Childhood-onset Growth Hormone Deficiency Research Articles

Characterization of patients stopping GH therapy for childhood-onset growth hormone deficiency in belgium - luxemburg

Characterization of patients stopping GH therapy for childhood-onset growth hormone deficiency in belgium - luxemburg

Brain white matter alterations in young adult male patients with childhood-onset growth hormone deficiency: a diffusion tensor imaging study.

This study aimed to detect white matter changes and different effects of thyroid hormone on the white matter integrity in young adult male patients with childhood-onset growth hormone deficiency (CO-GHD), compared with healthy people. Magnetic resonance imaging (structural imaging and diffusion tensor imaging) was performed in 17 young adult male patients with CO-GHD and 17 healthy male controls. The white matter volume, mean diffusivity (MD) values and fractional anisotropy (FA) values were quantified and compared between two groups (CO-GHD group vs. control group). We assessed the interaction effects between thyroid hormone and groups (CO-GHD group vs. control group) on white matter integrity. Patients with CO-GHD exhibited similar white matter volumes compared with controls. However, compared with the controls, patients with CO-GHD showed a significant reduction in FA values in six clusters and a substantial increase in MD values in four clusters, mainly involving the corticospinal tracts, corpus callosum and so on. Moreover, after correcting for insulin-like growth factor-1 levels, the significant interaction effects between groups (CO-GHD group vs. control group) and serum free thyroxine levels on MD values were noted in three clusters, mainly involving in superior longitudinal fasciculus and sagittal stratum. In conclusion, young males with CO-GHD showed white matter changes in multiple brain regions and different effects of thyroid hormone on the white matter integrity.

An audit of the management of childhood-onset growth hormone deficiency (CO-GHD) at completion of linear growth

An audit of the management of childhood-onset growth hormone deficiency (CO-GHD) at completion of linear growth

Identifying patient-related predictors of permanent growth hormone deficiency.

Isolated childhood growth hormone deficiency (GHD) can persist into adulthood, and re-testing at the transition period is needed to determine whether continued growth hormone therapy is indicated. Here, our objective was to identify predictors of permanent GHD. Retrospective single-centre study of patients with childhood-onset GHD who were re-tested after adult height attainment. Auxological, clinical, laboratory, and MRI data throughout follow-up were collected. We included 101 patients. At GH treatment initiation, age was 8.1 ± 0.4 years, height -2.25 ± 0.8, and BMI -0.27 ± 0.1 SDS. The 29 (28.7%) patients with persistent GHD had lower height SDS (-2.57 ± 0.1 vs. -2.11 ± 0.1, p<0.001) and mean GH peaks (8.4 ± 1.0 vs.13.2 ± 0.5 mIU/L, p<0.001) at GHD diagnosis; at adult height, they had lower IGF1 (232 ± 19.9 vs. 331 ± 9.1 ng/mL, p<0.001) and higher BMI SDS (-0.15 ± 0.27 vs. -0.73 ± 0.13, p<0.005). By multivariate analysis, the best predictive model included height and BMI SDS, both GH peaks, and MRI findings at diagnosis. Patients with height at diagnosis <-3 SDS had a 7.7 (95% IC 1.4-43.1, p=0.02) fold higher risk of persistent GHD after adjustment on BMI SDS. An abnormal pituitary region by MRI was the strongest single predictor (7.2 times, 95% CI 2.7-19.8) and after multivariate analysis adjustment for GH peaks and height SDS at diagnosis, the risk increased to 10.6 (1.8 - 61.3) times. Height <-3 SDS at GHD diagnosis and pituitary MRI abnormalities should lead to a high index of suspicion for persistent GHD.

