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Adult growth hormone deficiency (AGHD) is a rare disease with both physiological and psychological effects for untreated patients. AGHD symptoms can improve over time with GH treatment. Here we have analyzed the long-term effectiveness and safety of short-acting GH replacement therapy (GHRT) in treatment naïve and nonnaïve patients with AGHD using real-world data from the NordiNet® International Outcome Study and American Norditropin® Studies: Web Enabled Research Program. Outcomes were compared between 3 age groups, comprised of patients aged 18 to 29 years, 30 to 39 years, and 40 to 59 years. The safety outcome was the incidence of nonserious and serious adverse reactions and serious adverse events by age group. Efficacy outcomes included mean GH exposure by age group alone, by sex and age group, or based on estrogen usage in female patients; IGF-I SD score (SDS) levels by sex and age group; mean glycated hemoglobin by sex and age group; and mean non-high-density lipoprotein cholesterol by sex and age group. The incidence rates of adverse events and reactions did not statistically differ between the 3 groups. Mean IGF-I SDS levels reached a normal range (−2 to 2) in ≥80% of patients from all groups in the effectiveness analysis set by year 2. Together with previous reports of older patients, these results support the real-world safety and efficacy of short-acting GHRT among all ages of patients with AGHD.

Background/Objectives: Patients with isolated adult-onset growth hormone (GH) deficiency may present with hepatic steatosis and metabolic dysfunction. The effect of replacement therapy on metabolic phenotype has not been exhaustively studied yet. Methods: Patients with isolated adult-onset GH deficiency (GHD) were enrolled and prescribed GH-replacement therapy. DEXA scans for assessing body composition, anthropometric and biochemical parameters were evaluated at baseline and after 12 months of therapy. A fatty liver index, hepatic steatosis index and Fibrosis 4-test were calculated at baseline and after 12 months of therapy. Results and Conclusions: In our cohort, GH replacement therapy in adults with isolated adult-onset GHD is associated with weight loss and reduction of BMI (p < 0.001), amelioration in body composition with reduction in fat mass and trunk fat (respectively, p = 0.023 and p = 0.02), amelioration in lipid profile (significant reduction of total and LDL cholesterol and increase in HDL cholesterol) and reduction in fatty liver index (p = 0.021). Further long-term, randomized studies with bigger cohorts and advanced diagnostics are needed to confirm these results of our exploratory study.

Growth hormone (GH) replacement in adulthood results in variable bone responses as a function of the gonadic hormonal milieu. We performed a retrospective analysis of a large cohort of adult males and females with confirmed GH deficiency (GHD) prior to treatment and during 3 years of replacement therapy. Potential confounders and effect modifiers were taken into account. Sixty-four adult patients with GHD (20 females and 44 males; mean age 34 years, range 18–64) were included in the analysis. GH replacement induced a different effect on bone in males compared to females. Bone mineral content increased in males and decreased in females at the lumbar spine, total femur, and femoral neck; bone mineral density showed a similar trend at the lumbar spine and femoral neck. There was no significant gender difference in bone area at any measured bone site. In both sexes we observed a similar trend for serum markers of bone remodeling. Sex predicted bone outcome on multivariate analysis, as did age, onset of GHD (childhood/adulthood), pretreatment bone mass, baseline body mass index (BMI), and BMI change during GH replacement. Serum IGF-I levels during treatment did not show any relationship with bone outcome at any measured site. This study confirms that bone responsiveness to GH replacement in adult GHD varies as a function of sex even after controlling for potential confounders and highlights the importance of other cofactors that may affect the interaction between GH replacement therapy and bone remodeling.

Assessed by conventional echocardiography the influence of growth hormone deficiency (GHD) and effects of replacement therapy on left ventricle (LV) function and mass (LVM) have shown inconsistent results. We aimed to evaluate cardiac function before and during replacement therapy employing the gold standard method cardiac magnetic resonance imaging (CMRI) and measurements of circulating levels of B-type natriuretic peptides. Sixteen patients (8 males and 8 females, mean age 49 years (range 18-75)) with severe GHD and 16 matched control subjects were included. CMRI was performed at baseline and after 1 year of GH replacement therapy. IGF-I, B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) were measured after 0, 1, 2, 3, 6 and 12 months of treatment. IGF-I Z-score increased from (median (IQR)) −2.3 (−3.8 to −1.4) to 0.5 (−0.3 to 1.7). LVM index (LVMI), ejection fraction (range 63-80%), cardiac output index and levels of BNP and NT-proBNP were similar at baseline in patients compared to controls (P-values from 0.09 to 0.37). The patients had significantly smaller LV end-diastolic volume index (P = 0.032) and end-systolic volume index (P = 0.038). No significant change in LV systolic function or LVM occurred during 1 year of GH treatment. BNP levels were unchanged (P = 0.88), whereas NT-proBNP tended to decrease (P = 0.052). Assessed by the highly sensitive and precise CMRI method, untreated GHD was not associated with impaired systolic function or reduced LVMI and 1 year of GH replacement using physiological doses did not influence cardiac mass or function.

