Penelope Trimpou

High correlation between quantitative ultrasound and DXA during 7 years of follow-up

Ultrasound is a quick, cheap and non-radiating device for assessing bone quality. We wanted to validate the method for clinical and epidemiological use. Eighty women, aged 53-73 years, with osteoporosis and/or fractures were followed repeatedly during 7 years. Quantitative ultrasound (QUS) measurements (LUNAR Achilles) were compared with bone mineral density (BMD) and bone mineral content (BMC) estimated by DXA (LUNAR) in regions of interest. Changes in the speed of sound, broadband ultrasound attenuation and stiffness were positively correlated with changes in BMD and BMC in all regions measured with DXA (r=0.20-0.53; p=0.09 to <0.0001). The QUS t-score at the left heel was positively correlated with the t-score at the right heel (r=0.90, p<0.0001). The DXA t-score of the left vs. the right femur was also positively correlated (r=0.72-0.86; p<0.0001). A t-score<-2.5 S.D. was found in 70% and 56% at baseline, and 74% and 65% at follow-up measured with QUS and DXA, respectively. The mean sensitivity of QUS vs. DXA was 79% and the mean specificity 45% over a 7-year period. A QUS t-score of <-3.65 S.D. was consistent with a DXA t-score of <-2.5 S.D. In conclusion, QUS was well correlated with DXA in all regions over the 7-year period. QUS can be used in settings without access to DXA and in epidemiological studies. The sensitivity was high but the specificity was low, implicating that DXA, if available, is recommended before treatment for osteoporosis. However, treatment can be started without DXA at a QUS t-score<-3.65 S.D., and especially in the presence of fractures.

Excess Mortality in Women and Young Adults With Nonfunctioning Pituitary Adenoma: A Swedish Nationwide Study

CONTEXT 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. OBJECTIVE 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. DESIGN 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. SETTINGS This was a nationwide, population-based study. PATIENTS 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). INTERVENTION There were no interventions. MAIN OUTCOME MEASURES Standardized mortality ratios (SMRs) and annual incidence rates were calculated using the Swedish population as reference and presented with 95% confidence intervals. RESULTS 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). CONCLUSIONS 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.

Effect of Growth Hormone Treatment on Fractures and Quality of Life in Postmenopausal Osteoporosis: A 10-Year Follow-Up Study

CONTEXT Growth hormone (GH) treatment increases bone mineral density (BMD) in women with postmenopausal osteoporosis. OBJECTIVE The objective was to report bone data, fractures, and quality of life (QoL) in a 10-year follow-up of women who had received GH for 3 years and compared with controls followed in parallel. DESIGN AND SETTING A follow-up of a double-blind, placebo-controlled study conducted at Sahlgrenska University Hospital was performed. PATIENTS Eighty women aged between 50 and 70 years with osteoporosis and estrogen hormone replacement were studied and compared with an age-matched random population sample of women (n = 120) from the World Health Organization Monitoring of Trends and Determinants in Cardiovascular Disease project (Gothenburg, Sweden). INTERVENTIONS Patients were randomized to GH 1.0 U or GH 2.5 U recombinant human GH or placebo sc daily during 3 years. All received calcium 750 mg and vitamin D 400 U and were followed up during 10 years. MAIN OUTCOME MEASURES BMD and bone mineral content were measured with dual-energy X-ray absorptiometry. QoL was estimated with the 36-item Short Form. RESULTS GH increased BMD and bone mineral content dose dependently in all regions (P = .01, GH 1.0 U, and P = .0006, GH 2.5 U vs placebo). After 10 years the number of fractures decreased from 56% to 28% (P = .0003) in patients evenly distributed between groups. In controls, fractures increased from 8% to 32% (P = .0008). QoL did not change during GH treatment or during the 10-year follow-up and did not differ compared with controls. CONCLUSION GH treatment was beneficial for bone and fracture outcome after 10 years but did not affect the QoL of the women with postmenopausal osteoporosis.

Life Expectancy in Patients with Pituitary Adenoma Receiving Growth Hormone Replacement

OBJECTIVE Hypopituitarism has been associated with increased mortality. The excess mortality may be due to untreated growth hormone (GH) deficiency but also due to various underlying disorders. We therefore analysed mortality in patients with only one underlying disorder, non-functioning pituitary adenoma (NFPA), with and without GH replacement therapy (GHRT). DESIGN AND METHOD Patients with NFPA in the western region of Sweden, 1997-2011, were identified through the National Patient Registry and cross-referenced with several National Health Registries. All patient records were reviewed. Standardised mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated using the general population as reference. Cox-regression models were performed to identify predictors of mortality. RESULTS A total of 426 NFPA patients with 4599 patient-years were included, of whom 207 had used GHRT and 219 had not received GHRT. Median (range) follow-up in patients with and without GHRT was 12.2 (0-25) and 8.2 (0-27) years, respectively. Other pituitary hormone deficiencies were more frequent in the GHRT group than those in the non-GHRT group. SMR was 0.65 (95% CI, 0.44-0.94; P = 0.018) for the GHRT group and 1.16 (0.94-1.42; P = 0.17) for the non-GHRT group. Direct comparison between the groups showed reduced mortality among those who were GH replaced (P = 0.0063). The SMR for malignant tumours was reduced in the GHRT-group (0.29; 0.08-0.73; P = 0.004) but not in untreated patients. CONCLUSIONS Selection bias explaining some of the results cannot be excluded. However, NFPA patients with GHRT had reduced overall mortality compared with the general population, and death due to malignancy was not increased. This suggests that long-term GHRT is safe in adult patients selected for treatment.

