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Positive rate-sensitive corticosteroid feedback mechanism of ACTH secretion in Cushing's disease

H L Fehm, K H Voigt, G Kummer

    The Journal of Clinical Investigation
    |July 1, 1979
    PubMed

    Insights

    Patients with Cushing's disease post-adrenalectomy exhibit a paradoxical ACTH rise due to a reversed rapid corticosteroid feedback mechanism. The delayed, dose-sensitive feedback remains intact, but dexamethasone response is diminished.

    Area of Science:

    • Endocrinology
    • Neuroendocrinology
    • Physiology

    Background:

    • Cushing's disease involves dysregulated corticosteroid feedback.
    • Understanding the dynamic ACTH response is crucial for defining this disturbance.

    Purpose of the Study:

    • To investigate the dynamic aspects of the ACTH response to corticosteroid administration in patients with Cushing's disease after total adrenalectomy.
    • To compare these responses with those in Addison's disease patients.

    Main Methods:

    • Administered cortisol via infusion and bolus injection using varied designs to alter input signals.
    • Measured plasma ACTH concentrations at short intervals using radioimmunoassay.

    Main Results:

    • Constant rate cortisol infusion caused a paradoxical ACTH rise in Cushing's patients, unlike the inhibition seen in controls.
    • Rapid cortisol increases triggered ACTH rises in Cushing's patients, correlating with control group decreases.
    • Bolus cortisol injections showed similar time-courses in both groups, indicating intact delayed feedback.

    Conclusions:

    • The rapid, rate-sensitive corticosteroid feedback mechanism is inverted to a positive one in Cushing's disease post-adrenalectomy.
    • The delayed, dose-sensitive feedback mechanism remains undisturbed.
    • Dexamethasone's ability to activate rate-sensitive feedback is significantly reduced.

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