The Influence of Different Hydrocortisone Replacement Doses on the Partitioning and Flexibility of Ectopic Lipids in Patients With Corticotropic Hypopituitarism
The Influence of Different Hydrocortisone Replacement Doses on the Partitioning and Flexibility of Ectopic Lipids in Patients With Corticotropic Hypopituitarism
This study aims at assessing the effect of today's standard of hydrocortisone dosage versus
 previous hydrocortisone dosage on flexibility and partitioning of ectopic lipid depots (IMCL
 and IHCL) after a standardised fat load followed by a short-term aerobic exercise in patients
 with corticotropic pituitary insufficiency.
Background

 The investigators and others have shown that long-term hydrocortisone replacement therapy at
 higher doses of hydrocortisone replacement therapy at higher doses of hydrocortisone
 replacement (as previously recommended) is associated with higher mortality. The
 pathophysiology for the association of hydrocortisone-replacement dose and mortality remains
 unclear. A possible underlying mechanism is nonalcoholic fatty liver disease which is more
 prevalent in patients with hypopituitarism. Patients with non-alcoholic fatty liver disease
 are at a higher risk for overall-mortality.

 It remains to be established whether the insulin resistance, associated with increased
 intrahepatocellular lipids and increased intramusculoskeletal lipids, is implicated in the
 pathophysiology of these epidemiological findings.

 Interestingly, it has been shown that a reduction of hydrocortisone replacement dose from
 20-30mg/d to 10-15mg/d resulted in a loss of body fat and a significant decrease of plasma
 total cholesterol and triglyceride concentration. The effect of IMCL and IHCL is so far
 unknown.

 Patients with hypopituitarism with hydrocortisone replacement therapy provide a unique
 disease model to study the short-term effects of previously recommended dose (higher dose) of
 hydrocortisone versus lower dose of HC replacement therapy on ectopic lipids (IMCL; IHCL)
 lipids, as well as on subcutaneous and visceral fat mass and on parameters of insulin
 resistance. Combining MRI and MR-spectroscopy techniques, different fat mass (subcutaneous
 and visceral) and ectopic lipids can be repeatedly and non-invasively assessed.

 Objective

 To investigate the impact of today's standard of hydrocortisone dosage (lower) versus
 previous (higher) hydrocortisone dosage on flexibility and partitioning of ectopic lipid
 depots after a standardised fat load followed by a short-term aerobic exercise in patients
 with corticotropic pituitary insufficiency.

 Methods

 Ectopic lipids are measured by MR-spectroscopy, separate assessment of visceral and
 subcutaneous fat mass will be performed by MR-imaging, standardized exercise capacity test
 using spiroergometry. Short-time exercise consists of 2h aerobic cycling at 50% VO2max.
 Laboratory analysis include lipid profile, free fatty acids, HOMA-Index, hormones.
Inclusion Criteria:

 -  Written informed consent

 -  Male and female patients

 -  Corticotropic pituitary insufficiency

 -  Capable to exercise during 120 minutes on a bicycle

 -  Normal ECG during ergometry

 Exclusion Criteria

 -  Concomitant medication with NSAID, anticoagulants, digoxin, salbutamol,
 anticonvulsants, cholinesterase inhibitor, pancuronium

 -  Abnormal liver, renal or thyroid function, heart failure

 -  Hemophilia

 -  Diabetes mellitus

 -  Severe dyslipidemia

 -  Active neoplasia

 -  Women who are pregnant or breast feeding

 -  Intention to become pregnant during the course of the study

 -  Lack of safe contraception

 -  Known or suspected non-compliance

 -  Drug or alcohol abuse

 -  Inability to follow the procedures of the study

 -  Participation in another study with investigational drug within the 30 days preceding
 and during the study

 -  Previous enrolment into current study

 -  Enrolment of the investigator, his/her family members, employees and other dependent
 persons

 -  Inability to exercise

 -  Contraindications to exposure to a 3 T magnetic field

 -  Major depression, psychosis, claustrophobia