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M Christ-Crain

Publications and source records attributed to M Christ-Crain.

13 recordsLinked to original sources

Circulating levels of copeptin, a novel biomarker, in lower respiratory tract infections.

BACKGROUND: Vasopressin has haemodynamic as well as osmoregulatory effects, and reflects the individual stress response. Copeptin is co-synthesized with vasopressin, directly mirroring vasopressin levels, but is more stable in plasma and serum. Both levels are increased in patients with septic shock. Lower respiratory tract infections (LRTI) are a precursor of sepsis. Thus, we investigated circulating levels and the prognostic use of copeptin for the severity and outcome in patients with LRTI. MATERIALS AND METHODS: Five hundred and forty-five consecutive patients with LRTI and 50 healthy controls were evaluated. Serum copeptin levels were measured with a new chemiluminescent sandwich immunoassay. RESULTS: Of the 545 patients, 373 had community-acquired pneumonia (CAP), 60 acute exacerbations of chronic obstructive pulmonary disease (COPD), 59 acute bronchitis, 13 exacerbations of asthma and 40 other final diagnoses. Copeptin levels were significantly higher in patients with LRTI as compared to controls (P < 0.001) with highest levels in patients with CAP. Copeptin levels increased with increasing severity of CAP, as classified by the pneumonia severity index (PSI) (P < 0.001). In patients who died, copeptin levels on admission were significantly higher as compared to levels in survivors [70.0 (28.8-149.0) vs. 24.3 (10.8-43.8) pmol L(-1), P < 0.001]. The area under the receiver operating curve (AUC) for survival was 0.75 for copeptin, which was significantly higher as compared to C-reactive protein (AUC 0.61, P = 0.01), leukocyte count (AUC 0.59, P = 0.01) and similar to procalcitonin (AUC 0.68, P = 0.21). CONCLUSIONS: Copeptin levels are increased with increasing severity of LRTI namely in patients with CAP and unfavourable outcome. Copeptin levels, as a novel biomarker, might be a useful tool in the risk stratification of patients with LRTI.

Aged↗

Circulating levels of pro-atrial natriuretic peptide in lower respiratory tract infections.

OBJECTIVE: To analyse the mid region of plasma N-terminal pro-atrial natriuretic peptide (MR-proANP) levels in patients with lower respiratory tract infections to evaluate its prognostic use for the severity of disease and outcome. DESIGN: Prospective observational study. Setting. Emergency department of a university hospital. SUBJECTS: A total of 545 consecutive patients with lower respiratory tract infections and 50 healthy controls. Interventions. MR-proANP was measured in serum from all patients using a new sandwich immunoassay. RESULTS: MR-proANP levels (median [IQR], in pmol L(-1)) were significantly higher in patients with lower respiratory tract infections when compared with controls (138.0 [74.1-279.0] vs. 72.7 [62.5-89.5], P < 0.001), with highest levels in patients with community-acquired pneumonia (CAP). MR-proANP, but not C-reactive protein (CRP) levels, gradually increased with increasing severity of CAP, classified according to the pneumonia severity index (PSI) score (P < 0.001). On admission, MR-proANP levels were significantly higher in nonsurvivors when compared with survivors (293.0 [154.0-633.0] vs. 129.0 [71.4-255.0], P < 0.001). In a receiver operating characteristic (ROC) analysis for the prediction of survival of patients with CAP the area under the ROC curve (AUC) for MR-proANP was 0.69, similar when compared with the PSI (AUC 0.74, P = 0.31), and better when compared with other biomarkers, i.e. procalcitonin (AUC 0.57, P = 0.08), CRP (AUC 0.52, P = 0.02), and leucocyte count (AUC 0.56, P = 0.07). CONCLUSIONS: MR-proANP levels are increased in lower respiratory tract infections, especially in CAP. Together with other clinical, radiographic and laboratory findings, MR-proANP levels might be helpful for the risk stratification in CAP.

Acute Disease↗

Pro-A-type and N-terminal pro-B-type natriuretic peptides in different thyroid function states.

