Clinical testing of the hypothalamic-pituitary-adrenocortical system in states of hypo- and hypercortisolism

Variability in the secretion of corticotropin-releasing hormone, adrenocorticotropic hormone and cortisol and understandability of the hypothalamic-pituitary-adrenal axis dynamics--a mathematical study based on clinical evidence

“…So we consider only the slow-feedback mechanism in our model and exclude the fast-feedback mechanism. A short negative-feedback loop of ACTH on the secretion of CRH also exists (Greenspan & Strewler, 1993;Gwinup & Johnson, 1975;Larsen et al, 2003). Here, the long feedback loop has only been considered and short feedback loop from pituitary to hypothalamus has been excluded for simplicity of the mathematical model (see Fig.…”

“…But they ignored the long negative-feedback effect of cortisol on CRH production at the hypothalamus. In contrast, several clinical evidences confirm the existence of the long negative-feedback effect of cortisol on CRH and the delay therein (Greenspan & Strewler, 1993;Gwinup & Johnson, 1975;Larsen et al, 2003;Veldhuis et al, 2001). They also did not verify whether the model can predict any physiological changes following adrenalectomy or hypophysectomy.…”

Measuring adrenal function in out-patients using topical corticosteroids

“…The insulin stress test is the most informative single test available but it necessitates keeping the patient in hospital for the day and is therefore time-consuming and not easy to conduct in a busy out-patient clinic. The use ofthe short tetracosactrin test (James & Landon, 1968) is simple, but again is time-consuming, and involves patients staying in the clinic for longer than usual; it also requires careful timing of blood sampling and this is not always practicable when large numbers of patients are being examined. Collection of 24 h urine samples for estimation of oxogenic steroids is not easy for the out-patient.…”

“…It is known that plasma cortisol levels undergo significant circadian variation (James & Landon, 1970) and also that corticosteroids are released from the adrenals in bursts, and levels therefore also undergo episodic variation (Gwinup & Johnson, 1975). The circadian rhythm correlates with the sleep -wake cycle and, in the majority of patients, levels are at a peak at about 9.00 a.m. After this they decline and patients with normal adrenal function can have very low levels by late afternoon.…”