Complications
Growth hormone (GH) deficiency has been associated with cardiovascular disease, osteopenia/osteoporosis, alteration in body composition, decreased life expectancy, psychological disturbances, and insulin resistance.
Cardiovascular disease
Early epidemiologic data showed that patients with hypopituitarism who were on hormone replacement therapy, not including GH, had increased cardiac events, suggesting an association of GH deficiency with cardiovascular disease. [
14,
28,
29,
30,
31] Patients with GH deficiency have increased rates of the presence of markers of cardiovascular disease, such as greater intima-media thickness of the carotid arteries, reduced left ventricular mass, decreased ejection fraction, high levels of serum low-density lipoprotein (LDL) cholesterol (LDL-C) and triglycerides, low levels of high-density lipoprotein (HDL) cholesterol (HDL-C), and high coronary calcium scores. [
14,
29,
30,
32] GH therapy improves certain markers of cardiovascular disease, such as serum lipids (reduction of LDL-C levels and increase in HDL-C levels), systolic function, intima-media thickness of the carotid arteries, endothelial function, left ventricular mass, and cardiac output. [
29,
33,
34,
35] However, evidence is limited regarding the effect of GH replacement therapy on cardiovascular morbidity and mortality. [
28,
29,
36]
A study that evaluated the prevalence of metabolic syndrome and associated cardiovascular complications in adult-onset GH deficiency during GH replacement therapy found an essentially unchanged prevalence of metabolic syndrome in these patients during 1 year of GH therapy. [
37] However, there was a significant reduction in abnormal waist circumference (
P< 0.001), a significant increase in impaired glucose metabolism (
P < 0.001), and a decrease in HDL-C (
P = 0.011). Moreover, over a 7-year period of GH therapy, those with metabolic syndrome had a 66% higher risk of developing a new coronary disease compared to those without metabolic syndrome (
P = 0.0016). [
37]
Osteopenia/osteoporosis
Patients with GH deficiency have reduced bone mineral density and increased rates of fractures. [
38,
39] A gender difference in the response to GH treatment has been hypothesized, as bone mineral density has been show to improve with this therapy more in men than in women. [
40,
41,
42] The effect of GH therapy on fracture rate was less pronounced, with stabilization of the incidence of clinical fracture after GH treatment. [
40]
Effect on body composition
Patients with GH deficiency tend to have a relative increase in fat mass with a preferential increase in visceral fat and a relative decrease in muscle mass. [
43,
44] GH therapy decreases total body fat and increases muscle mass. [
43,
45] Some, but not all, studies have shown increased muscle strength along with improved exercise capacity and physical performance after GH therapy. [
45,
46,
47]
In an observational retrospective monocentric study of 47 patients with GH deficiency who were treated with GH during childhood, investigators evaluated changes in pediatric growth parameters relative to an increase of insulin-like growth factor-1 (IGF-I) z-score as well as other indexes of GH response, such as body composition and lipid profile, after 1 year of treatment in adulthood. [
48] The investigators noted the following [
48] :
- Positive correlation between final growth velocity in the last year of childhood GH treatment and an increase in IGF-I z-score in GH-treated adults ( P< 0.01), but no significant positive correlation between the main parameters that evaluate response to GH treatment in children and adults
- No correlation between growth-promoting effects of GH as child and metabolic changes induced by GH as adult
- Negative correlation between weight at the end of childhood GH treatment and the IGF-I response during first year of treatment in adults ( P < 0.05)
- Potential predictive response of the final growth velocity in children to GH treatment in adulthood
Decreased life expectancy
Patients with hypopituitarism have decreased life expectancy compared with age- and gender-matched healthy people despite replacement with adrenal, thyroid, and gonadal hormones, primarily owing to cardiovascular and cerebrovascular disease. [
7,
49,
50,
51] Therefore, it has been speculated that GH deficiency in patients with hypopituitarism is associated with premature mortality. [
7] However, other factors potentially contribute to the increased mortality in these patients, including the following [
7] :
- Administration of cranial radiation to treat the pituitary disease
- Use of different thyroid, gonadal, and glucocorticoid replacement regimens, including what is currently considered high doses of glucocorticoids
- Unavailability of effective treatments for hyperlipidemia and hypertension during the survey periods
There are no published studies on the effect of GH therapy on mortality. Observational data suggest a lower mortality in those who receive GH therapy compared to those who remain untreated, but these findings may be a result of selection bias. [
36]