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Featured researches published by Line Billaud.


The New England Journal of Medicine | 1990

Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy.

Jean-Pierre Luton; Sonia Cerdas; Line Billaud; Guy Thomas; Brigitte Guilhaume; Xavier Bertagna; Marie-Hélène Laudat; Albert Louvel; Yves Chapuis; Philippe Blondeau; André Bonnin; Henri Bricaire

Adrenocortical carcinoma is a rare tumor, and only limited information is available about its natural history and the effects of therapy. We studied 105 patients (75 female and 30 male; mean age, 46 years) with adrenocortical carcinoma who were referred to us between 1963 and 1987. The average duration of symptoms before diagnosis was 8.7 months. At the time of diagnosis, 68 percent of the patients had endocrine symptoms, and 30 percent had distant metastases. Hormonal studies showed that 79 percent of the tumors were functional. Eighty patients underwent surgery, and 59 also received the adrenal cytotoxic agent mitotane. The median disease-free interval after surgery was 12.1 months (range, 1 to 175). Tumor dissemination occurred in 82 percent of the patients, most commonly to the lung, liver, and adjacent organs. The median survival time was 14.5 months (range, less than 1 to 175), and the five-year survival was 22 percent. Age over 40 years and the presence of metastases at the time of diagnosis were the only factors recognized as indicating a poor prognosis. Mitotane controlled hormonal secretion in 75 percent of the patients. Eight mitotane-treated patients had partial tumor regression, but the drug did not have a significant effect on survival. We conclude that adrenocortical carcinoma carries a poor prognosis. Mitotane therapy may offer transient benefits, particularly in controlling endocrine symptoms.


The New England Journal of Medicine | 1985

Late-Onset Adrenal Hyperplasia in Hirsutism

Frédérique Kuttenn; P. Couillin; François Girard; Line Billaud; Monique Vincens; Chafika Boucekkine; Jean-Christophe Thalabard; Thierry Maudelonde; Poli Spritzer; Irène Mowszowicz; A. Boué; Pierre Mauvais-Jarvis

We studied the incidence of late-onset adrenal hyperplasia as a cause of hirsutism, its association with the major histocompatibility complex, and its clinical expression. Twenty-four of 400 women seen because of hirsutism were found to have late-onset adrenal hyperplasia, diagnosed on the basis of a high plasma level of 17-hydroxyprogesterone, and its marked increase after ACTH stimulation. The degree of hirsutism varied widely. Plasma antigen levels were high, especially the level of androstenedione, whereas 5 alpha-reductase activity, considered to be a good index of peripheral androgen utilization, showed frequent normal or low values. The 24 patients were genotyped, along with 84 family members, and plasma hormones were measured in the family members. We found a high correlation between late-onset adrenal hyperplasia and HLA antigens B14 and Aw33. Similar biologic profiles were observed in the patients and those of their siblings who were HLA identical (n = 9), confirming that late-onset adrenal hyperplasia is linked to the histocompatibility complex. These nine siblings had no hirsutism. We therefore conclude that the role of skin sensitivity to androgens is important in determining the clinical expression of this disorder.


The Journal of Clinical Endocrinology and Metabolism | 2009

Clinical and Molecular Characterization of a Cohort of 161 Unrelated Women with Nonclassical Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency and 330 Family Members

Maud Bidet; Christine Bellanné-Chantelot; Marie-Béatrice Galand-Portier; Véronique Tardy; Line Billaud; Kathleen Laborde; Christiane Coussieu; Yves Morel; Christelle Vaury; Jean-Louis Golmard; Aurélie Claustre; Etienne Mornet; Zeina Chakhtoura; Irène Mowszowicz; Anne Bachelot; Philippe Touraine; Frédérique Kuttenn

