Question

Why hypothalamic-pituitary function tests done before 8:00 AM?

Answer 1

In evaluation of the hypothalamic pituitary adrenal (HPA) axis, static measurement of hormones is seldom useful. In general, if one is suspicious of hypofunction of the HPA axis, then dynamic testing to stimulate either adrenocorticotrophic hormone (ACTH) or cortisol is indicated. On the other hand, if one is concerned about Cushing’s syndrome (CS), an overproduction of cortisol or ACTH, then response to suppression with dexamethasone is usually indicated. American Endocrine Society Clinical Guidelines recommend one of the following tests for the initial CS testing: at least two measurements of urinary-free cortisol (UFC), two measurements of late night salivary cortisol (LNSC), 1 mg overnight dexamethasone suppression test (DST) or a longer low-dose DST [1]. Cortisol measurement (serum, UFC or salivary) is the end point for each recommended test. Despite recent literature reports describing utility of direct salivary and urine cortisol measurements in CS diagnosis, most clinicians prefer provocative testing due to the variable nature of cortisol and ACTH secretion in normal physiological states. Cortisol is secreted under the direction of ACTH and follows a diurnal variation, with peak values at 08:00 h and a nadir at 22:00 h. In CS, diurnal variation is lost and PM cortisol level is inappropriately elevated. Superimposed on this diurnal pattern are 8-10 pulsatile peaks released during the course of a 24 hour period. Therefore depending on the instance when blood is sampled, there can be significant variation in the absolute values of ACTH and serum cortisol. Due to this variability of cortisol and ACTH levels, it may be challenging to distinguish pituitary dependent Cushing’s disease from pseudo-Cushing’s states. Cunningham et al conducted the study where blood was sampled and cortisol measured every 20 to 30 minutes for 24 hours. The group demonstrated that both circadian and pulse amplitudes of cortisol secretion were decreased in Cushing’s disease.This section provides and overview of methodologies commonly used in clinical laboratories for direct determinations of cortisol and ACTH, regardless of whether they are a part of a provocative testing series or direct, non-stimulated hormone assessment.