Weight‐related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency

Mah, Peak Mann; Jenkins, Richard C.; Rostami‐Hodjegan, Amin; Newell‐Price, John; Doane, A.; Ibbotson, V.; Tucker, Geoffrey T.; Ross, Richard

doi:10.1111/j.1365-2265.2004.02106.x

Cited by 213 publications

(211 citation statements)

References 23 publications

(30 reference statements)

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“…Typical hydrocortisone replacement regimens have been excessive (3), with a supraphysiologic rise in serum cortisol soon after the dose and subphysiologic concentrations at other times of the day (4,5). Researchers have found a significant increase in the mortality of hypopituitary patients treated with R25-30 mg of hydrocortisone per day (6,7).…”

Section: Introductionmentioning

confidence: 99%

Thrombospondin-1 is a glucocorticoid responsive protein in humans

Barclay

Petersons

Keshvari

et al. 2016

European Journal of Endocrinology

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Objective: Thrombospondin-1 (TSP1) is a matricellular protein whose gene expression has previously been shown to increase acutely after exposure to dexamethasone in vitro. The aim of this study was to determine if TSP1 is altered by acute and chronic states of glucocorticoid excess in human subjects. Design and methods: Three studies have been undertaken to assess the difference or change in TSP1 in response to altered glucocorticoid activity: i) an acute interventional study assessed the effects of a single 4 mg dose of dexamethasone in 20 healthy volunteers; ii) a cross-sectional study compared plasma TSP1 in 20 healthy volunteers and eight patients with Cushing's syndrome; iii) an interventional study assessed the effect on plasma TSP1 of an increase in hydrocortisone dose from %20 mg/day to 30 mg/day for 7 days in 16 patients with secondary adrenal insufficiency. Results: In healthy volunteers, 4 mg dexamethasone significantly increased peripheral blood mononuclear cell (PBMC) TSP1 mRNA levels (P!0.0001) and plasma TSP1 concentrations (P!0.0001), peaking at 12 h. Median (interquartile range) plasma TSP1 was higher in Cushing's, 638 (535-756) ng/ml, than in healthy volunteers, 272 (237-336) ng/ml (P!0.0001). Plasma TSP1 O400 ng/ml diagnosed Cushing's syndrome with sensitivity of 100% and specificity of 85%. The higher hydrocortisone dose increased plasma TSP1 from 139 (86-199) to 256 (133-516) ng/ml, (P!0.01) in patients with secondary adrenal insufficiency. Conclusions: TSP1 is a glucocorticoid responsive protein in humans. Further research is required to determine if plasma TSP1 has a role as a glucocorticoid biomarker.

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Section: Introductionmentioning

confidence: 99%

Thrombospondin-1 is a glucocorticoid responsive protein in humans

Barclay

Petersons

Keshvari

et al. 2016

European Journal of Endocrinology

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“…Patients on a thrice-daily regimen show levels of cortisol, which are much more constant and better imitate physiological cortisol rhythm when compared with those on a twice-daily regimen (13). The use of weight-adjusted dosing before food showed decreased inter-patient variability in maximum cortisol concentration from 31 to 7%, and reduced overexposure to !5%, and thrice-daily weight-adjusted dosing has been recommended as the preferred HC regime (14). It is a clinical experience, however, that patient compliance with thrice-daily dosing is far from absolute for many patients.…”

Section: Different Regimens and Dosesmentioning

confidence: 99%

“…Newer estimates of the cortisol production rate (see above) indicate that 15-20 mg total daily HC is required. Unfortunately, HC has a short plasma half-life and patients taking this tablet wake with undetectable cortisol levels, thus achieving peak cortisol levels an hour after dosing (14,62). The pharmacokinetics of 20 mg HC has been studied after i.v.…”

Section: Different Regimens and Dosesmentioning

confidence: 99%

“…These are inconvenient to perform, but may have particular merit in situations where patients are on drugs that interact with HC through enzyme induction or inhibition resulting in lower or higher cortisol levels respectively (see below). A simple, practical and effective way of monitoring cortisol is to measure a single serum cortisol 4 h after dosing, and to compare this to a dosing nomogram that allows prediction of the cortisol and hence total cortisol exposure (14).…”

Section: Difficulties With Monitoring Hc Replacementmentioning

confidence: 99%

“…Some clinicians favour use of prednisolone or dexamethasone, with doses based on equipotent anti-inflammatory effect (11), but doses that have an equipotent effect on the cardiovascular system are not fully established. Moreover, monitoring treatment remains a challenge, and is based on clinical assessment and biochemical parameters (12)(13)(14). Recently, efforts have focused on the development of newer formulations of HC to provide circadian glucocorticoid replacement therapy aimed to imitate more closely the normal physiological cortisol rhythm (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Debono

Ross²,

Newell‐Price

2009

European Journal of Endocrinology

Self Cite

113

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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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