BACKGROUND: Recent recognition of its broad pathophysiological importance has triggered an increased interest in 25-hydroxyvitamin D [25(OH)D]. By consequence, throughput in 25(OH)D testing has become an issue for clinical laboratories, and several automated assays for measurement of 25(OH)D are now available. The aim of this study was to test the accuracy and robustness of these assays by comparing their results to those of an isotope dilution/online solid-phase extraction liquid chromatography/tandem mass spectrometry (ID-XLC-MS/MS) method. We put specific focus on the influence of vitamin D-binding protein (DBP) by using samples with various concentrations of DBP.

IMPORTANCE High-sensitivity cardiac troponin I testing is widely used to evaluate patients with suspected acute coronary syndrome. A cardiac troponin concentration of less than 5 ng/L identifies patients at presentation as low risk, but the optimal threshold is uncertain. OBJECTIVE To evaluate the performance of a cardiac troponin I threshold of 5 ng/L at presentation as a risk stratification tool in patients with suspected acute coronary syndrome.

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An estimated 4-6% of fitness center visitors uses anabolic-androgenic steroids (AAS). Reliable data about adverse reactions of AAS are scarce. The HAARLEM study aimed to provide insight into the positive and negative effects of AAS use. One hundred men (≥18 years) who intended to start an AAS cycle on short notice were included for follow-up. Clinic visits took place before (T 0), at the end (T 1), and three months after the end of the AAS cycle (T 2), and one year after the start of the cycle (T 3), and comprised a medical history, physical examination, laboratory analysis, and psychological questionnaires. During the follow-up period, four subjects reported a serious adverse event, that is, congestive heart failure, acute pancreatitis, suicidal ideation, and exacerbation of ulcerative colitis. All subjects reported positive side effects during AAS use, mainly increased strength (100%), and every subject reported at least one negative health effect. Most common were fluid retention (56%) and agitation (36%) during the cycle, and decreased libido (58%) after the cycle. Acne and gynecomastia were observed in 28% and 19%. Mean alanine transaminase (ALT) and creatinine increased 18.7 U/l and 4.7 µmol/L, respectively. AAS dose and cycle duration were not associated with the type and severity of side effects. After one-year follow-up (T 3), the prevalence of observed effects had returned to baseline. There was no significant change in total scores of questionnaires investigating wellbeing, quality of life, and depression. In conclusion, all subjects experienced positive effects during AAS use. Four subjects experienced a serious adverse event. Other side effects were mostly anticipated, mild, and transient. K E Y W O R D S anabolic steroids, bodybuilding, doping in sports, performance and image-enhancing drugs, strength training 428 | SMIT eT al.

STUDY QUESTION What is the speed and extent by which endogenous testosterone production and spermatogenesis recover after androgen abuse? SUMMARY ANSWER Testosterone concentrations normalized within 3 months after discontinuation of androgen abuse in most subjects but recovery of spermatogenesis took longer—approximately 1 year. WHAT IS KNOWN ALREADY An estimated 4–6% of amateur strength athletes use androgens. Abuse of supraphysiological doses of androgens completely suppresses endogenous testosterone production and spermatogenesis. STUDY DESIGN, SIZE, DURATION Prospective and observational cohort study in which 100 male amateur athletes participated for 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS Subjects (≥18 years) were included if they had not used androgens for at least 3 months and intended to start an androgen cycle within 2 weeks. Clinic visits took place before (T0), at the end (T1), and 3 months after the end of the cycle (T2), and 1 year after start of the cycle (T3), and included a blood test for gonadotrophins and sex hormones, and semen analysis. MAIN RESULTS AND THE ROLE OF CHANCE During androgen abuse, 77% of subjects had a total sperm count (TSC) below 40 million. Three months after the end of the cycle (T2), total (−1.9 nmol/l, CI −12.2 to 8.33, P = 0.71) and free (−38.6 pmol/l, CI −476 to 399, P = 0.86) testosterone concentrations were not different compared to baseline, whereas mean TSC was 61.7 million (CI 33.7 to 90.0; P < 0.01) lower than baseline. At the end of follow-up (T3), there was no statistically significant difference for total (−0.82 nmol/l, CI −11.5 to 9.86, P = 0.88) and free (−25.8 pmol/l, CI −480 to 428, P = 0.91) testosterone compared to baseline, but there was for TSC (−29.7 million, CI −59.1 to −0.39, P = 0.05). In nine (11%) subjects, however, testosterone concentrations were below normal at the end of follow-up (T3), and 25 (34%) subjects still had a TSC below 40 million. LIMITATIONS, REASONS FOR CAUTION The follow-up period (after the cycle) was relatively short, especially considering the long recovery time of spermatogenesis after discontinuation of androgens. WIDER IMPLICATIONS OF THE FINDINGS Endogenous testosterone production and spermatogenesis recover following androgen abuse in the vast majority of users. Nevertheless, not all users achieve a normalized testicular function. This may especially be the case for athletes with a high past exposure to androgens. STUDY FUNDING/COMPETING INTEREST(S) There is no conflict of interest. The study was funded by the Spaarne Gasthuis academy. TRIAL REGISTRATION NUMBER N/A.

