Childhood-onset Growth Hormone Deficiency Research Articles

"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)

Effect of long term rhgh treatment on bone mineral density in patients with childhood onset growth hormone deficiency

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

MON-LB56 Metabolic Profile in 107 Patients With Childhood Onset Growth Hormone Deficiency (CO-GHD) at the Time of Transition From Pediatric to Adulthood Endocrine Care

Vulnerability of the transitional period from childhood to adulthood is particularly challenging in treatment of adolescents with CO-GHD. Altered metabolic profile is well described in GHD, but relevant large monocentric studies in transition patients and young adults with CO-GHD are lacking.Patients and Methods: In a monocentric, observational, retrospective cross-sectional study conducted from 2005-2019, 107 CO-GHD patients were analyzed (17-26 years old, 80 males) at the time of transfer from pediatric to adult endocrine care. Median age at transfer was 19.6 ± 2.2 years. Subjects with congenital and idiopathic GHD (CON) were compared with age-, sex- and BMI-matched patients with hypothalamic/pituitary tumor history (TUM). Glycaemia and insulin during OGTT (peak and AUC), HbA1c, serum total cholesterol, HDL, LDL and triglycerides were analyzed in all patients.Results: Congenital and idiopathic causes of CO-GHD were more frequent than hypothalamic/pituitary tumoral causes (74.8% vs. 25.2%). All patients received GH replacement during childhood for average duration of 5.4 ± 1.4yrs. GH replacement was discontinued prior to transfer for 2.7 ± 0.9yrs. Glycaemia peak, glycaemia AUC and insulin peak in OGTT were not significantly different in TUM vs. CON (p>0.05). However, insulin AUC in OGTT was significantly higher in TUM compared to CON (134.38 ± 23.2 vs 114.62 ± 12.4; p<0.05). HbA1c was similar between the two groups (5.2 ± 0.4% TUM vs 5.0 ± 0.3% CON; p>0.05). Total cholesterol (5.2 ±1.1 vs 4.5 ± 0.8 mmol/l; p>0.05), LDL (3.1 ± 0.9 vs 2.7 ± 0.8 mmol/l; p>0.05) and triglycerides (2.1 ± 1.1 vs 1.1 ± 0,7 mmol/l; p<0.05) were increased in TUM compared to CON, while HDL was decreased in TUM group (1.0±0.1 vs 1.4±0,3 mmol/l; p<0.05).Conclusion: Patients with CO-GHD caused by hypothalamic/pituitary tumors are burdened with a worse metabolic profile at the time of childhood to adulthood transition compared to matched transition patients with congenital CO-GHD.

SAT-LB11 Adult Growth Hormone Deficiency Transition Care From Pediatric to Adult Services: Insights From a US Advisory Board

Background: Transition care of patients with childhood-onset GH deficiency (CO-GHD) who were treated with GH during childhood remains an ongoing challenge with substantial variation in coordination of care, clinical assessment, and management among pediatric and adult services. Despite the availability of clinical guidelines providing a framework for transition care of adolescents with CO-GHD, many patients discontinue therapy during the transition phase. Methods: A panel of pediatric and adult US endocrinologists with extensive experience in treating transition patients convened in October 2019 as part of an advisory board to address current clinical unmet needs and to share learnings based on a structured transitional plan to strive for optimal management of these patients. Results: It is acknowledged that pediatric endocrinologists play a crucial role in initiating the transition process, which involves close communication and direct collaboration between pediatric and adult services to reduce delays in identifying patients and resuming GH therapy in adulthood; adult endocrinologists need to increase their awareness of the importance of potential benefits and extent of long-term safety of GH therapy in adult patients. There is also a need for consensus guidelines or a white paper that focuses on transition care and endorsed by pediatric and adult organizations. Because not all patients with CO-GHD will have persistent GHD as adults, there is a need to improve the identification and timely retesting of those who will require continuity of GH therapy into adulthood. An increase in accessibility for retesting and guidance on appropriate GH dosing once persistent GHD is confirmed are other important factors. Certain subpopulations of pediatric patients (e.g., cancer survivors; patients with congenital hypopituitarism, optic nerve hypoplasia, treated sellar masses, and traumatic brain injury) should be prioritized in determinations of when and how retesting should be performed. The viewpoints of both pediatric and adult endocrinologists were presented at this meeting, and comprehensive considerations and suggestions were discussed. Conclusion: Transition care of patients with CO-GHD requires a collaborative multidisciplinary approach to ensure continuity of care between pediatric and adult services and to improve bone health and reduce long-term cardiometabolic risks. The major challenge is to effectively ensure that transition patients are retested and offered adult GH therapy without delay. Current guidelines should be more focused on transition patients, addressing key areas of uncertainty as evidenced by variable clinical practices. A clearly structured transition protocol is vital, and these insights provide useful, practical guidance to clinicians to establish best practices when transitioning adolescents with persistent CO-GHD to adult services.

