[Is there a place for stepped hormone assay in the development of hyperandrogenism?] / Comment j'explore Le dosage hormonal étagé a-t-il une place dans la mise au point des hyperandrogénies ?

Clinical hyperandrogenism is common in women. Nevertheless, it is important to identify the cause. As the hyperandrogenism may be ovarian or adrenal in origin, making the difference requires hormonal testing and ovarian and/or adrenal imaging. We present the case report of a patient explored in our clinic, that illustrates the difficulties to determine the origin of the endocrine disorder. The interest of employing selective ovarian and adrenal venous catheterization to aid in the diagnosis and the localization of the androgen-secreting tumor is discussed.

L'hyperandrogénie clinique est un motif de consultation fréquent. Le diagnostic différentiel permet d'établir l'étiologie parmi les causes ovariennes ou surrénaliennes. Outre le repérage de signes pathognomoniques cliniques, des examens complémentaires biologiques et iconographiques sont nécessaires pour la mise au point. Les difficultés diagnostiques sont illustrées à partir d'un cas clinique traité dans notre institution. L'intérêt du bilan hormonal étagé par cathétérisation des veines ovariennes et surrénaliennes afin de localiser l'origine de la sécrétion hormonale pathologique est discuté.

[An update in intrauterine contraception]. / Nouveautés en contraception intra-utérine.

Intrauterine devices (IUD) are the oldest of the modern contraceptives. There are currently two types of IUDs: copper IUD (Cu-IUD) and levonorgestrel IUD (LNG-IUD). Both offer high contraceptive effectiveness. Although they have been used for decades, the literature still brings its share of new information on IUDs: impact on oncological risk, non-contraceptive benefits, rare adverse effects, and impact on women's well-being. In addition, Cu-DIU is recognized as the most effective emergency contraceptive and can be inserted up to 5-7 days after the at-risk sexual intercourse. Research is now looking at the effectiveness of LNG-IUD in emergency contraception. Finally, new IUD concepts are also being evaluated: they should allow a reduction in the rate of expulsion, intermenstrual and heavy menstrual bleeding, an increase in comfort and in IUDs duration of use. This article makes an update on the latest developments in terms of intrauterine contraceptives.

Le dispositif intra-utérin (DIU) est le plus ancien des contraceptifs modernes. On distingue les DIU au cuivre (Cu-DIU) et les DIU au lévonorgestrel (LNG-DIU). Ils offrent une haute efficacité contraceptive. Bien qu'ils soient utilisés depuis des décennies, la littérature apporte encore aujourd'hui son lot de nouvelles informations sur les DIU: impact sur le risque oncologique, bénéfices non contraceptifs, effets indésirables rares et impact sur le bien-être des femmes. Par ailleurs, le Cu-DIU est reconnu comme étant le contraceptif d'urgence le plus efficace, pouvant être inséré jusqu'à 5-7 jours après le rapport à risque. La recherche se penche maintenant sur l'efficacité du LNG-DIU en contraception d'urgence. Enfin, de nouveaux concepts de DIU sont aussi à l'étude : ils devraient permettre une réduction du taux d'expulsion, une diminution des méno- et métrorragies, une augmentation du confort et une plus longue durée d'utilisation. Cet article fait le point sur les dernières nouveautés en termes de contraceptifs intra-utérins.

[How to explore... hyperandrogenism associated with insulin resistance ? An example based on the HAIR-AN syndrome.] / Comment j'explore une hyperandrogénie dans un contexte d'insulinorésistance. Un exemple basé sur le syndrome HAIR-AN.

HAIR-AN, a syndrome associating hyperandrogenism, insulin resistance and acanthosis nigricans, is currently considered as a severe form of polycystic ovary syndrome. The physiopathology of this syndrome relies on the insulin resistance which is the basis of a vicious circle : the resulting hyperinsulinism leads to an excessive production of androgens. The latter increases abdominal fat deposition which in turn worsens the insulin resistance. Hyperinsulinism is also responsible for the acanthosis nigricans by stimulating the IGF-1 receptors on keratinocytes and fibroblasts. Hyperandrogenism is clinically translated into hirsutism that can be severe. Frequently, menstrual irregularity and obesity are part of the syndrome. HAIR-AN syndrome begins soon after puberty and is currently under-diagnosed. Treatment relies on an improvement in insulin-resistance by a loss of body weight and the use of insulin sensitizers. Moreover, anti-androgenic drugs will help improving hirsutism. Although more invasive, bariatric surgery has shown a great efficacy in this syndrome : by permitting a substantial loss of weight, it often normalizes insulin-sensitivity, allowing for improvements in hyperandrogenism and acanthosis nigricans.