It has been suggested that growth hormone (GH) may play a regulatory role in male reproductive function. To express full anabolic effect in immature boys testosterone apparently requires the presence of GH. In GH-deficient adults, GH replacement therapy exerts a variety of anabolic actions, some of which are similar to the effects of gonadal steroids. However, little is known about the potential effects of GH on gonadal steroids and on dynamic tests of pituitary-gonadal function in adults with GH deficiency. We evaluated the pituitary-gonadal axis in a 4-month double-blind, placebo-controlled GH study in 13 young males with childhood-onset GH deficiency of which 6 had isolated GH deficiency. GH treatment significantly increased serum levels of total IGF-I from 98 (68) to 323 (126) microg/l, free IGF-I from 0.48 (0.47) to 2.24 (1.66) microg/l, IGFBP-3 from 1,874 (1,178) to 3,520 (778) microg/l and ALS levels from 9,182 (5,524) to 16,872 (6,278) microg/l (all p < 0.0001). We found no differences in basal testosterone levels in the 13 patients between the GH and placebo treatment periods (21.9 (5.1) vs. 24.5 (8.1) nmol/l, nonsignificant). Furthermore, no effect of GH on the testicular response to hCG after 72 h was seen compared to placebo (36.2 (6.4) vs. 38.8 (10.3) nmol/l). In addition, no differences existed in basal SHBG, DHT, free testosterone, delta4-adion and DHEA-S levels. There were no statistically significant differences in maximal FSH and LH response to a GnRH challenge between the GH and the placebo periods (15.7 (5.3) vs. 18.0 (8.8) U/l and 47.0 (26.4) vs. 40.4 (26.5) U/l, respectively). Furthermore, there was no effect on cortisol responses after ACTH between the GH and the placebo periods. However, significantly higher estradiol levels were seen after GH treatment (110 (50) pmol/l) compared to after placebo (89 (34) pmol/l, p = 0.03). Prostate-specific antigen levels decreased after GH treatment compared to after placebo (0.42 (0.54) vs. 0.47 (0.48) microg/l) and this difference almost reached statistical significance (p = 0.059). Inhibin-B levels were significantly lower in hypogonadal patients substituted with androgens, but GH had no effect on inhibin-B levels. In conclusion, GH replacement therapy in 13 GH-deficient young adult males resulted in significant increases in total and free IGF-I as well as in ALS levels in all patients, but had no significant effect on: (1) the pituitary FSH and LH response to GnRH; (2) basal and hCG-stimulated levels of androgens and SHBG; (3) basal inhibin-B levels; (4) ACTH-stimulated cortisol secretion. By contrast, GH administration had subtle anti-androgenic effects in terms of elevated elevated estradiol levels and decreased prostate-specific antigen levels, although both parameters remained within the normal range. Thus, at the level of blood chemistry the effects of GH administration do not appear to involve major alterations in the pituitary-gonadal axis.

The current increase of life expectancy is associated with the presence of endocrine diseases in the elderly. The management of hypopituitarism in this group of patients is a challenging task. A correct diagnosis, which represents an essential requisite for an appropriate medical treatment, can be difficult because of the physiological changes occurring in pituitary function with aging, which may lead to challenges in the interpretation of laboratory results. Furthermore, the treatment requires several careful considerations: the need to restore the hormonal physiology with replacement therapies must be balanced with the need to avoid the risks of the over-replacement, especially in the presence of concomitant cardiovascular and metabolic disease. Interactions with other drugs able to modify the absorption and/or the metabolism of hormonal replacement therapies should be considered, in particular for the treatment of hypoadrenalism and hypothyroidism. The most important challenges stem from the lack of specific studies focused on the management of hypopituitarism in older people.

