[Don't neglect metabolic syndrome]. / Vignette diagnostique de l'étudiant. Ne pas négliger le syndrome métabolique.

The concept of «metabolic syndrome¼ was brought to the forefront in the early 2000s in international literature, but this interest seems to have faded somewhat in recent years. However, this constellation of cardiovascular risk factors should not be neglected. Taken individually, they hardly seem problematic, but when they are present within the same individual, they significantly increase the risk of cardiovascular morbidity and mortality. This clinical vignette aims to draw attention to the usefulness of the search for metabolic syndrome in clinical practic.

Le concept de «syndrome métabolique¼ a été mis en avant de la scène au début des années 2000 dans la littérature internationale, mais cet intérêt semble s'être quelque peu estompé au cours des dernières années. Il convient cependant de ne pas négliger cette constellation de facteurs de risque cardiovasculaire qui, pris individuellement, ne paraissent guère problématiques, mais qui, lorsqu'ils co-existent chez une même personne, augmentent sensiblement le risque de morbi-mortalité. Cette vignette clinique a pour but d'attirer l'attention sur l'importance de la recherche d'un syndrome métabolique dans la pratique clinique.

Tracking Macroprolactin: Use of an Optimized Polyethylene Glycol Precipitation Method More Compatible with the Requirements and Processes of Automated Core Laboratories.

BACKGROUND: Macroprolactin (MPRL) is a large circulating form of a multimeric prolactin currently thought to be biologically inactive. Because of its ability to interfere with prolactin detection in most of the current 2-site immunoassays, the presence of MPRL can lead to inappropriate diagnosis of hyperprolactinemia and unnecessary investigations and treatments. The main objective of our study was to establish an optimized polyethylene glycol (PEG) precipitation method that could be used in automated core laboratory settings. METHODS: The PEG precipitation method adopted in our laboratory (2 min, 19744g) was compared to a standard procedure (30 min, 1500g). We also tested the stability over time (44, 99, and 261 days) of PEG solutions. Post-PEG prolactin concentrations were used for method comparisons, and discrepancies with the classic recovery calculation were also studied. RESULTS: The higher g-force centrifugation method adopted in our laboratory generated results in agreement with a standard procedure (slope of 1.00, y intercept of -0.8 ng/mL). The PEG solution was stable for at least 261 days (P = 0.72), and the post-PEG reference values as definition of macroprolactinemia revealed a closer association to clinical presentations than the recovery calculation. CONCLUSIONS: We established an optimized PEG precipitation procedure that meets the requirements of core laboratory settings with a more stable PEG solution, less processing samples based on the 30-100 ng/mL screening interval, a lower sample volume, no incubation time, and a higher g-force centrifugation process. Along with post-PEG reference values found in literature, this method could facilitate the widespread introduction of MPRL screening in cases of hyperprolactinemia.

Analysis of the discriminant ability of shorter versions of the French ADAM questionnaire.

OBJECTIVE: To investigate whether shorter versions of the ADAM test, a screening questionnaire for andropause, provide better diagnostic value than the original tool. METHODS: Five thousand and twenty-eight volunteer men aged 50-70 years attending a screening campaign for andropause, provided a fasting blood sample and completed the French ADAM test. Logistic regression analysis identified items that best predict andropause defined as serum free testosterone level below 70 ng/l. ROC curves assessed the diagnostic value of modified versions of the ADAM test, obtained by elimination of the less relevant predictors of andropause. RESULTS: Only four items of the ADAM questionnaire may account for the diagnosis of andropause. These items concerned loss of height, decrease in libido and in enjoyment of life and deterioration in work performance. Item 9 was borderline significant. The area under the ROC curve for the short versions varied slightly from 0.555 to 0.560. As expected, model 6 has a greater specificity (56.02%) than the original tool while the efficiency increased slightly (54.85%). CONCLUSION: The modified versions of the ADAM test do not provide better diagnostic value than the original tool.

Limited usefulness of CA125 measurement in the management of Hodgkin's and non-Hodgkin's lymphoma.

