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Isolated congenital ACTH deficiency: a cleavage enzyme defect?
Author(s) -
Nussey S. S.,
Soo ShluChing,
Gibsonf S.,
Gout I.,
White A.,
Bain M.,
Johnstone A. P.
Publication year - 1993
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1993.tb02381.x
Subject(s) - endocrinology , medicine , glucocorticoid , adrenocorticotropic hormone , radioimmunoassay , enzyme , proopiomelanocortin , acth receptor , cleavage (geology) , polymerase chain reaction , biology , chemistry , hormone , gene , biochemistry , paleontology , fracture (geology)
Summary 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.