Childhood-onset Growth Hormone Deficiency Research Articles

Adult mortality or morbidity is not increased in childhood-onset growth hormone deficient patients who received pediatric GH treatment: an analysis of the Hypopituitary Control and Complications Study (HypoCCS)

BackgroundThe French Safety and Appropriateness of Growth Hormone treatments in Europe (SAGhE) cohort has raised concern of increased mortality risk during follow-up into adulthood in certain patients who had received growth hormone (GH) treatment during childhood. The Hypopituitary Control and Complications Study monitored mortality and morbidity of adult GH-deficient patients including those with childhood-onset GH deficiency (COGHD) who received GH treatment as children.PurposeEvaluate risk of mortality, cancer, myocardial infarction (MI) and stroke in a prospective observational study.MethodsCOGHD patients [n = 1,204, including 389 diagnosed with idiopathic COGHD (ICOGHD)] had received pediatric GH treatment. Standardized mortality ratios (SMRs), and cancer standardized incidence ratios (SIRs) in patients without a prior cancer were estimated relative to reference populations. Crude incidence rates were estimated for MI and stroke.ResultsNo increased mortality or cancer incidence was observed, as compared with reference populations, during a follow-up of 3.7 ± 3.3 years (mean ± SD). The overall SMR for COGHD was 1.14 [95 % confidence interval (CI) 0.55–2.10], and for ICOGHD, 0.33 (0.01–1.84). The overall cancer SIR for COGHD was 0.27 (0.01–1.50), and for ICOGHD, 0.00 (0.00–2.45). No incident case of MI was reported. The crude stroke incidence rate [181.3 per 100,000 person-years] in COGHD patients was consistent with the rates reported in reference populations. No incident case of stroke was identified in ICOGHD patients who are presumed to have no increased stroke risk factors.ConclusionsThe results indicate no increased risk of mortality or incidence of cancer, stroke, or MI in adult GH-deficient patients who had previously received pediatric GH treatment.

Update in Mortality in GH-Treated Patients

During GH therapy for 2.3-9.6 years, male adult-onset GH-deficient patients with a diagnosis of a nonfunctioning adenoma have no increased all-cause mortality. However, women with adult-onset GH deficiency (GHD) are still at slightly higher risk. This general improvement in mortality is due to a more contemporary regimen of cardiovascular drugs, a refinement of surgical procedures, besides the introduction of GH therapy improved hormone replacement regimens with lowered glucocorticoid replacement, updated approaches of sex steroids for women, and less use of cranial radiotherapy. The underlying disease is the most important predictor for mortality: eg, a craniopharyngioma, malignant causes of hypopituitarism, previous Cushing's disease, and the presence of diabetes insipidus/aggressive tumors. The main cause of increased mortality was cerebrovascular diseases and infectious/respiratory diseases in ACTH-deficient patients. Furthermore, there was a significant impact of young age at disease onset and of death from secondary brain tumors, with a higher risk after cranial radiotherapy. Reports on four cohorts of GH-treated childhood-onset GHD patients have been published. Two of them included only patients with idiopathic isolated GHD, neurosecretory dysfunction, idiopathic short stature, or being born short for gestational age. Increased mortality in circulatory disorders, ill-defined diseases, and bone cancer were recorded in one study, but not in the other smaller study, where suicide and accidents caused the majority of deaths. A third childhood-onset GHD cohort included patients with a background of malignant tumors, craniopharyngioma, pituitary adenomas, pituitary aplasia/hypoplasia, and trauma. An increase of all-cause mortality was recorded in both males and females. The fourth cohort included isolated GHD and idiopathic short stature (60%), but also diagnosis of chronic renal failure and Turner's syndrome. In these latter studies, an underlying serious condition was the most important factor for death, with central nervous system tumors (recurrent or new tumor) being the leading cause of mortality.

