Successful Treatment of Estrogen Excess in Primary Bilateral Macronodular Adrenocortical Hyperplasia with Leuprolide Acetate
| Autor: | Vladimir Valera Romero, Andreas G. Moraitis, Fady Hannah-Shmouni, Richard A Failor, Annabel Berthon, Maria J. Merino, Andrew P. Demidowich, Constantine A. Stratakis, Fabio R. Faucz, Spyridon A. Mastroyannis |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Adenoma medicine.drug_class Endocrinology Diabetes and Metabolism Receptor expression Clinical Biochemistry 030209 endocrinology & metabolism Biochemistry Article 03 medical and health sciences Cushing syndrome 0302 clinical medicine Endocrinology 3' 5'-Cyclic-GMP Phosphodiesterases Internal medicine medicine Humans Mastodynia Aged Adrenal Hyperplasia Congenital Base Sequence Staining and Labeling Adrenal cortex business.industry Phosphoric Diester Hydrolases Biochemistry (medical) Estrogens General Medicine Sequence Analysis DNA Middle Aged Receptors LH medicine.disease Immunohistochemistry 030104 developmental biology medicine.anatomical_structure Treatment Outcome Estrogen Leuprolide Luteinizing hormone business Tomography X-Ray Computed Hormone Follow-Up Studies |
| Zdroj: | Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 50(2) |
| ISSN: | 1439-4286 |
| Popis: | Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is an uncommon cause of adrenal Cushing syndrome (CS) in which cortisol and occasionally other steroid hormones can be secreted under the influence of aberrantly expressed G-protein coupled receptors (GPCRs) in the adrenal cortex. We describe the unique case of a 64-year-old postmenopausal female with PBMAH whose adrenal lesions expressed luteinizing hormone receptors (LHr). She presented initially with CS and underwent right adrenalectomy; a few years later she presented with macromastia and mastodynia, possibly due to estrogen excess from her remaining left adrenocortical masses. Testing before and after treatment with quarterly leuprolide acetate therapy and immunohistochemistry on tissue and targeted sequencing of the genes of interest were performed. Tissue from the patient’s right adrenal was tested for P450 aromatase (CYP19A1) and LHr expression; both were expressed throughout the hyperplastic cortex, although expression was more intense in the adenomatous areas. Targeted sequencing revealed a pathogenic PDE11A mutation, as well as variants in the ARMC5 and INHA genes. PDE11A expression was decreased in the adenoma but there was no loss of heterozygosity for the PDE11A locus. Because of the clinical presentation and LHr expression, quarterly leuprolide acetate therapy was started. Shortly after initiation of therapy, the patient reported decreased breast size and pain; she remains well controlled to date, after 10 years of treatment. This is the first description of a patient with PBMAH presenting with severe macromastia and mastodynia from what appears to be excess estrogen production from her adrenal tumor. The patient had a long-lasting response to chronic leuprolide acetate treatment, showing that drug therapy exploiting the aberrant receptor expression in PBMAH is possible even in the absence of cortisol overproduction. |
| Databáze: | OpenAIRE |
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