[Adrenal insufficiency of the adult]. / L'insuffisance surrénalienne chez l'adulte.

Adrenal insufficiency is a rare but life-threatening disorder. Clinical manifestations include fatigue, weight loss, gastrointestinal manifestations and skin hyperpigmentation, the latter being specific of primary adrenal failure. Because of non-specific clinical features of this rare disorder, diagnosis can be delayed and adrenal failure be revealed by an acute crisis. Adrenal insufficiency can be primary (Addison disease), most frequently autoimmune, or secondary, resulting from long term administration of exogenous glucocorticoids or more rarely from pituitary disorders. Monitoring of substitutive treatment is now well codified. Patient education is very important in this chronic disease that remains associated with a persistent high risk of adrenal crisis.

[Influence of hospitalisation on drug prescription in arterial hypertension and chronic conditions]. / Influence de l'hospitalisation sur la prescription médicamenteuse dans l'hypertension artérielle et les maladies chroniques.

OBJECTIVES: To evaluate the influence of hospitalization on drug prescription in chronic conditions. METHODS: Admission and discharge prescriptions from 92 patients consecutively admitted in a specialized department of the Assistance Publique-Hôpitaux de Paris hospital were recorded in a prospective two-month study. A Qualitative Therapeutical Score (QTS) was calculated as an estimation of qualitative modifications in the prescription. RESULTS: Patients admitted for an hospital stay of over 24h have more lines of prescription than patients admitted for an hospitalization shorter than 24h (5.7±4.2/d vs 2.9±2.5/d, P<0.01). For all the patients enrolled, the hospital stay is not associated with any change in the global number of treatments. However, in patients treated with antihyperstensive drug, the number of drug intakes decreases (2.6±1.5/d vs 1.9±1.4/d, P<0.05) as a consequence of an increase in the prescription of fixed-dose combinations. In patients with cardiovascular diseases, the QTS is higher and qualitative modifications are more often found in patients admitted for an hospital stay of over 24h than for those admitted for a an hospitalization shorter than 24h (0.57 vs 0.11; P<0.01 and 31% vs 11%; P<0.05 respectively). Antihypertensive drugs are the most represented drugs within these qualitative modifications. CONCLUSION: In patients with drug treatments for arterial hypertension or chronic conditions, hospitalization is not associated with quantitative but with qualitative modifications, especially for an over 24h hospital stay.

Serum levels of adhesion molecules ICAM-1 and VCAM-1 and tissue inhibitor of metalloproteinases, TIMP-1, are elevated in patients with autoimmune thyroid disorders: relevance to vascular inflammation.

Serum levels of ICAM-1 (Inter Cellular Adhesion Molecule-1), VCAM-1 (Vascular cell Adhesion Molecule-1-I), TIMP-1 (tissue inhibitor of metalloproteinases 1) and MMP-9 (Metalloproteinase 9) are well established markers of inflammation. The physiopathological link between inflammation, atherosclerosis and autoimmunity is well demonstrated. However, serum levels of these biomarkers in patients with autoimmune-mediated dysthyroidism, including their evolution after improvement of the thyroid disorder have not been assessed. So, we evaluated the circulating levels of these markers in autoimmune and in non-autoimmune-mediated dysthyroid patients, and their evolution after treatment of thyroid disease. We conducted a prospective study to evaluate these markers before and after treatment in hyperthyroid patients (n = 33; 28 patients with autoimmune disease), hypothyroid patients (n = 38; 33 patients with autoimmune disease) and euthyroid subjects (n = 33). At baseline, serum levels of ICAM-1, VCAM-1 and TIMP-1 were significantly elevated in patients with hyperthyroidism as compared to euthyroid and hypothyroid patients (respectively p = 0.0005 and p < 0.0001). In multivariate analysis, the differences remained significant for VCAM-1 and TIMP-1. Median levels of ICAM-1, VCAM-1 and TIMP-1 were significantly higher in patients with autoimmune-mediated dysthyroidism compared to euthyroid patients (respectively p < 0.0001 and p = 0.002). In hyperthyroid patients, ICAM-1, VCAM-1 and TIMP-1 concentrations fell significantly after they had become euthyroid (respectively p = 0.0006; p < 0.0001 and p = 0.0009), although VCAM-1 values remained higher than those observed in the control group (p = 0.005). We found that autoimmune-mediated dysthyroidism were associated with increased peripheral blood concentrations of VCAM-1, ICAM-1 and TIMP-1. Whether these biological abnormalities translate into increase intima remodelling and atherosclerosis remains to be studied.

[Subclinical hypothyroidism: a cardiovascular risk factor?]. / L'hypothyroidie infracinique: facteur de risque cardiovasculaire?

Although patent hypothyroidism is clearly associated with increased cardiovascular risk, the relationship between infraclinical hypothyroidism and cardiovascular disease remains controversial though probable. This relationship is mediated by the traditional risk factors (lipids, hypertension), by changes in parameters of inflammation and haemostasis, and by a direct effect of thyroid hormones on the vessel wall. The authors review the epidemiological evidence and the mechanisms underlying the association between infraclinical hypothyroidism and cardiovascular risk and the therapeutic implications of this association.