Monocentric study of 112 consecutive patients with childhood onset GH deficiency around and after transition

Our aim was to analyze a large cohort of childhood onset GH deficiency (CO-GHD) adults from a unique adult center, in order to analyze their clinical management and to study the metabolic and bone status in relation to GHD and to the other pituitary deficits, and to evaluate these parameters during the long-term follow-up. Observational retrospective cohort study on 112 consecutive CO-GHD adults transferred to our unit from 1st January 1994 to 1st March 2012. Evaluation of GHD in pediatrics and after transition was conducted following consensus guidelines. Data recorded from pediatric and adult files were GH doses, pituitary magnetic resonance imaging and function, and metabolic and bone status. Most patients presented with severe CO-GHD (64%) associated with other pituitary deficits (66%). CO-GHD was acquired in 56%, congenital in 33%, and idiopathic in 11% cases. Most patients (83%) stopped GH before transfer, at 16.3 years (median), despite persistence of GHD. Median age at transfer was 19.4 years. After transfer, GHD persisted in 101 patients and four of the 11 resolutive GHD were non idiopathic. IGF1 level was <-2 SDS in 70% of treated patients at transfer and in 34% of them after 3 years of treatment. Follow-up showed improvement in lipid profile and bone mineral density in severely persistent GHD patients under GH therapy. In multivariate analysis, the associated pituitary deficits seemed stronger determinant factors of metabolic and bone status than GHD. This study raises concern about discontinuation of GH replacement therapy in pediatrics in severely persistent GHD patients and about the often insufficient dose of GH in the treatment of adult patients.

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: UK stance on adult GH replacement: the economist vs the endocrinologist

In the UK, through the use of a forced economic model, endocrinologists are in the curious position of offering GH replacement to some patients with severe GH deficiency (GHD) but withholding it from other patients with even more severe GHD. This approach is counter-intuitive to endocrine practice in treating endocrine deficiency states. For all other endocrine deficiencies, one would opt for treating those with the most severe biochemical evidence of deficiency first. If this endocrine approach was applied to adult GH replacement in an era of rationing, one would start with the GHD patients with a pathologically low IGF1 level. Given that the prevalence of subnormal IGF1 levels in a GHD population is age-dependent, this would result in GH replacement being offered to more young adult onset (AO) GHD and childhood onset GHD adults, and less often to middle-aged and elderly AO GHD adults. This in itself has the added advantage that the skeletal benefits appear more real in the former cohort of patients.

Metabolic Safety of Growth Hormone in Type 1 Diabetes and Idiopathic Growth Hormone Deficiency

To evaluate metabolic consequences of growth hormone (GH) treatment in children with type 1 diabetes. This study is an analysis of metabolic changes in 37 patients with childhood-onset GH deficiency and type 1 diabetes, documented in the Diabetes Patienten Verlaufsdocumentationsystem database. Main outcome measures were changes in hemoglobin A1c and daily insulin requirements during GH therapy in children with GH deficiency and type 1 diabetes compared with a large cohort of adolescents with type 1 diabetes. Thirty-seven patients with type 1 diabetes and a diagnosis of idiopathic GH deficiency after onset of diabetes were compared with 48856 patients with type 1 diabetes. After adjustment for age, sex, duration of diabetes, and migration background, a significant difference in mean daily insulin requirement was seen between the 2 groups (1.0 IU/kg/day in subjects with GH deficiency and type 1 diabetes vs 0.85 IU/kg/day in controls; P < .01) and height-SDS (-2.0 in subjects with GH deficiency and diabetes vs +0.03 in controls; P < .0001). There was no significant between-group difference in hemoglobin A1 concentration, however (8.1% ± 1.4% in patients with GH deficiency and type 1 diabetes vs 8.2% ± 1.7% in those with type 1 diabetes only; P > .05). An increased daily insulin requirement should be considered in patients with type 1 diabetes treated with GH. With adequate adaptation of insulin dosage, metabolic control is not impaired during GH treatment.

