{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:16:19Z","timestamp":1791288979315,"version":"4.3.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing's syndrome (CS) and its familial clustering has been described previously. Recent studies identified that<jats:italic>ARMC5<\/jats:italic>mutations occur frequently in BMAH, but the relation between<jats:italic>ARMC5<\/jats:italic>mutation and the expression of aberrant G-protein-coupled receptor has not been examined in detail yet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied a large French-Canadian family with BMAH and sub-clinical or overt CS. Screening was performed using the 1-mg dexamethasone suppression test (DST) in 28 family members. Screening for aberrant regulation of cortisol by various hormone receptors were examined<jats:italic>in vivo<\/jats:italic>in nine individuals. Sequencing of the coding regions of<jats:italic>ARMC5<\/jats:italic>gene was carried out.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Morning ambulating cortisol post 1\u200amg DST were &gt;50\u200anmol\/l in 5\/8 members in generation II (57\u201368 years old), 9\/22 in generation III (26\u201346 years old). Adrenal size was enlarged at different degrees. All affected patients increased cortisol following upright posture, insulin-induced hypoglycemia and\/or isoproterenol infusion. \u03b2-blockers led to the reduction of cortisol secretion in all patients with the exception of two who had adrenalectomies because of \u03b2-blockers intolerance. We identified a heterozygous germline variant in the<jats:italic>ARMC5<\/jats:italic>gene c.327_328insC, (p.Ala110Argfs*9) in nine individuals with clinical or subclinical CS, in four out of six individuals with abnormal suppression to dexamethasone at initial investigation and one out of six individuals with current normal clinical screening tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Systematic screening of members of the same family with hereditary BMAH allows the diagnosis of unsuspected subclinical CS associated with early BMAH. The relation between the causative<jats:italic>ARMC5<\/jats:italic>mutation and the reproducible pattern of aberrant \u03b2-adrenergic and V<jats:sub>1<\/jats:sub>-vasopressin receptors identified in this family remains to be elucidated.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-15-0642","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T06:38:14Z","timestamp":1448433494000},"page":"85-96","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":73,"title":["ARMC5 mutations in a large French-Canadian family with cortisol-secreting \u03b2-adrenergic\/vasopressin responsive bilateral macronodular adrenal hyperplasia"],"prefix":"10.1093","volume":"174","author":[{"given":"Isabelle","family":"Bourdeau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Oble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Magne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"L\u00e9vesque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia Y","family":"C\u00e1ceres-Gorriti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Nolet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Awadalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanne","family":"Tremblay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Hamet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Candida Barisson Villares","family":"Fragoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Lacroix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"2015112418385977000_174.1.85.1","doi-asserted-by":"crossref","unstructured":"Lacroix A Feelders RA Stratakis CA Nieman LK . 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