QUESTIONS UNDER STUDY: Natriuretic peptides are produced predominantly in the heart and secreted in response to volume expansion and pressure overload. A wide spectrum of cardiac changes is observed in thyroid dysfunctions. This study investigates mid regional pro A-type (proANP) and N-terminal pro-B-type natriuretic peptide (NTproBNP) levels in different thyroid states and evaluates the effect of L-thyroxine treatment on natriuretic peptides in patients with subclinical hypothyroidism. METHODS: Case-control and double-blind, placebo-controlled trial. Sera from 161 female patients (35 with overt, 63 with subclinical hypothyroidism; 10 with overt, 14 with subclinical hyperthyroidism; 40 euthyroid controls) were analysed. ProANP and NT-proBNP were measured at baseline and 48 weeks after L-thyroxine treatment in subclinical hypothyroidism. RESULTS: Circulating proANP and NT-proBNP levels were higher in hyperthyroid patients than in hypothyroid and euthyroid patients (p <0.001). Plasma proANP levels tended to be lower in overt hypothyroidism than in subclinical hypothyroidism. ProANP and NT-proBNP levels correlated weakly to thyroid stimulating hormone (TSH) (r = -0.3 and -0.2, respectively). The natriuretic peptide levels of subclinical and overt hypothyroid subjects showed no difference with those of euthyroid subjects. L-thyroxine treatment had no effect on natriuretic peptide levels in subclinical hypothyroidism. CONCLUSION: Natriuretic peptide levels are altered in different thyroid states with a more pronounced effect in hyperthyroidism than in hypothyroidism. Hyperthyroidism should be considered in patients presenting with unclear symptoms and mildly elevated natriuretic peptide levels, as overt hyperthyroidism results in increased serum A- and B-type natriurectic peptide levels, typically seen in mild heart failure.

Atrial Natriuretic Factor↗

[Amiodarone-induced thyrotoxicosis: a diagnostic and therapeutic challenge].

Amiodaron is a widely used antiarrhytmic drug in a number of cardiac conditions. The most common side effects affect the thyroid gland (14-18% of treated patients) resulting in hypothyroidism or hyperthyroidism. We describe a complex case of amiodaron-induced thyrotoxicosis (AIT) and discuss the pathogenesis of the different subtypes (AIT I, II and mixed forms) and the diagnostic and therapeutic challenges in such patients.

Amiodarone↗

Amino-bisphosphonates in heterotopic ossification: first experience in five consecutive cases.

STUDY DESIGN: Retrospective, observational study in five consecutive cases. OBJECTIVES: The management of heterotopic ossification (HO), a frequent complication after spinal cord injury (SCI) and after orthopaedic surgery, is a therapeutic challenge with high recurrence rates of over 50%. Conflicting data were reported for Etidronate. The use of the more potent new generation of amino-bisphosphonates has been put forward in different inflammatory, dysmorphogenic bone disease. In order to try and halt the underlying dysfunctional bone metabolism we have studied the action of pamidronate in five consecutive high-risk patients with established HO of different etiology undergoing surgical removal. SETTING: University Hospital of Basel, Switzerland, Division of Endocrinology, Diabetology and Clinical Nutrition and the Department of Orthopedic Surgery. METHODS: In all five patients, ranging from 47 to 68 years of age, we used continuous pamidronate infusions perioperatively at a dosage of 120 mg in the first 12 h and subsequent reduction to 75-60-30-15 mg/12 h over a period of 10-14 days. RESULTS: None of these patients showed clinical, radiographical and laboratory signs of HO recurrence or new forming HO in the follow-up 5-54 month after surgery. Potential side effects of high-dose bisphosphonate therapy such as osteoporosis and osteomalacia were not reported in any case. CONCLUSION: We postulate that pamidronate might have pronounced beneficial effects in high-risk patients with established HO undergoing excision surgery. Since the therapeutic window of amino-bisphosphonates has not yet been defined and the minimal necessary doses for preventing new HO are unknown, further studies are encouraged to confirm our findings and to identify the necessary dosage and duration of treatment and to pinpoint, which patients will benefit most from this treatment.

Aged↗

Radioiodine uptake and thyroid hormone levels on or off simultaneous carbimazole medication: a prospective paired comparison.

