Modelling oral adrenal cortisol support

TL;DR

This paper presents a simplified linear kinetic model of oral hydrocortisone delivery for adrenal insufficiency, fitted to clinical data, to optimize dosing strategies and improve circadian cortisol responses.

Contribution

It introduces a novel simplified mathematical model incorporating glucocorticoid-protein binding dynamics for oral cortisol delivery.

Findings

The model accurately fits existing dosing data.

Standard dosing regimes produce circadian-like cortisol responses.

Alternative evenly spaced dosing yields more stable cortisol levels.

Abstract

A simplified mathematical model of oral hydrocortisone delivery in adrenal insufficiency is described; the model is based on three components (gastric hydrocortisone, free serum cortisol and bound serum cortisol) and is formulated in terms of linear kinetics, taking into account the dynamics of glucocorticoid-protein binding. Motivated by the need to optimise cortisol replacement in the situations of COVID-19 infection, the model is fitted to recently-published data on 50 mg dosing and earlier data on 10 mg dosing. The fitted model is used to predict typical responses to standard dosing regimes, which involve a larger dose in the morning and 1 or 2 smaller doses later in the day, and the same regimes with doses doubled. In all cases there is a circadian-like response, with early morning nadir. The model is also used to consider an alternative dosing strategy based on four equal and equally-spaced doses of 10, 20 or 30 mg per 24 h, resulting in a more even response resembling a response to sustained inflammatory stress.