Metabolic syndrome in adolescents and young adults with childhood-onset GH deficiency

Metabolic syndrome in adolescents and young adults with childhood-onset GH deficiency

United States multicenter study of factors predicting the persistence of GH deficiency during the transition period between childhood and adulthood

BackgroundMany patients with childhood-onset growth hormone (GH) deficiency do not fulfill diagnostic criteria for GH deficiency (GHD) after attainment of adult height and may not require long-term GH treatment. Patients with history of idiopathic GHD (IGHD) pose the greatest management dilemma, as data regarding factors predictive of persistent GHD in this group are lacking.ObjectivesThe objective of this study was to assess potential predictors of persistent GHD in a US patient cohort during transition from childhood to adulthood, particularly in patients with history of IGHD.MethodsWe studied 73 US patients with history of childhood-onset GHD screened at 21 US pediatric endocrine centers for a randomized clinical trial of GH replacement after attainment of adult height. The cohort comprised 42 boys/men and 31 girls/women aged14–22 years, who had received ≥1 year of GH treatment and had completed linear growth. The main outcome measures were sensitivity, specificity, positive and negative predictive values (PPV, NPV) of clinical and hormonal factors for persistent GHD (defined a priori in this study as peak GH < 5 μg/L).ResultsFor the cohort as a whole, the best predictors of persistent GHD (100% PPV) were history of organic hypothalamic-pituitary disorder or ≥2 additional pituitary hormone deficiencies (PHD). Best predictors of persistent GHD in patients with childhood history of IGHD were standard deviation scores (SDS) for serum insulin-like growth factor binding protein-3 (IGFBP-3) below -2.0, and for insulin-like growth factor-I (IGF-I) below -5.3 (measured ≥6 weeks after completion of GH treatment; PPV 100% for both), and age <4 years at original diagnosis (PPV 89%). IGF-I above -1.6 SDS had 100% NPV.ConclusionsUS patients with an organic cause of childhood-onset GHD or ≥2 additional PHDs may not require GH stimulation testing to reconfirm GHD after completion of childhood treatment. In contrast, patients with idiopathic childhood-onset GHD almost invariably require retesting, as GHD persists in only a minority (those who were very young at initial diagnosis and those who have subnormal IGFBP-3 or extremely low IGF-I after completion of childhood treatment). Subnormal posttreatment IGF-I (<-2.0 SDS) lacked predictive power for persistent GHD, whereas IGF-I > -1.6 SDS was 100% predictive of GH sufficiency.

Could zinc supplementation improve bone status in growth hormone (GH) deficient children?

Reduced bone mineral density (BMD) and increased fracture rate have been reported in subjects with either childhood or adult onset growth hormone (GH) deficiency (GHD), more severe in childhood onset GHD [1, 2]. A longer gap in GH replacement in adults with childhood onset GHD is associated with a lower bone mineralization and GH replacement has been suggested having a critical role in transition to adulthood to optimize bone accrual [3]. Furthermore, also a delay in starting GH replacement in GHD adults may be associated with a persistent increase in vertebral fracture risk [4]. However, many criticisms have been raised on these assumptions. Limitations of current bone imaging techniques have caused many artefacts about BMD and bone structure. Using appropriate size corrections, BMD is normal in children and adults with isolated GHD in several studies and the anabolic changes in muscle mass and strength may contribute to the observed bone changes [for critical reviews see 5, 6]. Briefly, many historical studies used T-scores in GHD children, comparing children’s BMD with adult reference data. On the other hand, when age—and sex—Z scores have been introduced for the pediatric population, height remained a confounding factor and being tall or short for age leads to a false negative or a false positive result for BMD Z-score, respectively. Since 2008, official positions of the International Society for Clinical Densitometry strongly recommend size correction for DXA measurements in the pediatric age [7]; however, no consensus exists how to correct measurements. To date, the most real effect of GHD on bone seems to be a reduction in bone volume ratio and trabecular thickness in both animal and human studies [5, 6]. Moreover, we must not forget that GH replacement causes biphasic effects on the bone remodeling with early stimulation of bone resorption followed by a sustained increase in bone formation [8]: some controversial results of published literature could be due to the time from the start of the therapy. On the other hand, it is unclear whether changes in BMD may really predict the fracture risk in patients with GHD, as well as other forms of secondary osteoporosis, being other markers of bone quality still searched. The first point in favor of the paper by Ekbote et al. [9] in this issue of Endocrine is that the Authors performed size correction for DXA bone mineral content (BMC) and bone area (BA) measurements using height. They showed that in Indian prepubertal children with isolated GHD, height adjusted BMC and BA significantly increased of 48 and 40 %, respectively, after 1 year of GH treatment. These changes were associated with an increase in height adjusted lean body mass and a decrease in height adjusted body fat. Many previous studies in childhood onset GHD, in particular in Italian and Dutch cohorts, reported an increase in BMC in the range of 2–10 %, significantly lower than that observed in the present study [5, 6]. However, it has to be emphasized that the majority of other studies did not perform any size correction. Furthermore, the population investigated in this study [9] presented a very low BMC at baseline and this aspect could have influenced the results. However, we can first speculate that when BMC is clearly reduced in GHD patients, a treatment with rhGH works in improving bone health. Bone metabolism is complex. Many factors tightly regulate BMC and bone accrual, mainly, among others, F. Prodam SCDU of Pediatrics, Department of Health Sciences, Universita del Piemonte Orientale ‘‘A. Avogadro’’, Novara, Italy

