) cases per 1 million inhabitants. During the observation period, 473 patients died against an expected 431, resulting in an SMR of 1.10 (1.00-1.20). Patients diagnosed at younger than 40 years of age had an increased SMR of 2.68 (1.23-5.09). The SMR for patients with hypopituitarism (n = 1500) was 1.06 (0.94-1.19), and for patients with diabetes insipidus (n = 145), it was 1.71 (1.07-2.58). The SMR was increased in women with NFPA (1.29; 1.11-1.48) but not in men (1.00; 0.88-1.12). Women, but not men, with a diagnosis of hypopituitarism and/or diabetes insipidus also had an increased mortality ratio. SMRs due to cerebrovascular (1.73; 1.34-2.19) and infectious diseases (2.08; 1.17-3.44) were increased, whereas the SMR for malignant tumors was decreased (0.76; 0.61-0.94).This nationwide study of patients with NFPA showed an overall excess mortality in women and in patients with a young age at diagnosis. Increased mortality was seen for cerebrovascular and infectious diseases.
Patients with secondary adrenal insufficiency (AI) have an excess mortality. The objective was to investigate the impact of the daily glucocorticoid replacement dose on mortality in patients with hypopituitarism due to non-functioning pituitary adenoma (NFPA).Patients with NFPA were followed between years 1997 and 2014 and cross-referenced with the National Swedish Death Register. Standardized mortality ratio (SMR) was calculated with the general population as reference and Cox-regression was used to analyse the mortality.The analysis included 392 patients (140 women) with NFPA. Mean ± s.d. age at diagnosis was 58.7 ± 14.6 years and mean follow-up was 12.7 ± 7.2 years. AI was present in 193 patients, receiving a mean daily hydrocortisone equivalent (HCeq) dose of 20 ± 6 mg. SMR (95% confidence interval (CI)) for patients with AI was similar to that for patients without, 0.88 (0.68-1.12) and 0.87 (0.63-1.18) respectively. SMR was higher for patients with a daily HCeq dose of >20 mg (1.42 (0.88-2.17)) than that in patients with a daily HCeq dose of 20 mg (0.71 (0.49-0.99)), P = 0.017. In a Cox-regression analysis, a daily HCeq dose of >20 mg was independently associated with a higher mortality (HR: 1.88 (1.06-3.33)). Patients with daily HCeq doses of ≤20 mg had a mortality risk comparable to patients without glucocorticoid replacement and to the general population.Patients with NFPA and AI receiving more than 20 mg HCeq per day have an increased mortality. Our data also show that mortality in patients substituted with 20 mg HCeq per day or less is not increased.
The objective of this study was to investigate whether there is a bidirectional association between testosterone concentrations and insulin resistance, in a prospective population study. A random population sample of 1400 men, aged 30-74, was examined in 2002-2005 in southwestern Sweden and followed up in 2012-2014 (N = 657). After excluding subjects without information on sex hormones and insulin resistance, 1282 men were included in the baseline study. Fasting measurements of plasma glucose, insulin and hormones were performed. Insulin resistance was defined using HOMA-Ir. Mean age at baseline was 47.3 ± 11.4 years. From the follow-up survey 546 men were included, mean age 57.7 ± 11.6 years. Low concentrations of total testosterone at baseline were significantly associated with high logHOMA-Ir at follow-up in a multivariable model including age, waist-hip ratio, physical activity, alcohol intake, smoking, LDL, CRP, hypertension, diabetes and logHOMA-Ir at baseline as covariates (β = -0.096, P = 0.006). Similar results were observed for bioavailable testosterone. Men within the lowest quartile of total testosterone at baseline had significantly higher logHOMA-Ir at follow-up than other quartiles (Q1 vs Q2 P = 0.008, Q1 vs Q3 P = 0.001, Q1 vs Q4 P = 0.052). Multivariable analysis of the impact of insulin resistance at baseline on testosterone levels at follow-up revealed no significant associations regarding testosterone concentrations (β = -0.003, P = 0.928) or bioavailable testosterone (β = -0.006, P = 0.873), when adjusting for baseline concentrations of total testosterone, age, waist-hip-ratio, LDL, CRP, physical activity, alcohol intake, smoking, hypertension and diabetes. Low testosterone concentrations at baseline predicted higher insulin resistance at follow-up, but high insulin resistance at baseline could not predict low testosterone at follow-up.
