Adult Replacement Therapy Research Articles

The influence of growth hormone (GH) therapy on cardiac performance in patients with childhood onset GH deficiency

Objective: There is accumulating evidence that growth hormone (GH) plays an important role in the maintenance of normal cardiac growth and function. Abnormalities in left ventricular diastolic function and impairment of systolic function have also been reported in patients with GHD. In this study, we investigated the effects of 12 months GH replacement therapy on cardiac functional indices measured by echocardiography, the ECG stress test and SPECT imaging. Design: Sixteen patients with childhood onset GHD (age 42.3 ± 13.1 years, 10 males) were investigated before, and after, 12 months of GH treatment at a dosage of 0.02 IU/kg/day (7 μg/kg/day). The GH administration resulted in serum IGF-I levels within the normal range in all the patients. The following investigations were performed initially and after 12 months: electrocardiography, systolic and diastolic blood pressure, heart rate measurement, a complete Doppler-echocardiographic examination, treadmill exercise test and Technetium-99m sestamibi single-photon emission computer tomography (SPECT) imaging at rest and after exercise. Results: Echocardiography showed improvement in left ventricular systolic function after GH treatment. End-systolic volume fell from 29.9 ± 12.4 to 24.4 ± 6.9 ml ( p < 0.05) and the ejection fraction increased from 56.2 ± 7.2% to 63.2 ± 6,1% ( p < 0.01). Left ventricular diameter and wall thickness did not change after GH treatment, although systolic increase in interventricular septum thickness (IVS%) and systolic increase in posterior wall thickness (PWT%) increased significantly (IVS% 52.2 ± 31.9% vs. 67.3 ± 30.4% and PWT% 48.7 ± 20.2% vs. 58.0 ± 17.7%, p < 0.01, p < 0.01, respectively). Contractile function, measured at midwall level, improved as left ventricular midwall fractional shortening (MWS) increased (16.11 ± 6.55 vs. 23.30 ± 5.89 %, p < 0.01) and stress-corrected MWS increased between the examinations performed before and after 12 months of GH treatment (90.97 ± 36.66 vs. 133.10 ± 32.84 %, p < 0.01). Diastolic function did not change, as assessed by early diastolic flow ( E), diastolic flow secondary to atrial contraction ( A), or the E/A ratio. The LV-mass index did not change significantly after GH treatment (78.4 ± 22.1 vs. 81.9 ± 21.1 g/m 2). After 12 months of GH treatment the myocardial performance index (MPI) decreased significantly from 0.483 ± 0.146 at baseline to 0.410 ± 0.086 at the end of the study ( p < 0.05). There was a trend towards an increase in exercise duration and capacity after GH treatment but the differences did not reach levels of statistical significance. SPECT imaging basally and after 12 months showed normal myocardial perfusion at rest and after exercise in all the patients. In conclusion, GH replacement therapy in adults with GHD demonstrated the beneficial effects on cardiac functions.

Long-Term Monitoring of Insulin-Like Growth Factor I in Adult Growth Hormone Deficiency: A Critical Appraisal

Serum insulin-like growth factor I (IGF-I) levels predominantly reflect the hepatic effect of growth hormone (GH). Compared with serum GH levels, which reflect pulsatile GH secretion, serum IGF-I levels exhibit no major diurnal variation and thus provide a better estimate of integrated GH secretion in an individual patient. Measurement of serum IGF-I levels allows reliable identification of states of GH excess. In contrast, in a large proportion of adults with severe GH deficiency, serum IGF-I levels are within the normal range. Serum IGF-I levels increase markedly in response to GH administration and are often used as a surrogate variable for overall responsiveness to such treatment. Current data, however, suggest a poor relationship between changes in or levels of IGF-I and efficacy variables such as body composition, muscle function and well-being. The use of serum IGF-I as a guide during dose titration in the initial phase of treatment and during long-term monitoring of GH replacement therapy in adults, and its use as a safety marker or predictor of future morbidity and mortality are discussed here.

Long-term improvement of quality of life during growth hormone (GH) replacement therapy in adults with GH deficiency, as measured by questions on life satisfaction-hypopituitarism (QLS-H).