Normocalcaemic, vitamin D-sufficient hyperparathyroidism - high prevalence and low morbidity in the general population: A long-term follow-up study, the WHO MONICA project, Gothenburg, Sweden.

There is limited knowledge about the natural history of normocalcaemic, vitamin D‐sufficient hyperparathyroidism (nHPT). The aim was to study the prevalence of nHPT and its relation to morbidity.

Secular trends in sex hormones and fractures in men and women.

OBJECTIVE To study secular trends in sex hormones, anthropometry, bone measures and fractures. DESIGN A random population sample was studied twice and subjects of similar age group were compared 13 years apart. METHODS X-ray-verified fractures were retrieved from a random population sample of 2400 men and women (participants 1616=67%) aged 25-64 years from the WHO, MONICA Project in Gothenburg, Sweden, in 1995 and 2008. Fasting serum hormones and calcaneal ultrasound were measured in every fourth subject. In fertile women, measurements were performed on cycle day interval 7-9. RESULTS In 2008, men had lower serum free testosterone than men of similar age in 1995 (P<0.001). Body composition, physical activity and fracture incidence were similar. In women, hormone replacement therapy (HRT) was lower in 2008, 7 vs 28% (P<0.0001), as was serum oestradiol, although use of tranquilisers and leisure time physical activity were higher. In 2008, the fracture incidence was higher in postmenopausal women, 29 vs 17% (P<0.001), and vertebral crush had increased from 8 to 19% of all fractures (P=0.031). Serum cholesterol and triglycerides were lower in all subjects in 2008 compared with that in 1995. CONCLUSIONS Secular trends were observed with lower serum testosterone in men in 2008, but no effect was seen on the fracture incidence of these fairly young men. In postmenopausal women in 2008, there was a higher fracture incidence along with more vertebral compressions. Lower HRT use, lower serum oestradiol and higher fall risk exposure due with more tranquilisers and leisure time physical activity in 2008 may explain the results.

The association between urinary cortisol excretion and cardiovascular risk factors, bone status and quality of life in the population.

OBJECTIVE Patients with glucocorticoid excess have increased cardiovascular risk, decreased bone mineral density and impaired quality of life (QoL). The aim of this study was to evaluate the association between urinary cortisol excretion and cardiovascular risk factors, bone status and QoL in the population. We hypothesized that higher cortisol excretion was associated with adverse cardiovascular risk profile, worse skeletal health and QoL. DESIGN, PATIENTS AND METHODS This was a cross-sectional study including a population sample (n=348), aged 38-77years. The mean age in women was 64.0±8.5years (n=276) and 60.3±10.2years in men (n=72). The metabolic syndrome, body composition measured with bioimpedance, calcaneal quantitative ultrasound, fractures and QoL evaluated with the Nottingham Health Profile, Psychological General Well-Being (PGWB) and the Short Form 36 (SF-36) were studied. Urinary free cortisol (UFC) was measured using radioimmunoassay. RESULTS UFC was higher in men (230±120nmol/L) compared to women (153±71; P<0.001) and decreased with increasing age (P<0.001). In a regression analysis, after adjustment for gender, age and body mass index, higher UFC was associated with higher fat-free mass (P<0.01), favourable calcaneal bone measurements (P<0.05), better general health measured with PGWB (P<0.01) and SF-36 (P=0.001) and tended to be negatively associated with the metabolic syndrome (P=0.07). CONCLUSION In contrast to our hypothesis, UFC in the upper physiological range was associated with a favourable cardiovascular risk profile, bone measures and QoL.

The impact of adjustments to the diagnostic criteria for biochemical remission in surgically treated patients with acromegaly

BACKGROUND The suggested criteria for biochemical remission in patients treated for acromegaly were recently modified. The aim of this project was to study to what extent this modification influences remission rates. DESIGN, PATIENTS AND METHODS This was a retrospective study of 55 consecutive patients [29 men; median age 47years (interquartile range 38-68)] diagnosed with acromegaly between 2003 and 2014. After treatment serum IGF-I and/or GH was measured according to a standardized protocol. The biochemical remission status was defined according to the clinical guidelines from 2010 and2014. RESULTS Out of 55 patients, 44 patients were primarily operated. Of these, 33 (75%) were evaluated 3-12months postoperatively by measuring serum IGF-I and GH during an oral glucose tolerance test. According to the 2010 guidelines, 11 patients (33%) were in biochemical remission, 15 patients (46%) were not and 7 patients (21%) had discordant results (normal IGF-I and high GH or vice versa). Applying the 2014 guidelines in the same group, 16 patients (49%) were in biochemical remission, 7 patients (21%) were not and 10 patients (30%) had discordant results. Thus, by using the most recent criteria for biochemical control, more patients were considered to be in remission, or with discordant results, and fewer patients not in remission (P<0.05). CONCLUSION An apparently minor adjustment of the criteria for biochemical control has a significant impact on remission status in patients treated for acromegaly, eventually affecting follow-up and treatment strategies.

High androgen levels protect against hypothyroidism.

Hypothyroidism is a common disorder, appearing mainly in women although less frequently found in women with polycystic ovary syndrome (PCOS). The objective was to test the hypothesis that hyperandrogenism might protect against hypothyroidism.

Higher menopausal age but no differences in parity in women with polycystic ovary syndrome compared with controls

To address the question of whether women with polycystic ovary syndrome (PCOS) reach menopause later than age‐matched controls, we conducted a follow‐up cohort study of women with well‐characterized PCOS that was diagnosed 24 years ago. The hypothesis was that women with PCOS would reach menopause later than non‐PCOS women. Parity during these 24 years was also studied.