Analysis of hematological parameters in rheumatoid arthritis patients receiving biological therapy: contribution to prevention of avoidable hematological complications.

Administration of biological therapy (BT) in rheumatoid arthritis (RA) patients is often associated with hematological complications, which result in switching among therapies. Thus, there is an instant need for suitable screening parameters that will help to individualize the therapy and minimize the onset of adverse effects. We analyzed the hematological profile of 99 RA patients receiving TNFα (Adalimumab - ADA, Golimumab - GOL, Etanercept - ETA) or IL-6 receptor (Tocilizumab - TCZ) inhibitors in order to find possible indicators to improve personalization of RA therapy. BTs significantly affect the levels of observed hematological parameters. In contrast to TNF-α inhibitors, TCZ normalized almost all monitored hematological parameters to values of healthy donors. Only GOL from the TNF-α inhibitors studied, was able to normalize neutrophil counts, as well as platelet indicators. Importantly, effects on the blood parameters (e.g. lymphocytes or platelet count) differ even within the same therapeutic group (anti-TNFα). Variable effects of individual biological agents in RA treatment point to importance to evaluate the patient's hematological profile to improve the selection of suitable BT. It will help to personalize the administration of BT and prevent unnecessary switching from an effective therapy just because of provocation of avoidable hematological complications.

Patients with COVID-19 pneumonia with 25(OH)D levels lower than 12 ng/ml are at increased risk of death.

OBJECTIVES: There is no consensus on specific serum 25-hydroxy vitamin D (25(OH) D) levels associated with higher risk of severe outcome in patients with coronavirus disease 2019 (COVID-19). According to the literature patients with serum 25(OH) D levels <12 ng/ml are clearly deficient at all ages. Our aim was to assess COVID-19 mortality in the settings of severe 25(OH) D deficiency. A cohort study of 357 patients with COVID-19 was conducted. Subjects were monitored until discharge or in-hospital death. At admission, severity parameters (C-reactive protein (CRP), IL-6, Charlson comorbidity index, etc.) were assessed. These parameters were compared regarding 25(OH) D levels threshold 12 ng/ml, where values below 12 ng/ml were considered absolute vitamin D deficiency. RESULTS: 25(OH) D levels at the time of admission were independently associated with mortality (p <0.05). Nonsurvivors (N = 168) had lower 25(OH) D levels, SO2, higher age, CRP, viral load, and Charlson comorbidity index in comparison to survivors. Patients with serum 25(OH) D levels <12 ng/ml had higher mortality (55% vs 45 %), viral load (21.5 vs 23.1), and Charlson comorbidity index (5.3 vs 4.4) than those with serum 25(OH) D levels >12 ng/ml (p <0.05). CONCLUSIONS: Patients with COVID-19 with serum 25(OH) D levels <12 ng/ml have higher mortality. Among other factors, severe vitamin D deficiency likely leads to poor outcome.

Vertebral Fractures Occur Despite Control of Acromegaly and Are Predicted by Cortical Volumetric Bone Mineral Density.

CONTEXT: Recent studies suggest that cortical bone could also play a role in vertebral fracture (VF) development in acromegaly. OBJECTIVE: Evaluate the occurrence of VFs and their relationship to dual energy x-ray absorptiometry-derived bone parameters. METHODS: A single-center 2-year prospective study of acromegaly patients was conducted. Each subject had L1-4 spine, femoral neck and total hip (TH) areal BMD measured using DXA, and trabecular bone score (TBS) measurement performed. 3D Shaper™ was used to assess proximal femur trabecular and cortical volumetric (v)BMD, cortical surface (s)BMD, and cortical thickness (Cth). VF assessment was performed using the lateral spine imaging IVA™ mode with a Hologic Horizon® densitometer using a semiquantitative approach. Study outcomes were assessed at 2 time points: baseline and month 24. RESULTS: 70 acromegaly patients (34 M/36F; average 55.1 years) were studied, including 26 with active disease. In 13 patients, 9 with controlled disease, VF was observed. A decrease in TBS, sBMD, neck trabecular vBMD, TH, and neck cortical vBMD in VF compared with non-VF subjects was observed (P < .05). Multivariate analysis of fracture prediction showed TH cortical vBMD as the best fracture prediction parameter with area under the curve of 0.774. TBS was negatively associated with fasting plasma glucose and glycated hemoglobin (HBA1c) at each time point during the follow-up. CONCLUSION: From the total number of 13 VF subjects, 9 were in the controlled disease group. The most sensitive and specific predictor of incident VF was TH cortical vBMD, suggesting that cortical bone is involved in fracture development.

