The Impact of Glucocorticoid Replacement Regimens on Metabolic Outcome and Comorbidity in Hypopituitary Patients

Filipsson, Helena; Monson, John P.; Kołtowska-Häggström, Maria; Mattsson, Anders; Johannsson, Gudmundur

doi:10.1210/jc.2006-0524

Cited by 287 publications

(276 citation statements)

References 35 publications

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“…Our results, showing a dose-related association with measures of QoL, are in accordance with these (7,8) and other previous smaller studies (15,21). The results are also in line with a study on 2424 hypopituitary patients from the KIMS database where the impact of GC replacement on cardiovascular risk factors was analysed (11). In that study, GC replacement had a clear doserelated association with increase in BMI, triglycerides, total cholesterol and LDL cholesterol.…”

Section: Discussionsupporting

confidence: 93%

“…For patients receiving treatment with CA, the HC equivalent (HCeq) dose was calculated. Thus, the equivalent dose of 20 mg HC was 25 mg for CA as previously described (11). Information on the specific diagnostic criteria used for diagnosis of ACTH insufficiency is not included in KIMS and is therefore dependent on the clinical practice at each participating centre.…”

Section: Patients and Study Designmentioning

confidence: 99%

“…More specifically, the aims were to compare QoL in adrenocorticotropic hormone (ACTH)-insufficient and -sufficient patients before and after growth hormone (GH) replacement therapy and to analyse the relationship between GC doses and/or type of GCs on QoL. In the light of the previous findings, indicating that adverse cardiovascular risk profile is associated with increasing GC doses (11), the main hypothesis was that ACTH-insufficient patients have a dose-dependent deteriorated QoL.…”

Section: Introductionmentioning

confidence: 99%

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The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients

Ragnarsson

Mattsson

Monson

et al. 2014

European Journal of Endocrinology

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Objective: Quality of life (QoL) is impaired in hypopituitary patients and patients with primary adrenal insufficiency. The aim of this study was to analyse the impact of glucocorticoid (GC) replacement on QoL. The main hypothesis was that ACTHinsufficient patients experience a dose-dependent deterioration in QoL. Design, patients and methods: This was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Data from 2737 adult GH-deficient (GHD) hypopituitary patients were eligible for analysis. Thirty-six per cent were ACTH sufficient and 64% ACTH insufficient receiving a meanGS.D. hydrocortisone equivalent (HCeq) dose of 22.3G8.7 mg (median 20.0). QoL at baseline and 1 year after commencement of GH replacement was assessed by the QoL-assessment of GHD in adults. Results: At baseline, no significant difference in QoL was observed between ACTH-sufficient and -insufficient patients. Increasing HCeq dose was associated with worse QoL. Patients on HCeq %10 mg had the best and patients receiving R25 mg demonstrated the poorest QoL. At 1 year of GH replacement, the improvement in QoL did not differ between ACTH-sufficient and -insufficient patients, and no association was observed between HCeq dose and QoL improvement. Conclusion: Adult hypopituitary patients with untreated GHD receiving GC replacement have similar QoL as ACTH-sufficient patients. Among ACTH-insufficient patients, there is a dose-dependent association between increasing dose and impaired QoL. This association may be explained by supraphysiological GC exposure although it remains plausible that clinicians may have increased GC doses in order to address otherwise unexplained QoL deficits.

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Section: Discussionsupporting

confidence: 93%

Section: Patients and Study Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients

Ragnarsson

Mattsson

Monson

et al. 2014

European Journal of Endocrinology

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“…Our data are supported by previous studies performed in patients with secondary hypoadrenalism, suggesting that long-term glucocorticoid replacement therapy can cause dyslipidemia, with a clear relation between glucocorticoid dose and levels of total cholesterol and LDL-cholesterol [14,30]. Differently from previous observations that found a positive correlation between hydrocortisone dose and HDL-cholesterol [10], we did not find any modification on HDL-cholesterol levels during PLEN.…”

Section: Discussionsupporting

confidence: 87%

Improvement of anthropometric and metabolic parameters, and quality of life following treatment with dual-release hydrocortisone in patients with Addison’s disease

et al. 2015

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Disclosure statement: The Authors have nothing to disclose. 2Abstract Purpose: In patients with Addison's disease (AD), a dual-release preparation of hydrocortisone (Plenadren, PLEN) has been demonstrated to maintain cortisol levels in a more physiological range than conventional glucocorticoid therapy, and to exert positive effects. This study aimed to assess variations of anthropometric, metabolic and hormonal parameters in patients with AD after switching from conventional hydrocortisone (HC) treatment to PLEN.Methods: in nineteen AD patients (15 F and 4 M, age 27-65 yr) treated with HC 20 mg/day thrice daily, body weight, BMI, waist circumference, fasting glucose, HbA1c, serum lipids, plasma renin activity (PRA), electrolytes and blood pressure were evaluated at baseline, and 1, 3, 6 and 12 months after switching from HC to PLEN. At baseline, and after 1 and 12 months of PLEN, blood ACTH and cortisol (at 0800 h at fasting, and 30, 60, 90, 120 and 240 minutes after drug ingestion), and health-related quality of life (HRQoL), using 30-AddiQoL questionnaire, were evaluated.Results: During PLEN, waist and serum lipid progressively decreased. After 12 months of PLEN, a significant difference was observed in waist circumference (P=0.007), HbA1c (P=0.002), total and LDL-cholesterol levels (P<0.05). ACTH levels at 240 minutes and the area under the curve (AUC) were lower (P<0.05) during PLEN than HC, while cortisol peaks and AUC were similar. 30-AddiQoL total score also improved (P=0.04) during PLEN.Conclusions: In Addison's disease patients, PLEN reduces central adiposity, and improves glucose and metabolism parameters and HRQoL.3

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“…In 333 consecutive patients with hypopituitarism diagnosed between 1956 and 1987, the overall mortality was higher than the age-and sex-matched normal population, with vascular disease accounting for 60 deaths compared with the 31 expected (19). The important adverse effects of even modest excess glucocorticoid dosing on cardiovascular risk has been assessed in a recent large Scandinavian study in 2424 patients with hypopituitarism (20). As a group those requiring glucocorticoid replacement had a higher waist circumference, total cholesterol, serum triglycerides and HbA1c.…”

Section: Cardiovascular Mortality and Morbiditymentioning

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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The Impact of Glucocorticoid Replacement Regimens on Metabolic Outcome and Comorbidity in Hypopituitary Patients

Abstract: HCeq doses of at least 20 mg/d in adults with hypopituitarism are associated with an unfavorable metabolic profile. CA replacement may have metabolic advantages compared with other GCs.

Cited by 287 publications

References 35 publications

The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients

The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients

Improvement of anthropometric and metabolic parameters, and quality of life following treatment with dual-release hydrocortisone in patients with Addison’s disease

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

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