Читать книгу Metabolic Syndrome Consequent to Endocrine Disorders - Группа авторов - Страница 22

The association between excess GC and MetS phenotype is well recognized in patients with Cushing’s syndrome. In GHD, as in obesity, there is an increased local 11-β hydroxysteroid dehydrogenase type 1 activity in the adipose tissue resulting in increased cortisol exposure [86].

Thus GHRT suppresses 11-β hydroxysteroid dehydrogenase type 1 activity thereby unmasking low adrenal reserve, leading to overt central hypocorticism which has to be replaced [86].

Recommended daily doses used for replacement of secondary adrenal insufficiency were reduced, during the last 10 years, as daily cortisol production rate was confirmed to be substantially lower than previously thought (9–11 mg/m², corresponding to 15–19 mg/day) [88].

Hypopituitary patients on GC replacement were more insulin resistant when they received HC than without HC. When HC dose was reduced from 20–30 mg to 10–15 mg/day, in 11 hypopituitary patients, body weight, total and abdominal fat mass, total cholesterol, and triglycerides decreased after 6–12 months [89]. Significant HC dose-response relationship was demonstrated, in more than 2,000 patients, for waist circumference, serum triglyceride concentration, total and LDL cholesterol, and BMI [18]. Hypopituitary ACTH-deficient patients receiving HC doses of <20 mg/day had similar metabolic profile to those who were ACTH sufficient [18]. The study clearly indicated that lower doses of HC (≤20 mg/day) are advocated for replacement therapy of secondary adrenal insufficiency and that doses above 20 mg/day are associated with increased mortality [17, 19].

Survey of the European Registry for Adrenal Insufficiency (EU AIR) revealed that the most common regime for dosing HC 15–20 mg/day, in patients with secondary adrenal insufficiency, was twice daily (47.8%) and thrice daily (30.1%) [90]. New once daily formulations aim to deliver cortisol in a more physiological fashion and improve metabolic profile and compliance of patients with hypopituitarism and secondary adrenal insufficiency [91].

It is important to remember that the reported risk of death from infectious diseases was 1.6-fold higher in patients with ACTH deficiency compared to ACTH sufficient patients with hypopituitarism [13]. Adrenal crisis and hyponatremia were also associated with an increased standardized mortality ratio for hypopituitary patients [13]. Important interactions with thyroxin, GH, and sex steroids should not be ignored since they can induce cortisol clearance and increase the risk for adrenal crisis [20].

The aim of daily GC replacement is to deliver sufficient cortisol for day to day activity in unstressed condition. However increased doses are needed during stressful conditions (surgery, trauma, acute illness). The aim of chronic GC replacement is to avoid under- and over-replacement in order to avoid adverse cardiometabolic risk and increased mortality as stated in the current guidelines and recommendations [87, 93].