Osteoporosis in premenopausal women.

In contrast to postmenopausal women diagnostic process and treatment of premenopausal osteoporosis in young women reamin poorly defined. A low bone mineral density in premenopausal women is not associated with the same risk of fractures as in postmenopausal women, therefore diagnosis requires not only densitometric examination but depends on the consideration of other risk factors. Most cases of premenopausal osteoporosis are associated with chronic diseases affecting bone metabolism. Treatment of the underlying disease may improve bone density as well as bone quality. Rarely, a bone-specific antiporotic therapy may be used, although quality evidence is scarce. This article will review current opinion on definition, diagnosis and treatment of premenopausal osteoporosis.

Microscopic polyangiitis.

Microscopic polyangiitis is a rare, systemic, necrotizing, pauci-immune, ANCA associated small vessel vasculitis, with no evidence of granulomatous inflammation. Diagnosing microscopic polyangiitis is often difficult because of it´s presentation by a number of non-specific symptoms. We treated a 35-year old patient, who was admitted for migrating arthritis and fever with papulous rash. In this case, we want to point out the importance of considering the diagnosis of MPA and similar rare diseases in the process of differential diagnosis, mainly in patients presenting with non-specific symptoms, because the mortality of this disease without adequate treatment is alarmingly high.

Strength training as a supplemental therapy for androgen deficiency of the aging male (ADAM): study protocol for a three-arm clinical trial.

INTRODUCTION: Androgen deficiency of the ageing male is a clinical syndrome resulting from the low production of androgens (testosterone levels <6.9 nmol/L) with symptoms including decline in lean mass, muscle strength, increases in body mass and overall fat mass. The aim of the study is to examine the effect of a 12 week strength training intervention on body composition, physical function, muscle cellular and molecular and selected biochemical markers of metabolic health in hypogonadal patients. METHODS AND ANALYSIS: The study is three-group controlled 12-week experiment to assess the effect of strength training on hypogonadal patients with testosterone replacement therapy and newly diagnosed males without testosterone replacement therapy. Age matched healthy eugonadal males are also engaged in strength training. Lean mass is used to determine sample size indicating, that 22 subjects per group will be sufficient to detect intervention related changes at the power of 0.90. All outcomes are collected before the intervention (pre-intervention assessments) and after the intervention (post-intervention assessments). Clinical outcomes are body composition (lean mass, fat mass and total body mass) measured by dual-energy X-ray absorptiometry, physical functioning assessed by physical tests and psychosocial functioning. The most important haematological and biochemical parameters included are glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, testosterone, luteinizing hormone, follicle-stimulating hormone, sexhormone-binding globulin, insulin and prostate-specific antigen. Muscle cellular and molecular outcomes are muscle fibre size and regulators of muscle fibre size. Muscle cellular outcomes are measured from muscle biopsies obtained from musculus vastus lateralis. ETHICS AND DISSEMINATION: This trial is approved by Ethics Committee of the University Hospital in Bratislava, Slovakia, (ref. trial number: 127/2017) and all subjects will be fully informed on the rationale, risks and benefits of the study and sign the written informed consent prior to entering the study. Results will be published in peer-reviewed journals and presented in scientific conferences. TRIAL REGISTRATION NUMBER: NCT03282682.

Novel aspects of the activation of NADPH oxidase in neutrophils of rheumatic patients on biological therapy.

