Plasma Cortisol response to ACTH does not accurately indicate the state of hypothalamic-pituitary-adrenal axis

Abstract

The hypothalamic-pituitary-adrenal function was studied in 55 patients with various pituitary disorders. In particular, the consistency between the responses of plasma cortisol to exogenous ACTH and to insulin hypoglycemia was investigated in 5 patients in whom cortisol response to insulin was absent; four of these patients showed a cortisol response to ACTH of variable degree. These 4 patients had surgical or functional hypothalamus-pituitary disconnection and showed a preserved cortisol response to lysine vasopressin. These data demonstrate the unreliability of ACTH test in assessing hypothalamic-pituitary-adrenal function in hypopituitary patients.

The pituitary–adrenal axis in adult thalassaemic patients

“…Different doses of synthetic ACTH, from 250 to 0.03 mg, have been used to optimize adrenal stimulation with the latter considered the minimal dose able to raise plasma cortisol values. Given the supraphysiological stimulation induced with the acute HDT, which allows ACTH levels at least double those measured during major physical stress (11,20), this challenge gives rise to a high rate of false negative responses, thus appearing less suitable to detect mild adrenal dysfunction (21)(22)(23). Therefore, we performed in our patients a low-dose tetracosactide test, which is considered at the moment more reliable than the standard high-dose challenge in detecting adrenal insufficiency, by inducing an ACTH increase in the same magnitude as that obtained by ITT (24,25) and major physical stress (26).…”

Adrenal status in children with septic shock using low-dose stimulation test*

“…Earlier studies used a high dose of corticotropin (125-250 g) for stimulation of adrenals; this has been considered a pharmacologic dose, especially in small children (5). Such a high supraphysiologic dose can override adrenal resistance to adrenocorticotropic hormone (ACTH) and result in a normal cortisol response, even in patients with acute secondary adrenal insufficiency (6). Moreover, a patient may have an appropriately high serum cortisol concentration but be unable to respond further after corticotropin injection (no reserve).…”

Peri‐operative steroid supplementation

“…The SST has been criticised [56,57] and a number of case reports have documented instances in which the short synacthen test failed to diagnose unequivocally symptomatic secondary hypoadrenalism [58,59]. The SST may be less reliable in assessing the HPA axis in patients withdrawing from steroids [60,61], those with pituitary disease [62] and in the first 14 days following pituitary surgery [63].…”