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Anne Bachelot, Marion Lapoirie, Jerome Dulon, Monique Leban, Raphaele Renard Penna, and Philippe Touraine

We conducted a retrospective study on the long-term effect of mitotane treatment on testicular adrenal rest tumors (TARTs) in 5 adult patients with classic 21-hydroxylase deficiency,. After 60 months of mitotane treatment, a decrease of adrenal steroids was observed in 4 patients. Testicular ultrasonography showed complete disappearance of TART in 2 patients, stabilization in 2 patients and a halving of TART volume in the remaining patient. Sperm count improved notably in 2 patients who had normal baseline inhibin B levels and small inclusions, thus enabling cryopreservation of the subjects’ semen. Four years of follow-up of these two patients after the withdrawal of mitotane showed no recurrence of TART and persistent normal testicular function. In conclusion, mitotane should be used as a last resort in CAH patients in the cases of azoospermia associated with TARTs but normal inhibin B levels, as it can improve long-term endocrine and exocrine testicular function.

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Anne Bachelot, Jean Louis Golmard, Jérôme Dulon, Nora Dahmoune, Monique Leban, Claire Bouvattier, Sylvie Cabrol, Juliane Leger, Michel Polak, and Philippe Touraine


Adverse outcomes in adult congenital adrenal hyperplasia (CAH) patients are frequent. The determinants of them have not yet been established.


To establish the prevalence of adverse outcomes and to find determining factors for each of them.

Design, patients, and methods

Cross-sectional monocentric study of 104 patients with childhood onset of CAH (71 women, 33 men). Analysis established first the determinants of clinical, hormonal, genetic variables and second a composite criterion for some of the outcomes and determinants.


BMI was above 25 kg/m2 in 44% of the cohort, adrenal hyperplasia and/or nodules were present in 45% of the patients, and irregular menstrual cycles and hyperandrogenism were found in 50 and 35% of the women respectively. In univariate analysis, the determinants of these outcomes were all linked to disease control, especially 17-hydroxyprogesterone (17OHP) and androstenedione concentrations. Low weight was a determinant of abnormal bone mineral density (BMD) (60% of the cohort). Multivariate analysis confirmed these data. A classic form (CF) of CAH was a determinant of testicular adrenal rest tumors (TARTs) (36% of the men). Total cumulative glucocorticoid dose was a determinant of BMI and TART, whereas fludrocortisone dose was a determinant of TART (P=0.03). In men, the composite criterion was associated with androstenedione concentration and CF. In women, the composite criterion was associated with total testosterone concentration.


The present study confirms the high prevalence of adverse outcomes in CAH patients. These are, most often, related to disease control. The impaired health status of adults with CAH could therefore be improved through the modification of treatment.

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Antonio Gallo, Emmanuelle Chaigneau, Christel Jublanc, David Rosenbaum, Alessandro Mattina, Michel Paques, Florence Rossant, Xavier Girerd, Monique Leban, and Eric Bruckert


Cardiovascular disease is one of the main causes of morbidity in active acromegaly due to the increased prevalence of risk factors and arterial consequences of increased growth hormone levels. No in vivo study has evaluated the consequences of acromegaly on the retinal microvasculature.


The aim of this study was to identify in vivo the presence of morphological alterations of retinal arterioles in subjects with acromegaly.

Patients and methods

Single-center retrospective study of a cohort of 60 subjects with acromegaly, matched to 60 controls, who were referred for adaptive optics camera (AOC) from September 2014 to December 2016. Of the subjects with acromegaly, 19 had an active disease (AD) and 41 a controlled disease (CD) based on the IGF1 ratio (IGF1r). Retinal arteriolar remodeling was previously assessed using adaptive optics camera (AOC) in order to measure wall-to-lumen ratio (WLR), wall thickness (WT), internal diameter (ID) and wall cross sectional area (WCSA).


WLR was significantly higher in AD subjects compared to CD subjects and controls (AD: 0.311 ± 0.06, CD: 0.279 ± 0.04, controls: 0.281 ± 0.04, P = 0.031). A significant positive correlation was observed between WLR and IGF-1r (R 2 = 0.215, P < 0.001), even after adjustment for gender, age, systolic blood pressure (SBP) and the presence of dopamine agonist treatment (R 2 = 0.406, P < 0.001). Retinal arteriolar anatomical indices were comparable between CD and controls.


Active acromegaly is associated with the presence of small retinal arteriolar remodeling. These results provide new perspectives to better stratify cardiovascular risk and consequently optimize treatment in acromegaly.

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Lee S Nguyen, Nathalie Rouas-Freiss, Christian Funck-Brentano, Monique Leban, Edgardo D Carosella, Philippe Touraine, Shaida Varnous, Anne Bachelot, and Joe-Elie Salem


HLA-G is an immune checkpoint molecule, naturally expressed during pregnancy, playing a critical role in the tolerance of the fetal semi-allograft from the maternal immune system. While HLA-G expression levels are associated with progesterone, the influence of other hormones is still unclear. Congenital adrenal hyperplasia (CAH) represents an adequate model to study the hormonal influence on biomarkers as it leads to impaired cortisol biosynthesis and increased progesterone and androgens production due to 21-hydroxylase enzyme deficiency.


In a cross-sectional study of CAH patients matched on sex and age with healthy control, the association between circulating levels of soluble HLA-G and hormones was assessed by use of non-parametric analyses tests. Multivariable linear regressions were performed on normalized data.


Overall, 83 CAH patients and 69 healthy controls were included. Among CAH patients, all were under glucocorticoid and 52 (62.6%) were under mineralocorticoid supplementation. Compared to controls, CAH patients had increased HLA-G levels (15 vs 8 ng/mL, P = 0.02). In controls, HLA-G level was independently associated with progesterone and estradiol (β = 0.44 (0.35–1.27) and −0.44 (−0.94, −0.26) respectively, both P values = 0.001). In CAH patients, HLA-G level was independently associated with mineralocorticoid supplementation dosage (β = 0.25 (0.04–0.41), P = 0.001) and estradiol (β = −0.22 (−0.57, −0.02), P < 0.001).


CAH patients had higher HLA-G levels than healthy controls. HLA-G level was positively associated with progesterone and corticosteroid supplementation, and negatively with estradiol. The association between mineralocorticoid, renin and HLA-G levels may suggest a role of the renin-angiotensin system in the expression of soluble HLA-G.