The relationship between inflammation and formation of reactive oxygen species (ROS) is still not completely understood and excessive inflammatory reaction is attributed to increased yet also to reduced ROS formation. To compare ROS formation in severe and low inflammation, neutrophil oxidative burst was analyzed in rheumatic patients before and during therapy with TNFα- or interleukin-6 receptor-neutralizing antibodies. Intracellular and extracellular ROS productions were evaluated on the basis of luminol- and isoluminol-enhanced chemiluminescence in isolated peripheral neutrophils. Disease activity score DAS28 and platelet to lymphocyte ratio were used as markers of arthritis activity and the intensity of systemic inflammation. Biological therapy effectively reduced the intensity of inflammation. Of the twenty-six patients studied eighteen achieved remission or low disease activity. Highly active arthritis persisted only in one patient, though prior to the therapy it was evident in all subjects tested. In patients receiving biological therapy, intracellular chemiluminescence was significantly higher than in patients before this therapy; ROS produced by neutrophils extracellularly were not affected. The increased ROS formation associated with reduced inflammation supports the need to revise the view of the role of ROS in inflammation - from toxic agents promoting inflammation towards a more complex view of ROS as regulators of immune pathways with inflammation-limiting capacity. From this perspective, the interference with neutrophil-derived oxidants may represent a new mechanism involved in the anti-inflammatory activity of biological therapy.

Biologic treatment in comparison to methotrexate has positive effect on trabecular bone score in rheumatoid arthritis patients: 1-year follow-up.

INTRODUCTION: Biologic treatment may influence activity of rheumatoid arthritis (RA), as well as areal bone mineral density (aBMD). Decreased aBMD explains the fracture risk in RA patients only partially. The trabecular bone score (TBS), novel texture parameter reflects degradation of trabecular bone and therefore could be used as a further parameter to predict the risk of fragility fracture. OBJECTIVE: To compare the effects of biological disease-modifying antirheumatic drugs (bDMARDs) and conventional synthetic (cs) DMARDs (methotrexate) on aBMD and TBS in patients suffering from active RA. METHODS: A 12 month prospective trial was performed in 105 active RA patients. The cohort was divided into two groups: group 1 (n = 84, mean age 54 yrs) treated with bDMARDs and group 2 (n = 21, mean age 53 yrs) treated with csDMARDs. The mean daily dose of prednisone at baseline was 6.2 and 6.6 mg (NS) between group 1 and 2, respectively. Patients with anti-osteoporotic treatment were not included. All patients received calcium (600 mg) and cholecalciferol (800IU). Lumbar spine (LS) and FN aBMD (by DXA, Hologic) were measured at baseline and after 1 year of treatment. TBS was generated using TBS Insight software (Medimaps, Switzerland). RESULTS: Treatment with bDMARDS led to decrease in mean prednisone dose and to increase of 1.7% (p < 0.05) in TBS and OC levels of 26% (p < 0.001) but not on aBMD and CTX after treatment. The greatest TBS increase (2.7%, p < 0.05) was observed in premenopausal females within group 1. No effect of csDMARDS on measured parameters was observed. CONCLUSION: Treatment of patients suffering from active RA with bDMARDs in comparison to csDMARDS led to increase of TBS, with greater increment of TBS in premenopausal women, despite no change in aBMD.

Non-invasive DXA-derived bone structure assessment of acromegaly patients: a cross-sectional study.

Introduction Impaired bone microarchitecture is involved in vertebral fracture (VF) development among acromegaly patients. Aim of the study Comparison of DXA-derived bone parameters, areal BMD (aBMD), trabecular bone score (TBS) and 3D-SHAPER parameters in acromegaly patients with healthy controls. Methods This cross-sectional study evaluated acromegaly patients and a control group of healthy subjects. In all subjects, a single measurement of pituitary axis hormone levels, bone turnover markers, aBMD, (total hip (TH) and lumbar spine (LS)), TBS and 3D-SHAPER of the proximal femur region was performed. All subjects underwent DXA assessment of VF using the semiquantitative approach. Results One hundred six patients with acromegaly (mean age 56.6 years, BMI 30.2 kg/m2) and 104 control subjects (mean age 54.06 years, 28.4 BMI kg/m2) were included. After adjustment for weight, LS aBMD, TBS and TH trabecular volumetric BMD (vBMD) remained lower (P = 0.0048, <0.0001 and <0.0001, respectively) while cortical thickness (Cth) at TH and neck remained thicker (P = 0.006) in acromegaly patients compared with controls. The best multivariate model (model 1) discriminating patients with and without acromegaly included TBS, TH trabecular vBMD and TH Cth parameters (all P < 0.05). Twenty-two VFs (13 acromegaly subjects) were recognized. In these subjects after adjustment for age, FN aBMD, TH cortical sBMD and TH cortical vBMD remained significantly associated with the prevalent VF (OR = 2.69 (1.07-6.78), 2.84 (1.24-6.51) and 2.38 (1.11-5.10) for neck aBMD, TH cortical sBMD and TH cortical vBMD respectively)). The AUCs were similar for each parameter in this model. Conclusions Acromegaly patients, regardless of VF presence, have lower trabecular bone quantitative parameters, but those with VFs had decreased cortical density.

