Therapy of Endocrine disease: Long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review

Abstract

Background: The beneficial effects of recombinant human GH (rhGH) therapy in GH deficient (GHD) adults are well-established in the short term. However, data documenting the effects during prolonged follow-up are relatively scarce. Objective: To evaluate the reported effects of rhGH replacement (R5 years) in GHD adults on biochemical and anthropometric parameters, quality of life (QoL), bone metabolism, muscle strength, serious adverse events and mortality. Methods: We conducted a systematic literature search. Quality assessment of retrieved papers was performed using a quality assessment based on the modified STROBE statement. Results: We included 23 prospective studies with a rhGH treatment duration ranging from 5 to 15 years. Overall, beneficial effects were reported on QoL, body composition, lipid profile, carotid intima media thickness and bone mineral density. In contrast, the prevalence of the metabolic syndrome, glucose levels, BMI and muscle strength were not, or negatively, influenced. Most of the studies were uncontrolled, lacked the presence of a control group (of non-treated GHD patients), and reported no data on lipid-lowering and anti-diabetic medication. Overall mortality was not increased. Conclusion: rhGH treatment in adult GHD patients is well-tolerated and positively affects QoL in the long term. However, the metabolic and cardiovascular effects during long-term treatment are variable. The low numbers of long-term studies and studied patients and lack of control data hamper definite statements on the efficacy of prolonged treatment. Therefore continuous monitoring of the effects of rhGH replacement to enable an adequate risk-benefit analysis that may justify prolonged, potentially life-long, treatment is advisable.

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

“…GHD patients usually have decreased HDL and increased LDL cholesterol, as we found in our study, and the beneficial effects of GHT have been well documented, although a limitation of most studies is the lack of data concerning lipid-lowering treatment or the chronic use of these [35]. Our data, showing an improvement in total and HDL cholesterol in patients not receiving specific treatment, are in agreement with a series of studies which have confirmed that long-term GHT leads to a significant improvement in lipid profile [41], although other studies did not report any significant effect [42,43].…”

“…The impairment in glucose metabolism, characterized by insulin resistance and mainly due to increased BMI and impaired body composition, has been often reported in GHD [6,44,45], but discordant data have been shown as regards the effect of GHT on it [35]. In our cohort of subjects we found that the GHD group did not differ significantly from the control group for fasting glucose, insulin and HbA1c levels and that these parameters did not significantly change during GHT.…”

“…These data are also in agreement with the main results on long-term effects of GHT on BMI and WC, which appear to be inconclusive. Indeed, both BMI and WC have been found to be increased or unchanged during GHT [34,35]. Conversely, GHT has overt favorable effects on body composition, mainly evaluated by dual-energy X-ray absorptiometry (DEXA).…”

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

“…During follow-up, despite an increase in waist circumference (especially in previous NFPA), the positive effect of GH treatment on lipid profile was evident in both groups. These positive effects of long-term GH treatment in all GHD patients on lipid profile have been demonstrated before, except for triglycerides for which results remain inconclusive (34,35), also in patients with GHD after acromegaly positive effects have been reported (17,20,28). However, most studies do not or are unable to take into account the use of lipid-lowering medication.…”

Hypopituitarism—needs modern individualized treatment

“…increased fat mass, reduced lean mass, osteopenia, an unfavorable lipid profile, reduced muscle strength, fatigue) has been recognized since the early 1990s [14]. Long-term studies on the effect of GH replacement therapy have since shown an improvement in many of these features, such as improved lean body mass, decreased body fat, beneficial effects on plasma lipids, positive effects on intima media thickness, improvement in bone mineral density, and better quality of life [15]. Lately, partly due to a recently published study, a growing body of evidence is showing that GH replacement therapy is associated with reduced excess mortality or normalized mortality compared to the general population [5,16].…”