Growth hormone deficiency with late-onset hypothalamic hypoadrenocorticism associated with respiratory and renal dysfunction: a case report

BackgroundThe prevalence of childhood-onset growth hormone (GH) deficiency (GHD) is estimated to be approximately 1 in 5000 or more, with the cause unknown in most cases (idiopathic isolated GHD). However, additional disorders of secretion of other pituitary hormones reportedly develop over time, with a frequency of 2–94% (median, 16%). Furthermore, median times to development of other anterior pituitary hormone deficiencies have been reported to be 6.4–9.4 years. On the other hand, adult patients affected by childhood-onset GHD reportedly develop impaired ventilation function due to reduced lung volumes and respiratory pressures, probably due to reductions in respiratory muscle strength. In addition, GH is known to play a role in stimulating the glomerular filtration rate (GFR), and the estimated GFR (eGFR) is decreased in patients with GHD.Case presentationThis case involved a 65-year-old woman. Her short stature had been identified at around 3 years of age, but no effective treatments had been provided. The patient was mostly amenorrheic, and hair loss became apparent in her late 30s. She developed hyperuricemia, dyslipidemia, and hypertension at 45 years of age. In addition, the patient was diagnosed with hypothyroidism at 50 years of age. At 58 years of age, endocrinological examination showed impaired secretion of thyroid-stimulating hormone, luteinizing hormone/follicle-stimulating hormone, and growth hormone, and magnetic resonance imaging showed an empty sella turcica. However, secretion ability of adrenocorticotropic hormone was retained. At 63 years of age, respiratory function tests confirmed a markedly restricted ventilation disorder (vital capacity, 0.54 L; percentage predicted vital capacity, 26.9%). Renal function had also decreased (eGFR, 25.0 mL/min/1.73 m2). Furthermore, she was diagnosed with hypothalamic secondary hypoadrenocorticism. The patient developed CO2 narcosis at 65 years of age, and noninvasive positive pressure ventilation was started.ConclusionsThe rare case of a 65-year-old woman with childhood-onset GHD with panhypopituitarism, including late-onset secondary hypoadrenocorticism in her 60s, associated with severely impaired respiratory function and renal dysfunction, was reported. In GHD patients with risk factors for progression from isolated GHD to combined pituitary hormone deficiency, such as empty sella turcica, lifelong endocrinological monitoring may be important.

Effects of 24 Weeks of Growth Hormone Treatment on Bone Microstructure and Volumetric Bone Density in Patients with Childhood-Onset Adult GH Deficiency.

Objective Adults with childhood-onset growth hormone deficiency (CO AGHD) have prominently impaired volumetric bone density (vBMD) and bone microarchitecture. Effects of recombinant human growth hormone (rhGH) on bone microarchitecture in CO AGHD were insufficiently evaluated. The objective of this study is to assess the effects of rhGH on bone microarchitecture and vBMD in CO AGHD patients. Design In this single-center prospective study, nine CO AGHD patients received rhGH treatment for 24 weeks. High-resolution peripheral quantitative computerized tomography (HR-pQCT) of distal tibia and radius was performed at baseline and at the end of treatment. Main outcomes were vBMD and morphometric parameters from HR-pQCT. Results After 24-week treatment, IGF-1 SDS gradually increased from −3.31 ± 1.56 to −1.92 ± 1.65 (p=0.113). Serum phosphate (1.17 ± 0.17 vs. 1.35 ± 0.18 mmol/L, p=0.030), alkaline phosphatase (83.6 ± 38.6 vs. 120.5 ± 63.7, p=0.045), and β-CTX (0.67 ± 0.32 vs. 1.09 ± 0.58, p=0.022) were significantly elevated. In distal tibia, total vBMD (200.2 ± 41.7 vs 210.3 ± 40.9 mg HA/cm3, p=0.017), cortical area (89.9 ± 17.7 vs 95.5 ± 19.9 mm2, p=0.032), and cortical thickness (0.891 ± 0.197 vs 0.944 ± 0.239 mm, p=0.028) were significantly improved. Trabecular area decreased from 795.3 ± 280.9 to 789.6 ± 211.4 mm2 (p=0.029). Trabecular bone volume fraction increased from 0.193 ± 0.038 to 0.198 ± 0.036 (p=0.027). In radius, cortical perimeter (74.1 ± 10.0 vs 75.0 ± 10.9 mm, p=0.034), trabecular thickness (0.208 ± 0.013 vs 0.212 ± 0.013 mm, p=0.008), trabecular separation (0.743 ± 0.175 vs 0.796 ± 0.199 mm, p=0.019), and inhomogeneity of network (Tb.1/N.SD) (0.292 ± 0.087 vs 0.317 ± 0.096 mm, p=0.026) were significantly improved, while trabecular number (1.363 ± 0.294 vs 1.291 ± 0.325 1/mm, p=0.025) decreased significantly. Conclusions Our results provide evidence for improvement of vBMD and bone microarchitecture in AGHD patients at a relatively early stage of rhGH treatment.