Obesity is associated with increased risk of fractures, especially at skeletal sites with a large proportion of cortical bone, such as the humerus and ankle. Obesity increases fracture risk independently of BMD, indicating that increased adipose tissue could have negative effects on bone quality. Microindentation assesses bone material strength index (BMSi) in vivo in humans. The aim of this study was to investigate if different depots of adipose tissue were associated with BMSi and cortical bone microstructure in a population based group of 202 women, 78.2 ± 1.1 (mean ± SD) years old. Bone parameters and subcutaneous (s.c.) fat were measured at the tibia with an XtremeCT device. BMSi was assessed using the OsteoProbe device, and based on at least 11 valid reference point indentations at the mid-tibia. Body composition was measured with dual X-ray absorptiometry. BMSi was inversely correlated to body mass index (BMI) (r = -0.17, p = 0.01), whole body fat mass (r = -0.16,p = 0.02), and, in particular, to tibia s.c. fat (r = -0.33, p < 0.001). Tibia s.c. fat was also correlated to cortical porosity (Ct.Po; r = 0.19, p = 0.01) and cortical volumetric BMD (Ct.vBMD; r = -0.23, p = 0.001). Using linear regression analyses, tibia s.c. fat was found to be independent of covariates (age, height, log weight, bisphosphonates or glucocorticoid use, smoking, calcium intake, walking speed, and BMSi operator) and associated with BMSi (β = -0.34,p < 0.001), Ct.Po (β = 0.18, p = 0.01), and Ct.vBMD (β = -0.32, p < 0.001). BMSi was independent of covariates associated with cortical porosity (β = -0.14, p = 0.04) and cortical volumetric BMD (β = 0.21, p = 0.02) at the distal tibia, but these bone parameters could only explain 3.3% and 5.1% of the variation in BMSi, respectively. In conclusion, fat mass was independently and inversely associated with BMSi and Ct.vBMD, but positively associated with Ct.Po, indicating a possible adverse effect of adipose tissue on bone quality and bone microstructure. Local s.c. fat in tibia was most strongly associated with these bone traits, suggesting a local or paracrine, rather than systemic, negative effect of fat on bone.
Because prevalent vertebral fracture (VF) is a strong predictor of future fractures, they are important to identify in clinical practice as osteoporosis medications are effective and can be used to reduce fracture risk in postmenopausal women with VF. Lateral spine imaging (LSI) with dual-energy X-ray absorptiometry (DXA) can be used to diagnose VFs accurately but is not widespread in clinical practice. The prognostic value of grade 1 (20% to 25% compression) VFs diagnosed by LSI with DXA has been insufficiently studied. The aim of this study was to determine if grade 1 VF is associated with incident fracture in older women. Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a population-based study of 3028 older women from Gothenburg, Sweden. Included women were 75 to 80 years of age at baseline, answered questionnaires, and were scanned with DXA (Discovery A, Hologic, Waltham, MA, USA). LSI was used to diagnose VFs, which were classified using the Genant semiquantitative method. Cox regression models were used to estimate the association between VFs at baseline and X-ray-verified incident fractures, with adjustment for confounders. Women with a grade 1 VF (n= 264) or a grade 2-3 VF (n= 349) were compared with women without any fracture (n= 1482). During 3.6 years (median, interquartile range [IQR] 1.5 years) of follow-up, 260 women had any incident fracture and 213 a major osteoporotic fracture (MOF). Women with only grade 1 VF had increased risk of any fracture (hazard ratio [HR] = 1.67; 95% confidence interval [CI] 1.18-2.36) and MOF (HR = 1.86; 95% CI 1.28-2.72). For MOF, this association remained after adjustment for clinical risk factors and femoral neck bone mineral density (BMD). In conclusion, grade 1 VFs were associated with incident MOF, also after adjustment for clinical risk factors and BMD, indicating that all VF identified by DXA should be considered in the evaluation of fracture risk in older women. (c) 2020 The Authors.Journal of Bone and Mineral Researchpublished by American Society for Bone and Mineral Research..