AIM: To allow radioiodine (RAI) treatment in patients with need for anti-thyroid drug medication and low RAI uptakes we investigated the feasibility of discontinuing carbimazole for 3 days to enhance the RAI uptake without concurrent exacerbation of hyperthyroidism. METHODS: We prospectively investigated RAI dynamics and thyroid hormone concentration in 12 patients with low RAI uptake (<30%) under simultaneous carbimazole medication and 3 days after discontinuation. At both time points fT(4), T(3) and TSH were monitored. RESULTS: Discontinuation of carbimazole for 3 days led to a significant increase of RAI uptake in all patients. We found an enhancement up to 4.9-fold compared to the measurement on carbimazole. The mean RAI uptake increased from 15.2 +/- 4.4% to 50.1 +/- 15.5% (p<0.001). The intrapersonal radioiodine half-life increased from 4.2 +/- 1.6 days to 5.4 +/- 0.7 days (p = 0.13). Mean thyroid hormone concentration was not affected by the three day withdrawal of anti-thyroid drugs and no patient suffered from an aggravation of biochemical hyperthyroidism. CONCLUSION: A withdrawal of carbimazole for 3 days is long enough to provide sufficiently high RAI uptakes for RAI treatment in patients with low RAI uptakes and short enough to avoid the risk of exacerbation of hyperthyroidism.

Adult↗

Value of gonadotropin-releasing hormone testing in the differential diagnosis of androgen deficiency in elderly men.

Elderly men with low testosterone (T) levels are increasingly diagnosed to have partial androgen deficiency of the aging male (PADAM). Frequently, magnetic resonance imaging is performed to exclude pituitary adenoma. The value of GnRH testing to differentiate PADAM from secondary hypogonadism is unknown. Serum levels of T as well as LH and FSH at baseline and after GnRH were evaluated in the following groups: 1) 24 elderly men with low serum T (<11.7 nmol/liter), 2) 25 elderly men with normal serum T levels (>11.7 nmol/liter), 3) 10 men with primary hypogonadism, 4) 24 men with secondary hypogonadism, and 5) 13 healthy young volunteers. In elderly men, T levels were lower (P < 0.001) and gonadotropin levels higher (P = 0.03) compared with younger controls. LH and FSH response to GnRH was higher in elderly men with low T levels (PADAM) compared with elderly men with normal T levels (P = 0.02 and P < 0.001) in the presence of similar basal gonadotropin levels. To differentiate secondary hypogonadism from PADAM with a sensitivity of 100%, a T less than 10 nmol/liter had a specificity of 50%. This specificity was improved to 75% by using a cutoff of less than or equal to 15 mU/liter increase of LH upon GnRH stimulation. Overall, decreased T levels and increased LH levels in elderly men suggest a primary Leydig cell dysfunction. In the subgroup of elderly men with low T levels, an increased LH response to GnRH with normal basal LH levels suggests additional, possibly hypothalamic changes. To exclude secondary hypogonadism in PADAM, diagnostic accuracy can be improved by using GnRH testing.

Adult↗

Comparison of different methods for the measurement of serum testosterone in the aging male.

BACKGROUND: Circulating testosterone (T) levels, mainly non-SHBG bound fractions, decline with advancing age. Free (FT) and bioavailable (BT) testosterone levels have been suggested to represent more reliably the bioactive hormone at the tissue level as compared to total testosterone (TT) levels. However, there is an ongoing controversy as to which T assay is most appropriate in defining T deficiency in the aging male. METHODS: In a prospective observational study, TT, FT and BT levels were measured in 51 elderly men (55 to 70 years). TT levels were determined on two different days using 2 different assays. FT was calculated using TT, albumin and SHBG levels as well as measured directly by radioimmunoassay. The free androgen index (FAI) was calculated using the formula 100 x TT/SHBG. BT was obtained by precipitation of SHBG-bound T with ammonium sulphate. RESULTS: We found good correlations within different assays for TT (r = 0.87 to 0.91, p <0.001) and between TT and calculated FT (r = 0.66 to 0.84, p <0.001). In contrast, the correlation between TT and BT was poor (r = 0.17 to 0.19, p = ns). TT was equivalent to calcFT and was better in mirroring clinical sings of androgen deficiency in elderly men as compared to BT. The intra-individual day-to-day variance of TT levels was 14.8% (range 0.1-79%) with a coefficient of variance of 12.6%. CONCLUSION: Serum TT and the calculated FT fraction correlated well with each other and were superior in defining a group of elderly men with suspected androgen deficiency. In contrast, FT measured by direct RIA and BT reflected gonadal function poorly. Our data favour the repetitive use of TT when screening for androgen deficiency in elderly men.

Aged↗

Radioiodine therapy in hyperthyroidism: inverse correlation of pretherapeutic iodine uptake level and post-therapeutic outcome.

