COMPARATIVE RAPIDITY OF RESPONSE OF HEIGHT, LIMB MUSCLE AND LIMB FAT TO TREATMENT WITH HUMAN GROWTH HORMONE IN PATIENTS WITH AND WITHOUT GROWTH HORMONE DEFICIENCY
Authors: Tanner J. M. , Hughes P. C. R. , Whitehouse R. H. 
Published: December 2008

The widths of muscle and fat in the upper arm and calf have been measured radiologically before treatment and at intervals of 1, 3, 6 and 12 months during administration of human growth hormone in 41 pre-pubertal patients with "isolated" growth hormone deficiency and in 22 patients with multiple deficiencies following gross CNS lesions. Height was also measured. The curves of response of muscle and fat on the one hand and height on the other were strikingly dissimilar. A very rapid increase of muscle took place in the first month; but after 6 months the increments had fallen to normal values for size and bone age. Decrements in fat followed the same pattern. Height, however, showed a smaller increment in the first month than in the period 1 to 3 months in the "isolated" deficiency cases, and a much slower fall back towards normal.

The first-year height increment was not at all correlated with the first-month height increment in the "isolated" deficiency cases, though it had a correlation coefficient of 0.46 with the first-month muscle increment.

Nine cases of short stature not due to GH deficiency were similarly studied. There was considerable overlap between deficient and non-deficient in all responses in the first 3 months, though children in the top half of the responder's distribution could be distinguished.

A 1-month radiological test of responses to hGH in doubtful cases is proposed, using in all only 40 IU of hormone. It is emphasised that a small response of muscle and fat may occur in cases who do nevertheless respond in height to hGH administration; a large response in muscle and fat, however, is indicative that treatment will be effective, though it does not well predict the precise amount of height that may be gained.

It is well known that the muscles of hypophysectomized animals increase in size when they are given growth hormone (Bigland & Jehring 1952) and we have shown that the same occurs when human growth hormone is given to children with growth hormone deficiency (Tanner et al. 1971). The minimal period of administration that we studied was 3 months, but there is reason to think the response might be demonstrated in a shorter period, for the nitrogen balance becomes strongly positive in such patients after only a few days' treatment (Henneman et al. 1960) and presumably much of this nitrogen is incorporated into muscle. We have therefore examined changes in limb muscle, and also fat, over a period of 1 month, as well as 3, 6 and 12 months, and related the increase of muscle and decrease of fat to the height response over the same periods.

The diagnosis of growth hormone deficiency is still not invariably straightforward and a simple short-term therapeutic test would be of considerable value. Such a test should in the first place discriminate patients who respond with significant height growth during a year's treatment from those who do not, and secondly should if possible predict accurately the amount of height growth to be expected amongst the children who do show a response. This prediction cannot be made by the metabolic test (Clayton et al. 1971), presumably because that test relates only to the first few days of treatment. We deal with these two aspects in reverse order.