Table 8.

Systemic effects of glucocorticoid replacement therapy in patients with SAI, according to different drugs, treatment doses and therapy duration

Authors (Reference)	Study design	Num of  patients	Dose and types of glucocorticoid  replacement therapy	Systemic effect
Stewart et al. [151]	Retrospective observational	8818	HC less than 50 mg/day for 6–12 months	↑ hypertension, type 2 DM, hyperlipidaemia in patients vs health control
Filipsson et al. [153]	Prospective clinical trial	1707	1168 patients treated with HC 487 patients treated with CA 52 patients treated with PD	After adjustment for glucocorticoid dose: - PD treated patients had higher weight/height ratio; - CA treated patients had lower HbA1c levels, at 12 months of treatment No change in BMI, fasting blood glucose (FBG), total cholesterol, HDL, LDL, triglycerides (TG), at 12 months of treatment
Petersons et al. [155]	Clinical trial	17	≤ 20 mg/day HC or equivalent for a median duration of 32 (range 9 –95) months, then increased to 30 mg/day HC or equivalent for 7 days	↓ fasting AIx75 and fasting RHI with higher HC doses  → fasting glucose concentration, 2-h glucose concentration and insulin sensivity
Castinetti et al. [156]	Retrospective observational	122	Mean 19.9 mg daily HC or equivalent for a mean follow-up of 10.8 years	High HC doses in patients with dyslipidaemia and high blood pressure
Hayashi et al. [157]	Prospective Clinical trial	29	10, 20 and 30 mg/day HC for 4 weeks of treatment	↑ of adiponectin and HDL-C in HC-dose dependent manner
Werumeus Buning et al. [160]	Clinical trial	47	Group 1 first received a physiological lower dose of HC for 10 weeks (0.2–0.3 mg/kg/d), followed by a physiological higher dose for another 10 weeks (0.4–0.6 mg/kg/d). Group 2 received the two doses in reverse order	↑ systolic and diastolic blood pressure at higher HC dose treatment
Ragnarsson et al. [158]	Retrospective	204	Mean HC or equivalent dose 20,5 ± 5,8 mg/day	↓ BMD at lombar spine and femoral neck and ↑ the frequency of osteopenia in woman
Hammarstrand et al. [159]	Retrospective Swedish national patient register	193	Mean daily HC or equivalent dose of 20 ± 6 mg and HC dose per kg 0.25 ± 0.09	↑ SMR in patients treated with HC or eq dose > 20 mg/day or > 0.3 mg/Kg vs general population  → SMR in patients treated with HC or eq dose ≤ 20 mg/day or 0.3 mg/kg/day vs general population

↑ increase, ↓ reduction, → stable, DM Diabetes Mellitus, HC hydrocortisone, CA cortisone acetate, PD prednisone, HCeq hydrocortisone-equivalents, FBG fasting blood glucose, HbA1c glycated haemoglobin, HDL high-density lipoprotein, HDL-C HDL-cholesterol, LDL low-density lipoprotein, TG triglycerides, AIx75 augmentation index, RHI reactive hyperaemia index, BMD Bone Mineral Density, SMR standardized mortality ratio