Effect of growth hormone on bone status in growth hormone-deficient adults

Growth hormone deficiency (GHD) is associated with reduced bone mineral content and increased risk of osteoporotic fractures. Reduced peak bone mass might explain the low bone mineral density (BMD) among patients with childhood onset GHD (CO-GHD) whilst the cause of osteopenia in adult-onset GHD (AO-GHD) is not fully understood. Prospective multicentric study to asses bone status in GHD adults after two years of recombinant growth hormone replacement treatment. In 94 GHD adults (49 men; Ø 34.5 yrs) we have measured BMD and bone markers (CTX, osteocalcin) during two years of rhGH treatment (at baseline, after 3 and 6 months, and after 1 and 2 years). Patients were adequately substituted for GHD and other pituitary deficiencies. We have observed an increase in BMD-lumbar spine: n=42, 0.8155 →0.9418 g/cm2, p<0.0001; femoral neck n=41; 0.8468 →0.9031; p= 0.0004; BMD-whole body 1.0179 →1.0774; p=0.0003. We have compared gender difference: BMD-L-spine by 15.8 % in men (n=21) and by 5.6 % in women (n=19) (p= 0.008); BMD-femoral neck increased by 11.03 % in men and by about 3.0 % in women (p=0.032). In women, the initial decrease in BMD was recorded after 3 months. CO-GHD adults yielded a higher increase in BMD -L-spine (16.6 %, p=0.022). A correlation exists between IGF-I levels and BMD in lumbar spine (1st year: R=0.348, p=0.026; 2nd year: R= 0.33, p=0.0081) and between IGF-I and osteocalcin (1st year: R=0.383; p=0.0038). Two-year therapy with recombinant human growth hormone improved bone status. IGF-I appears to be a good indicator of rhGH effect on bone (Tab. 3, Fig. 9, Ref. 36). Text in PDF www.elis.sk.

The Challenge of Growth Hormone Deficiency Diagnosis and Treatment during the Transition from Puberty into Adulthood

In children with childhood-onset growth hormone deficiency, replacement GH therapy is effective in normalizing height during childhood and achieving adult height within the genetic target range. GH has further beneficial effects on body composition and metabolism through adult life. The transition phase, defined as the period from mid to late teens until 6–7 years after the achievement of final height, represents a crucial time for reassessing children’s GH secretion and deciding whether GH therapy should be continued throughout life. Evidence-based guidelines for diagnosis and treatment of growth hormone deficient children during transition are lacking. The aim of this review is to critically review the up-to-date evidence on the best management of transition patients in order to ensure the correct definitive diagnosis and establish the appropriate therapeutic regimen.

