CORTONE ACETATO, IDROCORTISONE E IDROCORTISONE A RILASCIO MODIFICATO: CONFRONTO TRA TERAPIE SOSTITUTIVE CONVENZIONALI ED INNOVATIVE IN PAZIENTI CON INSUFFICIENZA CORTICOSURRENALICA

Background: adrenal insufficiency is a chronic condition associated with several complications and with a negative impact on patients’ quality of life, especially due to the need of taking lifelong multiple daily doses of glucocorticoids replacement therapy. Endocrinologists’ goal is to identify the optimal replacement therapy, that can ensure the right glucocorticoids dose throughout the day, nearest to physiology, avoiding under- and over-treatment, usually associated with worst metabolic, cardiovascular and bone outcomes, impairment in quality of life and with an increase in mortality. Objectives: the aim of this study was to evaluate possible differences in efficacy and tolerability between three kind of replacement therapies, cortisone acetate (CA), hydrocortisone (HC) and the new modified-release (or dual-release) hydrocortisone (DRHC), in patients with primary (PAI) and secondary (SAI) adrenal insufficiency. Design and methods: 73 patients with adrenal insufficiency were retrospectively included in the study, 31 PAI and 42 SAI, and they were evaluated at diagnosis of adrenal insufficiency and after 1 year and 3 years of replacement therapy with CA (42 patients, 15 PAI and 27 SAI) or HC (19 patients, 9 PAI and 10 SAI) or DRHC (12 patients, 7 PAI e 5 SAI). Anthropometric data (age, sex, weight, height, BMI, blood pressure), metabolic and hormonal assays (glycemia, glycosylated haemoglobin -HbA1c-, total cholesterol, HDL, LDL, triglycerides, pituitary and adrenal function exams), bone assessment (PTH, Vitamin D and, where possible, femoral neck and lumbar spine T-score) and cardiovascular risk were collected in all patients. Results: weight and BMI were significantly higher in patients treated with CA than HC (P=0,01) and a similar trend was observed comparing CA with DRHC. Change in weight and BMI correlates with glucocorticoid dose and the average dose of CA was higher than the HC one (P=0,01). No differences were observed in glycemia and HbA1c among three groups. Patients presented significant lower diastolic blood pressure after one year of treatment with DRHC, compared to CA (P<0,01) and HC (P=0,03) and also cardiovascular risk is lower in DRHC than HC (P=0,04) and not so different from CA. Patients in DRHC with concomitant hypothyroidism were taking higher doses of levothyroxine than patients in CA (P<0,01), suggesting a possible influence of DRHC on levothyroxine absorption. Conclusions: our data demonstrate that none of the therapies is really superior to others, but suggest the importance of a “tailored” replacement treatment, considering that CA could have a worse metabolic outcome and also need higher doses and multiple administrations during the day. Despite the high cost, DRHC could be a reasonable choice, because of once-day administration, less weight gain and lower diastolic blood pressure and cardiovascular risk. The study is still ongoing, collecting missing data at three years and including patients with prediabetes, in which, as recently demonstrated, DRHC might be superior to conventional glucocorticoid replacement therapy.