Best Practice & Research Clinical Endocrinology & Metabolism
10Growth hormone replacement in adults – current standards and new perspectives
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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