BACKGROUND: High iodine uptake levels are widely accepted as a condition for successful treatment with radioiodine (RAI). However, the existing data are controversial and the correlation of pretherapeutic RAI uptake level and outcome of RAI therapy has not yet been quantified. The aim of this study was to analyze the influence of RAI uptake on the outcome after RAI treatment and to estimate uptake-dependent success rates. MATERIALS AND METHODS: We retrospectively analyzed 229 patients (m = 53, f = 176; age 64 +/- 14 years) suffering from toxic adenoma, multinodular goitre or Graves' disease, respectively. Clinical status and T3, fT4 and TSH levels were assessed 3, 6, 12 and 18 months after treatment. Successful treatment was defined as loss of hyperthyroidism 18 months after radioiodine therapy. Logistic regression was used to assess the relation between the maximum iodine uptake and the rate of success and hypothyroidism, respectively, after RAI treatment. RESULTS: Overall, patients presented with pretherapeutic RAI uptake values between 17% and 100%. Eighteen months after RAI treatment, an euthyroid state was achieved in 136 patients (60%), hypothyroidism occurred in 47 patients (20%) and 46 patients (20%) remained hyperthyroid. The patients with the lowest pretherapeutic RAI uptakes showed the highest success rates. The overall success rate significantly decreased from 92% at low RAI uptakes to 57% at high uptakes (P = 0.002). This effect was found in the patients suffering from multinodular goitre as well as in the patients with Graves' disease. CONCLUSION: In contrast to the current opinion, our results provide evidence that the pretherapeutic iodine uptake level and post-therapeutic outcome are inversely correlated.

Adenoma↗

Basal TSH levels compared with TRH-stimulated TSH levels to diagnose different degrees of TSH suppression: diagnostic and therapeutic impact of assay performance.

BACKGROUND: The estimated prevalence of endogenous subclinical hyperthyroidism varies from 4% to 6% and a basal thyroid stimulating hormone (TSH) level < 0.5 mU L-1 may be associated with increased mortality in subjects over 60 years of age who are not on thyroid medication. Exogenous TSH suppression is a mainstay in the treatment of thyroid cancer. Because of recent concerns about potential adverse effects, especially of endogenous TSH suppression on bone, the cardiovascular system and cognitive functions, subclinical hyperthyroidism obtained new clinical importance. We therefore re-evaluated the diagnostic value of basal and thyrotrop in TRH-stimulated serum TSH measurements using TSH assays with different sensitivities. MATERIALS AND METHODS: A total of 805 oral and nasal TRH stimulation tests were performed on 409 ambulatory subjects with low basal serum TSH concentrations of less than 0.1 mIU L-1. Basal serum TSH was measured either using a second generation assay (functional sensitivity > 0.03 mIU L-1) or two third generation assays (functional sensitivity 0.01 mIU L-1 and 0.007 mU L-1, respectively). Serum TSH concentration was determined before and 3 h after oral administration of 40 mg of TRH and before and 30 min after nasal administration of 2 mg of TRH. RESULTS: In the oral testing group, the basal TSH levels measured by the different TSH assays were 0.06 +/- 0.03, 0.04 +/- 0.02 and 0.03 +/- 0.02, respectively, whereas the peak TSH levels were 0.4 +/- 0.6, 0.4 +/- 0.6 and 0.3 +/- 0.5 in the patients with subclinical hyperthyroidism. In overt hyperthyroidism, the basal TSH levels were 0.06 +/- 0.02, 0.03 +/- 0.02 and 0.03 +/- 0.02, whereas the peak TSH levels were 0.19 +/- 0.3, 0.16 +/- 0.3 and 0.15 +/- 0.2, respectively. Basal TSH values could discriminate between different degrees of TSH suppression if measured with a third generation assay (P < 0.001), but not with a second generation assay. There was only a weak correlation between basal TSH and peak TSH when measured by a second generation assay (n = 126; r = 0.3; P < 0.001) in contrast to the strong correlation found using the third generation assays (n = 128; r = 0.7; P < 0.001 and n = 69; r = 0.8; P < 0.001, respectively). CONCLUSIONS: In view of the recent concerns about potential adverse effects in TSH suppression and based on our data, it is mandatory to select a TSH assay with a functional sensitivity of < or = 0.01 mIU L-1 for optimal titration of L-T4 suppressive therapy, especially in patients with thyroid cancer. If, however, only a second generation TSH assay is available, additional TRH testing allows a more careful titration of suppressive thyroxine therapy.

Administration, Intranasal↗