Isolated congenital ACTH deficiency: A cleavage enzyme defect?

S. S. Nussey, S. C. Soo, S. Gibson, I. Gout, A. White, M. Bain, A. P. Johnstone

    Research output: Contribution to journalArticlepeer-review


    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 β-endorphin (β-EP) were within the normal adult range during glucocorticoid replacement therapy; ACTH and β-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.
    Original languageEnglish
    Pages (from-to)381-385
    Number of pages4
    JournalClinical Endocrinology
    Issue number3
    Publication statusPublished - 1993


    • physiopathology: Adrenal Cortex
    • Adrenal Cortex Function Tests
    • deficiency: Adrenocorticotropic Hormone
    • analysis: DNA
    • Electrophoresis, Agar Gel
    • Female
    • Humans
    • congenital: Hypoglycemia
    • Infant
    • metabolism: Peptide Hydrolases
    • Pituitary Function Tests
    • physiopathology: Pituitary Gland, Anterior
    • Polymerase Chain Reaction
    • genetics: Pro-Opiomelanocortin


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