BACKGROUND: Several papers have reported an association of high CA125 serum levels with advanced non-Hodgkin's lymphoma (NHL) as well as a relationship between high CA125 values and poor outcome. PATIENTS AND METHODS: Ninety-nine patients with NHL or Hodgkin's disease (HD) underwent serum CA125 assessment at diagnosis. Gender, age, presence of B symptoms, performance status (PS), histology, sites of tumor involvement, presence of effusion, clinical stage, age-adjusted International Prognostic Index, C-reactive protein (CRP), Hb, lactate deshydrogenase (LDH) and beta2-microglobulin were evaluated for their association with serum CA125 levels. The impact of CA125 levels and other features on overall (OS) and progression-free (PFS) survival was also assessed. RESULTS: CA125 serum levels were elevated in 34% of the patients, including 19% of patients with aggressive NHL, 45% of patients with indolent NHL, and 29% of patients with HD. Univariate analyses showed that CA125 levels correlated with poor PS, the presence of B symptoms, advanced clinical stage, abdominal, bone marrow or mediastinal involvement, presence of effusions, high aaIPI, low Hb levels and high CRP, LDH or beta2-microglobulin levels. In multivariate analysis, bone marrow involvement, the presence of effusions, and high aaIPI were all associated with high CA125 serum levels. In univariate analyses, OS and PFS were affected by age (PFS only), poor PS, B symptoms, advanced clinical stage, bone marrow or abdominal involvement (PFS only), high aaIPI, low Hb, high CRP or beta2-microglobulin levels. OS and PFS were not different in patients with normal or elevated CA125 levels. Multivariate analyses showed significantly inferior OS and PFS in patients with high beta2-microglobulin but no influence of CA125. CONCLUSION: While CA125 serum level correlates significantly with a number of features associated with more aggressive disease, it does not enhance the performance of standard prognostic markers in the management of patients with NHL or HD.

No major month to month variation in free testosterone levels in aging males. Minor impact on the biological diagnosis of 'andropause'.

BACKGROUND: The measurement of bioavailable testosterone (BT) or free testosterone (FT) levels is currently considered the gold standard for the diagnosis of androgen deficiency in elderly men. While the impact of age on circulating testosterone levels (total, bioavailable and free) has been strongly documented, the existence of seasonal variations in testosterone levels remains debated. OBJECTIVE: We investigated whether seasonal variations in serum calculated free testosterone (cFT) levels may translate into variations in the prevalence of low testosterone levels. Diagnosis was on the basis of biochemical determinations and was cross-checked with the prevalence of clinical signs and symptoms of 'andropause', as assessed by the Androgen Deficiency in Aging Males (ADAM) questionnaire. METHODS: The study recruited 5028 men aged 50 years and over from September 2000 to January 2003. Their serum FT levels were assessed and they completed the French ADAM test. Men were considered eugonadal when cFT was > or =70 ng/l. The ADAM test was scored as described originally. The prevalence of 'andropause', diagnosed by the two methods, was compared throughout the year, on a month by month basis. RESULTS: The percentage of subjects with cFT levels below 70 ng/l increased significantly with age (P<0.001). Serum cFT levels (mean [SD]) varied significantly with the month of sampling (P<0.0001), the highest (88.1 [30.2] ng/l) and lowest (76.9 [28.0] ng/l) mean values occurring in April and in October, respectively. Conversely, the prevalence of testosterone deficiency (cFT<70 ng/l) reached a peak in October (45.7%) and a nadir in April (29.7%). Although the prevalence of 'andropause', based on the ADAM questionnaire, increased significantly with age (P<0.0001), no influence of the month of the year was noticed. CONCLUSIONS: Our results confirm a progressive age-related decline in FT levels. The monthly variations in serum FT values, observed throughout the year, do not show a major seasonal rhythm in elderly community-dwelling males, since the magnitude of the variations (<15%) remains marginal. This slight variation may, however, have an impact on the number of elderly men diagnosed with Partial Androgen Deficiency in Aging Males (PADAM).

Interest of the androgen deficiency in aging males (ADAM) questionnaire for the identification of hypogonadism in elderly community-dwelling male volunteers.

OBJECTIVE: To date, serum free testosterone measurement is considered to be the gold standard for the diagnosis of hypogonadism in elderly males but it is not available to all subjects suspected of a decrease in testicular function. Therefore, we evaluated whether the Androgen Deficiency in Aging Males (ADAM) questionnaire, in its original or in a modified 'quantitative' version (qADAM), could be used as a surrogate to biochemical determinations for the identification of hypogonadism in elderly males. METHODS: 5028 men, aged 50-70 years, spontaneously consulting for the assessment of their gonadal function were studied. ADAM and qADAM, allocating a value of 1 point for any positive answer to each of the 10 questions of the ADAM test, were assessed for their ability to discriminate between males with free testosterone levels below or above 70 ng/l. RESULTS: The sensitivity and specificity of the ADAM score were 81% and 21.6% respectively. The use of ADAM resulted in an appropriate classification of our population in normal or hypogonadal subjects in 44.5% of the cases. The area under the receiver operating characteristics (ROC) curve for the qADAM (0.529) revealed a highly marginal interest of this quantitative approach compared with the original scoring system. CONCLUSIONS: The ADAM test has a high sensitivity to identify aging males with low free testosterone levels. However, due to its lack of specificity, this test cannot be used as a surrogate to serum free testosterone testing for the identification of androgen deficiency in elderly, community-dwelling males.

Obesity and liver disease.

Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance. It is frequently associated with obesity, especially visceral fat, and is intimately related to fatty liver and markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. The identification of obese patients who may progress from steatosis to NASH and from NASH to fibrosis/cirrhosis is an important clinical challenge. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by a remarkable regression of liver steatosis in most patients, although increased inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome, and perhaps being part of it, especially in obese patients.