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| ID | Type | Description | Link |
|---|---|---|---|
| 2014 DR 4137 | Other Identifier | Swissmedic |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Higher hydrocortisone dose | Other | Established hydrocortisone replacement therapy plus 10mg of hydrocortisone |
|
| Lower hydrocortisone dose | Other | Established hydrocortisone replacement therapy plus placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydrocortisone | Drug | Established Hydrocortisone replacement therapy plus Hydrocortisone (10mg/day) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in flexibility of Intramyocellular Lipids (IMCL) Measured in mmol/L | Measured in mmol/L | 3 months |
| Change from baseline in flexibility of Intrahepatocellular Lipids (IHCL) Measured in mmol/L | Measured in mmol/L | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Free Fatty Acids (FFA) availability during exercise before and after additional hydrocortisone/placebo Measured in mmol/L | Measured in mmol/L | At baseline, 3 months |
| Flexibility of ectopic fat stores, defined as difference between intramyocellular/intrahepatocellular lipid concentration before and after exercise, and their possible relation to insulin sensitivity before and after additional hydrocortisone/placebo |
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Inclusion Criteria:
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Emanuel Christ, MD, PhD | Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Bern | Principal Investigator |
| Chris Boesch, MD, PhD | AMSM; Division of Radiology, University Hopsital of Bern, Inselspital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Berne | Bern | 3010 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9094069 | Background | Boesch C, Slotboom J, Hoppeler H, Kreis R. In vivo determination of intra-myocellular lipids in human muscle by means of localized 1H-MR-spectroscopy. Magn Reson Med. 1997 Apr;37(4):484-93. doi: 10.1002/mrm.1910370403. | |
| 18459045 | Background | Danilowicz K, Bruno OD, Manavela M, Gomez RM, Barkan A. Correction of cortisol overreplacement ameliorates morbidities in patients with hypopituitarism: a pilot study. Pituitary. 2008;11(3):279-85. doi: 10.1007/s11102-008-0126-2. |
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| Placebo | Drug | Established Hydrocortisone replacement therapy plus Placebo (0mg Hydrocortisone) |
|
| At baseline, 3 months |
| Free Fatty Acids (FFA) availability during exercise and the possible relation to insulin sensitivity before and after additional hydrocortisone/placebo Measured in mmol/L | Measured in mmol/L | At baseline, 3 months |
| Effect of exercise on insulin at baseline | At baseline |
| Effect of exercise on insulin at 3 months | 3 months |
| Effect of exercise on catecholamines at baseline | At baseline |
| Effect of exercise on catecholamines at 3 months | 3 months |
| Effect of exercise on growth hormone at baseline | At baseline |
| Effect of exercise on growth hormone at 3 months | 3 months |
| Effect of exercise on cortisol at baseline | At baseline |
| Effect of exercise on cortisol at 3 months | 3 months |
| Effect of exercise on lactate at baseline | At baseline |
| Effect of exercise on lactate at 3 months | 3 months |
| Effect of exercise on glucose at baseline | At baseline |
| Effect of exercise on glucose at 3 months | 3 months |
| Effect of exercise on inflammatory markers at baseline | At baseline |
| Effect of exercise on inflammatory markers at 3 months | 3 months |
| ID | Term |
|---|---|
| D007018 | Hypopituitarism |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D004700 | Endocrine System Diseases |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D006854 | Hydrocortisone |
| ID | Term |
|---|---|
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D015062 | 11-Hydroxycorticosteroids |
| D006889 | Hydroxycorticosteroids |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D015065 | 17-Hydroxycorticosteroids |
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