Efficacy and safety of growth hormone replacement therapy in Japanese adults with growth hormone deficiency: a post-marketing observational study

This large-scale observational study examined the long-term effectiveness and safety of growth hormone (GH) replacement therapy for adult GH deficiency (GHD) in Japanese clinical practice using the Hypopituitary Control and Complications Study database. The study included 402 GHD patients for safety analyses and a subset of 209 patients (149 adult-onset and 60 childhood-onset GHD patients) who had not previously received GH replacement therapy for the efficacy analyses. Data on clinical, metabolic, quality of life (QoL) characteristics, and all adverse events (AEs) were collected at baseline (start of GH treatment), 6 months, 1 year and 2 years. Over the observation period, there were improvements from baseline in insulin-like growth factor-I standard deviation scores (P<0.001), although the changes in metabolic parameters were minimal. QoL (Short Form-36) Z-scores significantly increased from baseline in both onset-type groups for several subscale domains (P<0.05). A total of 145 (36.1%) patients experienced ≥1 AE. Common AEs were hyperlipidaemia (2.7%) and hyperinsulinaemia (2.2%). Some patients experienced recurrent hypothalamic/pituitary tumour (events per 1000 patient-years: 2.78), new benign (0.93), malignant tumour (10.28) or other new tumour (0.93), new diabetes mellitus (7.45), and new stroke (3.71). Seven patients died during the observation period. Our safety findings are inconclusive about the associations between GH replacement and AEs, although the incidence of diabetes mellitus and cardiovascular events are similar to those reported in the Japanese general population. In conclusion, the key beneficial effects of GH replacement therapy for GHD are observed in routine clinical practice in Japan.

The cardiovascular system in growth hormone excess and growth hormone deficiency.

The clinical conditions associated with GH excess and GH deficiency (GHD) are known to be associated with an increased risk for the cardiovascular morbidity and mortality, suggesting that either an excess or a deficiency in GH and/or IGF-I is deleterious for cardiovascular system. In patients with acromegaly, chronic GH and IGF-I excess commonly causes a specific cardiomyopathy characterized by a concentric cardiac hypertrophy associated with diastolic dysfunction and, in later stages, with systolic dysfunction ending in heart failure if GH/IGF-I excess is not controlled. Abnormalities of cardiac rhythm and anomalies of cardiac valves can also occur. Moreover, the increased prevalence of cardiovascular risk factors, such as hypertension, diabetes mellitus, and insulin resistance, as well as dyslipidemia, confer an increased risk for vascular atherosclerosis. Successful control of the disease is accompanied by a decrease of the cardiac mass and improvement of cardiac function and an improvement in cardiovascular risk factors. In patients with hypopituitarism, GHD has been considered the under- lying factor of the increased mortality when appropriate standard replacement of the pituitary hormones deficiencies is given. Either childhood-onset or adulthood-onset GHD are characterized by a cluster of abnormalities associated with an increased cardiovascular risk, including altered body composition, unfavorable lipid profile, insulin resistance, endothelial dysfunction and vascular atherosclerosis, a decrease in cardiac mass together with an impairment of systolic function mainly after exercise. Treatment with recombinant GH in patients with GHD is followed by an improvement of the cardiovascular risk factors and an increase in cardiac mass together with an improvement in cardiac performance. In conclusion, acromegaly and GHD are associated with an increased risk for cardiovascular morbidity and mortality, but the control of GH/IGF-I secretion reverses cardiovascular abnormalities and restores the normal life expectancy.

