Effects of different doses of adrenocorticotrophic hormone on the serum lipoprotein profile in healthy subjects

Abstract

Adrenocorticotrophic hormone (ACTH) at pharmacological dosage has marked lipid-lowering effects that may have therapeutic implications. The rationale behind the present investigation was the possible use of ACTH as a lipid-lowering replacement for steroids. Thirty-two healthy individuals were randomly divided into four groups of 8 each. Three ACTH groups received different doses of ACTH1-24 intramuscularly (0.1 mg, 0.5 mg and 1.0 mg daily for four days) and the control group received NaCl 0.9% 1 ml intramuscularly daily for four days. Moreover, 8 healthy subjects were given ACTH1-24 1.0 mg intramuscularly five times at an interval of four days. Blood and urine samples were collected at regular intervals. ACTH treatment at the dose of 1.0 mg daily lowered the serum concentrations of low density lipoprotein (LDL) cholesterol and apolipoprotein B by 28% and 22%, respectively, which is similar to previous observations. ACTH treatment at the doses of 0.5 mg and 0.1 mg gave smaller reductions (17% and 12%, and 9% and 8%, respectively) resulting in near linear dose-response relationships. There were no changes in the control group. Only the ACTH dose of 1.0 mg resulted in significant changes when compared with the control group. During the ACTH administration at four-days intervals, the serum concentrations of LDL cholesterol and apolipoprotein B reached the lowest values at 48 hr after an injection, remained there at 72 hr but were rising again at 96 hr. For effective lipid reduction, an ACTH dose of about 1 mg is needed and it should be given more often than every fourth day, probably every second or third day. With regard to the cortisol exposure, the results should be viewed in the light of calculations, presented in the paper, that 1 mg of ACTH is equivalent to 90 mg of cortisol administered parenterally. © Basic & Clinical Pharmacology & Toxicology 2005.