American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for Management of Growth Hormone Deficiency in Adults and Patients Transitioning from Pediatric to Adult Care

American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for Management of Growth Hormone Deficiency in Adults and Patients Transitioning from Pediatric to Adult Care

Alterations in Cortical Thickness in Young Male Patients With Childhood-Onset Adult Growth Hormone Deficiency: A Morphometric MRI Study.

BackgroundThe growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis plays an important role in brain structure and maintenance of brain function. There is a close correlation between serum GH and IGF1 levels and age-related cognitive function. The effects of childhood-onset growth hormone deficiency (GHD)on brain morphology are underestimated so far.MethodsIn this cross-sectional study, T1-weighted magnetic resonance imaging was assessed in 17 adult males with childhood-onset GHD and 17 age and gender-matched healthy controls. The cortical thickness was analyzed and compared between the two groups of subjects. Effects of disease status and hormone levels on cortical thickness were also evaluated.ResultsAlthough there was no difference in whole brain volume or gray matter volume between the two groups, there was decreased cortical thickness in the parahippocampal gyrus, posterior cingulate gyrus and occipital visual syncortex in the adult growth hormone deficiency (AGHD) group, and increased cortical thickness in a partial area of the frontal lobe, parietal lobe and occipital visual syncortex in AGHD group. Cortical thickness of the posterior cingulum gyrus was prominently associated with FT3 serum levels only in control group after adjusting of IGF-1 levels.ConclusionThese results suggest that young adult male patients with childhood-onset GHD have alterations in cortical thickness in different brain lobes/regions.

Accuracy and Limitations of the Growth Hormone (GH) Releasing Hormone-Arginine Retesting in Young Adults With Childhood-Onset GH Deficiency.

Background: Re-testing for GH secretion is needed to confirm the diagnosis of GH deficiency (GHD) after adult height achievement in childhood-onset GHD (COGHD).Aim: To define the cut-off of GH peak after retesting with GH-releasing hormone plus arginine (GHRHarg) in the diagnosis of permanent GHD in COGHD of different etiology.Patients and methods: Eighty-eight COGHD (median age 17.2 y), 29 idiopathic GHD (IGHD), 44 cancer survivors (TGHD) and 15 congenital GHD (CGHD) were enrolled in the study; 54 had isolated GHD (iGHD) and 34 had multiple pituitary hormone deficiencies (MPHD). All were tested with insulin tolerance test (ITT) and GHRHarg. IGHD with a GH response to ITT ≥6μg/L were considered true negatives and served as the control group, and patients with a GH response <6μg/L as true positives. Baseline IGF-I was also measured. The diagnostic accuracy of GHRHarg testing and of IGF-I SDS in patients with GHD of different etiologies was evaluated by ROC analysis.Results: Forty-six subjects with a GH peak to ITT ≥6μg/L and 42 with GH peak <6 μg/L showed a GH peak after GHRHarg between 8.8–124μg/L and 0.3–26.3μg/L, respectively; 29 IGHD were true negatives, 42 were true positives and 17 with a high likelihood GHD showed a GH peak to ITT ≥6μg/L. ROC analysis based on the etiology indicated the best diagnostic accuracy for peak GH cutoffs after GHRHarg of 25.3 μg/L in CGHD, 15.7 in TGHD, and 13.8 in MPHD, and for IGF-1 SDS at −2.1 in CGHD, −1.5 in TGHD, and −1.9 in MPHD.Conclusions: Our findings indicate that the best cut-off for GH peak after retesting with GHRHarg changes according to the etiology of GHD during the transition age. Based on these results the diagnostic accuracy of GHRHarg remains questionable.

