Model-Based Cortisol Replacement Strategies for Patients With Adrenal Insufficiency

Abstract

Cortisol is an essential hormone secreted by the adrenal glands. Abnormally low level of cortisol is referred to as adrenal insufficiency. This paper focuses on devising treatment strategies for patients suffering from adrenal insufficiency using a model-based approach. Two conditions of adrenal insufficiency are analysed. They are hypothalamic-pituitary (HP) and adrenal gland disorders. The hypothalamus, pituitary, and adrenal glands constitute the hypothalamus-pituitary-adrenal (HPA) axis, which regulates stress and maintains physiological homeostasis through cortisol secretion. A comparative analysis of the existing mathematical models of the HPA axis is conducted. Based on this analysis, a novel model of the HPA axis is proposed that incorporates endogenous circadian rhythm. This proposed model is used to design effective cortisol replacement strategies. In addition, hydrocortisone replacement therapies are proposed and validated with clinical data from the literature. The results presented in this paper are applicable to patient-specific treatment strategies for individuals with adrenal insufficiency.