Metabolic Benefits Seen with GH Replacement
Published: June 20, 2010
* Explain to interested patients that for people with growth hormone deficiency, studies suggest that recombinant growth hormone therapy can have various metabolic benefits, such as increasing levels of "good" HDL cholesterol.
* Note that these studies were published as posters and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
SAN DIEGO -- Adults with growth hormone deficiency treated with recombinant human growth hormone (rhGH) therapy experience a variety of metabolic benefits, researchers reported here.
For example, among a group of 70 growth hormone deficient patients treated for three years with rhGH, levels of so-called "good" high density lipoprotein (HDL) cholesterol rose from a baseline mean level of 45 mg/dL to 56 mg/dL (P<0.001), according to Victor Oguntolu, MD, and colleagues from King's College University Hospital, London.
"Adult growth hormone deficiency is a well-recognized syndrome characterized by dyslipidemia, changes in body fat distribution, and premature atherosclerosis," he said in a poster session at the annual meeting of the Endocrine Society here.
Growth hormone deficiency usually results from tumor-induced damage to the pituitary gland, and patients often also experience decreases in bone mass and insulin resistance.
The link between growth hormone deficiency and elevated levels of harmful low density lipoprotein (LDL) cholesterol has been widely recognized, but the effects of growth hormone treatment on HDL have not previously been explored.
To analyze the possible effects on HDL, the King's College researchers conducted a retrospective study of 32 men and 38 women who had completed at least three years of treatment with rhGH.
All patients had peak growth hormone levels as measured during an insulin or glucagon stimulation test of below 9 mU/L.
Therapy with rhGH was initiated at a dose of 0.3 mg/day and increased to 0.5 mg/day in the first three months.
The dose of rhGH was further titrated in the first year with the goal of achieving a target insulin-like growth factor (IGF)-1 level between the age-specific mean and the upper limit of reference.
Significant improvements became evident after six months of treatment with rhGH, Oguntolu told MedPage Today.
At six months, the following were lipid levels compared with those at baseline:
* Total cholesterol, 224 mg/dL versus 234 mg/dL
* LDL, 131 mg/dL versus 139 mg/dL
* HDL, 50 mg/dL versus 45 mg/dL
* Triglycerides, 205 mg/dL versus 230 mg/dL
Aside from the significant improvements in HDL, further reductions in other lipids were seen at three years:
* Total cholesterol, 196 mg/dL, P<0.0001
* LDL, 101 mg/dL, P<0.001
* Triglycerides, 175 mg/dL, P<0.001
"Most previous studies have only followed patients up to 24 months, and it's after 24 months that HDL starts to change, whether patients are taking statins or not," Oguntolu said.
A second poster at the meeting addressed the influence of growth hormone replacement therapy among adults on the development of diabetes.
Among 5,143 patients treated for a mean of 3.9 years with rhGH, diabetes developed in 523, according to Anton Luger, MD, of the University of Vienna, and colleagues.
The incidence was 2.6 per 100 patient-years, a rate six times higher than what was expected in a reference population in southern Sweden.
However, these data are "reassuring," Luger told MedPage Today, because the patients who developed diabetes were older, had a worse lipid profile, and higher body mass index (BMI) and blood pressure than those who remained normoglycemic during rhGH therapy:
* Age: 52.7 years versus 48.5 years, P<0.0001
* BMI: 31.6 kg/m2 versus 28.9 kg/m2, P<0.0001
* HDL: 41 mg/dL versus 48.3 mg/dL, P<0.0001
* Systolic blood pressure: 132.9 mm Hg versus 127.9 mm Hg, P<0.0001
* Diastolic blood pressure: 81.1 mm Hg versus 79.6 mm Hg, P<0.0001
And although the observed-to-expected ratio for diabetes was elevated in patients receiving rhGH, the incidence fell with increasing duration of treatment and was not associated with IGF-1 standard deviation scores or growth hormone dose, Luger added.
Nonetheless, hormone deficient patients, especially those with an adverse risk profile, should be followed carefully, he cautioned.
Oguntolu and two co-investigators reported nothing to disclose. One investigator reported acting as consultant to Ipsen, Novo Nordisk, and Pfizer.
Luger is a medical advisory board member for Pfizer, and a speaker for Pfizer and Novo Nordisk. Two other investigators are employees of Pfizer.
Primary source: The Endocrine Society
Oguntolu V, et al "The effect of a 3-year growth hormone replacement on lipid profile of adults with growth hormone deficiency" ENDO 2010; Poster 1-267.
Additional source: The Endocrine Society
Luger A, et al "Incidence of diabetes mellitus in growth hormone (GH) deficient patients during GH replacement therapy -- an analysis of KIMS (Pfizer International Metabolic Database)" ENDO 2010; Poster 1-270.