Adherence, Attitudes and Beliefs of Growth Hormone Deficient Patients - A Questionnaire-based Cohort Study.

GHD is a chronic and systemic disease requiring daily replacement of growth hormone (GHRT). Adherence and attitudes of adult GHD patients are not well known. We sought to assess patients' knowledge of growth hormone deficiency (GHD) in association with treatment adherence and attitudes regarding available and upcoming treatment options. We performed a cross-sectional survey with a custom-made questionnaire at a single centre assessing data on demographics, knowledge of GHD, adherence and attitudes towards GHRT. Of 106 eligible patients actively followed for GHD 70 returned the completed survey (return-rate 66%, 34 m/36 f; age 56±14 years). 46 patients were actively treated, but almost one third (n=24) refused GHRT. 12 patients had participated in clinical trials with LAGH (long-acting growth hormone). Overall, patients with GHRT showed good adherence. Patients refusing GHRT mostly feared side effects and/or had a lack of information/perceived effect. Disease knowledge and level of education were higher in treated than untreated patients (p=0.023/0.017). Only 36% of respondents would initiate treatment with LAGH. Patients with prior LAGH experience and patients with childhood-onset GHD were more likely to adopt LAGH (p=0.048/0.031). Most often, misinformation causes patients to refuse GHRT. Possibly the understanding of their condition and consequences of non-treatment is limited. To improve adherence more focused educational and behavioural strategies may be needed. Willingness to begin a therapy with LAGH was lower than expected (36%). The reasons for reluctance against LAGH need to be elucidated.

Changes in body composition in male adolescents with childhood‐onset GH deficiency during transition

Restarting rhGH in adolescents with childhood-onset (CO-) GHD is usually based on GH retest, IGF-1, additional pituitary hormone deficiencies, pituitary morphology and history. Short-term changes in body composition in adolescents with CO-GHD when off rhGH may contribute to the identification of those in need of treatment continuation. This is a longitudinal single-centre study. The body composition of 90 male adolescents with low-likelihood severe GHD of adolescence was measured by DXA at the time of rhGH discontinuation and 6months thereafter. At diagnosis, mean age was 5.4years, height was -2.68 SDS and stimulated GH peak was 5.1ng/mL. RhGH treatment was stopped at 16.7years at near-final height of -0.44 SDS. The adolescents were re-examined after 3months off rhGH using both IGF-1 and GHRH-arginine tests. Severe GHD of adolescence was defined both by stimulated GH<16ng/mL and by IGF-1<-1.90 SDS. Males with severe GHD of adolescence (n=8) gained more relative and absolute fat mass and lost significantly more relative lean body mass after 6months off rhGH than healthy individuals (n=82; P<0.001). The sum of absolute fat mass gain and lean body mass loss (=body composition changes score; BCC score) correlated highly with the GH peak (R=0.17; P<0.001). A BCC score >7.0kg was 88% sensitive and 94% specific for detecting severe GHD of adolescence (AUC=0.975). Short-term body composition changes when off rhGH are good clinical markers of severe GHD in male adolescents. The novel BBC score is an aggregate of these changes.

Childhood-onset growth hormone deficiency: evaluation after reaching final adult height

Childhood-onset growth hormone deficiency: evaluation after reaching final adult height

SAT-437 The Patro Adults Study of Omnitrope® for the Treatment of Adult Patients with Growth Hormone Deficiency: Latest Safety Outcomes Including Diabetes Risk

