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Growth hormone replacement in adults – current standards and new perspectives

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Growth hormone deficiency (GHD) in adults is an established clinical syndrome characterised by adverse body composition with more body fat than lean body mass, unfavourable blood lipids, decreased physical fitness and poor quality of life. No specific biomarker for GHD exists and the sometimes difficult diagnosis should be made in accordance with, established guidelines. Measurements of insulin-like growth factor I (IGF-I) is often not sufficient for the diagnosis and stimulation tests of the GH reserve are required. After diagnosis of GHD, treatment with GH should be initiated with a low dose, and gradually increased aiming at obtaining an IGF-I level within the upper part of the normal range for age matched healthy controls. Most side effects are mild and transient and attenuated by gradual dose increments. Numerous studies have shown that GH treatment can improve body composition, cardiovascular risk factors, physical capacity and quality of life. However, studies on effects beyond 5 years are few and despite encouraging preliminary reports the ultimate endpoint demonstrating that GH treatment has beneficial effects on mortality, cardiovascular events and fractures without an increase in cancer incidence remain to be solidly demonstrated and studies to resolve these issues are awaited. Trials with long acting GH formulations are ongoing and available data indicate similar effects on outcome measures compared to the effects of daily injections.

This review will give an overview of clinically relevant issues of GHD including advice for management of these patients.

Section snippets

Physiology

Human growth hormone (GH) is a peptide with a molecular weight of 22 kDa. GH is synthesized and released from the anterior pituitary gland; a process induced by ghrelin and hypothalamic GHRH (Growth Hormone Releasing Hormone) and inhibited by somatostatin in addition to negative feedback by insulin-like growth factor I (IGF-I) [1]. The release of GH is pulsatile with bursts occurring especially during sleep; however, the size and the numbers of bursts are influenced by age, gender intercurrent

Growth hormone deficiency (GHD)

From Scandinavia the incidence of GHD has been reported to affect 1 per 100,000 people per year – with an estimated prevalence of 350/million [7]. The most common causes of GHD are pituitary adenomas or other sellar masses. As expected from the ubiquitous GH and IGF-I receptors GHD in adults is characterised by several signs and symptoms ∗[4], ∗[5], ∗[8]. These include impaired quality of life (QoL), reduced physical activity, increased body fat, decreased lean body mass and an adverse

Diagnosis of GHD

The diagnosis of GHD is established according to specific criteria for the maximal GH response to various different stimulation tests. The GH response to insulin hypoglycaemia (glucose <2 mmol/L), the insulin tolerance test (ITT), is regarded the golden standard ∗[4], ∗[5]. GHD with this testing is defined as a maximal GH response of <3 μg/L. However, it is important to realise, that several problems exist with GH measurements and that comparison of data from different laboratories and

Treatment with GH

At variance with the situation upon the discovery of insulin, where extracts from animal pancreatic tissue proved efficient in patients with diabetes, only human GH exerts any metabolic activity in man. Hence, it was not until the isolation of GH from human cadaveric pituitary glands by Raben and the subsequent purification in the late fifties that clinical use of the hormone became possible [20]. From 1960 treatment of growth retardation in hypopituitary children gradually became an accepted

Side effects

The adverse effects of GH treatment are usually mild and transient and depend on the GH dose used. Therefore, it is recommended to start with a low GH dose and slowly increase the dose until IGF-I is close to the mean of healthy controls. The side effects are often caused by fluid retention with oedema, muscle pain, joint stiffness and pain, paraesthesia, carpal tunnel syndrome and headache. When occurring, reducing the GH dose can usually relieve the side effects.

Because GH increases the

New perspectives

Daily injections – even by the subcutaneous route end even by the use of modern, thin needles – are often considered inconvenient by as well children (perception of pain) as adults (unnecessary troublesome). In addition the lack of immediate symptoms upon cessation of treatment (skipping one or more injections) might compromise the compliance to GH therapy. Hence, a reduction in the number of injections could be of benefit for compliance, and therefore long acting GH preparations might harbour

Summary

Deficiency of growth hormone in adults is characterised by adverse body composition with more body fat than lean body mass, unfavourable blood lipids, decreased physical fitness and poor quality of life. No specific biomarker for GHD exists and the sometimes difficult diagnosis should be made in accordance with, established guidelines. Treatment with GH should be initiated with a low dose, and gradually increased aiming at obtaining an IGF-I level within the upper part of the normal range for

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