THU172 Accuracy Of The Glucagon Testing In The Diagnosis Of Growth Hormone Deficiency During Transition

Abstract Disclosure: N. Di Iorgi: None. D. Guglielmi: None. N. Flavia: None. A. Allegri: None. D. Fava: None. E. Casalini: None. G. Patti: None. M. Maghnie: None. Objectives: To evaluate the accuracy of the Glucagon test (GST) compared with the Insulin Tolerance test (ITT) as the gold standard in the diagnosis of Growth Hormone deficiency (GHD) in young adults with childhood-onset GHD (COGHD). Methods: Eighty-six subjects with COGHD (33F, 55M) were evaluated by ITT and GST stimulation tests and IGF-1 SDS at adult height achievement (median age of 17.5; IQR 13.9-18.4 years). Subjects were recruited from a single Center and based on the AACE 2019 Guidelines [1] classified as 1. idiopathic isolated GHD (I-GHD n=40 with normal brain MRI); 2. organic moderate GHD (omGHD with less than 3 pituitary deficiencies-PD and IGF-1&amp;lt;0 SDS, total n=40; n=12 midline defects, n=2 ALL, n=26 CNS tumors); 3. congenital/genetic defects/organic severe GHD (osGHD ≥3 PD and IGF-1 &amp;lt;-2 SDS, total n=6; n=1 midline defect, n=5 CNS tumors). ROC analyses were performed in order to analyze the Sensitivity (Se) and Specificity (Sp) of the GH peak after GST and of IGF-1 SDS compared to ITT. A peak GH value &amp;lt;6μg/L after ITT was suggestive of permanent GHD [2]. Results: Median GH peak to ITT (0.2; IQR 0.01-0.7 μg/L) and GST (0.1; IQR 0.01-1.4μg/L) were lower in osGHD compared to I-GHD subjects (15.0; IQR 8.6-21.9 to ITT and 12.6; IQR 10.5-18.8 μg/L to GST, P’s &amp;lt;0.0001); similarly, GH peak to ITT (2.1; IQR 1.1-6.8 μg/L) and GL (2.7; IQR 1.2-5.8) were lower in omGHD compared to I-GHD subjects (P’s &amp;lt;0.0001). Mean IGF-1 were also lower in osGHD (-3.2 SDS; IQR -7.4- -2.9, P&amp;lt;0.0001) and in omGHD (-2.0 SDS; IQR -2.8 - -0.7; P&amp;lt;0.0001) compared to I-GHD subjects (0,1; IQR -0.6-1.1SDS). A GH peak value to GST of 7.59 mcg/L (Se 92.3%, Sp of 87.2%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 89.5% of the entire cohort while an IGF-1 cut-off of -1.45 SDS (Se 73%; Sp 93.5%; AUC=0.84; 95% CI, 0.75 - 0.94) correctly classified 83,1%. A GH peak value to GST of 5.81 mcg/L (Se 96.6%, Sp of 81.8%; AUC=0.95; 95% CI, 0.88-1.02) correctly classified 92.5% of omGHD patients while an IGF-1 cut-off of -1.64 SDS (Se 72.3%, Sp of 90.9%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 77.5% omGHD patients. Median BMI SDS was higher in patients with osGHD (1.8; IQR 1,6- 2.2, P&amp;lt;0.001) and omGHD (0.6; IQR 0.1- 1.8, P&amp;lt;0.001) compared to I-GHD (0.2; IQR -0.7- 1.1). GH peak to GST correlated with BMI SDS only in the total cohort (r -0.313, P=0.0031). Conclusions: Our results suggest that a peak value &amp;lt;6 μg/L after GST is accurate in detecting permanent GHD during transition in a cohort of patients with organic GHD with less than 3 pituitary defects and IGF-1 values &amp;lt;0 SDS; the GH response to GST could be affected by BMI SDS, but further studies are needed. [1] Yuen KCJ et al. Endocr Pract 2019; 25 (11):1191-1232. [2] Maghnie M et al, EJE 2005; 152:589-596. Presentation: Thursday, June 15, 2023

Management of childhood-onset growth hormone deficiency in patients transitioning from pediatric to adult care: A review of the literature and consensus report from a panel of experts in Saudi Arabia

Despite increased recognition of the importance of optimizing care for patients with childhood-onset growth hormone deficiency (CO-GHD) during the transition period from pediatric to adult services, its implementation in clinical practice in Saudi Arabia remains challenging. By an initiative from the Saudi Society of Endocrinology and Metabolism, a panel comprising 11 experts, including both pediatric and adult endocrinologists with practical experience in the clinical management of patients with CO-GHD, was convened to discuss issues relating to transition care in this patient population. The primary objective of this consensus document was to develop the first clinician-led consensus statement that establishes best practices when transitioning adolescents with persistent CO-GHD to adult care in Saudi Arabia. A modified Delphi method was applied to develop consensus statements. A literature review was performed, and 20 statements were subsequently formulated. After two rounds of Delphi, consensus was achieved for 18 of the 20 statements.

