The International Hormone Society’s Consensus Group of experts on Hormone Therapies Consensus nr 5 on “Growth Hormone Therapy of Milder Forms of Growth hormone Deficiency in Adults” of the 29-9-2005

After having reviewed the scientific literature and exchanged experiences between physicians from all over the world and who are competent in hormone therapies, we, members of the Consensus Group of Experts of the International Hormone Society, think the time is ripe to consider treating growth hormone deficiency in adults, not only severe, but also milder forms.

We acknowledge and approve the consensus that has been reached in many countries for growth hormone treatment of adults suffering from severe growth hormone deficiency after important head injury, surgery or radiation of tumours in the pituitary region. Generally, in such conditions there is a history of removal or severe inactivation of the pituitary gland, the endocrine gland that secretes growth hormone.

We think that the amount of supporting data on growth hormone’s beneficial effect is now sufficient to extend the recommendation of growth hormone treatment to patients with milder forms of growth hormone deficiency such as those that progressively appear in adults of increasing age, because of the progressive age-related decline of the pituitary gland.

The evidence is that growth hormone is not only essential for the growth of children, but also essential for mental and physical (in particular bone, muscular and cardiovascular) health of adults, including elderly persons. Growth hormone deficiency is often accompanied by fatigue, anxiety and depression, summarized in a low quality of life, often severe in persons whose growth hormone deficiency started in late adulthood, as confirmed in many studies. On the other hand, growth hormone treatment has been reported to considerably improve the quality of life, the mood and the sleep. Not treating the milder forms of growth hormone deficiency in elderly persons may much more seriously than thought before, adversely affect human health. The increased atherosclerosis and mortality, especially cardiovascular, that are found in individuals who suffer from severe growth hormone deficiency, and that partially or totally reverse with growth hormone correction, make it likely that such problems also occur in some degree in patients with more moderate deficiencies, and may likewise be improved by growth hormone injections.

We recommend the physicians to do a regular check-up of any patient treated with growth hormone. This includes doing a good clinical interview and examination, and laboratory tests every two to twelve months depending on the patient’s needs. A regular cancer screening, including breast and prostate examination, every year or six months eventually completed by ultrasound examination, and whenever necessary mammography, is essential to the Consensus Group of Experts of the International Hormone Society.

Concerning an eventual increase in risk of certain cancers with growth hormone, the data are conflicting. In some investigations protective effects against cancer are reported, while in other studies increases of risks for patients with high serum IGF-1 and low serum IGF-BP-3 were found. The most serious study done on patients treated with growth hormone compared to a group of untreated growth hormone-deficient adults showed an approximate 50 % decrease in cancer incidence and cancer mortality. Actually, there is no convincing evidence to believe there is an increase in cancer risk in most individuals treated with growth hormone. Nonetheless, we recommend physicians to administer only physiological doses that correct the deficiency, avoiding thereby carefully to overtreat. By following this principle, the physician further increases the safety of the treatment.

After thoroughly reviewing the report of two studies where critically-ill patients encountered a doubling of the mortality rate with growth hormone compared to a similar group of critically ill patients without growth hormone, we can say the following. This “negative” report forms an exception. The critically ill patients received clearly supraphysiological doses: 10 to 50 times higher than physiological. At physiological doses -20 to -40 % reductions of cortisol serum levels and urinary 17-hydroxy-steroids, the cortisol metabolites, have been observed. At supraphysiological doses the cortisol-reducing effect of growth hormone that in normal people is a way to prevent any excess in cortisol, more than probably weakens the critically-ill patient who crucially needs high doses of cortisol for his survival. The increased mortality of the treated patients was due to infections and polyorgan failure, conditions typical of severe adrenal failure. The results of the study are probably due to overtreatment and possibly also to neglectment of glucocorticoid supplementation, not to growth hormone per se. The use of physiological doses of growth hormone and more than probably glucocorticoid supplementation would have been much safer and might have reduced mortality rather than increase it.

In conclusion, no convincing data against the use of growth hormone in adults suffering from low growth hormone or IGF-1 levels have been found. On the contrary, adverse effects of persisting low growth hormone levels have been abundantly reported, as has their improvement or disappearance with growth hormone treatment.

We therefore recommend to treat with growth hormone cancer-free adults with low growth hormone and IGF-1 levels. Growth hormone treatment should be restricted to physiological doses and be accompanied by careful and regular check-ups.