Side Effects Associated with Low-Dose human growth hormone Replacement The dose of rhGH is an important consideration in the therapy of acquired GH-deficiency. Large, pharmacological doses of GH are often associated with the clinical sequelae of human growth hormone excess, including fluid retention and hypertension. However, increasingly smaller, physiological, doses of rhGH are currently being used for replacement in human growth hormone- deficient patients without such sequelae. At a dose of 0.03 mg/kg/week, Bengtsson et al. demonstrated only minor side effects including fluid retention and mild arthralgias in the majority of patients but did report carpal tunnel syndrome in one patient (6). In all cases, further reduction of the human growth hormone dosage resulted in amelioration of side effects. In another recent study in which a smaller dose of human growth hormone was used, 0.01 mg/kg was administered three times per week without any reported side effects (8). It remains unknown, however, whether chronic administration of GH at doses which keep IGF-I levels within the normal range will also improve key metabolic variables. Future Directions Growth hormone deficiency is an important cause of excess morbidity and even mortality. Evidence from a number of smaller studies indicates that human growth hormone replacement will improve body composition, lipid metabolism, bone density, cardiovascular function and psychological well being. Important issues remaining are the precise clinical definition of partial vs. complete human growth hormone deficiency in such patients and clarifying the best tests to make this diagnosis. In addition, it is unclear whether some of the observed beneficial effects reflect pharmacological GH therapy rather than physiologic human growth hormone replacement. Nevertheless, it is apparent that small doses, unassociated with sequelae of human growth hormone excess, may suffice to achieve the desired metabolic results. Definitive r ecommendations on dosage and the long term effects of human growth hormone therapy, particularly on cardiovascular morbidity and mortality, will be determined by the prospective studies now underway at the MGH and other centers around the country.