A case of Childhood onset GH deficiency being transitioned to adult endocrinology service- Three phases of GH replacement and dose/ device indications

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity.

The results of the studies on the pattern of insulin sensitivity (IS) are contradictory in patients with GH deficiency (GHD); however, the interference of the GHD onset stage, childhood or adulthood in the IS has not been assessed by euglycemic hyperinsulinemic clamp (EHC), a gold-standard method for the assessment of insulin sensitivity. In a prospective cross-sectional study, we assessed IS and body composition in 17 adults with hypopituitarism without GH replacement, ten with childhood-onset (COGHD) and seven with adulthood-onset (AOGHD) and compared them to paired control groups. COGHD presented higher IS (p = 0.0395) and a similar percentage of fat mass (PFM) to AOGHD. COGHD showed higher IS than the control group (0.0235), despite a higher PFM (0.0022). No differences were found between AODGH and the control group. In AOGHD and the control group, IS was negatively correlated with PFM (rs: −0.8214, p = 0.0234 and rs: −0.3639, p < 0.0344), while this correlation was not observed with COGHD (rs: −0.1152, p = 0.7514). Despite the higher PFM, patients with COGHD were more sensitive to insulin than paired healthy individuals, while patients with AOGHD showed similar IS compared to controls. The lack of GH early in life could modify the metabolic characteristics of tissues related to the glucose metabolism, inducing beneficial effects on IS that persist into adulthood. Thus, the glycometabolic findings in patients with COGHD seems to be not applicable to AOGHD.

Metabolic Impacts of Discontinuation and Resumption of Recombinant Human Growth Hormone Treatment during the Transition Period in Patients with Childhood-Onset Growth Hormone Deficiency.

Background Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period.Methods This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption.Results Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates.Conclusion GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.

Long-term Safety of Growth Hormone in Adults With Growth Hormone Deficiency: Overview of 15 809 GH-Treated Patients.

ContextData on long-term safety of growth hormone (GH) replacement in adults with GH deficiency (GHD) are needed.ObjectiveWe aimed to evaluate the safety of GH in the full KIMS (Pfizer International Metabolic Database) cohort.MethodsThe worldwide, observational KIMS study included adults and adolescents with confirmed GHD. Patients were treated with GH (Genotropin [somatropin]; Pfizer, NY) and followed through routine clinical practice. Adverse events (AEs) and clinical characteristics (eg, lipid profile, glucose) were collected.ResultsA cohort of 15 809 GH-treated patients were analyzed (mean follow-up of 5.3 years). AEs were reported in 51.2% of patients (treatment-related in 18.8%). Crude AE rate was higher in patients who were older, had GHD due to pituitary/hypothalamic tumors, or adult-onset GHD. AE rate analysis adjusted for age, gender, etiology, and follow-up time showed no correlation with GH dose. A total of 606 deaths (3.8%) were reported (146 by neoplasms, 71 by cardiac/vascular disorders, 48 by cerebrovascular disorders). Overall, de novo cancer incidence was comparable to that in the general population (standard incidence ratio 0.92; 95% CI, 0.83-1.01). De novo cancer risk was significantly lower in patients with idiopathic/congenital GHD (0.64; 0.43-0.91), but similar in those with pituitary/hypothalamic tumors or other etiologies versus the general population. Neither adult-onset nor childhood-onset GHD was associated with increased de novo cancer risks. Neutral effects were observed in lipids/fasting blood glucose levels.ConclusionThese final KIMS cohort data support the safety of long-term GH replacement in adults with GHD as prescribed in routine clinical practice.