Introduction: PATRO Adults is an international, longitudinal, non-interventional study of the long-term safety and efficacy of Omnitrope® (recombinant human growth hormone, rhGH; Sandoz) in adults treated in routine clinical practice. The study provides data on the long-term safety of rhGH in adult patients with severe GH deficiency (GHD). Methods: The study includes adult patients who are receiving treatment with Omnitrope® and have provided informed consent. Patients treated with another rhGH before starting Omnitrope® therapy are also eligible for inclusion. Here we report the latest safety data, with a focus on the risk of diabetes. Results: As of September 2018, 1298 patients had been enrolled on the study over >10 years; 1084 (83.5%) had adulthood-onset GHD (combined GHD, n=956) and 204 (15.7%) had childhood-onset GHD. Overall, 659 (50.8%) patients had been pre-treated with another rhGH. Mean (standard deviation [SD]) age was 49.3 (15.3) years, and mean (SD) body mass index was 29.5 (6.4) kg/m2. In total, 4009 adverse events (AEs) in 889 patients have been reported, with 643 (353 [27.2%] patients) of these regarded as serious. 154 AEs in 92 (7.1%) patients were suspected to be related to Omnitrope®; these included general disorders/administration site conditions in 23 patients, nervous system disorders in 23 patients and musculoskeletal/connective tissue disorders in 36 patients. A total of 20 serious AEs (SAEs) in 17 (1.3%) patients were suspected to be related to Omnitrope®, leading to treatment discontinuation in 5 patients. Overall, 328 patients (282 with combined GHD) have discontinued the study, 73 (61 with combined GHD) due to AEs (26 were considered related to rhGH treatment). To date, 22 cases of diabetes have been reported (21 in patients with combined GHD; 20 in patients with adult-onset GHD). Nine of these reports were SAEs, 2 of which were considered to be treatment-related. The first case was diabetes mellitus aggravation in a 45 year old male with adulthood-onset combined GHD, following 4-6 months of GH therapy; Omnitrope® was permanently discontinued. The second case was worsening of diabetes mellitus in a male aged 72 years with adulthood-onset combined GHD, following 19 years of GH therapy; Omnitrope® treatment was interrupted. Conclusions: Based on this interim analysis, Omnitrope® treatment in adults with GHD is well tolerated in a real-life clinical practice setting, irrespective of pre-treatment status. The ongoing PATRO Adults study will provide further data on the diabetogenic potential and overall safety of long-term GH treatment in this population.

Management options for pediatric growth hormone deficiency

ABSTRACTIntroduction: Growth hormone deficiency (GHD), in 1:4000 children, is congenital or acquired inability to produce serum GH from the pituitary. Management of pediatric GHD is evolving and requires review.Areas covered: Controversies about GHD continue regarding diagnostic criteria, referral criteria, testing, optimal treatment, safety, monitoring, and management during transition to adulthood. Efforts are ongoing to improve efficacy of GH therapy, including prolonging growth by delaying puberty, and once weekly preparations. Early diagnosis of GHD permits starting GH at a young age, normalizing height while keeping mid-normal IGF-I levels. After completion of linear growth, young adults with childhood-onset GHD are unlikely to re-start GH therapy unless the re-start is supervised by the pediatric endocrinologist, or unless the adult provider has experience with pituitary endocrinology.Expert opinion: GH replacement therapy for GHD has benefits for growth (in childhood) and for body composition, hematologic/cardiovascular/metabolic status, and quality of life in childhood leading into adulthood. Improved therapy combinations may lead to enhanced efficacy and better match with normal physiology. Diagnosis of GHD and early GH therapy for childhood cancer survivors with GHD is appropriate when supervised by a team of oncologists and endocrinologists. New approaches to improving outcomes require ongoing monitoring/surveillance.

Bone microarchitecture and volumetric bone density impairment in young male adults with childhood-onset growth hormone deficiency.

ContextAdult growth hormone deficiency (AGHD) is characterized by low bone density and increased risk of fracture. Bone microarchitecture is insufficiently evaluated in patients with childhood-onset AGHD (CO AGHD).ObjectiveTo assess volumetric bone density (vBMD) and bone microarchitecture in CO AGHD in early adulthood after cessation of recombinant growth hormone (rhGH) treatment.Design and subjectsCase–control study in a major academic medical center in Beijing, including 20 young male adults with CO AGHD and 30 age- and weight-matched non-athletic healthy men. High-resolution peripheral quantitative computerized tomography (HR-pQCT) of distal radius and tibia was performed.OutcomesThe main outcomes were vBMD and morphometry parameters from HR-pQCT.ResultsCompared with healthy controls, CO AGHD group had significantly decreased insulin-like growth factor 1 (IGF-1) level and IGF-1 SDS (P < 0.001). β-CTX and alkaline phosphatase levels in CO AGHD group were significantly increased (P < 0.001). CO AGHD group had significantly decreased total vBMD, cortical vBMD, trabecular vBMD, cortical area, cortical thickness as well as trabecular thickness and trabecular bone volume fraction of both tibia and radius (P < 0.001). CO AGHD patients had an 8.4 kg decrease in grip strength and a significant decrease in creatinine levels (P = 0.001). At both tibia and radius, by finite element analysis, bone stiffness and failure load of the CO AGHD patients were significantly decreased (P < 0.001). After adjusting for age, BMI and serum levels of testosterone and free thyroxin, serum IGF-1 level was a positive predictor for total vBMD, cortical vBMD, cortical area, trabecular vBMD, bone stiffness and failure load of both tibia and distal radius in all subjects.ConclusionsYoung adult male patients with childhood-onset adult growth hormone deficiency who are no longer receiving growth hormone replacement have prominently impaired volumetric bone density and bone microarchitecture and lower estimated bone strength.

