Lavin Chapter 12

Chapter 12 • Growth Hormone in Adults   137

hypothalamic tumor recurrence and cancer. Although there are benefits in diminishing and decreasing cardiovascular risk factors, reductions in cardiovascular mortality have yet to be confirmed. B. Adverse effects. The most common side effects are related to fluid retention as well as paresthesias, joint stiffness, peripheral edema, arthralgia, and myalgia. Carpal tunnel syndrome has been described in as many as 2% of patients. Most of these adverse reactions, however, improve with dose reduction. Benign intracranial hypertension has been linked to GH treatment in children, but only one case has been reported in adults. Gynecomastia has been reported in a very few elderly individuals receiving GH in high doses. C. GH and tumor formation. There is a concern that GH therapy could lead to tumor recurrence or the development of malignancies. However, an increase in recurrence rates of either intracranial or extracranial tumors has not been demonstrated in AGHDS. There are no published data of long-term observational studies in patients with AGHDS treated with GH that showed any increased incidence of cancer. D. Unmasking of thyroid and cortisol deficiency. Although it is not an adverse effect, GH replacement can cause a lowering of free thyroxine (T 4 ) levels, perhaps because of increased deiodination of T 4 , enhancing the extrathyroidal conversion of T 4 to tri-iodothyronine (T 3 ). Lowering of T 4 during treatment with GH, therefore, reflects biochemical unmasking of subclinical central hypothyroidism. GH treatment has also been found to cause a lowering of serum cortisol levels, revealing central hypoadrenalism that has been masked, likely because of enhanced conversion of cortisone to cortisol during the GH-deficient state. 11 β -Hydroxysteroid dehydro- genase type I isoenzyme acts as a reductase that converts cortisone to cortisol and is increased in GHD and reduced by GH replacement. Therefore, free T 4 levels and cortisol levels should be monitored during treatment. E. Contraindications. GH treatment is contraindicated in the presence of an active malignancy. GH treatment of patients with diabetes mellitus is not a contraindication, but may require adjustments in antidiabetic medication. F. Cardiovascular . The relevance of the beneficial effects of GH on the cardiovascular system is strongly suggested, but not fully proved. The results in a large cohort of GH-treated patients (the KIMS or Pharmacia & Upjohn database) demonstrated no difference in cardiovascular risk in comparison with that in a control population after a mean of 3 years. In one study, after GH treatment in the elderly, there were no significant changes in electrocardiogram parameters or blood pressure. In this study, patients with GHD did not show cardiac structural or functional differences compared with healthy controls, with no significant changes after GH treatment. G. Acromegaly. GH therapy is the recommended treatment in adult patients with GHD, but one argument against this is in acromegaly, in which there is excess GH, and the main cause of mortality is cardiovascular disease. H. Low IGF-1—not a risk factor. Among older adults, a decreasing IGF-1 level over time does not predict subsequent all-cause mortality. Studies do not confirm the hypothesis that the declining IGF-1 level is a mortality risk factor. In conclusion, there is no evidence that older adults with decreases in IGF-1 levels over a period of years have diminished likelihood of long-term survival. Of course, there are other studies countering these conclusions. I. Neoplasms 1. Although a theoretical increased risk of developing new or recurrent neoplasms has been suggested in some studies in adults, this increase has not been found in most studies of treatment in patients with adult-onset GHD. 2. “The long-term risks of high-dose growth hormone use are little studied, but available evidence suggests that long-term high-dose growth hormone may have serious medical consequences, including cardiac, endocrine, or respiratory effects, as well as increased risks for certain cancers,” said Brian Brennan at McLean Hospital in Belmont, MA and Harvard Medical School in Boston. Brian Brennan states that his findings suggest that mounting illicit GH abuse may represent a dangerous new form of drug abuse with potentially severe public health conse- quences. Individuals with prolonged excessive GH from a pituitary tumor have a tendency to develop tumors elsewhere in the body. This raises the concern that