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https://hdl.handle.net/2440/53951
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Type: | Journal article |
Title: | Familial vasopressin-sensitive ACTH-independent macronodular adrenal hyperplasia (VPs-AIMAH): clinical studies of three kindreads |
Author: | Gagliardi, L. Hotu, C. Casey, G. Braund, W. Ling, K. Dodd, T. Manavis, J. Devitt, P. Cutfield, R. Rudzki, Z. Scott, H. Torpy, D. |
Citation: | Clinical Endocrinology, 2009; 70(6):883-891 |
Publisher: | Blackwell Science Ltd |
Issue Date: | 2009 |
ISSN: | 0300-0664 1365-2265 |
Statement of Responsibility: | Gagliardi, Lucia; Hotu, Cheri; Casey, Graeme; Braund, Wilton J.; Ling, King-Hwa; Dodd, Thomas; Manavis, James; Devitt, Peter G.; Cutfield, Richard; Rudzki, Zbigniew; Scott, Hamish S.; Torpy, David J. |
Abstract: | Cushing's syndrome due to familial ACTH-independent macronodular adrenal hyperplasia (AIMAH) has been reported in small kindreds. In vasopressin-sensitive AIMAH (VPs-AIMAH), VP stimulates an aberrant, ACTH-independent increase in cortisol. The aims of this study were to (i) delineate the preclinical phenotype of VPs-AIMAH in a three-generation kindred (AIMAH-01) and two smaller kindreds (AIMAH-02 and AIMAH-03) and (ii) investigate the aetiology of VP sensitivity in AIMAH-01. Design: Clinical studies of three kindreds for adrenal tumours or early Cushing's and molecular studies of adrenal tumours (AIMAH-01). Patients: Thirty-three individuals, from three kindreds, were screened for perturbations of the hypothalamic-pituitary-adrenal axis or adrenal tumours. Measurements: Patients underwent clinical, biochemical and adrenal imaging investigations. Evaluation included low-dose (1 IU/70 kg) VP stimulation. Adrenal VP receptor (AVPR1A, AVPR1B, AVPR2) expression (AIMAH-01) was assessed using RT-PCR and immunohistochemistry (IHC). IHC for VP was also performed. Results: AIMAH-01 had three siblings with Cushing's, and four individuals with suppressed ACTH/aberrant VP responses and/or adrenal nodules. In AIMAH-02, a father and son were affected. AIMAH-03 had three siblings with Cushing's. RT-PCR showed adrenal overexpression of AVPR1A and AVPR1B. IHC detected AVPR1A. The adrenal tumour from one patient also stained weakly for VP and AVPR2. Conclusion: Adrenal nodules, suppressed ACTH and increased VP sensitivity may represent preclinical disease, allowing early detection, and treatment, of affected individuals. In AIMAH-01, increased VP sensitivity may be due to adrenal VP receptor overexpression. In these kindreds, VPs-AIMAH is familial, and autosomal dominant inheritance is most likely. |
Keywords: | Humans Adrenal Gland Neoplasms Adrenal Hyperplasia, Congenital Cushing Syndrome Vasopressins Receptors, Vasopressin Pedigree Gene Expression Adult Aged Middle Aged Female Male Adrenocorticotropic Hormone Young Adult |
DOI: | 10.1111/j.1365-2265.2008.03471.x |
Published version: | http://dx.doi.org/10.1111/j.1365-2265.2008.03471.x |
Appears in Collections: | Aurora harvest Surgery publications |
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