We hypothesized that a high circulating free fatty acid (FFA) concentration is involved in the pathogenesis of hyposomatotropism associated with obesity. To evaluate this hypothesis, 10 healthy premenopausal women (body mass index 33.8 +/- 1.0 kg/m(2)) were studied in the follicular phase of their menstrual cycle at two occasions with a time interval of at least 8 wk, where body weight remained stable. Subjects were randomly assigned to treatment with either acipimox (an inhibitor of lipolysis, 250 mg orally 4 times daily) or placebo in a double-blind crossover design, starting 1 day before admission until the end of the blood sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of growth hormone (GH) concentrations, and GH secretion was estimated by deconvolution analysis. Identical methodology was used to study GH secretion in a historical control group of age-matched normal weight women. GH secretion was clearly blunted in obese women (total daily release 66 +/- 10 vs. lean controls: 201 +/- 23 mU x l(Vd)(-1) x 24 h(-1), P = 0.005, where l(Vd) is lite of distribution volume). Acipimox considerably enhanced total (113 +/- 50 vs. 66 +/- 10 mU x l(Vd)(-1) x 24 h(-1), P = 0.02) and pulsatile GH secretion (109 +/- 49 vs. 62 +/- 30 mU x l(Vd)(-1) x 24 h(-1), P = 0.02), but GH output remained lower compared with lean controls. Further analysis did not show any relationship between the effects of acipimox on GH secretion and regional body fat distribution. In conclusion, acipimox unleashes spontaneous GH secretion in obese women. It specifically enhances GH secretory burst mass. This might mean that lowering of systemic FFA concentrations by acipimox modulates neuroendocrine mechanisms that orchestrate the activity of the somatotropic ensemble.

There are many causes of interference in immunoassays causing erratic patient results. A method-specific interference due to antiruthenium antibodies in Roche free thyroxine (fT4) and free triiodothyronine (fT3) assays has been described previously. As a result, a new generation fT4 assay has been introduced by Roche. We describe six cases of interference due to antiruthenium antibodies, where in four cases interference in the Roche thyroid-stimulating hormone (TSH) assay was found as well. This raised the question as to whether other assays on this platform would also give incorrect results in patients with antiruthenium antibodies. Interference due to antiruthenium antibodies was suspected because of discrepancies between clinical presentation and/or TSH, fT4 and fT3 results. Samples of these six patients were reanalysed in Roche Diagnostics Laboratory, where it was demonstrated that the found discrepancies were indeed caused by interfering antiruthenium antibodies. Subsequently, these patients were asked to donate some blood once more for further evaluation, and three subjects agreed to participate. Their plasma was used to assay 18 analytes on Modular E and on a ruthenium-independent platform. The results were compared taking into account the known differences between distinct methods. As expected, significant interference was found in TSH. Also, in the new generation fT4 assay, ruthenium-induced interference was still present. However, the other assays, both competitive and immunometric, did not show clear interference. We therefore conclude that although antiruthenium antibodies theoretically can interfere in all assays on the Modular E platform, this kind of interference is found in the thyroid hormone assays, without marked interference in the other assays.

Several studies suggest that the hypothalamopituitary-adrenal (HPA) axis is exceedingly active in obese individuals. Experimental studies show that circulating free fatty acids (FFAs) promote the secretory activity of the HPA axis and that human obesity is associated with high circulating FFAs. We hypothesized that HPA axis activity is enhanced and that lowering of circulating FFAs by acipimox would reduce spontaneous secretion of the HPA hormonal ensemble in obese humans. To evaluate these hypotheses, diurnal ACTH and cortisol secretion was studied in 11 obese and 9 lean premenopausal women (body mass index: obese 33.5 Ϯ 0.9 vs. lean 21.2 Ϯ 0.6 kg/m 2 , P Ͻ 0.001) in the early follicular stage of their menstrual cycle. Obese women were randomly assigned to treatment with either acipimox (inhibitor of lipolysis, 250 mg orally four times daily) or placebo in a double-blind crossover design, starting one day before admission until the end of the blood-sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of plasma ACTH and cortisol concentrations. ACTH and cortisol secretion rates were estimated by multiparameter deconvolution analysis. Daily ACTH secretion was substantially higher in obese than in lean women (7,950 Ϯ 1,212 vs. 2,808 Ϯ 329 ng/24 h, P ϭ 0.002), whereas cortisol was not altered (obese 36,362 Ϯ 5,639 vs. lean 37,187 Ϯ 4,239 nmol/24 h, P ϭ 0.912). Acipimox significantly reduced ACTH secretion in the obese subjects (acipimox 5,850 Ϯ 769 ng/24 h, P ϭ 0.039 vs. placebo), whereas cortisol release did not change (acipimox 33,542 Ϯ 3,436 nmol/24 h, P ϭ 0.484 vs. placebo).In conclusion, spontaneous ACTH secretion is enhanced in obese premenopausal women, whereas cortisol production is normal. Reduction of circulating FFA concentrations by acipimox blunts ACTH release in obese women, which suggests that FFAs are involved in the pathophysiology of this neuroendocrine anomaly. adrenocorticotropic hormone; spontaneous secretion; pituitary adrenal system; free fatty acids; obesity THE ENDOCRINE ENVIRONMENT is a powerful regulator of body fat storage. For example, the hypothalamo-pituitary-adrenal (HPA) ensemble profoundly affects body composition in animals and humans. Glucocorticoid administration promotes body weight gain in rodents (19,26,77), and hypercortisolism in patients with Cushing's syndrome leads in visceral depots to excess fat, which is readily reversed by lowering plasma cortisol levels (45, 70).Obese animal models are marked by an exceedingly active HPA ensemble. Genetically obese rodents have high levels of glucocorticoids (5, 6), adrenalectomy reduces body weight in these animals (12, 21), and subsequent corticosterone replacement restores the obese state (12,22,32,61,76). Adrenalectomy also attenuates diet-induced obesity. Removal of the adrenals reduces energy intake and adipose tissue weights in diet-induced obese rodents, which is reversed by glucocorticoid replacement (18,36,48,62).Various clinical studies suggest that the HPA axis is also h...