Weber-Christian disease: a case report.

Weber-Christian disease is a rare disease from the group of chronic fibrosing conditions characterized by inflamma-tion of the adipose tissue - panniculitis and fibrosing with frequent systemic manifestations. Etiopathogenesis of the disease is not fully known, participation of autoimmune mechanisms is anticipated. Here, we report a case of a patient with this rare disease, diagnosed after a long and demanding diagnostic process, including repeated lapa-rotomies. However, after immunosuppressive therapy, clinical and laboratory symptomatology improved rapidly as well as the patients quality of life. Key words: panniculitis - sclerosing mesenteritis - Weber-Christian disease.

Real-world Management of Women with Postmenopausal Osteoporosis Treated with Denosumab: A Prospective Observational Study in the Czech Republic and Slovakia.

INTRODUCTION: Osteoporosis is characterized by low bone mineral density (BMD) and an increased risk of fracture. In randomized controlled trials, denosumab has been shown to significantly reduce the fracture risk in women with osteoporosis. However, little is known about the real-world management of women who are prescribed denosumab. METHODS: This multicenter, prospective, observational real-world study in the Czech Republic and Slovakia evaluated the baseline characteristics and clinical management of women with postmenopausal osteoporosis prescribed denosumab for 24 months. RESULTS: A total of 600 women were included (300 in each country). In the Czech Republic and Slovakia, respectively, mean age at enrollment was 69.0 and 64.3 years, 67.7% and 30.0% of patients had a previous osteoporotic fracture, and 85.0% and 48.7% had previously received osteoporosis medication. In both countries, 'low BMD T score' and 'a history of osteoporotic fracture' were the main reasons for prescribing denosumab. Most patients received all four post-baseline denosumab injections (Czech Republic, 82.0%; Slovakia, 81.0%), and more than 98% of patients in both countries received all injections at the prescribing center. At 24 months, most patients experienced an increase in BMD T score for the lumbar spine, total hip, or femoral neck (Czech Republic, 69.7-91.7%; Slovakia, 67.1-92.9%). Adverse drug reactions were consistent with the known safety profile of denosumab. CONCLUSION: Baseline characteristics of patients receiving denosumab in the Czech Republic and Slovakia reflect the reimbursement criteria for this agent in each country. The findings of our study in patients who are at high risk for fracture are consistent with the growing body of evidence demonstrating the effectiveness of denosumab in real-world clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01652690. FUNDING: Amgen Inc.

High Serum Fractalkine is Associated with Lower Trabecular Bone Score in Premenopausal Women with Graves' Disease.

Chemokine CX3CL1 (fractalkine) may be an important factor linking thyroid status and bone remodeling, through tetrac, a derivative of thyroxine. This study explores the relationship between serum fractalkine levels and parameters of thyroid status and bone in premenopausal women with Graves' disease (GD) in comparison to healthy controls. This cross-sectional study included three premenopausal female groups: active GD; cured GD, and healthy age-, gender-, and BMI-matched controls. Measurement of serum fractalkine levels (Quantikine® ELISA), total amino-terminal peptide of procollagen type 1 (P1NP), CTx, thyroid hormones, BMD and trabecular bone score (TBS) were performed in all study subjects. Sixty women (21, 16, and 23 in active GD, cured GD, and healthy control groups, respectively) were included. Serum fractalkine levels were higher (p<0.05) in active and cured GD subjects compared to healthy controls (mean 0.7±0.14; 0.93±0.15, and 0.48±0.13 ng/ml, respectively). Lumbar spine BMD was lowest in the cured GD group in comparison to active GD and control group subjects (0.926±0.03; 1.016±0.03; 1.051±0.03 g/cm2; p<0.05, respectively). TBS was lower (p<0.05) in both GD groups than controls being lowest in those with active GD (1.395±0.02; 1.402±0.02, 1.469±0.02, respectively). Serum fractalkine concentration was positively correlated with fT4, and negatively correlated with TBS values. GD in pre-menopausal females is associated with increased serum fractalkine concentration and decreased TBS. Fractalkine may be a currently unappreciated link between hyperthyroidism and bone; further research into this possibility is needed.

