Human Growth Hormone Replacement in Adult Hypopituitary Patients: Long-Term Effects on Body Composition and Lipid Status—3-Year Results from the HypoCCS Database

Abstract

The Hypopituitary Control and Complications Study is an international surveillance study evaluating efficacy and safety of GH therapy of adult GH-deficient patients in clinical practice. The present report examined baseline data from 1,123 adult onset (AO) and 362 childhood onset (CO) patients, as well as efficacy in 242 patients who had completed 3 yr of GH treatment. At study entry, mean height, body mass index, waist to hip ratio, and lean body mass were significantly (P < 0.001 for each) lower in CO compared with AO patients. After 3 yr on GH, lean body mass was significantly increased in AO males and females and CO males but not CO females, whereas fat mass was significantly decreased in AO males only. Serum total cholesterol was decreased in females (-0.32 +/- 1.00 mmol/liter; P = 0.045) and males (-0.36 +/- 0.96 mmol/liter; P = 0.004). High-density lipoprotein (HDL) cholesterol was increased for females (0.10 +/- 0.26 mmol/liter; P = 0.026) and males (0.10 +/- 0.34 mmol/liter; P = 0.022). The low-density lipoprotein/HDL ratio was decreased in AO males (-0.93 +/- 2.00; P = 0.003), AO females (-0.65 +/- 0.74; P < 0.001), and CO females (-0.69 +/- 0.76; P = 0.038), but the decrease in CO males was not significant (-0.84 +/- 2.85; P = 0.273). In AO patients, lean body mass increase from baseline was greatest in the those younger than 40 yr old, less but still significant in the middle group (40-60 yr) and unchanged in older (>60 yr) patients; conversely, decreases in the low-density lipoprotein/HDL ratio were small and not significant in the younger patients but greater and significant in the middle and older age groups. During the 3-yr treatment, 114 (7.7%) patients discontinued, including 9 (0.6%) for tumor recurrences, 9 (0.6%) for neoplasia, and 9 (0.6%) for side effects. Therefore, these observational data showed significant long-term efficacy of adult GH replacement therapy on body composition and lipid profiles and indicate that age is an important predictor of response.

Adult GH deficiency throughout lifetime

“…In this analysis, both men and women in each age category demonstrated an improvement in WHR with 1 year GH replacement (36). An analysis of different aged patients enrolled in HypoCCS confirmed this finding, with older GHD patients (O60 years old) having a more pronounced decrease in WHR after 3 years GH treatment than younger patients, despite having no significant improvement in LBM (37). …”

“…2). Attanasio et al reviewed results from 242 HypoCCS patients and reported the greatest improvement in LDL/HDL ratio in patients aged 40-60 years when compared with both younger and older patients (37).…”

Growth Hormone (GH) Effects on Central Fat Accumulation in Adult Japanese GH Deficient Patients: 6-month Fixed-dose Effects Persist during Second 6-month Individualized-dose Phase

“…Thus, with prolonged GH treatment with a physiological replacement dose there is a trend for trunk FM values to normalize, which translates into a clinically relevant reduction of predicted cardiovascular risk. This is further supported by the changes in total and LDLcholesterol, which were consistent with long-term data in Caucasian patients [20].…”

“…The 48-week safety profile was consistent with published data [16,20,22,23] and available clinic experience in Caucasians and Japanese patients. There were two patients who developed signs of glucose intolerance under GH replacement; one of these was able to continue treatment after adequate dose reduction, but the second, with a borderline high BMI value for Japanese, had to discontinue.…”

“…Similar differences between AO and CO in responsiveness to GH replacement have been described in Caucasians [16,17,20], and surveillance reports indicate that in clinical practice GH dose in Caucasians is on average about 20% higher in CO than in AO patients [20]. This may be caused by the age and developmental difference existing between CO and AO, as CO patients are usually much younger than AO patients and many of them are still in the postpubertal/transition age when GH needs are higher than at older ages.…”