Prader-Willi syndrome (PWS) is characterized by a dysregulation of growth hormone (GH)/insulin-like growth factor I axis, as the consequence of a complex hypothalamic involvement. PWS' clinical picture seems to resemble the classic non-PWS GH deficiency (GHD), including short stature, excessive body fat, decreased muscle mass, and impaired quality of life. GH therapy is able to ameliorate the phenotypic appearance of the syndrome, as well as to improve body composition, physical strength, and cognitive level. In this regard, however, some pathophysiologic and clinical questions still remain, representing a challenge to give the most appropriate care to PWS patients. Data about the prevalence of GHD in PWS children are not unequivocal, ranging from 40% to 100%. In this context, to establish whether the presence (or not) of GHD may have a different effect on clinical course during GH therapy may be helpful. In addition, the comparison of GH effects in PWS children diagnosed as small for gestational age with those obtained in subjects born appropriate for gestational age is of potential interest for future trials. Emerging information seems to demonstrate the maintenance of beneficial effects of GH therapy in PWS subjects after adolescent years. Thus, GH retesting after achievement of final height should be taken into consideration for all PWS patients. However, it is noteworthy that GH administration exerts positive effects both in PWS adults with and without GHD. Another critical issue is to clarify whether the genotype-phenotype correlations may be relevant to specific outcome measures related to GH therapy. Moreover, progress of our understanding of the role of GH replacement and concomitant therapies on bone characteristics of PWS is required. Finally, a long-term surveillance of benefits and risks of GH therapy is strongly recommended for PWS population, since most of the current studies are uncontrolled and of short duration.

The aim of this review article is to highlight the consequences of COGHD after the end of linear growth on bone mass and body composition and the opposing beneficial effects of continuing GH replacement in the transition period and young adults. The role of growth hormone in the period of late adolescence and young adulthood is well established, mainly in achieving peak bone mass and a favorable body composition, characterized by muscle mass increase and fat mass reduction. Patients with childhood onset growth hormone deficiency (COGHD), after reaching the adult height, have a reduced bone mineral density and muscle mass with increased fat mass compared to healthy controls. Inadequate body composition is a predictor for cardiovascular risk, while low bone mass in early youth hallmarks the risk of osteoporosis and bone fractures in later life. Cessation of growth hormone replacement (GHr) after completion of growth will lead to delayed peak bone mass and unbalanced body composition with increased abdominal fat deposits. According to numerous clinical studies monitoring the effects of GH treatment on the physical and psychological status of patients with persistent GHD after completion of growth, we suggest continuing this treatment between 16 and 25 years of age. It is advised that GHr in the transition period be administered in intermediate doses between those for the pediatric population and those for the adult population. Usual daily GHr doses are between 0.3 and 0.5 mg but need to be individually optimized, with the aim of maintaining IGF-I in the age-specific normal range.

Purpose To elucidate the long-term efficacy and safety of growth hormone replacement therapy (GHRT) in Japanese patients with adult growth hormone deficiency (AGHD). Methods 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. Results 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. Conclusion We demonstrated the metabolic effectiveness and safety of GHRT in Japanese patients with AGHD over a long follow-up period of 16 years.

There is little scientific evidence regarding the safety of GHRT in LGG, where GH deficiency is common. Purpose: to compare the recurrence rate in children with midline LGG, depending on whether or not they have received GHRT, in order to assess its impact on the risk of tumor recurrence. Methods: This bicentric retrospective study included 124 patients under the age of 18 who were diagnosed with a midline low-grade glial tumor between 1998 and 2016. We also reviewed literature on this subject. The main outcome measure was tumor relapse, demonstrated by brain MRI. Results: There were 17 patients in the GH-supplemented group (14%) and 107 patients in the non-supplemented group (86%). Relapse occurred in 65 patients (45.5%); 7 patients died (4.9%); no deaths occurred in patients receiving GHRT. Two patients developed a second tumor (1.4%), none of which had received GHRT. Relapse concerned 36.4% of patients without GHRT and 52.9% of patients with GHRT. The difference was not statistically significant between the two groups (p = 0.3). Conclusion: GHRT does not lead to a statistically significant increase in risk of relapse for pediatric midline low-grade pediatric glioma in our cohort. Although these results appear reassuring, future natural history or prospective studies should be done to ascertain these findings. Nevertheless, these reassuring data regarding GHRT are in agreement with the data in the current literature.