Table 3.

Summary of endocrine dysfunctions and mechanisms in critical illness and ME/CFS.

Name of Axis	Dysfunctions Prolonged critical illness and ME/CFS	Mechanisms Prolonged critical illness
HPA Axis	Prolonged critical illness: - Lower than expected cortisol levels - Loss of pulsatile ACTH release ME/CFS: - Lower cortisol baseline - Blunted HPA axis response to stressors - Increased negative feedback - Loss of morning ACTH peak	Hypothalamus: cytokine-mediated increase in abundance and affinity of glucocorticoids receptors (GRs) inhibits CRH release Pituitary: increase in abundance of GRs inhibits ACTH release Adrenal gland: adrenal atrophy (due to lack of pulsatile ACTH stimulation during acute phase)
HPS Axis	Prolonged critical illness: - Loss of pulsatile GH release - Low or normal IGF-1 ME/CFS: - Low nocturnal GH - Mixed response to stimulation - Failed response to exercise (fibromyalgia) - Low or normal IGF-1	Hypothalamus: lack of stimulation by ghrelin; change in relative amounts of hypothalamic stimulating/inhibiting hormones (GHRH/GHIH) dampens GH release Pituitary: lack of stimulation by ghrelin dampens GH release
HPT Axis	Prolonged critical illness - Loss of pulsatile TSH release - Lower T3 - (Lower T4) - Higher rT3:T3 ME/CFS: - (Lower Free T3) - Higher rT3:T3	Hypothalamus: cytokine-induced alteration in set-point for release of TRH (local upregulation of T4 to T3 conversion) Pituitary: cytokine-mediated suppression of TSH secretion Thyroid gland: cytokine-mediated reduction in T4 secretion by the thyroid gland. Periphery: upregulation of T3 to rT3 conversion (notably in liver), tissue specific alteration in T3 uptake (i.e., reception and transport), etc.