Cтан серцево-судинної системи та ліпідний спектр при соматотропній недостатності у молодих дорослих із маніфестацією в дитячому віці (огляд літератури та власні спостереження)

Проведено аналіз наукової літератури стосовно особливостей клінічного перебігу дефіциту гормона росту (ДГР), що маніфестував у дитячому віці, у молодих дорослих. Акцент зроблено на стані ліпідного обміну, а також серцево-судинної системи хворих із ДГР, які не отримували лікування рекомбінантним гормоном росту (рГР). Наведені власні дані, отримані при обстеженні молодих дорослих із ДГР до лікування рГР та на його тлі. Встановлено наявність суттєвих порушень з боку показників ліпідного, вуглеводного обмінів і кардіальних параметрів у хворих, які довготривало не отримували патогенетичного лікування, а також позитивні зміни на тлі призначення препаратів рГР.

Mapping the journey of transition: a single-center study of 170 childhood-onset GH deficiency patients.

ObjectiveTo analyze metabolic parameters, body composition (BC), and bone mineral density (BMD) in childhood-onset GH deficiency (COGHD) patients during the transition period (TP).DesignSingle- center, retrospective study was performed on 170 consecutive COGHD patients (age 19.2 ± 2.0 years, range 16–25) transferred after growth completion from two pediatric clinics to the adult endocrine unit. Two separate analyses were performed: (i) cross-sectional analysis of hormonal status, metabolic parameters, BC, and BMD at first evaluation after transfer from pediatrics to the adult department; (ii) longitudinal analysis of BC and BMD dynamics after 3 years of GH replacement therapy (rhGH) in TP.ResultsCOGHD was of a congenital cause (CONG) in 50.6% subjects, tumor-related (TUMC) in 23.5%, and idiopathic (IDOP) in 25.9%. TUMC patients had increased insulin and lipids levels (P < 0.01) and lower Z score at L-spine (P < 0.05) compared to CONG and IDOP groups. Patients treated with rhGH in childhood demonstrated lower fat mass and increased BMD compared to the rhGH-untreated group (P < 0.01). Three years of rhGH after growth completion resulted in a significant increase in lean body mass (12.1%) and BMD at L-spine (6.9%), parallel with a decrease in FM (5.2%).ConclusionThe effect of rhGH in childhood is invaluable for metabolic status, BC, and BMD in transition to adulthood. Tumor-related COGHD subjects are at higher risk for metabolic abnormalities, alteration of body composition, and decreased BMD, compared to those with COGHD of other causes. Continuation of rhGH in transition is important for improving BC and BMD in patients with persistent COGHD.

Design of the ForesiGHt Trial: A Multicenter, Randomized, Placebo- and Active-Controlled Trial to Compare Once-Weekly TransCon hGH (lonapegsomatropin) to Placebo and Daily Somatropin in Adults With Growth Hormone Deficiency (GHD)

BackgroundAdult GHD results from insufficient growth hormone (GH) secretion from the anterior pituitary gland and may represent either a continuation of childhood-onset GHD or GHD acquired during adulthood. Clinically, adult GHD is associated with central adiposity, decreased lean muscle mass, increased fat mass, decreased bone mineral density, and reduced quality of life. Current standard of care consists of GH replacement via daily injections.Lonapegsomatropin is a long-acting prodrug of somatropin (hGH), designed to deliver unmodified hGH with a weekly exposure profile. Lonapegsomatropin consists of somatropin that is transiently bound to a carrier via a proprietary TransCon Linker. The carrier extends the duration of somatropin in the circulation through a shielding effect that minimizes renal excretion and receptor-mediated clearance of the prodrug. At physiologic conditions, lonapegsomatropin releases fully active, unmodified somatropin via autocleavage of the linker in a controlled manner.The safety and efficacy of lonapegsomatropin have previously been evaluated in two phase 3 trials and one long-term extension trial in pediatric GHD. Changes in body composition are an objective and sensitive endpoint that reflects biologic activity of GH and clinical efficacy of GH replacement. Methods: The primary objective of the foresiGHt trial is to evaluate the efficacy of once-weekly lonapegsomatropin compared to placebo at 38 weeks in adults with GHD. The trial will be conducted at approximately 120 sites in North America, Europe, Asia, and Oceania. Approximately 240 subjects will be randomized 1:1:1 to once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin (Norditropin®). Subjects will be treatment-naïve or without GH therapy for at least 12 months. Subjects with well-controlled non-insulin dependent diabetes mellitus (HbA1c ≤ 7.5%) will be eligible. Following screening, the 38-week treatment period will consist of a 12-week gradual dose titration period and 26 weeks of fixed dose maintenance. Fixed dosing will be used to ensure maximal comparability across the treatment arms in the trial. Three dosing groups per arm will be established to allow for differences in age and oral estrogen intake in women.The primary endpoint is change from baseline in trunk percent fat at week 38, as measured by dual energy X-ray absorptiometry (DXA). Secondary efficacy endpoints are change from baseline in trunk fat mass and change in total body lean mass at week 38. Exploratory efficacy endpoints include total body fat mass, trunk lean mass, visceral adipose tissue, and patient-reported outcomes. Conclusion: The ongoing global phase 3 foresiGHt trial is designed to assess the efficacy, safety, and tolerability of lonapegsomatropin by weekly administration, compared to weekly placebo and daily hGH replacement therapy in adults with GHD.