Questions on Life Satisfaction-Hypopituitarism (QLS-H) is a new quality-of-life (QoL) questionnaire developed for adults with hypopituitarism. To determine the effects of long-term GH treatment on QoL, we evaluated QLS-H Z-scores in 576 adult patients with GH deficiency (GHD) enrolled in HypoCCS, an international observational study, using data from five countries in which comparative QLS-H data from the general population were available. Baseline QLS-H Z-scores were significantly lower in GH-deficient patients than in the general population of the same age, gender, and nationality. Z-scores were also significantly lower in female patients vs. males (P = 0.006) and in adult-onset vs. childhood-onset GHD (P = 0.002). Multivariate analysis associated female gender, multiple pituitary hormone deficiencies, low serum IGF-I values (<75 micro g/liter), and concomitant antidepressant medication with low baseline Z-scores. QLS-H Z-scores increased from -1.02 +/- 1.43 (SD) at baseline to -0.25 +/- 1.34 (SD) after 1 yr of GH treatment (P < 0.001) and were no longer significantly different from the general population after 4 yr of treatment. There was no correlation between change in Z-score and GH dose or changes in IGF-I and IGF binding protein-3 during treatment. This study demonstrates that 1) improvements in QoL, as measured by the QLS-H, are maintained during long-term GH replacement therapy of adults with GHD, and 2) the QLS-H is a useful tool for evaluating QoL in hypopituitary patients treated in clinical practice. The authors suggest that evaluation of QoL should be a part of the routine clinical management of adult GH-deficient patients, complementing the measurement of surrogate biological markers or other clinical end points.

Childhood-onset growth hormone (GH) deficiency in adult life.

Over the last decade GH replacement therapy for adults has progressed in status from research study to a mainstream clinical indication. An area ripe for further research, however, is the difference between adults who developed GHD before and after completion of growth and puberty. That differences exist, not only in aetiology, but also in phenotype and response to GH therapy is clear. However, whether these differences are intrinsic to the timing of onset of GHD, or related to secondary factors including the method of assessment or dose of GH employed is uncertain. This chapter discusses the current state of knowledge in this area and poses further questions, not only for the researcher attempting to understand the mechanisms underlying these differences, but also for the physician seeking to ameliorate the impact of GHD in patients who acquired GHD in childhood.

Long-term growth hormone replacement therapy in hypopituitary adults.

Growth hormone deficiency (GHD) in the adult has now been fully recognised as a clinical entity characterised by abnormal body composition, osteopenia, impaired quality of life, cardiac dysfunction and an adverse lipid profile. While short-term studies of GH replacement have demonstrated irrefutably a favourable effect on all if not most features of GHD, data on long-term administration spanning more than 2 years are still scarce. Experience of GH replacement up to 5 to 10 years indicate that the beneficial effects on body composition, predominantly a decrease in body fat and an increase in lean mass, is maintained during treatment. Long-term GH therapy also increases muscle strength and exercise performance. All data, with one exception, are consistent with a significant increase in bone mass during prolonged GH therapy. The most distinct effect on bone was observed in the worst affected individuals and in males. Improvement in quality of life is documented shortly after initiation of GH replacement and is maintained during long-term studies. This may explain the reduction in days of sick leave seen during GH therapy. The beneficial effect on cardiovascular risk factors is sustained over a prolonged period of time, revealing a reduction in intima wall thickness, and an improvement in serum lipid levels and clotting parameters. The increase in lipoprotein(a) levels with GH therapy in some studies may be disturbing, but difficulties in measuring this parameter and inconsistencies between the different studies makes it difficult to estimate its real impact. No data are yet available to show that GH replacement will normalise or even improve mortality rate and fracture rate. Adverse events associated with GH replacement therapy are mainly secondary to fluid retention as a result of excess dose administration. This can be adequately prevented by monitoring GH replacement according to serum insulin-like growth factor (IGF)-I levels. From what is currently known, GH replacement does not increase the prevalence of diabetes mellitus, and does not induce new neoplasms or recurrence of the primary brain tumour; however, longer follow-up studies are needed to provide definitive answers. In conclusion, it appears not only that long-term GH replacement therapy in adults with GHD is a procedure that can be safely used, but that GH replacement should be considered as a possible life-long therapy in order to maintain its benefits.

Coronary risk in growth hormone deficient hypopituitary adults: increased predicted risk is due largely to lipid profile abnormalities.

