Somatic mutations in adrenals from patients with primary aldosteronism not cured after adrenalectomy suggest common pathogenic mechanisms between unilateral and bilateral disease

in European Journal of Endocrinology
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  • 1 Université de Paris, PARCC, Inserm, Paris, France
  • | 2 Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service d’Anatomie Pathologique, Paris, France
  • | 3 Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Unité Hypertension Artérielle, Paris, France
  • | 4 Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France

Correspondence should be addressed to M-C Zennaro or F L Fernandes-Rosa; Email: maria-christina.zennaro@inserm.fr or fabio.fernandes-rosa@inserm.fr

*(M-C Zennaro and F L Fernandes-Rosa contributed equally as senior authors)

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Objective

Primary aldosteronism (PA) is the most common form of secondary and curable hypertension. Different germline and somatic mutations are found in aldosterone-producing adenoma (APA) and familial forms of the disease, while the causes of bilateral adrenal hyperplasia (BAH) remain largely unknown. Adrenalectomy is the recommended treatment for patients with APA; however, 6% of patients are not cured and show persistent PA after surgery suggesting BAH. The objective of this study was to analyze clinical data of patients with APA without biochemical success after adrenalectomy as well as the histological and genetic characteristics of their adrenal glands.

Design and methods

Clinical data of 12 patients with partial and absent biochemical cure were compared to those from 39 PA patients with hormonal cure after surgery. Histological, morphological, and genetic characterization of the adrenals was carried out by CYP11B2 and CYP11B1 immunostaining and by CYP11B2-guided NGS.

Results

Patients with absent hormonal cure displayed a longer duration of arterial hypertension and lower lateralization index of aldosterone production. In ten patients, APAs expressing CYP11B2 were identified. No difference in histological and morphological characteristics was observed between patients with or without a hormonal cure. Somatic mutations in APA driver genes were identified in all CYP11B2 positive APAs; CACNA1D mutations were the most frequent genetic abnormality.

Conclusions

Patients with partial and absent biochemical cure were diagnosed later and exhibited a lower lateralization index of aldosterone production, suggesting asymmetric aldosterone production in the context of BAH. Somatic mutations in adrenal glands from those patients indicate common mechanisms underlying BAH and APA.

Supplementary Materials

    • Supplementary methods
    • Table S1. Baseline and follow up clinical data from PA patients non-cured after adrenalectomy
    • Table S2. Biochemical data from PA patients non-cured after adrenalectomy
    • Table S3. Comparison of histological characteristics of adrenals from non-cured PA patients
    • Table S3. Comparison of histological characteristics of adrenals from non-cured PA patients

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
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