Pulsatile Subcutaneous Hydrocortisone Replacement in Primary Adrenal Insufficiency

Area of Science:

• Endocrinology
• Pharmacology
• Metabolism

Background:

• Endogenous cortisol secretion follows a pulsatile pattern crucial for gene signaling.
• Current glucocorticoid replacement therapies often fail to replicate this natural rhythm in primary adrenal insufficiency.
• This discrepancy can lead to suboptimal physiological responses and hormonal imbalances.

Purpose of the Study:

• To compare pulsatile cortisol pump treatment with continuous pump and oral therapies.
• To evaluate the impact of different cortisol delivery methods on 24-hour serum corticosteroid levels and plasma ACTH.
• To assess the feasibility of mimicking endogenous cortisol rhythmicity via subcutaneous infusion.

Main Methods:

• An open-labeled, two-week, nonrandomized cross-over study involving five patients with adrenal insufficiency.
• Comparison of pulsatile and continuous cortisol pump administration against conventional oral glucocorticoid therapy.
• Monitoring of 24-hour serum corticosteroid levels and plasma ACTH.

Main Results:

• Pulsatile pump treatment successfully restored ultradian cortisol rhythmicity, showing multiple peaks in serum and subcutaneous levels.
• Subcutaneous cortisol and cortisone levels were higher with both pump methods compared to oral therapy.
• Pulsatile pump treatment maintained ACTH within physiological ranges for most of the 24-hour cycle, unlike oral therapy.

Conclusions:

• Mimicking endogenous cortisol rhythm through ultradian subcutaneous infusion is feasible and effective.
• Pulsatile cortisol infusion demonstrated superiority over continuous pump and oral therapies in normalizing 24-hour ACTH levels.
• Oral replacement therapy may result in lower free cortisol bioavailability compared to subcutaneous infusion methods.