Hypopituitarism in adults is associated with increased vascular mortality, which has been attributed to GH deficiency. To compare the lipid profile and coronary risk predicted by the Framingham Heart Study equation in GH-deficient hypopituitary patients and healthy age and gender-matched controls. A cross-sectional observational study. We studied 50 adult-onset growth hormone deficient hypopituitary patients (23F, 27M), on appropriate conventional hormone replacement and 45 controls (22F, 23M) matched for age, gender and smoking habit. The subjects (age range 30-75 years) were free from diabetes, hypertension, ischaemic heart disease (IHD) and peripheral vascular disease. All hypogonadal male patients were on testosterone replacement therapy. A similar proportion of female patients (8/23) and controls (7/22) were on HRT. Body mass index (BMI), waist-hip ratio (WHR) and blood pressure were recorded. After an overnight fast blood glucose, total-cholesterol, triglycerides, HDL-cholesterol, apolipoproteins A-I, B and Lp (a) were measured. Coronary risk was calculated for each individual from age, gender, systolic blood pressure, total and HDL cholesterol, smoking habit and presence of diabetes and left ventricular hypertrophy using the Framingham equation. BMI and WHR were significantly increased in GHD hypopituitary adults of both sexes, but to a greater extent in females. Triglycerides were elevated in both sexes. Total and LDL-cholesterol were increased in both sexes (significantly only in males), and HDL cholesterol and apo A-I were lower (significantly only in females). The reduction in HDL cholesterol was correlated negatively with adiposity (BMI), particularly when centrally distributed (WHR) in patients and controls. LDL cholesterol did not correlate to adiposity but higher levels were present in GH-deficient subjects. The total to HDL cholesterol ratio was significantly increased in patients of both genders (P = 0.002). There were no differences in the apolipoproteins B and Lp(a) between patients and controls. Absolute risk (mean +/- SEM) of a fatal or non-fatal coronary event during the next 5 years was significantly greater in GHD hypopituitary patients than control subjects (4.82 +/- 0.73% vs. 2.94 +/- 0.53, P = 0.04). Cardiovascular risk relative to the local population (RR) was significantly higher in GHD hypopituitary adults (RR = 1.43 CL 1.06-1.80, P = 0.011) but not in the control group (1.08 CL 0.59-1.6). When divided by gender, RR for male patients was not increased (1.14 CL 0.83-1.45, P = 0.096). However, female patients had significantly higher RR (1.7 CL 1.05-2.5, P = 0.048). The RR for male and female controls was not different from the local population. Changes in lipid levels help to explain the results from risk factor modelling which show increased coronary risk in growth hormone deficient hypopituitary patients, particularly females. The abnormal lipid profile is characterized in both genders by an increase in the total to HDL ratio [corrected], an important parameter in the Framingham equation. The lipid abnormalities conferring increased risk is related to growth hormone deficiency either directly (LDL) or indirectly through increased central obesity (HDL) [corrected]. Adverse calculated coronary risk might provide a new objective indication for consideration of GH replacement therapy in adults.

Growth Hormone Therapy in Adults

The importance of growth hormone (GH) deficiency in adults became evident 10 to 15 years ago, when the first clinical studies on GH replacement therapy in adults were published. Since then, a number of studies have been reported showing that GH replacement therapy can improve this condition. Adult GH deficiency (GHD) is now recognized as a specific clinical syndrome and the first reports of long-term use of GH (up to 10 years) are now being published. The aim of this paper was to review the accumulated data on the various clinical aspects of adult GHD.

Body Composition and Quality of Life as Markers of the Efficacy of Growth Hormone Replacement Therapy in Adults

Growth hormone (GH) replacement therapy in GH-deficient adults should be initiated with a low dose, independent of body weight or body surface area. Measurements of serum insulin-like growth factor I (IGF-I) concentrations, as well as clinical examinations aimed at detecting signs of fluid excess, are important as safety markers to avoid overtreatment with GH. At present, there is no optimal marker for the long-term efficacy of GH replacement therapy. The long-term maintenance dose of GH should, therefore, be titrated in each individual based on the clinical response, with the aim of normalizing body hydration, other measurements of body composition, quality of life and well-being, and biochemical indices such as serum IGF-I concentration.

Evidence-based approach to growth hormone replacement therapy in adults, with special emphasis on body composition.

In the past decade, a large number of controlled clinical trials have reported positive effects of growth hormone (GH) replacement therapy in GH-deficient adults. The majority of these studies have been carried out in accordance with the guidelines for Good Clinical Practice. The data thus accumulated offer a solid baseline for practicing evidence-based medicine within this area of endocrinology.