Changes in BMI and Management of Patients with Childhood Onset Growth Hormone Deficiency in the Transition Phase

We aimed at evaluating BMI changes during GH therapy pause, to assess the transfer pattern between children and adult medical services in our clinic and to confirm the previous growth hormone deficiency (GHD) diagnosis. Retrospective cohort study. We identified 75 transition patients (age at first visit <25 years) with pituitary deficiency (ICD-10:E.23) and GHD referred to our clinic between 2000-2009. Out of 75 patients with GHD (45 males, 30 females), 20 subjects suffered from an idiopathic GHD (iGHD) and 55 from an organic GHD (oGHD). During the GH therapy pause (26.4±34.8 months), we observed a significant BMI increase (23.6±4.4 to 27.1±7.2, p=0.02). Most males with iGHD discontinued endocrinologic control and GH substitution completely (5 patients out of 20) or after the first contact (3 patients out of 20). Most females with GHD continued medical control after transferral (22 patients). We retested 34/75 patients with GHD (45.3%). The preferred test was the growth hormone-releasing hormone-arginine (GHRH-arginine) (20/34 patients, 58.9%), followed by the insulin hypoglycemia test (IHT) alone (9 patients). 4 patients received both, the GHRH-arginine and the IHT. Seven retested patients with iGHD (63.6%) and all oGHD retested patients were still deficient. Our results provide information on negative effects of the discontinuation of GH treatment during the transition phase and should help to improve the compliance with treatment in this group of patients. Paediatric and adult endocrinologists participating together in a transition programme should emphasize on the positive effect of GH substitution in adulthood. Efforts should be made to particularly improve the transferral of male adolescents with iGHD, since they seem to escape medical care.

Psychosocial health and levels of employment in 851 hypopituitary Swedish patients on long-term GH therapy

The psychosocial health and working capacity in hypopituitary patients receiving long-term growth hormone (GH) therapy are unknown. Psychosocial health and levels of employment were compared between GH deficient (GHD) patients on long-term replacement and the general population. In a Swedish nationwide study, 851 GHD patients [101 childhood onset (CO) and 750 adult onset (AO)] and 2622 population controls answered a questionnaire regarding current living, employment and educational level, alcohol consumption and smoking habits. The median time on GH therapy for both men and women with CO GHD was 9 years and for AO GHD 6 years, respectively. As compared to the controls, the GHD patients were less often working full time, more often on sick leave/disability pension, and to a larger extent alcohol abstainers and never smokers (all; P<0.05). Predominantly CO GHD women and men, but to some extent also AO GHD women and men, lived less frequently with a partner and more often with their parents. Particularly AO GHD craniopharyngioma women used more antidepressants, while AO GHD men with a craniopharyngioma used more analgesics. A working capacity to the level of the general population was not achieved among hypopituitary patients, although receiving long-term GH therapy. Patients were less likely to use alcohol and tobacco. The CO GHD population lived a less independent life.

P03-31 Factors affecting IGF-I response to Growth Hormone (GH) replacement therapy during transition in patients with childhood-onset GH deficiency

P03-31 Factors affecting IGF-I response to Growth Hormone (GH) replacement therapy during transition in patients with childhood-onset GH deficiency

P03-45 GH retesting and lipid profile in childhood-onset GHD when reaching final adult height

P03-45 GH retesting and lipid profile in childhood-onset GHD when reaching final adult height

P01-47 Effects of 10 years of GH replacement therapy in adults with GH deficiency of childhood or adulthood onset

P01-47 Effects of 10 years of GH replacement therapy in adults with GH deficiency of childhood or adulthood onset

Mortality and socioeconomic status in adults with childhood onset GH deficiency (GHD) is highly dependent on the primary cause of GHD

Childhood onset GH deficiency (CO-GHD) is associated with increased morbidity and mortality; however, the patients' socioeconomic profile as adults is not fully known. Register study using Danish nationwide registries. Two hundred and sixty GHD males and 156 GHD females and 25,358 male and 15,110 female controls were included. Information was obtained concerning cohabitation, parenthood, education, income, retirement, convictions, and death. Income was analyzed using conditional logistic regression, and other outcomes were analyzed using Cox regression. Subgroups of GHD patients with malignant tumors, craniopharyngioma, idiopathic GHD, and others were investigated separately. Both male and female GHD patients had a significantly worse outcome on all studied socioeconomic parameters. Fewer GHD patients lived in partnerships and entered them later (male hazard ratio (HR): 0.31; female HR: 0.33), had fewer parenthoods (male HR: 0.26; female HR: 0.26), lower educational level (male HR: 0.58; female HR: 0.48), lower income, higher risk of retirement (male HR: 13.4; female HR: 24.2), and fewer convictions (male HR: 0.67; female HR: 0.49). Mortality was increased (male HR: 10.7; female HR: 21.4). Adjusted for marital and educational status, male HR of death was 5.2 and female HR 10.5. Patients with idiopathic GHD had a socioeconomic profile similar to controls. The primary causes of CO-GHD and concomitant diseases severely impair socioeconomic conditions and impact mortality; only the subgroup of patients with idiopathic GHD conditions was similar to the background population.

