{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:37:01Z","timestamp":1791286621340,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,11,5]],"date-time":"2008-11-05T00:00:00Z","timestamp":1225843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> Cushing's syndrome due to familial ACTH\u2010independent macronodular adrenal hyperplasia (AIMAH) has been reported in small kindreds. In vasopressin\u2010sensitive AIMAH (VPs\u2010AIMAH), VP stimulates an aberrant, ACTH\u2010independent increase in cortisol. The aims of this study were to (i) delineate the preclinical phenotype of VPs\u2010AIMAH in a three\u2010generation kindred (AIMAH\u201001) and two smaller kindreds (AIMAH\u201002 and AIMAH\u201003) and (ii) investigate the aetiology of VP sensitivity in AIMAH\u201001.<\/jats:p><jats:p><jats:bold>Design\u2002<\/jats:bold> Clinical studies of three kindreds for adrenal tumours or early Cushing's and molecular studies of adrenal tumours (AIMAH\u201001).<\/jats:p><jats:p><jats:bold>Patients\u2002<\/jats:bold> Thirty\u2010three individuals, from three kindreds, were screened for perturbations of the hypothalamic\u2013pituitary\u2013adrenal axis or adrenal tumours.<\/jats:p><jats:p><jats:bold>Measurements\u2002<\/jats:bold> Patients underwent clinical, biochemical and adrenal imaging investigations. Evaluation included low\u2010dose (1\u00a0IU\/70\u00a0kg) VP stimulation. Adrenal VP receptor (AVPR1A, AVPR1B, AVPR2) expression (AIMAH\u201001) was assessed using RT\u2010PCR and immunohistochemistry (IHC). IHC for VP was also performed.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> AIMAH\u201001 had three siblings with Cushing's, and four individuals with suppressed ACTH\/aberrant VP responses and\/or adrenal nodules. In AIMAH\u201002, a father and son were affected. AIMAH\u201003 had three siblings with Cushing's.<\/jats:p><jats:p>RT\u2010PCR showed adrenal overexpression of AVPR1A and AVPR1B. IHC detected AVPR1A. The adrenal tumour from one patient also stained weakly for VP and AVPR2.<\/jats:p><jats:p><jats:bold>Conclusion\u2002<\/jats:bold> Adrenal nodules, suppressed ACTH and increased VP sensitivity may represent preclinical disease, allowing early detection, and treatment, of affected individuals. In AIMAH\u201001, increased VP sensitivity may be due to adrenal VP receptor overexpression. In these kindreds, VPs\u2010AIMAH is familial, and autosomal dominant inheritance is most likely.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2008.03471.x","type":"journal-article","created":{"date-parts":[[2008,11,5]],"date-time":"2008-11-05T08:21:27Z","timestamp":1225873287000},"page":"883-891","source":"Crossref","is-referenced-by-count":42,"title":["Familial vasopressin\u2010sensitive ACTH\u2010independent macronodular adrenal hyperplasia (VPs\u2010AIMAH): clinical studies of three kindreds"],"prefix":"10.1111","volume":"70","author":[{"given":"Lucia","family":"Gagliardi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheri","family":"Hotu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Casey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilton 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