Growth hormone replacement therapy in adults

Log in or Register Subscribe to journalSubscribe Get new issue alertsGet alerts Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. Subscribe to eTOC Secondary Logo Journal Logo All Articles Images Videos Podcasts Blogs Advanced Search Toggle navigation Subscribe Register Login Articles & Issues Current IssueAll Previous IssuesPrevious Issues ; Current Opinion in Endocrinology, Diabetes and ObesityPrevious Issues - The Endocrinologist (1991 - 2010)Published Ahead-of-Print VideosFor Authors Submit a ManuscriptInformation for AuthorsLanguage Editing ServicesAuthor Permissions Journal Info About the JournalEditorial BoardAdvertisingOpen AccessSubscription ServicesReprintsRights and Permissions All Articles Images Videos Podcasts Blogs Advanced Search

The Treatment of Growth Hormone Deficiency in Adults

In analogy with other hormonal replacement therapy GH treatment should be commenced with a low starting dose, independent of body weight or body surface area. Hormonal replacement should mimic the normal physiology to minimize the risk of side effects in the life-long replacement of adults. We should, therefore, consider individual responsiveness and also be aware of the difference between pattern of GH under normal condition and during s.c. administration. The safety and monitoring of GH replacement therapy in adults have been addressed in the Growth Hormone Research Society Consensus Guidelines for Diagnosis and Treatment of Adults with GH Deficiency from the Port Stephens Workshop, April 1997. Besides finding better and more accurate biochemical markers for choosing correct GH replacement dose, future research should address the long-term benefits and safety with GH replacement in adults, with special emphasize on incipient risks in terms of cardiovascular disease and of neoplasia, in particular.

Treatment of Growth Hormone Deficiency in Adults

In analogy with other hormonal replacement therapy GH treatment should be commenced with a low starting dose, independent of body weight or body surface area. Hormonal replacement should mimic the normal physiology to minimize the risk of side effects in the life-long replacement of adults. We should, therefore, consider individual responsiveness and also be aware of the difference between pattern of GH under normal condition and during s.c. administration. The safety and monitoring of GH replacement therapy in adults have been addressed in the Growth Hormone Research Society Consensus Guidelines for Diagnosis and Treatment of Adults with GH Deficiency from the Port Stephens Workshop, April 1997. Besides finding better and more accurate biochemical markers for choosing correct GH replacement dose, future research should address the long-term benefits and safety with GH replacement in adults, with special emphasize on incipient risks in terms of cardiovascular disease and of neoplasia, in particular.

For-Profit Versus Not-for-Profit Dialysis Care for Children With End Stage Renal Disease

Over the last 2 decades, for-profit dialysis units have become the most common providers of renal replacement therapy for adults with end stage renal disease (ESRD) and have had an increasing role in the dialysis of children. We undertook a study to determine whether dialysis facility profit status influences the choice of dialysis therapy in the pediatric population. Cross-sectional study of national data from the Health Care Financing Administration. Free-standing and hospital-based outpatient dialysis facilities in the United States. A total of 1568 children and adolescents (</=19 years of age) eligible for US Medicare ESRD benefits in 1994. The association between dialysis modality choice and the profit status of the facility. Crude associations were estimated by the OR of a patient being treated with peritoneal dialysis (PD) versus hemodialysis at nonprofit versus for-profit facilities. Adjusted associations were estimated using logistic regression analysis. In bivariate analysis, children with ESRD dialyzed at nonprofit facilities were nearly three times as likely as those at for-profit facilities to be on PD (OR: 2.9; 95% CI: 2.3,3.6). In multivariate analysis, after controlling for patient age, sex, race, cause and duration of ESRD, free-standing versus hospital-based facility, and the pediatric expertise of the facility, patients at nonprofit facilities were more than twice as likely as those dialyzed at for-profit facilities to be on PD (OR: 2.3; 95% CI: 1.6, 3.4). After taking into account the clustering of patients within facilities, the association between nonprofit status and the use of PD persisted (OR: 2.2; 95% CI: 1.5,3.2). Children with ESRD treated at nonprofit facilities are more likely to receive PD than are those treated at for-profit facilities even after controlling for other patient and facility characteristics. This finding suggests that clinical decision making for pediatrics may be influenced by the ownership of the health care facility in which the patient is treated.

Effects of two years of growth hormone (GH) replacement therapy on bone metabolism and mineral density in childhood and adulthood onset GH deficient patients.