Contribution of Genetic Factors to Lower DHEAS in Patients with Rheumatoid Arthritis.

OBJECTIVE: Lower production of adrenal androgens has been confirmed in females with rheumatoid arthritis (RA); however, the mechanisms of this finding are not completely understood. The aim of our study was to assess the contribution of genetic factors associated with variability of dehydroepiandrosterone sulfate (DHEAS) levels to lower DHEAS in female RA patients. METHODS: 448 RA and 648 healthy controls were genotyped for single-nucleotide polymorphisms (SNPs) in genes ZKSCAN5 (rs11761528), SULT2A1 (rs2637125), HHEX (rs2497306), and ARPC1A (rs740160). Serum DHEAS concentrations were measured in 112 RA patients and 91 healthy women. RESULTS: The allele frequencies in DHEAS-related loci were similar in RA and controls. RA patients had significantly lower serum DHEAS concentrations compared to healthy women. The cumulative number of alleles associated with lower DHEAS within genes ZKSCAN5, SULT2A1, HHEX, and ARPC1A present in each individual negatively correlated with DHEAS levels in RA patients, but not in controls. Linear regression analysis showed significant effect of polymorphisms in genes ZKSCAN5 and ARPC1A on serum DHEAS levels in female RA patients but not in the control group. CONCLUSION: Our findings suggest that complex interactions exist between genotype and adrenal androgen hypofunction in RA.

Decrease of trabecular bone score reflects severity of Crohn's disease: results of a case-control study.

OBJECTIVES: Osteoporosis and osteopaenia are known chronic complications of inflammatory bowel diseases. The trabecular bone score (TBS) provides an indirect measurement of bone microarchitecture, independent of bone mineral density (BMD). PATIENTS AND METHODS: The study was designed as a case-control study with the aim to assess and compare bone quantity and quality in patients with Crohn's disease (CD). We purposefully excluded postmenopausal women and patients on long-term corticosteroid therapy. RESULTS: The cohort consisted of 50 CD patients and 25 healthy controls who matched in age, sex, weight, or vitamin D status. There was no significant difference between CD patients versus controls in the mean lumbar BMD of 0.982±0.119 versus 0.989±0.12 g/cm and the mean TBS score of 1.37±0.12 versus 1.38±0.12. We observed significantly lower TBS, but not lumbar BMD, in CD patients with stricturing (B2, 1.36±0.08) or penetrating (B3, 1.32±0.11) disease compared with those with luminal disease (B1, 1.42±0.11; P=0.003 and <0.0001, respectively). We also observed lower mean±SD TBS in patients on versus not on anti-tumour necrosis factor-α therapy: 1.341±0.138 versus 1.396±0.099, respectively. However, the difference between these groups failed to reach statistical significance (P=0.11). No similar finding was seen comparing lumbar BMD in these groups. CONCLUSION: For the first time, it was observed that TBS, but not BMD, correlates with the severity of CD. Our results therefore suggest that TBS can potentially help to identify high fracture risk CD patients better than BMD alone.

Less strict intervention thresholds for the FRAX and TBS-adjusted FRAX predict clinical fractures in osteopenic postmenopausal women with no prior fractures.