Childhood-onset growth hormone deficiency and the transition to adulthood: current perspective.

Childhood-onset growth hormone deficiency (CO-GHD) is an endocrine condition associated with a broad range of health issues from childhood through to adulthood, which requires particular attention during the transition period from adolescence to young adulthood. There is uncertainty in the clinical practice of the management of CO-GHD during transition regarding the clinical assessment and management of individual patients during and after transition to obtain optimal follow-up and improved health outcomes. Despite the availability of clinical guidelines providing the framework for transition of young adults with CO-GHD, there remains substantial variation in approaching transitional care among pediatric and adult services. A well-structured and coordinated transitional plan with clear communication and direct collaboration between pediatric and adult health care to ensure optimal management of adolescents with CO-GHD during transition is needed.

National Program of Severe Growth Hormone Deficiency Treatment in Adults and Adolescents after Completion of Growth Promoting Therapy.

Growth hormone (GH) has been used in the treatment of short stature in children with GH deficiency (GHD) for 60 years, and for about 30 years also in the treatment of adults with GHD, in whom such treatment is carried out due to metabolic indications. In Poland, GH treatment is reimbursed only in children with GHD, while so far it has not been refunded in adults with GHD. There are two groups of adults (or adolescents after growth completion) with GHD, who require GH therapy: patients with GHD that occurred in childhood (childhood-onset GHD - CO-GHD) and patients with GHD acquired in adulthood (adulthood-onset GHD - AO-GHD). This review presents a brief outline of the history of GH treatment in humans, the latest data on the causes and symptoms of GHD in adults, and the complications of untreated GHD. Current recommendations regarding diagnosis, treatment and monitoring of GH therapy in adults are also discussed. Moreover, the review paper presents the objectives, assumptions, and plans of implementation of the "National Treatment Program for Severe Growth Hormone Deficiency in Adults and Adolescents after Completion of the Growth Promoting Therapy", as well as the expected health and economic effects of introduction of GH treatment in adults with GHD in Poland.

Resistance exercise alone improves muscle strength in growth hormone deficient males in the transition phase.

Background During the transition phase (TP), patients with growth hormone deficiency (GHD) exhibit decreased muscle strength. Studies assessing the effects of resistance exercise alone on muscle strength in these individuals are scarce. The objective of this study was to evaluate the effects of a program of resistance exercise (PRE) on parameters of muscle strength in subjects in the TP and with childhood-onset GHD treated with recombinant GH (rGH). Methods Sixteen male patients were enrolled and divided into two groups: GHD (n=9) and GH sufficiency (GHS, n=7). Patients with GHD underwent a 12-week PRE followed by another 12-week PRE plus rGH, while GHS patients underwent a 12-week PRE alone. Dynamic knee muscle strength was evaluated using an isokinetic dynamometer. Results Before PRE, there were significant differences between the groups regarding the results of flexor peak torque (FPT) normalized to body weight (BW-FPT) in the dominant (DO, p=0.008) and non-dominant (ND, p=0.01) limbs, and in the agonist/antagonist (A/A) ratio in the DO (p=0.02) and ND (p=0.006) limbs. After PRE in the GHD group, values of FPT and BW-FPT in both limbs increased significantly (p<0.001) and independently of rGH, while the A/A ratio value improved significantly (p<0.001) in the ND limb. Conclusions A short period of PRE alone was sufficient to improve parameters of muscle strength in young male adults with childhood-onset GHD.