The aim of the current study was to evaluate bone metabolism and mass before and after 2 years of GH replacement therapy in adults with childhood or adulthood onset GH deficiency. Thirty-six adults with GH deficiency, 18 with childhood onset, 18 with adulthood onset GH deficiency and 28 sex-, age-, height- and weight-matched healthy subjects entered the study. Biochemical indexes of bone turnover such as serum osteocalcin, serum carboxyterminal telopeptide of type-I procollagen, urinary hydroxyproline/creatinine and deoxypyridinoline/creatinine, of soft tissue formation such as aminoterminal propeptide of type-III and bone mineral density were evaluated. Childhood onset GH deficient patients had significantly decreased bone (osteocalcin: 2.5+/-1.3 vs 6.6+/-4.8 mcg/l, p<0.001) and soft tissue formation (aminoterminal propeptide of type III: 273+/-49 vs 454+/-23 U/I, p<0.001) indexes and normal bone resorption indexes (serum carboxyterminal telopeptide of type-I procollagen: 105+/-48 vs 128+/-28 mcg/l p=NS; urinary hydroxyproline/creatinine: 0.19+/-0.16 vs 0.28+/-0.16 mmol/mol, p=NS; urinary deoxypyridinoline/creatinine: 21 +/-10 vs 25+/-8 mcmol/mol, p=NS) compared to healthy subjects. On the contrary, no significant difference in bone turnover indexes between adulthood onset GH deficient patients and healthy subjects was found. Moreover, significantly decreased bone mineral density at any skeletal site and at whole skeleton was found in GH deficient patients compared to healthy subjects (e.g. femoral neck: 0.74+/-0.13 vs 0.97+/-0.11 g/cm2, p<0.001). In addition, a significant reduction of bone mineral density was found in childhood compared to adulthood onset GH deficient patients at any skeletal site, except at femoral neck. After 3-6 months of treatment, both groups of patients had a significant increase in bone turnover and in soft tissue formation. In particular, in childhood onset GH deficient patients after 3 months osteocalcin increased from 2.5+/-1.3 to 7.9+/-2.1 mcg/l, p<0.001 aminoterminal propeptide of type-III from 273+/-49 to 359+/-15 U/I p<0.001; serum carboxyterminal telopeptide of type-I procollagen from 105+/-48 to 201+/-45 mcg/l, p<0.001; urinary hydroxyproline/creatinine from 0.19+/-0.16 to 0.81+/-0.17 mmol/mol, p<0.001; urinary deoxypyridinoline/creatinine from 21 +/-10 to 54+/-20 mcmol/mol, p<0.001; while in adulthood onset GH deficient patients after 6 months osteocalcin increased from 4.2+/-3.6 to 6.5+/-1.9 mcg/l, p<0.05; aminoterminal propeptide of type- III from 440+/-41 to 484+/-37 U/I, p<0.05; serum carboxyterminal telopeptide of type-I procollagen from 125+/-40 to 152+/-22 mcg/l, p<0.05; urinary hydroxyproline/creatinine from 0.24+/-0.12 to 0.54+/-0.06 mmol/mol, p<0.001; urinary deoxypyridinoline/creatinine from 23+/-8 to 42+/-5 mcmol/mol, p<0.001. No significant difference in bone turnover between pre- and post-treatment period was found after 18-24 months of GH therapy. Conversely, bone mineral density was slightly reduced after 3-6 months of GH therapy, while it was significantly increased after 18-24 months. In fact, femoral neck bone mineral density values significantly rose from 0.74+/-0.13 g/cm2 to 0.87+/-0.11 g/cm2 (pre-treatment vs 2 years of GH treatment values). In conclusion, patients with childhood or adulthood onset GH deficiency have osteopenia that can be improved by long-term treatment with GH.

Assessment of corticosteroid replacement therapy in adults with adrenal insufficiency.

Recent work has taught us that our conventional approach to corticosteroid replacement therapy requires review. Specifically, the doses of hydrocortisone we have used are probably too high for the majority, and should ideally be administered in three or more doses through the day. Nevertheless, there is not much hard evidence that excessive glucocorticoid replacement per se will lead to adverse effects such as osteoporosis, even though it may exacerbate any tendency in those who are predisposed to it for other reasons. As such, there is no compelling need for using determinations of either UFC excretion or of the serum cortisol profile in the routine management of patients on replacement therapy. Nevertheless, such measures may be considered in those thought to be at particular risk of osteoporosis, and in whom it is felt that special effort should be made to ensure that they are receiving the minimum dose possible. In such circumstances, a cortisol day curve is likely to be of more value than measurement of UFC.

The provision of renal replacement therapy for adults in England and Wales: recent trends and future directions.

