What factors have impact on glucocorticoid replacement in adrenal insufficiency: a real-life study

Abstract

Purpose The impact of patient's characteristics on glucocorticoid (GC) replacement therapy in adrenal insufficiency (AI) is poorly evaluated. Aims of this study were to assess the influence of sex and body weight on GC dosing and to describe the choice of GC in AI of different etiologies. Methods We retrospectively evaluated hydrocortisone (HC) equivalent total daily dose (HC-TDD) and per-kg-daily dose (HC-KDD) in 203 patients (104 primary AI [pAI], 99 secondary AI [sAI]) followed up for ≥ 12 months. They were treated with HC, modified-release HC (MRHC) or cortisone acetate (CA) and fludrocortisone acetate (FCA) in pAI. Results At baseline, CA was preferred both in pAI and sAI; at last visit, MRHC was most used in pAI (49%) and CA in sAI (73.7%). Comparing the last visit with baseline, in pAI, HC-TDD and HC-KDD were significantly lower (p = 0.04 and p = 0.006, respectively), while FCA doses increased during follow-up (p = 0.02). The reduction of HC-TDD and HC-KDD was particularly relevant for pAI women (p = 0.04 and p = 0.002, respectively). In sAI patients, no change of HC-KDD and HC-TDD was observed, and we found a correlation between weight and HC-TDD in males (r 0.35, p = 0.02). Conclusions Our real-life study demonstrated the influence of etiology of AI on the type of GC used, a weight-based tailoring in sAI, a likely overdosage of GC treatment in pAI women at the start of treatment and the possibility to successfully increase FCA avoiding GC over-treatment. These observations could inform the usual clinical practice.

Renin and electrolytes indicate the mineralocorticoid activity of fludrocortisone: a 6 year study in primary adrenal insufficiency

“…Before our study, the previously longitudinal assessment of FC treatment in PAI described a median time between assessments of 433 days (without an intermediate visit, and the longer follow-up lasted less than 6 years) [ 20 ]. Our observation period, close to a study recently reported in patients with adrenal insufficiency [ 28 ], is sufficient to propose a modification in the replacement treatment and consistent to observe a measurable clinical-endocrine difference. A long-term follow-up is of utmost importance because the modification of a lifelong treatment, to personalize replacement therapy, requires several attempts and a close doctor-patient relationship to increase treatment adherence and reduce therapeutic inertia [ 29 ].…”

“…Before our study, the previously longitudinal assessment of FC treatment in PAI described a median time between assessments of 433 days (without an intermediate visit, and the longer follow-up lasted less than 6 years) [20]. Our observation period, close to a study recently reported in patients with adrenal insufficiency [28], is sufficient to propose a modification in the replacement treatment and consistent to observe a measurable clinical-endocrine difference.…”

“…Short-acting GCs are the most used, as expected [ 32 ], and CA is the preferred in Italy, because HC is not immediately available and needs specific prescription by an endocrinologist [ 28 ]. CA and HC treatment was used respectively in 50% and in 40% of the cohort at the last follow-up visit (20% direct-release HC and 20% MR-HC), especially in patients with autoimmune PAI.…”

“…According to the interplay between GC and FC, a prospective and controlled study can pave the way to novel strategy of treatment. Through follow-up, a general reduction of GC has been reported (mean decrease of 16%), according to the modern concept of reducing hormonal treatment to prevent cardiovascular and skeletal cortisol-related comorbidities [ 28 , 32 , 33 ]. The observed reduction in total and LDL cholesterol in the longitudinal evaluation can reflect both an increased use of lipid lowering medication in the aging patients and the reduction of GC treatment, as observed in hypopituitary patients [ 34 ].…”