ISOLATED CONGENITAL ACTH DEFICIENCY - A CLEAVAGE ENZYME DEFECT

被引:27
作者
NUSSEY, SS
SOO, SC
GIBSON, S
GOUT, I
WHITE, A
BAIN, M
JOHNSTONE, AP
机构
[1] ST GEORGE HOSP,SCH MED,DEPT CHILD HLTH,LONDON SW17 0RE,ENGLAND
[2] UNIV MANCHESTER,HOPE HOSP,DEPT MED,SALFORD M6 8HD,LANCS,ENGLAND
[3] LUDWIG INST CANC RES,LONDON W1P 8BT,ENGLAND
关键词
D O I
10.1111/j.1365-2265.1993.tb02381.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The pro-opiomelanocortin (POMC) gene encodes adrenocorticotrophin (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 (CRH1-41). ACTH precursors, quantitated by two-site immunuradiometric assay, were clearly measurable prior to treatment and were stimulated by CRH1-41 and suppressed by glucocorticoid administration. Concentrations of POMC, N-terminal pro-opiocortin (N-POC) and beta-endorphin (beta-EP) were within the normal adult range during glucocorticoid replacement therapy; ACTH and beta-lipotrophin 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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页码:381 / 385
页数:5
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