Little is known about the clinical relevance of treating post-menopausal women with no prior history of fragility fracture and bone mineral densities (BMD) within the osteopenic range. In recent years, in addition to BMD and FRAX fracture probability assessments, a surrogate measure of bone micro-architecture quality, called the trabecular bone score (TBS), has been proven to predict future fragility fractures independently of both BMD and the FRAX. In this retrospective analysis of a follow-up study, we compared three risk assessment instruments-the FRAX, the TBS, and a TBS-adjusted FRAX score-in their ability, to predict future fragility fractures over a minimum of five years of follow-up among post-menopausal osteopenic women with no prior fragility fractures. We also sought to determine if more- versus less-stringent criteria were better when stratifying patients into higher-risk patients warranting osteoporosis-targeted intervention versus lower-risk patients in whom intervention would usually be deemed unnecessary. Over a mean 5.2 years follow-up, 18 clinical fragility fractures were documented among 127 women in the age 50 years and older (mean age = 66.1). On multivariate analysis utilizing regression models and Kaplan-Meier curve analysis, less-stringent criteria for the FRAX and TBS-adjusted FRAX were capable of predicting future fractures (with sensitivity/specificity of 83/31; 39/77 and 78/50% for TBS, FRAX and TBS-adjusted FRAX, respectively), while more-stringent criteria were incapable of doing so (with sensitivity/specificity of 56/60; 39/77 and 39/74 for TBS, FRAX and TBS-adjusted FRAX, respectively). Neither TBS threshold alone was a significant predictor of future fracture in our study. However, hazard ratio analysis revealed slight superiority of the TBS-adjusted FRAX over the FRAX alone (HR = 3.09 vs. 2.79). Adjusting the FRAX tool by incorporating the TBS may be useful to optimize the detection of post-menopausal osteopenic women with no prior fractures who warrant osteoporosis-targeted therapy.

[Bone quality in patients with acromegaly]. / Kvalita kosti u akromegalikov.

The impact of acromegaly on bone and the risk of fractures has not been sufficiently investigated. GH hypersecretion stimulates bone turnover, leading to an increase in bone turnover markers. Normal or even increased bone mineral density (BMD) in comparison to healthy controls have been reported, but there are some works where decreased BMD was observed among acromegaly patients with hypogonadism, particularly at lumbar spine. Less pronounced effect of GH overproduction was observed at the femoral neck, as explained by the positive effect of hypersecretion on the cortical bone (due to periosseal ossification). Several studies have documented morphometric vertebral fractures (VF) in 1/3 of acromegaly patients. The major risk factors leading to the development of VF include hypogonadism, diabetes mellitus and previous VF. Because the risk of fractures does not correlate with BMD most of the studies are currently focused on bone quality, bone strength and microstructure.Key words: bone microstructure - growth hormone - IGF1 - vertebral fractures.

[Issues related to secondary osteoporosis associated with growth hormone deficiency in adulthood]. / Problematika sekundárnej osteoporózy pri deficite rastového hormónu v dospelosti.

Growth hormone (GH) increases linear bone growth through complex hormonal reactions, mainly mediated by insulin like growth factor 1 (IGF1) that is produced mostly by hepatocytes under influence of GH and stimulates differentiation of epiphyseal prechondrocytes. IGF1 and GH play a key role in the linear bone growth after birth and regulation of bone remodelation during the entire lifespan. It is known that adult GH deficient (GHD) patients have decreased BMD and increased risk of low-impact fractures. Most data gathered thus far on the effect of GH replacement on bone status comprise the measurement of quantitative changes of bone mass. Some animal studies with GHD showed that the bone microarchitecture, measured using computed tomography methods, is significantly compromised and improve after GH replacement. However, human studies did not show significantly decreased bone microarchitecture, but limited methodological quality does not allow firm conclusions on this subject.Key words: bone mass - bone quality - fracture - growth hormone - IGF1.

Increased intracellular and extracellular oxidant production in phagocytes of rheumatic patients treated with biological therapy - whole blood quantification.

Infectious complications, resulting from reduced activity of immune cells, are the most severe and common adverse effects of biological therapy. This study analyzed the effect of biological therapy on blood phagocytes, focusing on the formation of reactive oxygen species (ROS), an important factor in the defence against invading pathogens. Intra- and extracellular ROS production were recorded separately, on the basis of luminol and isoluminol chemiluminescence in patients treated with antibodies against tumor necrosis factor-α or against interleukin-6 receptor. In comparison to healthy donors or to rheumatic patients treated with classical immunosuppressive drugs, biological therapy increased ROS formation in both compartments. This indicates that the anti-microbial activity of blood phagocytes was not reduced by TNFα- or IL-6-neutralizing therapy, at least in terms of ROS. The method presented does not require blood fractionation, which could modify activity of phagocytes and cause loss of some subpopulations of these cells. The technique is simple, requires microliter volumes of blood and is thus well applicable to clinical studies.