A longer interval without GH replacement and female gender are associated with lower bone mineral density in adults with childhood-onset GH deficiency: a KIMS database analysis

Childhood-onset GH deficiency (COGHD) is associated with low bone mineral density (BMD). Adults with persistent COGHD may be at risk for insufficient bone accrual or bone loss during adulthood. The purpose of this study was to identify BMD predictors and to characterize the effects of GH replacement on BMD in COGHD adults with persistent GHD. Retrospective analysis of the KIMS database. Variables predicting standardized BMD (sBMD) were identified. The effect of GH replacement (3 years) on BMD was examined. Three hundred and fourteen COGHD adults (148 women, 166 men; 62 non-naïve, 178 semi-naïve, and 74 true naïve, depending on length and timing of previous GH replacement), who had BMD measured in lumbar spine (LS) and femoral neck (FN) at study entry. In semi-naïve subjects, a longer gap in GH replacement between childhood and adulthood was predictive of lower sBMD in the FN (r=-0.18, P=0.038). TSH deficiency predicted lower sBMD in the LS (r=-0.16, P=0.052). In true naïve patients, a longer gap between onset of pituitary disease and study entry (r=-0.35, P=0.012), and female gender (r=-0.27, P=0.043) independently predicted lower sBMD in the FN. There were no differences in BMD increases between non-naïve, semi-naïve, and true naïve subjects on GH replacement. In semi-naïve subjects a longer interval off GH replacement was associated with lower sBMD in the FN. Among true naïve patients, a longer gap between the onset of pituitary disease and GH replacement, and female gender predicted lower sBMD in the FN.

Growth hormone effects on cortical bone dimensions in young adults with childhood-onset growth hormone deficiency

SummaryGrowth hormone (GH) treatment in young adults with childhood-onset GH deficiency has beneficial effects on bone mass. The present study shows that cortical bone dimensions also benefit from GH treatment, with endosteal expansion and increased cortical thickness leading to improved bone strength.IntroductionIn young adults with childhood-onset growth hormone deficiency (CO GHD), GH treatment after final height is reached has been shown to have beneficial effects on spine and hip bone mineral density. The objective of the study was to evaluate the influence of GH on cortical bone dimensions.MethodsPatients (n = 160; mean age, 21.2 years; 63% males) with CO GHD were randomised 2:1 to GH or no treatment for 24 months. Cortical bone dimensions were evaluated by digital x-ray radiogrammetry of the metacarpal bones every 6 months.ResultsAfter 24 months, cortical thickness was increased compared with the controls (6.43%, CI 3.34 to 9.61%; p = 0.0001) and metacarpal index (MCI) (6.14%, CI 3.95 to 8.38%; p < 0.0001), while the endosteal diameter decreased (−4.64%, CI −7.15 to −2.05; p < 0.001). Total bone width did not change significantly (0.68%, CI −1.17 to 2.57%; not significant (NS)). A gender effect was seen on bone width (p < 0.0001), endosteal diameter (p < 0.01) and cortical thickness (p < 0.01), but not with MCI (NS).ConclusionsCortical bone reacts promptly to reinstitution of GH beyond the attainment of final height by increasing the cortical thickness through endosteal bone growth. This leads to a higher peak bone mass and may reduce the risk of cortical bone fragility later in life.