We assessed the level of provision of renal replacement therapy for adults in England and Wales. All autonomous main renal units in England (n = 52) and Wales (n = 5) were surveyed in 1996. Data for England were compared to the 1993 National Renal Review. The acceptance rate in England 1995 was 82 (80-85) per million population (p.m.p.) compared with 67 (65-70) p.m.p. in 1991-2. The rate in 1995 in Wales was 109 (98-122) p.m.p. The prevalence rate in England was 476 p.m.p. at end-1995 compared to 393 p.m.p. in 1993, in Wales it was 487 p.m.p. The number of main renal units in England did not rise between 1993 and 1995; capacity was increased by use of more treatment shifts and temporary haemodialysis stations, and by opening more satellite units. The main growth was in hospital haemodialysis. There was an uneven geographical distribution of services. Patients accepted were older with more comorbidity. The use of better-quality processes of dialysis increased. The steady-state position for RRT will not be reached for over a decade. Health authorities will face continued pressure to fund increases in quantity and quality improvements. A stronger evidence base of the effectiveness of therapies, and a national registry to monitor the equity and cost-effectiveness of services are needed.

Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency

Based on the increasing body of evidence that aduhs with growth hormone deficiency (GHD) have impaired health, which improves with growth hormone (GH) replacement, many countries have already approved the use of GH for replacement therapy in adults with GHD. To ensure that patients are appropriately identified and treated, the Growth Hormone Research Society (GRS) convened a workshop on 14-17 April 1997 in Port Stephens, Australia, to formulate consensus guidelines for the diagnosis and treatment of adults with GHD. The GRS invited scientists with expertise in the field, representatives from industry involved in the manufacture of recombinant human GH and representatives from health authorities from a number of countries to attend the workshop, all of whom contributed to the manifesto as detailed below. These guidelines were first published in J Clin Endocrinol Metab ~ and are reproduced here with kind permission of The Endocrine Society (@ 1998, The Endocrine Society).

Growth Hormone Deficiency in Adults

Although growth hormone has been in clinical use for almost 40 years to promote linear growth in children with growth hormone deficiency, replacement therapy in adults was previously not deemed clinically indicated. However, intensive research over the past decade has led to important advances in our medical knowledge and improvements in the care for patients with growth hormone deficiency. Well-controlled clinical trials have demonstrated beneficial effects of replacement therapy with recombinant human prion-free growth hormone (rhGH; somatropin). The most important restoration parameters include reduction of cardiovascular risk factors and improved lipid profile, normalised body composition, improved exercise capacity and bone mass, as well as enhanced psychological well-being. Some important issues regarding growth hormone deficiency and long term somatropin treatment are unresolved, such as diagnostic criteria and the potential for malignancy and impaired glucose tolerance. Furthermore, the effect on hard end-points such as life expectancy or vertebral fracture rate is unknown, but is expected to emerge from physician-managed, multinational databases. Consequently, at this point somatropin therapy should be given in conjunction with clinical trials.

Guidelines for optimizing growth hormone replacement therapy in adults.

To minimize the rate of side-effects, a retrospective analysis of 28 studies of GH replacement therapy in adults indicates that the maintenance dose should usually not exceed 1.0 IU/m2/day (about 1.5-2.0 IU/day) in GHD patients 40-60 years old, or 1.5 IU/m2/day (about 2.5-3.0 IU/day) in GHD patients 20-40 years old. GHD women may tolerate, and in fact may need, higher replacement doses, though this issue requires further investigation. GH treatment should be started at a low dose, i.e. about 1.0 IU/day, and increased gradually, by about 0.5 IU per month, until the target dose is reached. In the absence of side-effects, the GH dose may be either too low, adequate, or too high. Measurement of GH-dependent serum markers provides the most promising approach to detect both GH depletion and excess, with serum IGF-I concentration the current method of choice. Clinical awareness of symptoms of GH excess remains important, however, particularly in patients with IGF-I levels in the high normal range.

Growth hormone treatment for growth hormone deficient adults.

Growth hormone (GH) deficiency in adults is now recognized as a clinical syndrome with characteristic signs and symptoms. Numerous trials with daily subcutaneous biosynthetic human growth hormone (hGH) have been conducted in this patient group. Generally, improvements in insulin-like growth factor levels, decreases in total fat mass and increases in lean body mass are recorded with no overall effect on total body weight. Variable effects on serum cholesterol, bone mineral density and quality of life have also been reported. The true place of GH replacement therapy in adults has yet to be defined. Several questions relating to the dose, duration of treatment, long-term side-effects, quality of life changes and health economic implications of treatment still need to be assessed.