Growth Hormone Deficiency and Growth Hormone Replacement in Childhood Cancer Survivors.

Growth hormone deficiency (GHD) is common in childhood cancer survivors (CCS). Major risk factors for GHD include radiation therapy, both cranial and total body irradiation, and tumor location. Some newer anti-cancer therapies may impact growth and the GH-IGF-1 axis as well. While untreated childhood-onset GHD adversely impacts adult height in CCS, longstanding GHD can cause or exacerbate multiple metabolic and skeletal health problems. This chapter discusses considerations in the diagnosis and treatment of GHD in CCS and discusses long-term outcomes in survivors of childhood cancer who have GHD.

Adult growth hormone deficiency: Optimizing transition of care from pediatric to adult services

ObjectiveMost patients with childhood-onset growth hormone deficiency (CO-GHD) receive treatment with exogenous growth hormone (GH) to facilitate the attainment of their full potential adult height. Recent evidence suggests that continuing GH administration during the transition period between the end of linear growth and full adult maturity is necessary for proper body composition and bone and muscle health, and may also have beneficial effects on metabolic parameters, bone mineral density, and quality of life. The timing of this transition period coincides with the transfer of care from a pediatric to an adult endocrinologist, creating the potential for a care gap as a consequence of losing the patient to follow-up. DesignAn advisory board comprising both pediatric and adult endocrinologists was assembled to address current clinical unmet needs and to collaborate on a structured transitional plan for optimal management of patients with CO-GHD. Insights/conclusionThe advisors suggest collaborative, multidisciplinary approaches to ensure continuity of care; ongoing testing and monitoring of GHD status into adulthood; and a clearly structured protocol that includes practical guidance for clinicians to establish best practices for transitioning older adolescents with persistent CO-GHD to adult care.

Adherence to growth hormone therapy guidelines in a real-world French cohort of adult patients with growth hormone deficiency

ObjectiveUsing real-world data from patients with growth hormone deficiency (GHD), we evaluated whether clinical practice in France adheres to international guidelines regarding somatropin dose adjustment, and assessed the long-term effectiveness and safety of somatropin. MethodsData were obtained from a national prospective systematic longitudinal routine follow-up programme of naive/non-naive adults with childhood-onset (CO) or adult-onset (AO) GHD treated with Norditropin® (Novo Nordisk A/S). ResultsBetween 2003 and 2006, 331 treatment-naive and non-naive adults with severe GHD were enrolled and followed for a median duration of approximately 5 years; 328 patients were available for analysis. At baseline, mean patient age was 39.2 years; median standard deviation score (SDS) for insulin-like growth factor−1 (IGF-1) level was −2.2 in naive patients, subsequently fluctuating between −0.1 and +0.3 SDS during the study period. Mean GH doses ranged between 0.25 and 0.51mg/day (naive patients) and 0.39 and 0.46mg/day (non-naive patients). Despite generally receiving a higher somatropin dose, women (naive/non-naive) tended to have lower IGF-1 levels than men. Median somatropin dose was consistently higher in patients with CO-GHD than patients with AO-GHD. Extreme IGF-1 values (<–2 or >+2 SDS) were not systematically accompanied by somatropin dose adjustments. Waist circumference improved in approximately one third of patients, at a mean 3.5 years. Somatropin was well tolerated; there were no cardiovascular or cerebrovascular events during the 5-year analysis period. ConclusionCurrent clinical practice of physicians in France follows international guidelines regarding somatropin dose adjustment in adults with GHD. However, dose adjustments are not always sufficient, notably in women, and treatment effects may have been delayed due to low somatropin dose (Clinical trial registration NCT01580605).

