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

Abstract

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.

Group 4: Replacement therapy for adrenal insufficiency

“…In terms of quality of life, Ragnarsson et al showed in a retrospective cohort study of 2737 patients, that the quality of life index was lowest in patients with corticotroph deficiency treated with > 25 mg/day hydrocortisone and highest in patients treated with 10 mg/day [5]. This confirms the quality of life data reported in 2 prospective crossover studies on a total of 200 patients [21,22].…”

“…There is no data presently to show if cortisone acetate, which undergoes conversion to cortisol through the action of 11beta-HSD-1 in the liver, is superior or inferior to hydrocortisone [3,4]. It should be noted that this enzyme is inhibited by the GH/IGF1 system, and could be theoretically less efficient in patients with a deficit in GH replacement, although this was not reported in a retrospective cohort study published by Ragnarsson et al [5]. Cortisone acetate is more readily accessible in some European countries, for example Italy [6].…”

MANAGEMENT OF ENDOCRINE DISEASE: Quality of life tools for the management of pituitary disease

“…QoL is also impaired by the presence of postoperative ACTH insufficiency (25). Initial hydrocortisone treatment is followed by great symptomatic improvement, but chronic hydrocortisone substitution is shown to be associated with lower QoL, perhaps due to high, nonphysiological glucocorticoid doses (26).…”

“…In males, low testosterone is associated with physical impairment (i.e., reduced muscle strength or osteoporosis), as well as psychological disturbances (depression, anxiety and sexual dysfunctions like decreased libido), often associated to infertility which is another common complaint, all of which negatively impact on QoL (29). Using the generic SF-36 questionnaire, more problems in the areas of role-physical, vitality, physical functioning, general health and role-emotional were observed in hypogonadal patients when compared to healthy controls (25). After the replacement therapy with testosterone, vitality, physical role, general health and emotional role parameters improved, but were still below the reference values.…”

Modified-release hydrocortisone decreases BMI and HbA1c in patients with primary and secondary adrenal insufficiency

“…Similarly, too low doses can lead to fatigue and a higher frequency of adrenal crisis, deteriorating HRQoL (21). A recent retrospective cross-sectional study in SAI patients has found that higher HC doses were associated with worse HRQoL, and that patients with doses lower than 10 mg/day had the best HRQoL and patients receiving more than 25 mg/day the poorest HRQoL (22). Another study found that AI patients with doses higher than 30 mg/day have lower HRQoL levels than patients with lower doses (6).…”