[Graves' disease and autoimmune thrombocytopenic purpura: distinct outcomes of the two diseases]. / Maladie de Basedow et purpura thrombopénique auto-immun: l'évolution n'est pas toujours parallèle.

The association of idiopathic thrombocytopenic purpura and Graves' disease is rare. Hence, little is known about the outcomes of these two diseases when associated. We report two cases of idiopathic thrombocytopenic purpura associated with Graves' disease, in which the two diseases had distinct outcomes. Thus, the hypothesis of cross-reaction between antithyroid antibodies and platelet epitopes, which has been proposed to explain the association, seems unlikely.

Chronic paroxysmal hemicrania in a patient with a macroprolactinoma.

We report a patient with headaches meeting the criteria of chronic paroxysmal hemicrania, as defined by the International Headache Society classification. Headaches were fully responsive to indomethacin during the first 3 months of treatment but recurred when daily doses were lowered. Investigations revealed a macroprolactinoma. Headaches stopped after cabergoline treatment. This report further suggests that patients with paroxysmal hemicrania should be investigated for pituitary abnormalities.

Effect of levothyroxine replacement therapy on coagulation and fibrinolysis in severe hypothyroidism.

OBJECTIVE: We previously demonstrated that patients suffering from moderate hypothyroidism were at increased risk of thrombosis contrasting with the bleeding tendency of those presenting severe hypothyroidism. The latter state is associated with hemostatic anomalies including von Willebrand type 1 disease and increased fibrinolytic capacity. With the exception of von Willebrand type 1 disease, reversibility of hemostatic changes is not established after levothyroxine replacement therapy. Therefore our objective was to analyze the reversibility of these anomalies. MATERIALS AND METHODS: We analyzed the impact of levothyroxine treatment on lipid parameters, fibrinogen, platelet count, D-dimers, alpha2 antiplasmin activity, plasminogen activity, tissue plasminogen activator antigen (t-PA Ag), plasminogen activator inhibitor type 1 antigen (PAI-1 Ag) and coagulation factors (factor VIII coagulant, von Willebrand factor antigen, von Willebrand factor and factor IX) in 23 patients with severe hypothyroidism (TSH level > 50 mU/ I). RESULTS: Mean fibrinogen levels increased by 14.2% while t-PA Ag and PAI-1 Ag increased by 42.6 and 69%, respectively, after correction of hypothyroidism. Interestingly, post-treatment PAI-1 Ag levels tended to be higher in patients with normal-high final TSH levels than in patients with normal-low final TSH levels. Our results suggest that normalization of fibrinolysis is obtained after a transient decrease of fibrinolytic activity. We also confirmed the correction of coagulation factor abnormalities upon levothyroxine replacement therapy. CONCLUSIONS: We demonstrated that the coagulation disorders and the hyperfibrinolytic status of severe hypothyroid patients were corrected upon levothyroxine therapy. However, the clinical consequences of the transient decrease of the fibrinolytic activity during the course of TSH normalization need further studies.

Adrenal insufficiency after adrenal hemorrhage.

Acute adrenal hemorrhage (AAH) is an extremely rare disorder, especially in adults, and may be difficult to diagnose because of its nonspecific presentation. We report a case of AAH following a sepsis, resulting in persistant adrenal insufficiency contrasting with the radiologic normalisation of the adrenals on computed tomography (CT) scan imaging.

Relationship of circulating C-reactive protein levels to thyroid status and cardiovascular risk in hyperlipidemic euthyroid subjects: low free thyroxine is associated with elevated hsCRP.

The mechanism(s) by which low circulating levels of thyroid hormones may lead to development of premature atherosclerosis remain to be established. These mechanisms include indirect effects of thyroid hormones on cardiovascular risk factors such as plasma lipoproteins, homocysteine and fibrinogen. High-sensitivity C-reactive protein (hsCRP) has been identified as an independent predictor of cardiovascular events. We presently investigated the relationship between hsCRP and free thyroxine (FT4) levels in a large population of euthyroid hyperlipidemic patients (n=429, mean age: 47.1 years, 28% of current smokers). None of these subjects presented a recent history of infection or inflammatory disease and those taking drugs known to influence thyroid or hsCRP were excluded. Serum FT4 levels were measured by radioimmunoassay and CRP, by a high-sensitivity immunoassay. In the population of non-smokers, plasma FT4 levels were negatively and significantly correlated with those of hsCRP (r=-0.13, P=0.02). Significant correlations between FT4 levels and age (r=-0.16, P=0.003), glycemia (r=-0.14, P=0.01), and fibrinogen (r=-0.18, P=0.001) were equally observed. Upon division of the population on the basis of FT4 tertiles, the mean level of hsCRP was significantly higher in non-smoker patients with the lowest FT4 tertile as compared to those displaying the highest FT4 level (3.04mg/l versus 1.77mg/l, respectively, P<0.05). No correlation between FT4 levels and CRP was found in smokers.In conclusion, we demonstrate that hsC-reactive protein is significantly negatively correlated with free thyroxine levels in non-smoker hyperlipidemic patients, suggesting that low thyroxine levels in euthyroid hyperlipidemic subjects constitute a new biomarker of elevated cardiovascular risk.