SFEBES2009 Poster Presentations Steroids (36 abstracts)
Corticosteroid-binding globulin (CBG) deficiency caused by a novel mutation in exon 3
I Perogamvros 1 , D Henley 2, , K Hadfield 4 , C Underhill 5 , W Newman 4 , G Hammond 5 , S Lightman 2 , D Ray 6 & P Trainer 1
1Department of Endocrinology, Christie Hospital, Manchester, UK; 2Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK; 3Faculty of Medicine, Dentistry & Health Sciences, University of Western Australia, Perth, Western Australia, Australia; 4Academic Unit of Medical Genetics, University of Manchester, Manchester, UK; 5Child and Family Research Institute and Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada; 6Endocrine Sciences Research Group, University of Manchester, Manchester, UK.
Inherited CBG deficiencies are rarely reported and only 3 causative mutations in 4 families have been described. The objective of this study was to investigate a family with potential CBG deficiency.
The index case, a 29-year-old female of Pakistani origin with consanguineous parents, presented with hirsutism and a slightly elevated 17-OHP. In a subsequent Short Synacthen Test (SST) 17-OHP was normal but serum cortisol (SerC) values were abnormal (case 1 on Table). CBG measurement revealed low levels while the salivary cortisol (SalC) response to SST was normal (see Table, mean normal response at 60 min: 36.2±13.7 nmol/l). Three siblings had an SST and CBG measured:
| Cases | SerC (nmol/l) | SalC (nmol/l) | CBG (31–53.4 mg/l) |
| 1 (♀, index case) | <50, 115 | 7.2, 41.5 | 17 |
| 2 (♀) | <50, 416 | 2.1, 57 | 19.6 |
| 3 (♂) | 304, 606 | 7.1, 32.5 | 32.7 |
In an ultradian rhythm study of the index case, 2 am–12 pm deconvolution analysis for SerC confirmed low mean secretion pulse mass (61 nmol/l) and 12 secretory episodes produced a mean secretion interpulse interval of 37 min-approximately double the normal frequency. ACTH values were within an expected ultradian range.
Genetic analysis revealed the two affected sisters being homozygotes and the unaffected brother a heterozygote for a novel mutation involving a c.776g>t transversion in exon 3 causing a change in p.259G>V. Preliminary analyses of the cortisol-binding properties of CBG in the affected family members are consistent with a very marked reduction in cortisol-binding affinity.
We report a novel CBG gene mutation that affects cortisol binding and total SerC levels. Despite the increased frequency in cortisol pulsatility, SalC and ACTH results indicate normal free cortisol in the affected individuals. Further cortisol binding studies and family testing are currently under way.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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