Circadian hydrocortisone infusions in patients with adrenal insufficiency and congenital adrenal hyperplasia

Merza, Zayd; Rostami‐Hodjegan, Amin; Memmott, A.; Doane, A.; Ibbotson, V.; Newell‐Price, John; Tucker, Geoffrey T.; Ross, Richard

doi:10.1111/j.1365-2265.2006.02544.x

Cited by 89 publications

(64 citation statements)

References 19 publications

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“…1). In the patients with CAH, very high plasma ACTH and 17-hydroxyprogesterone levels were present before the morning dose and at the end of conventional HC treatment, in contrast to significantly lower levels of both ACTH and 17-hydroxyprogesterone after circadian infusion (17) (Fig. 2).…”

Section: Circadian Hc Infusionsmentioning

confidence: 94%

“…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%

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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: Circadian Hc Infusionsmentioning

confidence: 94%

Section: Introductionmentioning

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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“…Similarly, patients with congenital adrenal hyperplasia (CAH) receive suppression treatment with long-acting glucocorticoids, which is limited by the risk of glucocorticoid over-dosage. Recently, a small clinical study found that circadian HC infusions in patients with CAH and AD improved biochemical control as measured by ACTH and 17-OH-progesterone (15). CSHI may be a means to Table 1.…”

Section: Discussionmentioning

confidence: 99%

Continuous subcutaneous hydrocortisone infusion in Addison’s disease

Løvås

Husebye²

2007

eur j endocrinol

141

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Objective: The conventional replacement therapy in Addison's disease (AD) does not restore the normal diurnal cortisol rhythm. We explored the feasibility and safety of continuous s.c. hydrocortisone infusion (CSHI) as a novel mode of glucocorticoid replacement therapy. Design and methods: Seven patients with AD were treated with CSHI in an open-labelled clinical study for up to three months. Adequacy of glucocorticoid replacement was assessed by 24 h blood and saliva sampling in one patient and by salivary cortisol day curves in six outpatients. Subjective health status was monitored by the Short Form-36 questionnaire. Results: CSHI re-established the circadian variation and normal levels of cortisol in the patients, with minor day-to-day variation. Most of the patients could reduce their glucocorticoid dose considerably without adverse reactions. The treatment was well tolerated and positively evaluated by the patients. Conclusions: CSHI is technically feasible and safe in patients with AD. A daily dose of w10 mg/m 2 body surface area/day restores the circadian variation and normal levels of salivary cortisol in most patients, which is close to the estimated daily requirement. We hypothesise that selected patients will benefit from restoration of the circadian cortisol rhythm.

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“…A potential drawback of this type of monitoring is that high plasma ACTH levels are found in patients with primary adrenal insufficiency without pituitary pathology. In patients with Addison's disease plasma ACTH measured before morning glucocorticoid is frequently very elevated, but this suppresses rapidly 120 minutes after morning glucocorticoid (20,21). In contrast, those with Nelson's syndrome fail to show incomplete suppression, and a cut-point of 200 pg/ml appears to be useful to define Nelson's syndrome (12).…”

Section: Monitoringmentioning

confidence: 99%

Nelson's Syndrome

Munir

Newell‐Price

2007

Arq Bras Endocrinol Metab

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Nelson's syndrome is a potentially severe complication of bilateral adrenalectomy performed in the treatment of Cushing's disease, and its management remains difficult. Of all of the features of Nelson's syndrome, the one that causes most concern is the development of a locally aggressive pituitary tumour, which, unusually for pituitary disease, may occasionally cause death from the tumour itself. This feature is especially pertinent given the increasing use in Cushing's disease of laparoscopic bilateral adrenal surgery as a highly effective treatment modality to control cortisol-excess. Despite numerous studies and reports, there is no formal consensus of what defines Nelson's syndrome. Thus, some will define Nelson's syndrome according to the classical description with an evolving pituitary mass after bilateral adrenalectomy, whereas others will rely on increasing plasma ACTH levels, even in the absence of a clear pituitary mass lesion on MRI. These factors need to be borne in mind when considering the reports of Nelson's syndrome, as there is great heterogeneity, and it is likely that overall the modern 'Nelson's syndrome' represents a different disease entity from that of the last century. In the present paper, clinical and epidemiological features of Nelson's syndrome, as well as its treatment modalities, are reviewed.

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Circadian hydrocortisone infusions in patients with adrenal insufficiency and congenital adrenal hyperplasia

Abstract: In patients with poor biochemical control of Addison's disease and CAH, a 24-h circadian infusion of hydrocortisone can decrease morning ACTH and 17-hydroxyprogesterone levels to near normal.

Cited by 89 publications

References 19 publications

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Continuous subcutaneous hydrocortisone infusion in Addison’s disease

Nelson's Syndrome

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