Considéré comme une forme sévère du syndrome des ovaires micropolykystiques, le syndrome de HAIR-AN associe une hyperandrogénie, une résistance à l'insuline et un acanthosis nigricans. La base physiopathologique du syndrome HAIR-AN est un cercle vicieux ayant pour point de départ la résistance à l'insuline : l'hyperinsulinisme qui en résulte entraîne une production excessive d'androgènes. Ces derniers, en aggravant le dépôt de graisse abdominale, majorent la résistance à l'insuline. Il s'agit donc d'un phénomène auto-entretenu. En stimulant le récepteur à l'IGF-1 des kératinocytes et des fibroblastes, l'hyperinsulinisme est également responsable de l'acanthosis nigricans. L'hyperandrogénie se traduit cliniquement par un hirsutisme pouvant être sévère. On notera fréquemment aussi une irrégularité menstruelle et une obésité. Le syndrome HAIR-AN débute tôt après la puberté et est actuellement sous-diagnostiqué. Le traitement est, avant tout, celui de la résistance à l'insuline et nécessite donc une perte de poids associée à l'utilisation de molécules insulino-sensibilisatrices. De plus, des traitements hormonaux anti-androgéniques aideront également à diminuer le hirsutisme. Plus invasive, la chirurgie bariatrique a cependant démontré une grande efficacité chez ces patientes : en permettant une perte de poids conséquente, elle normalise souvent la sensibilité à l'insuline, ce qui améliore significativement l'hyperandrogénie et l'acanthosis nigricans.

IFN-γ and TNF-α potentiate prostaglandin D2-induced human eosinophil chemotaxis through up-regulation of CRTH2 surface receptor.

Prostaglandin D2 (PGD2) receptor CRTH2, is a pro-inflammatory molecule involved in eosinophil recruitment to the allergic airway. We investigated the expression of CRTH2 in eosinophil from allergic rhinitis patients (AR) and tested the modulatory role of several TH1 and TH2 cytokines closely related to the allergic immunological response, on the expression of CRTH2 receptor, utilizing human eosinophil cell line (Eol-1).The expression of CRTH2 was tested by immunohistochemistry and flow cytometry (FACS). Chemotaxis was performed in micro-chemotaxis chambers. It is shown that the expression of CRTH2 by eosinophils was significantly higher in the nasal tissue and peripheral blood of AR patients, when compared to control subjects. PGD2 exhibited a typical bell shape dose response in attracting eosinophil from AR patients with optimal activity at 10(-7) M. Eol-1 cell surface expression of CRTH2 was significantly up-regulated by 10 ng/ml IFN-γ and TNF-α. The percentage of Eol-1 cells expressing the receptor increased by IFN-γ and TNF-α from 12.74%±2.66 to 55%±8 and 33.8%±9.4, respectively. PGD2-induced Eol-1 chemotaxis was not blocked by SB203580, H-89 Dihydrochloride, Bisindo-lylmaleimide, or Genistein. PGD2-induced Eol-1 chemotaxis was potentiated by IFN-γ and TNF-α without changing the signal transduction pathway. Correlation of our results to peripheral blood eosinophils from allergic rhinitis patients confirmed that 3 hour pretreatment of eosinophils by 10 ng/ml IFN-γ and TNF-α, increased the mean fluorescence intensity (MFI) of CRTH2 from 8.23 to 9.68 and 9.38, respectively, and potentiated PGD2-induced eosinophil chemotaxis. Our results demonstrate a novel synergism between PGD2, IFN-γ and TNF-α, in eosinophil chemotaxis.

Serum creatine kinase relationship to postural constraints in manual work.

Serum creatine kinase (CK) variations during work and subjective assessments of postural discomfort were analysed in 30 workers assigned to three different tasks in a rolling mill. After four days of work, serum CK levels were significantly increased above control levels. No difference was found between the tasks studied. Inter-individual variability in CK response was large: a marked CK increase was only seen in 21 workers, while 5 workers showed a marked CK decrease. The postural discomfort sensations increased with work in each group, with their location in the body being related to the characteristics of each task or workplace. No relationship was found between the postural discomfort scores and CK changes. Results showed that determination of an individual baseline CK level was difficult to achieve in an occupational setting. It is concluded that CK variations cannot reliably be used in the field for detection of individuals exposed to excessive postural constraints. Their use as a screening tool in groups of workers assigned to similar tasks deserves further study.

[Study of lung symptomatology and lung function in steelworkers]. / Studie van de longsymptomatologie en longfunctie bij staalarbeiders.

We have examined 272 steelworkers, aged 45 to 55 years, by means of the ECSC-questionnaire and the following lung function tests: vital capacity (VC) and forced expiratory volume in one second (FEV1), residual volume (RV) and total lung capacity (TLC); maximal expiratory flow rates (Vmax, Vmax 50, Vmax 75); specific airways conductance (SGaw); slope of the N2 alveolar plateau after oxygen inhalation (delta N2) and the bolus closing volume (CV). The influence of smoking on respiratory symptoms and lung function was confirmed. In order to assess the influence of occupational pollution a sample of 163 workers was classified according to smoking habits and workplace (either LD-steelplant and continuous casting department, or sheet rolling mill). In the nonsmokers group we found that the workers from the steelplant and continuous casting department (n = 12) had a significantly lower SGaw value (delta = 0.065 cm H2O-1 . s-1, p less than 0.01) and a significantly higher CV value (delta = 4.5% VC, p less than 0.05) than the workers from the sheet rolling mill (n = 11). Differences in FEV1/VC, Vmax 50 and Vmax 75 were not significant, but were also consistent with a slight airflow obstruction in the steelplant workers. In the smokers (n = 99) and exsmokers (n = 41) groups no differences existed between both working categories. Our results suggest that nonsmoking workers from the steelplant and the continuous casting department have undergone moderate, but detectable effects from industrial pollution. These effects are probably masked by those of tobacco in smokers and exsmokers.