The optimal management of growth hormone deficiency (GHD) during childhood is to promote linear growth and to achieve adult height within the target height range. Adults with GHD have been reported to have reduced lean body mass, bone mineral density (BMD) and increased cardiovascular risk¹⁾. The goal of growth hormone (GH) replacement in adulthood is to improve body composition, to reduce cardiovascular risk factors, and to improve quality of life²⁾.

Despite growing evidence on benefits of GH therapy in adults with GHD, there are still obstacles for GH therapy due to high cost, necessities for daily injections, and lack of awareness regarding its indication. The transition period is arbitrarily defined as the period of adolescence after linear growth is completed when GH replacement is required due to ongoing GHD³⁾. Continuation of GH therapy without interruption is recommended for adolescents transitioning to adulthood by guidelines of American Association of Clinical Endocrinologists and The Endocrine Society^4,5). However, the national health insurance of Korea covers the cost for GH therapy until females and males reach their final height of 150 and 160 cm, and resume after age 18 years. Therefore, most patients with GHD are obligated to have interruption period of GH replacement. In addition, GH stimulation testing is required before restart of GH therapy even in the presence of multiple pituitary hormone deficiency with structural abnormalities in the hypothalamus or pituitary gland.

This study investigated changes in laboratory findings and body composition after a year of GH replacement in adults with childhood-onset GHD (CO-GHD). In addition, we analyzed correlation between GH interruption period and endocrine or anthropometric parameters.

This study demonstrated that GH replacement in adult GHD had a positive effect on lipid profile; serum LDL-cholesterol level significantly decreased, whereas HDL-cholesterol increased. Although 41 patients had hypothyroidism which could affect on lipid metabolism⁶⁾, most patients with central hypothyroidism were adequately supplemented with L-thyroxine. Similar to previous meta-analysis⁷⁾, GH treatment significantly reduced LDL-cholesterol and LDL/HDL-cholesterol ratio. However, body weight and BMI did not show significant change. Previous studies showed that GH therapy is effective in increasing lean body mass, decreasing fat mass, and decreasing central adiposity²⁾. However, body composition was not checked in the present study. Since central adiposity and increased fat mass may contribute to the increased incidence of cardiovascular mortality, dual x-ray absorptiometry should be used to quantify changes in body composition⁸⁾.

GHD is also associated with reduced BMD and high risk of osteoporosis and fractures. Meta-analysis has shown significant increase in lumbar spine and femur neck BMD by GH replacement therapy in adults with GHD, especially in males⁹⁾. Recent prospective study reported bone remodeling marker including osteocalcin and carboxy-terminal collagen crosslinks increased during GH replacement¹⁰⁾. Although our study did not evaluate BMD, it is required to evaluate fracture risks in adults with GHD.

Re-evaluation of GH status is recommended after at least one month of discontinuation of GH replacement³⁾. However, CO-GHD patients caused by organic brain lesions with three or more pituitary hormone deficiency do not require re-evaluation of GH status in transition period³⁾. In our cohort, 82.2% of patients had three or more pituitary hormone deficiency in addition to GHD, and all of them turned out to be adult GHD at re-evaluation.

There was no significant relationship between period of GH interruption and lipid profile or BMI in the present study. However, a deterioration of lipid profile, increased LDL/HDL-cholesterol ratio has been reported in GHD adolescents after discontinuation GH therapy. Longer duration of GH interruption aggravated lipid profile¹¹⁾. Meanwhile, serum IGF-1 and IGFBP-3 levels were correlated with GH interruption period. Although normal IGF-1 levels do not exclude a diagnosis of GHD patients, IGF-1 and IGFBP-3 may represent helpful markers of GH secretary status.

Another challenge in adult GHD is to establish an optimal dose of GH replacement. Dose of GH therapy should be individualized to achieve normal serum IGF-1 levels⁵⁾. The Endocrine Society recommended that a starting doses for patients aged 30-60 years and less than 30 years are 200-300 µg/day and 400-500 µg/day, respectively⁵⁾. Daily dosing should be increased by 100-200 µg every 1 to 2 months⁵⁾. Dose titration can be based on good clinical response, side effects, and subnormal range of IGF-1 levels¹⁾. The age at start of GH replacement for adult GHD was around 20 years, our patients received 440 µg/day and they did not have any side effects of GH therapy.

In conclusion, this study showed improvement of lipid profile during GH replacement. Meanwhile, body weight and BMI were not affected by GH replacement. This study included a small number of patients and followed up patients with GHD for relatively short periods. Thus, long-term follow-up is needed to evaluate the efficacy of clinical and endocrine parameters.