CONTEXT Nonclassical congenital adrenal hyperplasia (NC-CAH) due to partial 21-hydroxylase deficiency is one of the most frequent autosomal recessive diseases. OBJECTIVE The aim of this study was to determine the genotype/phenotype relationship in probands and family members. PATIENTS AND METHODS A total of 161 NC-CAH unrelated women diagnosed on late-onset symptoms, mainly hirsutism, and post-ACTH 17-hydroxyprogesterone more than 10 ng/ml, and 330 of their relatives was explored. CYP21A2 was genotyped in 124 probands. RESULTS The most frequent mutation was V281L. One severe mutation was found in 63.7% of probands, and surprisingly two severe mutations in four probands. Contrasting with the absence of clinical differences, basal testosterone, and androstenedione, basal and post-ACTH 17-hydroxyprogesterone were significantly higher in probands carrying at least one severe mutation than in those with two mild mutations (P < 0.01). Among the 330 family members, 51 were homozygotes or compound heterozygotes, and 42 were clinically asymptomatic; 242 were heterozygotes and 37 unaffected. Post-ACTH 21-deoxycortisol (21dF) was significantly higher in heterozygotes than in unaffected, however, an overlap existed. In 12 heterozygotes, post-ACTH 21dF was below 0.55 ng/ml, the cutoff value usually accepted for suggesting heterozygosity. CONCLUSIONS The study of family members underlines the variable expression of NC-CAH even within a family, suggesting that modifier factors may modulate phenotype expression. Post-ACTH 21dF cannot reliably detect heterozygous subjects. Considering the high frequency of heterozygotes in the general population, it is essential to genotype the partner(s) of the patients with one severe mutation to offer genetic counseling.


Obstetrical & Gynecological Survey | 1992

Fertility in Women With Late-Onset Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Sylvie Feldman; Line Billaud; Jean-Christophe Thalabard; Marie-Charles Raux-Demay; Irène Mowszowicz; Frédérique Kuttenn; Pierre Mauvais-Jarvis

Fertility was evaluated in 53 female patients with late-onset adrenal hyperplasia (LAH) due to 21-hydroxylase deficiency. The majority of patients (n = 33) were seen for isolated postpubertal hirsutism, 9 patients consulted for sterility, and 11 for irregular menstrual cycles. At the time of diagnosis, the ages of patients ranged from 15-40 yr (mean +/- SD, 24.6 +/- 5.2). No patient had major signs of virilization. The plasma 17-hydroxyprogesterone level was higher than normal in all patients (26.8 +/- 18.9 nmol/L; range, 3.4-139.4) and dramatically increased to 140.1 +/- 80.6 nmol/L (range, 35.2-324.2) after ACTH treatment. Plasma androgen levels were high (testosterone, 3.25 +/- 2.03 nmol/L; delta 4-androstenedione, 13.65 +/- 5.60 nmol/L). Plasma basal and LHRH-stimulated values were normal for FSH and high for LH. Basal and TRH-stimulated plasma PRL levels were normal. Among these 53 LAH patients, only 20 desired a pregnancy. These had a total of 38 pregnancies. Ten patients became pregnant before the diagnosis of LAH and without any treatment; they had a total of 18 pregnancies, 12 of which were successful. Moreover, 19 normal pregnancies without any spontaneous abortion were carried to term by 14 of 16 hydrocortisone-treated patients. One patient needed the association of one cure of clomiphene citrate. Hypofertility in LAH patients seems, therefore, to be relative. Its mechanism is hormonal, with anovulation or dysovulation, due to the continuous steroid feedback of adrenal origin on the hypothalamo-pituitary axis. Hydrocortisone is the appropriate treatment in most cases, reducing adrenal androgen overproduction and relieving hypothalamic-pituitary gonadotropin function, thereby making possible cyclic ovarian activity and ovulations.