ESE audit on management of Adult Growth Hormone Deficiency in clinical practice.

1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD. On-line survey in endocrine centres throughout Europe. Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018. Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved. Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.

"Non-Classical" Indication for Provocative Testing of Growth Hormone: A Retrospective Cohort Study in Adult Patients Under Replacement Therapy.

Adult growth hormone deficiency (GHD) is considered a rare condition. Current guidelines state that GH provocative test is indicated in patients affected by organic hypothalamic/ pituitary disease or with a history of head injury, irradiation, hemorrhage or hypothalamic disease with multiple pituitary deficiencies. Nevertheless, the clinical picture related to GHD may be subtle. We have retrospectively evaluated the indication to GHRH+arginine test in our monocentric cohort of patients treated with hrGH in order to assess whether other conditions had been considered as a rationale for provocative testing. Ninety-six patients (51 females and 45 males), aged 19-67 years were included. The GHRH+arginine test had been performed in 29 patients with organic hypothalamic/pituitary disease and in 4 patients for Childhood onset-GHD (CoGHD). In other patients, the diagnosis was suspected for "non classical" reasons in the clinical picture suspected for GHD. Classical indications included previously known primary empty sella (n=15), pituitary surgery (n=14), pituitary cyst (n=1), non-secreting pituitary tumors (n=3) but more than half of the patients (57.3%) had been studied for "non classical" indications: metabolic syndrome (n=25), asthenia (n=13), heart failure (n=4), osteoporosis (n=6), unexplained hypoglycaemia (n=1) and infertility (n=6). The latter represented a significant percentage in the male subgroup under 45 ys. IGF-1 levels were lower than 50th percentile in 63% of patients. Finally, among non-classical reasons, organic pituitary disease was discovered in 22 patients. Idiopathic GHD may be unrecognized due to its subtle manifestations and that an extended use of dynamic GH tests may reveal such conditions. A potential field of investigation could be to identify subsets of patients with clinical conditions caused or worsened by underlying unrecognized GHD.

Current concepts of the diagnosis of adult growth hormone deficiency

In adults, growth hormone (GH) deficiency is associated with increased visceral adiposity, decreased lean body mass, bone mineral density and exercise capacity, dyslipidemia, insulin resistance, increased cardiometabolic and fracture risk, and impaired quality of life. The aim of the present article is to review the diagnosis of GH deficiency in adults. To avoid overdiagnosis of GH deficiency, it is critical to evaluate only patients at risk for pituitary dysfunction, including those who have had sellar masses, pituitary surgery, radiation therapy, traumatic brain injury, subarachnoid hemorrhage or childhood onset GH deficiency. Evaluation for GH deficiency should be undertaken after testing and replacement of other pituitary hormone deficits. Since GH secretion is pulsatile, measuring serum GH levels randomly is not helpful in establishing the diagnosis of GH deficiency. Serum insulin-like growth factor I (IGF-I) levels lack substantial diurnal variation but also lack sufficient sensitivity and specificity in the diagnosis of GH deficiency in adults. However, adults with multiple (≥3) additional pituitary hormone deficiencies, risk factors for hypopituitarism and low serum IGF-I levels are very likely to be GH deficient. In most cases, the diagnosis of GH deficiency requires stimulation testing. These tests involve the administration of a pharmacologic agent that normally stimulates GH release from pituitary somatotrophs, including insulin, glucagon, growth hormone releasing hormone-arginine or macimorelin, followed by sampling of serum specimens at regular intervals for GH assay. Patients with a peak GH level that is below a predetermined cutpoint are classified as GH deficient. A systematic approach to the diagnosis of GH deficiency is essential in order to accurately identify adults who may benefit from GH replacement.

Body composition and bone mineral density in 107 patients with childhood onset growth hormone deficiency (CO-GHD) at the time of transition from pediatric to adulthood endocrine care

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)