Variability in hydrocortisone plasma and saliva pharmacokinetics following intravenous and oral administration to Patients with adrenal insufficiency

Thomson, Alison; Devers, MC; Wallace, Andrew M.; Grant, Donna; Campbell, Kevin J.; Freel, Marie; Connell, John

doi:10.1111/j.1365-2265.2007.02812.x

Cited by 44 publications

(49 citation statements)

References 24 publications

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“…This is a feasible way of monitoring cortisol levels but some studies show wide inter-individual variability in plasma and salivary profiles of cortisol, and a poor correlation between salivary and plasma measurements has been shown in patients with adrenal insufficiency (80). In others, the correlation is far better and this approach used for monitoring (81).…”

Section: Difficulties With Monitoring Hc Replacementmentioning

confidence: 99%

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Debono

Ross²,

Newell‐Price

2009

European Journal of Endocrinology

116

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Patients with adrenal insufficiency need lifelong glucocorticoid replacement, but many suffer from poor quality of life, and overall there is increased mortality. Moreover, it appears that use of glucocorticoids at the higher end of the replacement dose range is associated with increased risk for cardiovascular and metabolic bone disease. These data highlight some of the inadequacies of current regimes.The cortisol production rate is estimated to be equivalent to 5.7-7.4 mg/m 2 per day, and a major difficulty for replacement regimes is the inability to match the distinct circadian rhythm of circulating cortisol levels, which are low at the time of sleep onset, rise between 0200 and 0400 h, peaking just after waking and then fall during the day. Another issue is that current dose equivalents of glucocorticoids used for replacement are based on anti-inflammatory potency, and few data exist as to doses needed for equivalent cardiovascular and bone effects. Weight-adjusted, thrice-daily dosing using hydrocortisone (HC) reduces glucocorticoid overexposure and represents the most refined regime for current oral therapy, but does not replicate the normal cortisol rhythm. Recently, proof-of-concept studies have shown that more physiological circadian glucocorticoid therapy using HC infusions and newly developed oral formulations of HC have the potential for better biochemical control in patients with adrenal insufficiency. Whether such physiological replacement will have an impact on the complications seen in patients with adrenal insufficiency will need to be analysed in future clinical trials.

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Section: Difficulties With Monitoring Hc Replacementmentioning

confidence: 99%

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Debono

Ross²,

Newell‐Price

2009

European Journal of Endocrinology

116

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show abstract

“…Serum cortisol peaks after taking HC, and then drops to lower than normal levels before the next dose; there is no night-time rise, so patients wake up with very low cortisol levels that contribute to early morning fatigue, a major drawback of current replacement regimes (3,18). Salivary cortisol assays have been suggested for assessing HC-based glucocorticoid replacement, but literature data differ in terms of its reliability (19,20,21,22). Cortisone acetate (CA) is an oral glucocorticoid that needs hepatic conversion to cortisol by the enzyme 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1).…”

Section: Introductionmentioning

confidence: 99%

Assessment of glucocorticoid therapy with salivary cortisol in secondary adrenal insufficiency

Ceccato

Albiger

Reimondo

et al. 2012

European Journal of Endocrinology

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Context: Appropriate glucocorticoid replacement therapy in adrenal insufficiency (AI) is crucial, given the risks of chronic under-or overtreatment, particularly in patients on multiple medications. Salivary sampling allows for non-invasive, stress-free cortisol measurement. Objective: To determine whether salivary cortisol measurement is helpful in assessing the adequacy of glucocorticoid therapy with cortisone acetate (CA) in patients with secondary AI. Design: A prospective cohort study at the Endocrinology Unit of Padua University Hospital. Methods: Six samples of salivary cortisol were collected from 28 patients with secondary AI on CA treatment and from 36 healthy volunteers at fixed times of the day, and used to calculate salivary cortisol levels at each time point and the area under the curve (AUC) across the different sampling times. Results: Salivary cortisol levels were lower in patients than in controls in the morning but no differences were found in the afternoon or at night before resting. Salivary cortisol levels were higher in patients immediately following CA administration. Ten patients showed an AUC above the 97.5th percentile of controls, without clinical signs of hypercortisolism, and salivary cortisol levels 90 min after each dose of CA predict the AUC. All patients had severe GH deficiency and there were no differences in salivary cortisol levels or AUC between patients treated or not with GH. Conclusions: Two salivary cortisol determinations, able to predict the daily AUC, may allow for assessing the adequacy of glucocorticoid replacement therapy in secondary AI and for identifying cases of overor undertreatment.

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“…It should be noted that patients with an area under curve higher than the control 97.5th percentile showed no obvious signs of overdose [50]. Conversely, Thomson et al showed great variability in salivary cortisol in a crossover study of 27 patients being treated with hydrocortisone (oral or IV), and did not show a good correlation between plasma and saliva levels, making it difficult to employ in current practice [51]; • cortisol in hair: hair growth (1 cm per month) and the correlation between cortisol level in the hair and exposure to glucocorticoids could allow detection of overdose or underdosage in patients with adrenal insufficiency. A pilot study showed no significant difference between patients and female control subjects, but a difference was observed between male subjects [52]; • plasma ACTH: plasma ACTH does not assist in evaluating glucocorticoid replacement therapy with classic rapid release hydrocortisone since ACTH is always high in the morning on waking and then decreases rapidly after administration of hydrocortisone in primary adrenal insufficiency [53].…”

Section: Adult Patientsmentioning

confidence: 99%

Group 4: Replacement therapy for adrenal insufficiency

Castinetti

Guignat

Bouvattier

et al. 2017

Annales d'Endocrinologie

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Variability in hydrocortisone plasma and saliva pharmacokinetics following intravenous and oral administration to Patients with adrenal insufficiency

Cited by 44 publications

References 24 publications

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Assessment of glucocorticoid therapy with salivary cortisol in secondary adrenal insufficiency

Group 4: Replacement therapy for adrenal insufficiency

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