Obstetrical & Gynecological Survey | 1990

Cyproterone Acetate versus Hydrocortisone Treatment in Late-Onset Adrenal Hyperplasia

Poli Mara Spritzer; Line Billaud; Jean-Christophe Thalabard; Pascal Birman; Irène Mowszowicz; Marie-Charles Raux-Demay; François Clair; Frédérique Kuttenn; Pierre Mauvais-Jarvis

Thirty late-onset adrenal hyperplasia patients consulting for isolated hirsutism were randomly divided into two groups; group 1 (n = 16) was treated with hydrocortisone in order to suppress androgen adrenal secretion, and group 2 (n = 14) received cyproterone acetate (CPA) antiandrogen therapy to inhibit peripheral androgen activity. The clinical and hormonal effects of each type of treatment were evaluated. Before treatment, the clinical and hormonal profiles of the two patient groups did not differ significantly. Excellent clinical evolution in terms of the regression of hirsutism was observed in the CPA-treated patients (54% decrease in the clinical score in 1 yr), in contrast with the slight decrease in hirsutism (26%) after hydrocortisone treatment. In hydrocortisone-treated patients, plasma androgen decreased to normal levels: testosterone from 3.05 +/- 1.45 to 1.46 +/- 0.42 nmol/L and delta 4-androstenedione from 13.6 +/- 4.1 to 6.33 +/- 1.47 nmol/L. Conversely, in CPA-treated patients, only a slight decrease in testosterone from 2.98 +/- 1.98 to 2.29 +/- 0.64 nmol/L and in delta 4-androstenedione from 12.9 +/- 5.9 to 9.86 +/- 2.23 nmol/L was observed. This slight decrease in plasma androgens contrasts with the rapid clinical improvement after CPA. These results emphasize the importance of peripheral receptivity to androgens in the clinical expression of hyperandrogenism. Moreover, they indicate that peripheral antiandrogen therapy may be more appropriate in late-onset adrenal hyperplasia patients than conventional adrenal inhibition using cortisone therapy.


The Journal of Clinical Endocrinology and Metabolism | 1990

Cyproterone Acetate Versus Hydrocortisone Treatment in Late-Onset Adrenal Hyperplasia

Poli Mara Spritzer; Line Billaud; Jean-Christophe Thalabard; Pascal Birman; Irène Mowszowicz; Marie-Charles Raux-Demay; François Clair; Frédérique Kuttenn; Pierre Mauvais-Jarvis


The Journal of Clinical Endocrinology and Metabolism | 2001

Phenotype-Genotype Correlation in 56 Women with Nonclassical Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

C. Deneux; Véronique Tardy; Anne Dib; Etienne Mornet; Line Billaud; Daniel Charron; Yves Morel; Frédérique Kuttenn


The Journal of Clinical Endocrinology and Metabolism | 1992

Fertility in women with late-onset adrenal hyperplasia due to 21-hydroxylase deficiency

S Feldman; Line Billaud; Jean-Christophe Thalabard; Marie-Charles Raux-Demay; Irène Mowszowicz; Frédérique Kuttenn; P. Mauvais-Jarvis


Revue de Médecine Interne | 2010

Prsentation et pronostic des adnomes thyrotropes: propos de trois observations

H. Latrech; Alexandra Rousseau; E. Le Marois; Line Billaud; Xavier Bertagna; Said Azzoug; Marie-Laure Raffin-Sanson


/data/revues/02488663/v31i12/S0248866310009963/ | 2010

Présentation et pronostic des adénomes thyréotropes : à propos de trois observations

H. Latrech; A. Rousseau; E Le Marois; Line Billaud; Xavier Bertagna; S. Azzoug; Marie-Laure Raffin-Sanson

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Irène Mowszowicz

Necker-Enfants Malades Hospital

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Marie-Charles Raux-Demay

Necker-Enfants Malades Hospital

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François Clair

Necker-Enfants Malades Hospital

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Poli Mara Spritzer

Universidade Federal do Rio Grande do Sul

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Anne Dib

Necker-Enfants Malades Hospital

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Maud Bidet

Necker-Enfants Malades Hospital

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