Safety Of Growth Hormone Replacement Therapy Research Articles

Long-term metabolic effectiveness and safety of growth hormone replacement therapy in patients with adult growth hormone deficiency: a single-institution study in Japan.

To elucidate the long-term efficacy and safety of growth hormone replacement therapy (GHRT) in Japanese patients with adult growth hormone deficiency (AGHD). We conducted a retrospective study. A total of 110 patients with AGHD receiving GHRT were enrolled. Clinical and laboratory data were collected annually from the beginning of the study. Statistical analysis was performed using a linear mixed-effects model. Of all patients, 46.4% were males, 70.9% had adult-onset GHD, and follow-up was up to 196 months, with a median of 68 months. The insulin-like growth factor-1 standard deviation score increased after the start of GHRT and remained constant for more than 11 years. Seventeen patients were followed up for more than 11 years. The body mass index increased. Waist circumference decreased in the short term but increased in the long term. The diastolic blood pressure decreased 1-5 years after the start of GHRT, and the systolic blood pressure increased 11 years after GHRT. Moreover, a long-term decrease in low-density lipoprotein cholesterol, an increase in high-density lipoprotein cholesterol, and a decrease in aspartate aminotransferase and alanine aminotransferase levels were observed. The glycosylated hemoglobin level increased after 3 years. The bone mineral density in the lumbar spine and total hip increased significantly 3 years after the start of GHRT. Finally, the number of adverse events was eight. We demonstrated the metabolic effectiveness and safety of GHRT in Japanese patients with AGHD over a long follow-up period of 16 years.

PMON60 Growth Hormone (GH) Replacement Therapy (GHRT) in Patients with Adult GH Deficiency (AGHD) Aged ≥60 Years: Data from NordiNet® IOS and the ANSWER Program

Abstract There are limited data on the effectiveness and safety of GHRT in older patients with AGHD. We compared real-world GHRT outcomes in older (aged ≥60 years) versus middle-aged (35–<60 years) adults. NordiNet® IOS (NCT00960128) and ANSWER (NCT01009905) were non-interventional studies investigating long-term effectiveness and safety of GHRT with Norditropin® (somatropin, Novo Nordisk). Safety was assessed in the Full Analysis Set (FAS) from both studies (non-GH-naïve patients included). The Effectiveness Analysis Set (EAS) was from NordiNet® IOS only (GH-naïve patients; ANSWER-EAS included patients previously treated for ≤6 months). Serious adverse reactions (SARs) and non-serious ARs (NSARs) with a suspected causal relationship to GHRT, and serious adverse events (SAEs) not considered related to GHRT are presented as incidence rates per 1000 patient-years and as incidence rate ratios (IRRs) for older versus middle-aged adults. Of the 759 patients in the EAS, 545 were middle-aged and 214 older adults, mean (standard deviation) age 48.5 (7.0) and 67.2 (4.9) years, with 45.9% and 39.3% females, respectively. At baseline, GH dose was 0.24 (0.16) and 0.20 (0.10) mg/day, insulin-like growth factor-I standard deviation score (IGF-I SDS) was -0.94 (1.40) and -0.82 (1.36) and BMI was 29.29 (6.09) and 28.95 (4.58) kg/m2, respectively. Mean follow-up was 5.4 (4.3) and 5.3 (3.9) years, respectively. Of the 2348 patients in the FAS, 1696 were middle-aged and 652 older adults, aged 48.4 (7.1) and 67.1 (5.1) years, of which 52.4% and 43.3% were female, respectively. Baseline GH dose was 0.32 (0.24) and 0.26 (0.18) mg/day, IGF-I SDS was -0.58 (1.53) and -0.27 (1.54) and BMI was 30.50 (7.26) and 29.42 (5.39) kg/m2, respectively. Mean follow-up was 5.2 (4.5) and 4.7 (3.9) years, respectively. Mean GH exposure was greater in women than men, and in middle-aged than older women (FAS); it increased slightly over time in all groups. Baseline IGF-I SDS was slightly higher in older versus middle-aged women, but not men (EAS). Mean IGF-I SDS increased from below 0 to values ≤1.24 with GHRT. Mean changes in BMI (EAS) and HbA1c (EAS and FAS) were small and similar between age groups in both sexes. No statistically significant differences were observed between older and middle-aged adults regarding incidence rates for NSARs (5.66 vs 5.38; IRR [mean; 95%CI] 1.051 [0.604;1.831]) and SARs (1.00 vs 2.52; IRR 0.396 [0.119;1.324]). As expected, SAE incidence rate (considered unrelated to GHRT) was higher in the older group (16.64 vs 9.04, IRR 1.840 [1.291;2.622]). Similarly, the IRRs of patients ≥75 (n=59) years versus the middle-aged group were only significant for SAEs (23.09 vs 9.04; IRR 2.553 [1.113;5.855]). These data suggest similar clinical outcomes with GHRT in patients with AGHD aged ≥60 compared with 35–<60 years without additional risk of adverse drug reactions in older patients. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Growth Hormone Excess and Cancer

AGING IS ACCOMPANIED by a decline in growth hormone (GH) and insulin-like growth factor–1 (IGF-1) levels.1–3 At present, definitive answers regarding the long-term safety of GH replacement therapy in the normal elderly population are not yet clear. One concern is whether or not serum GH and IGF-1 levels increased above normal age-matched levels are associated with enhanced tumorigenesis and/ or cancer aggressiveness and mortality. This important question can be addressed by examining in vitro and in vivo effects of GH and IGF-1 on tumor initiation and progression, especially using transgenic models. Another approach is to evaluate cancer risk in patients with acromegaly, an experiment of nature in which patients harboring GH secreting pituitary tumors exhibit high GH, IGF-1 and IGF1 binding protein–3 (IGFBP-3) serum levels.4

Normal Values of Insulin-Like Growth Factor I and Their Clinical Utility in Adults

The concentration of circulating insulin-like growth factor I (IGF-I) is a potential marker for growth hormone (GH) deficiency in adults. Indeed, researchers have shown that IGF-I levels are of greater diagnostic value than other possible markers, such as IGF-binding protein 3 (IGFBP-3) and the acid-labile subunit (ALS). Accurate age-matched normative data are essential to give patient data diagnostic meaning. Such data are assay specific and must exclude those individuals with certain confounding medical conditions. Post-diagnosis, monitoring of IGF-I and IGFBP-3 levels can be used to assess the efficacy and safety of GH replacement therapy. Furthermore, IGF-I levels, and possibly ALS levels, can be used to aid the diagnosis and monitoring of acromegaly. For example, acromegaly can be excluded in patients with normal IGF-I levels if liver failure and malnutrition/malabsorption are ruled out.

Dosing, Monitoring, and Safety of Growth Hormone-Replacement Therapy in Adults With Growth Hormone Deficiency

Dosing, Monitoring, and Safety of Growth Hormone-Replacement Therapy in Adults With Growth Hormone Deficiency