Effects of growth hormone deficiency on body composition and biomarkers of cardiovascular risk after definitive therapy for acromegaly

Abstract

Background Both growth hormone (GH) excess and GH deficiency are associated with body composition and biomarkers of cardiovascular risk in patients with pituitary disorders. However, the effects of developing GH deficiency after definitive treatment of acromegaly are largely unknown. Objective To determine whether development of GH deficiency after definitive therapy for acromegaly is associated with increased visceral adiposity and biomarkers of cardiovascular risk compared to GH sufficiency after definitive therapy for acromegaly. Design Cross-sectional Patients We studied three groups of subjects, all with a history of acromegaly (n=76): subjects with subsequent GH deficiency (GHD; n=31), subjects with subsequent GH sufficiency (GHS; n=25), and subjects with active acromegaly (AA; n=20). No study subjects were receiving somatostatin analogues, dopamine agonists or hGH. Measurements Body composition (by DXA), abdominal adipose tissue depots (by cross-sectional CT), total body water (by bioimpedance analysis) and carotid intima-media thickness (IMT) were measured. Fasting morning serum was collected for high-sensitivity C-reactive protein (hsCRP), lipids and lipoprotein levels. An oral glucose tolerance test was performed, and homeostasis model of assessment-insulin resistance (HOMA-IR) was calculated. Results Abdominal visceral adipose tissue, total adipose tissue, and total body fat were higher in subjects with GHD than GHS or AA (p < 0.05). Subcutaneous abdominal fat was higher, and fibrinogen and IMT were lower in GHD (but not GHS) than AA (p < 0.05). Patients with GHD had the highest hsCRP, followed by GHS, and hsCRP was lowest in AA (p < 0.05). Fasting glucose, 120-minute glucose, fasting insulin, HOMA-IR, and percent total body water were lower in GHD and GHS than AA (p < 0.05). Triglycerides were higher in GHS than AA (p < 0.05). Lean body mass, mean arterial pressure, total cholesterol, HDL, and LDL were comparable among groups. Conclusions Development of GHD after definitive treatment of acromegaly may adversely affect body composition and inflammatory biomarkers of cardiovascular risk but does not appear to adversely affect glucose homeostasis, lipids and lipoproteins, or other cardiovascular risk markers.

Impact of adult growth hormone deficiency on metabolic profile and cardiovascular risk [Review]

“…Also, the acromegaly-related cardiac abnormalities could worsen after the development of GHD [101]. However, clinical studies do not fully confirm these theoretical hypotheses, as they found a BMI slightly increased [102][103][104] or, even, similar [105][106][107][108] in acroGHD compared to GHD and acromegalic populations. At the same time, while one work reported that acroGHD patients were more hypertensive, dyslipidemic, and diabetic than GHD subjects [109], other Authors pointed out a comparable prevalence of glucose abnormalities and dyslipidemia, as well as a similar amount of body fat and lean mass between acroGHD and refcerebrovascular [5, [82][83][84][85][86][87].…”

Effect of long-term GH replacement therapy on cardiovascular outcomes in GH-deficient patients previously treated for acromegaly: a sub-analysis from the Dutch National Registry of Growth Hormone Treatment in Adults

“…In three studies, patients who were GH sufficient after treatment for acromegaly or active acromegaly were used as controls. These studies demonstrated that GHD after treatment for acromegaly is associated with a more impaired metabolic profile (15,16,27). Studies using GHD of other etiologies or after treatment for a NFPA as comparator demonstrated no differences in clinical presentation (6,17,26).…”

“…To date, ten studies (Table 4) investigated the characteristics of GHD and/or the effect of GH treatment on cardiovascular outcome measures in GHD patients after treatment for acromegaly (6,15,16,17,18,19,20,26,27,28). In three studies, patients who were GH sufficient after treatment for acromegaly or active acromegaly were used as controls.…”

“…Only a few studies have investigated the characteristics of patients with GHD after treatment for GH hypersecretion and an unfavorable metabolic profile has been suggested (15,16). GH treatment has been demonstrated to show improvement in the metabolic parameters in acromegalic patients with GHD (17,18).…”

Clinical predictors of GH deficiency in surgically cured acromegalic patients

“…GHD in adults is associated with a decreased lean body mass and increased fat mass, dyslipidemia, increased frequency of cardiovascular events, lower bone mineral density, and increased mortality (6,7,8). Even in patients with acromegaly, GHD development after treatment adversely affects the body composition and inflammatory biomarkers of cardiovascular risk (9). In cured acromegalic patients with GHD, GH replacement therapy has been proven to improve the body composition, dyslipidemia, and the quality of life without causing any adverse effects such as malignancy or altered glucose metabolism (10).…”