Isolated congenital ACTH deficiency: a cleavage enzyme defect? |
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| Authors: | S. S. Nussey,Shlu-Ching Soo,S. Gibsonf&dagger ,I. Gout&Dagger ,A. White&dagger ,M. Bain§ ,A. P. Johnstone |
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| Affiliation: | Departments of Cellular and Molecular Sciences, Hope Hospital, Salford M6 8HD;Department of Medicine, University of Manchester, Hope Hospital, Salford M6 8HD;The Ludwig Institute for Cancer Research, Courtauld Building, 91 Riding House Street, London W1P 8BT, UK;Child Health, St George's Hospital Medical Schjool, London |
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| Abstract: | The pro-opiomelanocortin (POMC) gene encodes adreno-corticotrophin (ACTH) which is derived from precursors by proteolytic cleavage. Congenital, isolated ACTH deficiency is rare but may be familial and fatal. The aetiology is unknown though defects at both hypothalamus and adenohypophysis have been postulated. We have studied a female presenting with hypoglycaemia in the neonatal period. When studied at 6 weeks of age, ACTH was unmeasurable even after injection of corticotrophin releasing hormone (CRH,_41). ACTH precursors, quantitated by two-site immunuradiometric assay, were clearly measurable prior to treatment and were stimulated by CRH, 4, and suppressed by glucocorticoid administration. Concentrations of POMC, N-terminal pro-opiocortin (N-POC) and β-endorphin (β-EP) were within the normal adult range during glucocorticoid replacement therapy; ACTH and βMipotrophin remained undetectable. The secretion of glucagon, measured by radioimmunoassay, in response to hypoglycaemia was normal. By sequencing polymerase chain reaction products from the patient's genomic DNA, the entire coding region of the POMC gene was established to be normal. The results are compatible with a cleavage enzyme defect. |
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