Cross-sectional area of the median nerve is increased in primary autoimmune hypothyroidism and decreases upon treatment with thyroxine.

BACKGROUND: The purpose of this study was to assess changes in the cross-sectional area (CSA) of nervus medianus by ultrasound in newly diagnosed primary hypothyroid patients after thyroxine replacement treatment. PATIENTS AND METHODS: The cohort comprised 30 patients with newly diagnosed primary autoimmune hypothyroidism. These were subsequently compared with 30 controls, matched for sex, BMI and age. Ultrasound evaluation, including measurement of CSA at the level of the pisiform bone or tunnel inlet was performed at baseline and after 3months. A CSA threshold of more than 10mm(2) was considered pathological. RESULTS: CSA was increased in patients compared with controls (9.8±0.7mm(2) vs 7.2±1.1mm(2); P<0.001). Thyroxin substitution increased fT4 levels (baseline, 11.0±0.6pmol/L vs 15.5±0.4pmol/L; P<0.001) and decreased TSH (baseline, 23.9±6.0mIU/L vs 2.7±0.2mIU/L; P<0.001). Thyroxine treatment decreased CSA to 8.4mm(2)±0.3mm(2) (P=0.033). Before treatment, four patients experienced distal paresthesia in the median nerve distribution area. Increased CSA pathognomonic for carpal tunnel syndrome found in two symptomatic patients normalized after 3months. No clinical symptoms were observed after 3months. A positive correlation was found between TSH and CSA (R=0.155, P=0.05) before treatment. CONCLUSION: Our study demonstrates that increase in median nerve CSA caused by primary autoimmune hypothyroidism can be fully reversible after achieving target levels of TSH and fT4.

TRABECULAR BONE SCORE CHANGE DIFFERS WITH REGARD TO 25(OH)D LEVELS IN PATIENTS TREATED FOR ADULT-ONSET GROWTH HORMONE DEFICIENCY.

OBJECTIVE: Vitamin D is important in bone health. However, potential relationships of concomitant vitamin D deficiency with growth hormone deficiency (GHD) and the possibility that vitamin D inadequacy may alter the skeletal effects of growth hormone (GH) replacement therapy have not been adequately evaluated. METHODS: A prospective study was conducted in adult-onset GHD patients treated with recombinant human GH (rhGH) for 2 years. Trabecular bone score (TBS), lumbar spine (LS) bone mineral density (BMD), total hip (TH) BMD, and 25-hydroxyvitamin D (25(OH)D) levels were assessed at baseline and 24 months. The study cohort was divided based on 25(OH)D levels into 2 groups with the cutoff defined as the 50(th) percentile at each follow-up time point. RESULTS: Fifty-seven patients (29 males/28 females, mean age 34.4 years) were studied. After 24 months of GH replacement, LS BMD increased by 7.6% and TH BMD increased by 4.5% (both P<.05), with no difference according to 25(OH)D levels. TBS increased (+1.39 ± 3.6%) in those whose 25(OH)D was above the 50(th) percentile but decreased (-1.36 ± 5.6%, P<.05) in the cohort below the 50(th) percentile of 25(OH)D. Positive correlations were observed between baseline levels of IGF-1 and 25(OH)D (R = 0.37, P<.001) and between 24-month 25(OH)D and TBS (R = 0.25, P<.05). CONCLUSION: A differential effect of GH on TBS change was observed; TBS increased only in the cohort with 25(OH)D above the 50(th) percentile. Vitamin D sufficiency may be required to obtain optimal effects of GH treatment on bone quality, as assessed by TBS, in GHD adults. ABBREVIATIONS: AO-GHD = adult-onset GHD BMD = bone mineral density BMI = body mass index Ca = calcium CTx = carboxyterminal collagen crosslinks CV = coefficient of variation DXA = dual energy X-ray absorptiometry ECLIA = enzyme-labeled chemiluminescent immunometric assay GH = growth hormone GHD = growth hormone deficiency IGF-1 = insulin-like growth factor 1 LS BMD = lumbar spine BMD OC = osteocalcin 25(OH)D = 25-hydroxyvitamin D P = phosphorus PTH = parathyroid hormone rhGH = recombinant human GH TBS = trabecular bone score TH BMD = total hip BMD.